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Evaluate regularly for hearing loss in line with local guidance.","classification":"Optional","phenotypes":{"MT-RNR1":"uncertain risk of aminoglycoside-induced hearing loss"},"activityscore":{},"population":"general","comments":"Individuals without MT-RNR1 aminoglycoside-induced hearing loss increased risk variants are still at risk of aminoglycoside-associated hearing loss, especially with high drug levels or prolonged courses."},{"lookupkey":{"MT-RNR1":"increased risk of aminoglycoside-induced hearing loss"},"drugname":"streptomycin","guidelinename":"MT-RNR1 and Aminoglycosides","implications":{"MT-RNR1":"Very high risk of developing hearing loss if administered an aminoglycoside antibiotic."},"drugrecommendation":"Avoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.","classification":"Strong","phenotypes":{"MT-RNR1":"increased risk of aminoglycoside-induced hearing loss"},"activityscore":{},"population":"general","comments":"If no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring)."},{"lookupkey":{"MT-RNR1":"normal risk of aminoglycoside-induced hearing loss"},"drugname":"streptomycin","guidelinename":"MT-RNR1 and Aminoglycosides","implications":{"MT-RNR1":"Normal risk of developing hearing loss if administered an aminoglycoside antibiotic."},"drugrecommendation":"Use aminoglycoside antibiotics at standard doses for the shortest feasible course with therapeutic dose monitoring. 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The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use. If a amitripyline is warranted, consider a 50% reduction of recommended starting dose. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Normal Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Normal Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Normal Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Normal Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. 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Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Normal Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Normal Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Normal Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Normal Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Normal Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Normal Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Normal Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use. If amitripyline is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use. If amitripyline is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use. If amitripyline is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use. If amitripyline is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use. If amitripyline is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Indeterminate"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremely high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"G6PD":"Normal"},"drugname":"hydroxychloroquine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Rapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"G6PD":"Deficient"},"drugname":"hydroxychloroquine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs"},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Indeterminate"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of fluvoxamine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use. If a amitripyline is warranted, consider a 50% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"UGT1A1":"Indeterminate"},"drugname":"atazanavir","guidelinename":"UGT1A1 and Atazanavir","implications":{"UGT1A1":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"UGT1A1":"Indeterminate"},"activityscore":{"UGT1A1":"n/a"},"population":"general","comments":"UGT1A1*80 is in very high linkage disequilibrium with *28 and *37. In the rare event that *80 is detected but *28 and *37 are not, there are not enough clinical data to predict metabolizer status with certainty. However, if only *80 is interrogated and the patient is heterozygous or homozygous for *80, an intermediate or poor metabolizer phenotype may be inferred, respectively."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use. If amitripyline is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use. If amitripyline is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use. If amitripyline is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use. If amitripyline is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use. If amitripyline is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid amitriptyline use; If amitriptyline is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Likely Poor Metabolizer"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"No Result"},"drugname":"amitriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"G6PD":"Normal"},"drugname":"aspirin","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"<= 1g per day","comments":"aspirin ≤ 1 g/day"},{"lookupkey":{"G6PD":"Deficient"},"drugname":"aspirin","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"<= 1g per day","comments":"aspirin ≤ 1 g/day. Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs"},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"aspirin","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"<= 1g per day","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for for acute exacerbation of chronic hemolysis."},{"lookupkey":{"G6PD":"Variable"},"drugname":"aspirin","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"<= 1g per day","comments":"aspirin ≤ 1 g/day. Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"aspirin","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"<= 1g per day","comments":"aspirin ≤ 1 g/day"},{"lookupkey":{"UGT1A1":"Normal Metabolizer"},"drugname":"atazanavir","guidelinename":"UGT1A1 and Atazanavir","implications":{"UGT1A1":"Reference UGT1A1 activity; very low likelihood of bilirubin-related discontinuation of atazanavir."},"drugrecommendation":"There is no need to avoid prescribing of atazanavir based on UGT1A1 genetic test result. Inform the patient that some patients stop atazanavir because of jaundice (yellow eyes and skin), but that this patient's genotype makes this unlikely (less than about a 1 in 20 chance of stopping atazanavir because of jaundice).","classification":"Strong","phenotypes":{"UGT1A1":"Normal Metabolizer"},"activityscore":{"UGT1A1":"n/a"},"population":"general","comments":"All studies correlating UGT1A1 genotypes with atazanavir adverse events have involved ritonavir boosting. However, concentration-time profiles are equivalent when boosted with either cobicistat or ritonavir (PMID 23532097), and bilirubin-related adverse events including discontinuation of atazanavir occur in a similar percentage of patients prescribed atazanavir with cobicistat or ritonavir (PMID 23532097). Associations between UGT1A1 genotype, bilirubin elevations, and atazanavir/r discontinuation therefore almost certainly translate to atazanavir/cobicistat. \"reference\" function refers to the UGT1A1 allele to which other alleles are compared."},{"lookupkey":{"UGT1A1":"Intermediate Metabolizer"},"drugname":"atazanavir","guidelinename":"UGT1A1 and Atazanavir","implications":{"UGT1A1":"Somewhat decreased UGT1A1 activity; low likelihood of bilirubin-related discontinuation of atazanavir."},"drugrecommendation":"There is no need to avoid prescribing of atazanavir based on UGT1A1 genetic test result. Inform the patient that some patients stop atazanavir because of jaundice (yellow eyes and skin), but that this patient's genotype makes this unlikely (less than about a 1 in 20 chance of stopping atazanavir because of jaundice).","classification":"Strong","phenotypes":{"UGT1A1":"Intermediate Metabolizer"},"activityscore":{"UGT1A1":"n/a"},"population":"general","comments":"All studies correlating UGT1A1 genotypes with atazanavir adverse events have involved ritonavir boosting. However, concentration-time profiles are equivalent when boosted with either cobicistat or ritonavir (PMID 23532097), and bilirubin-related adverse events including discontinuation of atazanavir occur in a similar percentage of patients prescribed atazanavir with cobicistat or ritonavir (PMID 23532097). Associations between UGT1A1 genotype, bilirubin elevations, and atazanavir/r discontinuation therefore almost certainly translate to atazanavir/cobicistat."},{"lookupkey":{"UGT1A1":"Poor Metabolizer"},"drugname":"atazanavir","guidelinename":"UGT1A1 and Atazanavir","implications":{"UGT1A1":"Markedly decreased UGT1A1 activity; high likelihood of bilirubin-related discontinuation of atazanavir."},"drugrecommendation":"Consider an alternative agent particularly where jaundice would be of concern to the patient. If atazanavir is to be prescribed, there is a high likelihood of developing jaundice that will result in atazanavir discontinuation (at least 20% and as high as 60%).","classification":"Strong","phenotypes":{"UGT1A1":"Poor Metabolizer"},"activityscore":{"UGT1A1":"n/a"},"population":"general","comments":"All studies correlating UGT1A1 genotypes with atazanavir adverse events have involved ritonavir boosting. However, concentration-time profiles are equivalent when boosted with either cobicistat or ritonavir (PMID 23532097), and bilirubin-related adverse events including discontinuation of atazanavir occur in a similar percentage of patients prescribed atazanavir with cobicistat or ritonavir (PMID 23532097). Associations between UGT1A1 genotype, bilirubin elevations, and atazanavir/r discontinuation therefore almost certainly translate to atazanavir/cobicistat."},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If < 200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If < 200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If < 200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If < 200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If < 200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If < 200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Possibly higher atomoxetine concentrations as compared to normal metabolizers but questionable clinical significance. Intermediate metabolizers with an activity score of 1 may be at an increased risk of discontinuation as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If < 200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Decreased metabolism of atomoxetine and higher atomoxetine concentrations as compared to normal metabolizers. Individuals with activity score of 1.0 with CYP2D6*10 may be at an increased risk of discontinuation as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and if no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a plasma concentration 2 to 4 hours after dosing. If response is inadequate and concentration is < 200 ng/mL, consider a proportional dose increase to achieve a concentration to approach 400 ng/mL. If unacceptable side effects are present at any time, consider a reduction in dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Decreased metabolism of atomoxetine and higher atomoxetine concentrations as compared to normal metabolizers. Intermediate metabolizers may be at an increased risk of discontinuation as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and if no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a plasma concentration 2 to 4 hours after dosing. If response is inadequate and concentration is < 200 ng/mL, consider a proportional dose increase to achieve a concentration to approach 400 ng/mL. If unacceptable side effects are present at any time, consider a reduction in dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Decreased metabolism of atomoxetine and higher atomoxetine concentrations as compared to normal metabolizers. Intermediate metabolizers may be at an increased risk of discontinuation as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and if no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a plasma concentration 2 to 4 hours after dosing. If response is inadequate and concentration is < 200 ng/mL, consider a proportional dose increase to achieve a concentration to approach 400 ng/mL. If unacceptable side effects are present at any time, consider a reduction in dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Significantly decreased metabolism of atomoxetine may result in higher concentrations as compared to non-poor metabolizers. This may increase the occurrence of side effects, but also a greater improvement of ADHD symptoms as compared to non-poor metabolizers in those who tolerate treatment. Poor metabolizer status is associated with lower final dose requirements as compared to non-poor metabolizers."},"drugrecommendation":"Initiate with a dose of 0.5 mg/kg/day and if no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a plasma concentration 4 hours after dosing. If response is inadequate and concentration is < 200 ng/mL, consider a proportional dose increase to achieve a concentration to approach 400 ng/mL. If unacceptable side effects are present at any time, consider a reduction in dose.","classification":"Strong","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"pediatrics","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"pediatrics","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of fluvoxamine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Possibly higher atomoxetine concentrations as compared to normal metabolizers but questionable clinical significance. Intermediate metabolizers with an activity score of 1 may be at an increased risk of discontinuation as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated."},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Decreased metabolism of atomoxetine and higher atomoxetine concentrations as compared to normal metabolizers. Individuals with activity score of 1.0 with CYP2D6*10 may be at an increased risk of discontinuation as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 40 mg/day and if no clinical response and in the absence of adverse events after 2 weeks increase dose to 80 mg/day. If response is inadequate after 2 weeks consider obtaining a plasma concentration 2-4 h after dosing. If concentration is <200 ng/mL, consider a proportional dose increase to achieve a concentration to approach 400 ng/mL. If unacceptable side effects are present at any time, consider a reduction in dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Decreased metabolism of atomoxetine and higher atomoxetine concentrations as compared to normal metabolizers. Intermediate metabolizers may be at an increased risk of discontinuation as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 40 mg/day and if no clinical response and in the absence of adverse events after 2 weeks increase dose to 80 mg/day. If response is inadequate after 2 weeks consider obtaining a plasma concentration 2-4 h after dosing. If concentration is <200 ng/mL, consider a proportional dose increase to achieve a concentration to approach 400 ng/mL. If unacceptable side effects are present at any time, consider a reduction in dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Decreased metabolism of atomoxetine and higher atomoxetine concentrations as compared to normal metabolizers. Intermediate metabolizers may be at an increased risk of discontinuation as compared to poor metabolizers."},"drugrecommendation":"Initiate with a dose of 40 mg/day and if no clinical response and in the absence of adverse events after 2 weeks increase dose to 80 mg/day. If response is inadequate after 2 weeks consider obtaining a plasma concentration 2-4 h after dosing. If concentration is <200 ng/mL, consider a proportional dose increase to achieve a concentration to approach 400 ng/mL. If unacceptable side effects are present at any time, consider a reduction in dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"Significantly decreased metabolism of atomoxetine may result in higher concentrations as compared to non-poor metabolizers. This may increase the occurrence of treatment-emergent side effects, but also a greater improvement of ADHD symptoms as compared to non-poor metabolizers in those who tolerate treatment. Poor metabolizer status is associated with lower final dose requirements as compared to non-poor metabolizers."},"drugrecommendation":"Initiate with a dose of 40 mg/day and if no clinical response and in the absence of adverse events after 2 weeks increase dose to 80 mg/day. If response is inadequate after 2 weeks, consider obtaining a plasma concentration 2 to 4 hours after dosing. If concentration is <200 ng/mL, consider a proportional dose increase to achieve a concentration to approach 400 ng/mL. If unacceptable side effects are present at any time, consider a reduction in dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"adults","comments":"Therapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL."},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"atomoxetine","guidelinename":"CYP2D6 and Atomoxetine","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"adults","comments":"n/a"},{"lookupkey":{"SLCO1B1":"Increased Function"},"drugname":"atorvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses based on disease-specific guidelines.","classification":"Strong","phenotypes":{"SLCO1B1":"Increased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"SLCO1B1":"Normal Function"},"drugname":"atorvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses based on disease-specific guidelines.","classification":"Strong","phenotypes":{"SLCO1B1":"Normal Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"SLCO1B1":"Possible Decreased Function"},"drugname":"atorvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased atorvastatin exposure as compared to normal function which may translate to increased myopathy risk"},"drugrecommendation":"Prescribe ≤40mg as a starting dose and adjust doses of atorvastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for 40mg dose. If dose >40mg needed for desired efficacy, consider combination therapy (i.e., atorvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Moderate","phenotypes":{"SLCO1B1":"Possible Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Decreased Function"},"drugname":"atorvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased atorvastatin exposure as compared to normal function which may translate to increased myopathy risk"},"drugrecommendation":"Prescribe ≤40mg as a starting dose and adjust doses of atorvastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for 40mg dose. If dose >40mg needed for desired efficacy, consider combination therapy (i.e., atorvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Moderate","phenotypes":{"SLCO1B1":"Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Poor Function"},"drugname":"atorvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased atorvastatin exposure as compared to normal and decreased function which may translate to increased myopathy risk."},"drugrecommendation":"Prescribe ≤20mg as a starting dose and adjust doses of atorvastatin based on disease-specific guidelines. If dose >20mg is needed for desired efficacy, consider rosuvastatin or combination therapy (i.e., atorvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Moderate","phenotypes":{"SLCO1B1":"Poor Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Indeterminate"},"drugname":"atorvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"SLCO1B1":"Indeterminate"},"activityscore":{},"population":"general","comments":"n/a"},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites and higher concentrations of MeMPNs compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with standard starting dose (e.g., 2 mg/kg/day for autoimmune diseases). During therapy, adjust doses of azathioprine based on disease-specific guidelines. It usually takes at least 2 weeks to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites and higher concentrations of MeMPNs compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern. TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites and higher concentrations of MeMPNs compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern. TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Poor Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremely high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremely high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremely high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremely high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with reduced starting doses (20%-50% of standard starting dose) if standard starting dose is ≥ 2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Moderate","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with reduced starting doses (20%-50% of standard starting dose) if standard starting dose is ≥ 2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Moderate","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with reduced starting doses (20%-50% of standard starting dose) if standard starting dose is ≥ 2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Moderate","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with reduced starting doses (20%-50% of standard starting dose) if standard starting dose is ≥ 2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Moderate","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"hydroxychloroquine","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for acute on chronic hemolysis"},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Indeterminate"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites and higher concentrations of MeMPNs compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with standard starting dose (e.g., 2 mg/kg/day for autoimmune diseases). During therapy, adjust doses of azathioprine based on disease-specific guidelines. It usually takes at least 2 weeks to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Indeterminate"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Indeterminate"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Normal Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with standard starting dose (e.g., 2 mg/kg/day for autoimmune diseases). During therapy, adjust doses of azathioprine based on disease-specific guidelines. It usually takes at least 2 weeks to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Indeterminate"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"n/a"},"drugrecommendation":"Neither TPMT or NUDT15 phenotype could be assigned based on genotyping performed. Consider evaluating TPMT erythrocyte activity to assess TPMT phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"TPMT":"No Result","NUDT15":"Normal Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with standard starting dose (e.g., 2 mg/kg/day for autoimmune diseases). During therapy, adjust doses of azathioprine based on disease-specific guidelines. It usually takes at least 2 weeks to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"No Result","NUDT15":"Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"No Result","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"No Result","NUDT15":"Poor Metabolizer"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"TPMT":"No Result","NUDT15":"Indeterminate"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"n/a"},"drugrecommendation":"Neither TPMT or NUDT15 phenotype could be assigned based on genotyping performed. Consider evaluating TPMT erythrocyte activity to assess TPMT phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"No Result"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites and higher concentrations of MeMPNs compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with standard starting dose (e.g., 2 mg/kg/day for autoimmune diseases). During therapy, adjust doses of azathioprine based on disease-specific guidelines. It usually takes at least 2 weeks to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"No Result"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"No Result"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"No Result"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremely high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"No Result"},"drugname":"azathioprine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"n/a"},"drugrecommendation":"Neither TPMT or NUDT15 phenotype could be assigned based on genotyping performed. Consider evaluating TPMT erythrocyte activity to assess TPMT phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"HLA-A":"*31:01 positive","HLA-B":"*15:02 negative"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Greater risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Normal risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"If patient is carbamazepine-naïve and alternative agents are available, do not use carbamazepine.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ naive","comments":"Other aromatic anticonvulsants have very limited evidence, if any, linking SJS/TEN, DRESS, and/or MPE with the HLA-A*31:01 allele, and thus no recommendation can be made with respect to choosing another aromatic anticonvulsant as an alternative agent. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-A":"No Result","HLA-B":"*15:02 negative"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"n/a","HLA-B":"Normal risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"Use carbamazepine per standard dosing guidelines.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ naive","comments":"HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835)."},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"n/a"},{"lookupkey":{"HLA-A":"*31:01 negative","HLA-B":"*15:02 positive"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Greater risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"If patient is carbamazepine-naïve, do not use carbamazepine.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ naive","comments":"Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered."},{"lookupkey":{"HLA-A":"*31:01 positive","HLA-B":"*15:02 positive"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Greater risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Greater risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"If patient is carbamazepine-naïve, do not use carbamazepine.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ naive","comments":"Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered."},{"lookupkey":{"HLA-A":"No Result","HLA-B":"*15:02 positive"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"n/a","HLA-B":"Greater risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"If patient is carbamazepine-naïve, do not use carbamazepine.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ naive","comments":"Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered."},{"lookupkey":{"HLA-A":"*31:01 negative","HLA-B":"No Result"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"n/a"},"drugrecommendation":"Use carbamazepine per standard dosing guidelines.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ naive","comments":"HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835)."},{"lookupkey":{"HLA-A":"*31:01 positive","HLA-B":"No Result"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Greater risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"n/a"},"drugrecommendation":"If patient is carbamazepine-naïve and alternative agents are available, do not use carbamazepine.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ naive","comments":"Other aromatic anticonvulsants have very limited evidence, if any, linking SJS/TEN, DRESS, and/or MPE with the HLA-A*31:01 allele, and thus no recommendation can be made with respect to choosing another aromatic anticonvulsant as an alternative agent. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-A":"*31:01 negative","HLA-B":"*15:02 negative"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Normal risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"Use carbamazepine per standard dosing guidelines.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ naive","comments":"HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835)."},{"lookupkey":{"HLA-A":"*31:01 negative","HLA-B":"*15:02 negative"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Normal risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"Use carbamazepine per standard dosing guidelines.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ-no alternatives","comments":"HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835)."},{"lookupkey":{"HLA-A":"*31:01 positive","HLA-B":"*15:02 negative"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Greater risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Normal risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"If patient is carbamazepine-naïve and alternative agents are not available, consider the use of carbamazepine with increased frequency of clinical monitoring. Discontinue therapy at first evidence of a cutaneous adverse reaction.","classification":"Optional","phenotypes":{},"activityscore":{},"population":"CBZ-no alternatives","comments":"n/a"},{"lookupkey":{"HLA-A":"No Result","HLA-B":"*15:02 negative"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"n/a","HLA-B":"Normal risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"Use carbamazepine per standard dosing guidelines.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ-no alternatives","comments":"HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835)."},{"lookupkey":{"HLA-A":"*31:01 negative","HLA-B":"*15:02 positive"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Greater risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"If patient is carbamazepine-naïve, do not use carbamazepine.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ-no alternatives","comments":"Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered."},{"lookupkey":{"HLA-A":"*31:01 positive","HLA-B":"*15:02 positive"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Greater risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Greater risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"If patient is carbamazepine-naïve, do not use carbamazepine.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ-no alternatives","comments":"Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered."},{"lookupkey":{"HLA-A":"No Result","HLA-B":"*15:02 positive"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"n/a","HLA-B":"Greater risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"If patient is carbamazepine-naïve, do not use carbamazepine.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ-no alternatives","comments":"Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered."},{"lookupkey":{"HLA-A":"*31:01 negative","HLA-B":"No Result"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"n/a"},"drugrecommendation":"Use carbamazepine per standard dosing guidelines.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ-no alternatives","comments":"HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835)."},{"lookupkey":{"HLA-A":"*31:01 positive","HLA-B":"No Result"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Greater risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"n/a"},"drugrecommendation":"If patient is carbamazepine-naïve and alternative agents are not available, consider the use of carbamazepine with increased frequency of clinical monitoring. Discontinue therapy at first evidence of a cutaneous adverse reaction.","classification":"Optional","phenotypes":{},"activityscore":{},"population":"CBZ-no alternatives","comments":"n/a"},{"lookupkey":{"HLA-A":"*31:01 negative","HLA-B":"*15:02 negative"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Normal risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"Use carbamazepine per standard dosing guidelines.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ use >3mos ","comments":"HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835)."},{"lookupkey":{"HLA-A":"*31:01 positive","HLA-B":"*15:02 negative"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Greater risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Normal risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"The latency period for cutaneous adverse drug reactions is variable depending on phenotype; however, all usually occur within three months of regular dosing. Therefore, if the patient has previously used carbamazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine.","classification":"Optional","phenotypes":{},"activityscore":{},"population":"CBZ use >3mos ","comments":"Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital."},{"lookupkey":{"HLA-A":"No Result","HLA-B":"*15:02 negative"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"n/a","HLA-B":"Normal risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"Use carbamazepine per standard dosing guidelines.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ use >3mos ","comments":"HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835)."},{"lookupkey":{"HLA-A":"*31:01 negative","HLA-B":"*15:02 positive"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Greater risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (~4-28 days), and cases usually occur within three months of dosing; therefore, if the patient has previously used carbamazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine in the future.","classification":"Optional","phenotypes":{},"activityscore":{},"population":"CBZ use >3mos ","comments":"Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered."},{"lookupkey":{"HLA-A":"*31:01 positive","HLA-B":"*15:02 positive"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Greater risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"Greater risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (~4-28 days), and cases usually occur within three months of dosing; therefore, if the patient has previously used carbamazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine in the future.","classification":"Optional","phenotypes":{},"activityscore":{},"population":"CBZ use >3mos ","comments":"Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered."},{"lookupkey":{"HLA-A":"No Result","HLA-B":"*15:02 positive"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"n/a","HLA-B":"Greater risk of carbamazepine-induced SJS/TEN"},"drugrecommendation":"The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (~4-28 days), and cases usually occur within three months of dosing; therefore, if the patient has previously used carbamazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine in the future.","classification":"Optional","phenotypes":{},"activityscore":{},"population":"CBZ use >3mos ","comments":"Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered."},{"lookupkey":{"HLA-A":"*31:01 negative","HLA-B":"No Result"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Normal risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"n/a"},"drugrecommendation":"Use carbamazepine per standard dosing guidelines.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"CBZ use >3mos ","comments":"HLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/TEN, and its use is currently recommended to guide use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN (PMID 25355835)."},{"lookupkey":{"HLA-A":"*31:01 positive","HLA-B":"No Result"},"drugname":"carbamazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-A":"Greater risk of carbamazepine-induced SJS/TEN, DRESS, and MPE","HLA-B":"n/a"},"drugrecommendation":"The latency period for cutaneous adverse drug reactions is variable depending on phenotype; however, all usually occur within three months of regular dosing. Therefore, if the patient has previously used carbamazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine.","classification":"Optional","phenotypes":{},"activityscore":{},"population":"CBZ use >3mos ","comments":"Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital."},{"lookupkey":{"CYP2C9":"2.0"},"drugname":"celecoxib","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"1.5"},"drugname":"celecoxib","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Mildly reduced metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8."},{"lookupkey":{"CYP2C9":"1.0"},"drugname":"celecoxib","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities"},"drugrecommendation":"Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events such as blood pressure and kidney function during course of therapy.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8."},{"lookupkey":{"CYP2C9":"0.5"},"drugname":"celecoxib","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Initiate therapy with 25-50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25-50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady state is reached (at least 8 days for celecoxib after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"0.0"},"drugname":"celecoxib","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Initiate therapy with 25-50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25-50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady state is reached (at least 8 days for celecoxib after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"n/a"},"drugname":"celecoxib","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"2.0"},"drugname":"flurbiprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"1.5"},"drugname":"flurbiprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Mildly reduced metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8."},{"lookupkey":{"CYP2C9":"1.0"},"drugname":"flurbiprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities"},"drugrecommendation":"Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events such as blood pressure and kidney function during course of therapy.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8."},{"lookupkey":{"CYP2C9":"0.5"},"drugname":"flurbiprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Initiate therapy with 25-50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25-50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady state is reached (at least 8 days for celecoxib after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"G6PD":"Variable"},"drugname":"hydroxychloroquine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"hydroxychloroquine","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"CYP2C9":"0.0"},"drugname":"flurbiprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Initiate therapy with 25-50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25-50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady state is reached (at least 8 days for celecoxib after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"n/a"},"drugname":"flurbiprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"2.0"},"drugname":"ibuprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"1.5"},"drugname":"ibuprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Mildly reduced metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8."},{"lookupkey":{"CYP2C9":"1.0"},"drugname":"ibuprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities"},"drugrecommendation":"Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events such as blood pressure and kidney function during course of therapy.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8."},{"lookupkey":{"CYP2C9":"0.5"},"drugname":"ibuprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Initiate therapy with 25-50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25-50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady state is reached (at least 8 days for celecoxib after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"0.0"},"drugname":"ibuprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Initiate therapy with 25-50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25-50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady state is reached (at least 8 days for celecoxib after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"n/a"},"drugname":"ibuprofen","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"2.0"},"drugname":"lornoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"1.5"},"drugname":"lornoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Mildly reduced metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8."},{"lookupkey":{"G6PD":"Normal"},"drugname":"vitamin c","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"1.0"},"drugname":"lornoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities"},"drugrecommendation":"Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events such as blood pressure and kidney function during course of therapy.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8."},{"lookupkey":{"CYP2C9":"0.5"},"drugname":"lornoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Initiate therapy with 25-50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25-50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady state is reached (at least 8 days for celecoxib after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"0.0"},"drugname":"lornoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Initiate therapy with 25-50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25-50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady state is reached (at least 8 days for celecoxib after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"n/a"},"drugname":"lornoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"G6PD":"Normal"},"drugname":"chloramphenicol","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"chloramphenicol","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs"},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"chloramphenicol","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for acute on chronic hemolysis"},{"lookupkey":{"G6PD":"Variable"},"drugname":"chloramphenicol","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"chloramphenicol","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"chloroquine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"chloroquine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs"},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"chloroquine","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for acute on chronic hemolysis"},{"lookupkey":{"G6PD":"Variable"},"drugname":"chloroquine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"chloroquine","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"vitamin c","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for acute on chronic hemolysis"},{"lookupkey":{"G6PD":"Variable"},"drugname":"vitamin c","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"vitamin c","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"vitamin k","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"vitamin k","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs"},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"vitamin k","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for acute on chronic hemolysis"},{"lookupkey":{"G6PD":"Variable"},"drugname":"vitamin k","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"vitamin k","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"CYP2C19":"Ultrarapid Metabolizer"},"drugname":"citalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Increased metabolism of citalopram and escitalopram to less active compounds when compared to CYP2C19 rapid and normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, and adequate efficacy is not achieved at standard maintenance dosing, consider titrating to a higher maintenance dose.","classification":"Strong","phenotypes":{"CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"CYP2C19":"Rapid Metabolizer"},"drugname":"citalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Increase in metabolism of citalopram and escitalopram to less active compounds when compared to CYP2C19 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Initiate therapy with recommended starting dose. If patient does not adequately respond to recommended maintenance dosing, consider titrating to a higher maintenance dose or switching to a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19.","classification":"Optional","phenotypes":{"CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"CYP2C19":"Normal Metabolizer"},"drugname":"citalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"citalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Reduced metabolism when compared to CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose."},{"lookupkey":{"CYP2C19":"Intermediate Metabolizer"},"drugname":"citalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Reduced metabolism when compared to CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.","classification":"Moderate","phenotypes":{"CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose."},{"lookupkey":{"CYP2C19":"Likely Poor Metabolizer"},"drugname":"citalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Reduced metabolism of citalopram and escitalopram to less active compounds when compared to CYP2C19 normal and intermediate metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, consider a lower starting dose, slower titration schedule and 50% reduction of the standard maintenance dose as compared to normal metabolizers.","classification":"Strong","phenotypes":{"CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Per the FDA warning, citalopram 20 mg/day is the maximum recommended dose in CYP2C19 poor metabolizers due to the risk of QT prolongation. FDA product labeling additionally cautions that citalopram dose should be limited to 20 mg/day in patients with hepatic impairment, those taking a CYP2C19 inhibitor, and patients greater than 60 years of age."},{"lookupkey":{"CYP2C19":"Poor Metabolizer"},"drugname":"citalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Reduced metabolism of citalopram and escitalopram to less active compounds when compared to CYP2C19 normal and intermediate metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, consider a lower starting dose, slower titration schedule and 50% reduction of the standard maintenance dose as compared to normal metabolizers.","classification":"Strong","phenotypes":{"CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Per the FDA warning, citalopram 20 mg/day is the maximum recommended dose in CYP2C19 poor metabolizers due to the risk of QT prolongation. FDA product labeling additionally cautions that citalopram dose should be limited to 20 mg/day in patients with hepatic impairment, those taking a CYP2C19 inhibitor, and patients greater than 60 years of age."},{"lookupkey":{"CYP2C19":"Indeterminate"},"drugname":"citalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Indeterminate"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Ultrarapid Metabolizer"},"drugname":"escitalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Increased metabolism of citalopram and escitalopram to less active compounds when compared to CYP2C19 rapid and normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, and adequate efficacy is not achieved at standard maintenance dosing, consider titrating to a higher maintenance dose.","classification":"Strong","phenotypes":{"CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"CYP2C19":"Rapid Metabolizer"},"drugname":"escitalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Increase in metabolism of citalopram and escitalopram to less active compounds when compared to CYP2C19 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Initiate therapy with recommended starting dose. If patient does not adequately respond to recommended maintenance dosing, consider titrating to a higher maintenance dose or switching to a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19.","classification":"Optional","phenotypes":{"CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"CYP2C19":"Normal Metabolizer"},"drugname":"escitalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"escitalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Reduced metabolism when compared to CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose."},{"lookupkey":{"CYP2C19":"Intermediate Metabolizer"},"drugname":"escitalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Reduced metabolism when compared to CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.","classification":"Moderate","phenotypes":{"CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose."},{"lookupkey":{"CYP2C19":"Likely Poor Metabolizer"},"drugname":"escitalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Reduced metabolism of citalopram and escitalopram to less active compounds when compared to CYP2C19 normal and intermediate metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, consider a lower starting dose, slower titration schedule and 50% reduction of the standard maintenance dose as compared to normal metabolizers.","classification":"Strong","phenotypes":{"CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Per the FDA warning, citalopram 20 mg/day is the maximum recommended dose in CYP2C19 poor metabolizers due to the risk of QT prolongation. FDA product labeling additionally cautions that citalopram dose should be limited to 20 mg/day in patients with hepatic impairment, those taking a CYP2C19 inhibitor, and patients greater than 60 years of age."},{"lookupkey":{"CYP2C19":"Poor Metabolizer"},"drugname":"escitalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"Reduced metabolism of citalopram and escitalopram to less active compounds when compared to CYP2C19 normal and intermediate metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, consider a lower starting dose, slower titration schedule and 50% reduction of the standard maintenance dose as compared to normal metabolizers.","classification":"Strong","phenotypes":{"CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"Per the FDA warning, citalopram 20 mg/day is the maximum recommended dose in CYP2C19 poor metabolizers due to the risk of QT prolongation. FDA product labeling additionally cautions that citalopram dose should be limited to 20 mg/day in patients with hepatic impairment, those taking a CYP2C19 inhibitor, and patients greater than 60 years of age."},{"lookupkey":{"CYP2C19":"Indeterminate"},"drugname":"escitalopram","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Indeterminate"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2C9":"n/a"},"drugname":"tenoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use. If clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use. If clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use. If clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use. If clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use. If clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use. If clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use. If clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use. If clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use. If clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use. If clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use. If a clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use. If a clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use. If a clomipramine is warranted, consider a 50% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. 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Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. 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Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid clomipramine use; If clomipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. 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Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of morphine leading to higher risk of toxicity"},"drugrecommendation":"Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Normal Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Likely Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"No Result"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Rapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Indeterminate"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Likely Poor Metabolizer"},"drugname":"clomipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Increased clopidogrel active metabolite formation; lower on-treatment platelet reactivity; no association with higher bleeding risk"},"drugrecommendation":"If considering clopidogrel, use at standard dose (75 mg/day)","classification":"Strong","phenotypes":{"CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{},"population":"CVI ACS PCI ","comments":"For cardiovascular indications of acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). ACS and/or PCI includes patients undergoing PCI for an ACS or non-ACS (elective) indication."},{"lookupkey":{"CYP2C19":"Rapid Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Normal or increased clopidogrel active metabolite formation; normal or lower on-treatment platelet reactivity; no association with higher bleeding risk"},"drugrecommendation":"If considering clopidogrel, use at standard dose (75 mg/day)","classification":"Strong","phenotypes":{"CYP2C19":"Rapid Metabolizer"},"activityscore":{},"population":"CVI ACS PCI ","comments":"For cardiovascular indications of acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). ACS and/or PCI includes patients undergoing PCI for an ACS or non-ACS (elective) indication."},{"lookupkey":{"CYP2C19":"Normal Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity"},"drugrecommendation":"If considering clopidogrel, use at standard dose (75 mg/day)","classification":"Strong","phenotypes":{"CYP2C19":"Normal Metabolizer"},"activityscore":{},"population":"CVI ACS PCI ","comments":"For cardiovascular indications of acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). ACS and/or PCI includes patients undergoing PCI for an ACS or non-ACS (elective) indication."},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of morphine leading to higher risk of toxicity"},"drugrecommendation":"Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"Avoid standard dose clopidogrel (75 mg) if possible. Use prasugrel or ticagrelor at standard dose if no contraindication.","classification":"Strong","phenotypes":{"CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{},"population":"CVI ACS PCI ","comments":"For cardiovascular indications of acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). ACS and/or PCI includes patients undergoing PCI for an ACS or non-ACS (elective) indication. The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Intermediate Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"Avoid standard dose (75 mg) clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication.","classification":"Strong","phenotypes":{"CYP2C19":"Intermediate Metabolizer"},"activityscore":{},"population":"CVI ACS PCI ","comments":"For cardiovascular indications of acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). ACS and/or PCI includes patients undergoing PCI for an ACS or non-ACS (elective) indication."},{"lookupkey":{"CYP2C19":"Likely Poor Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication.","classification":"Strong","phenotypes":{"CYP2C19":"Likely Poor Metabolizer"},"activityscore":{},"population":"CVI ACS PCI ","comments":"For cardiovascular indications of acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). ACS and/or PCI includes patients undergoing PCI for an ACS or non-ACS (elective) indication. The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Poor Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication.","classification":"Strong","phenotypes":{"CYP2C19":"Poor Metabolizer"},"activityscore":{},"population":"CVI ACS PCI ","comments":"For cardiovascular indications of acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). ACS and/or PCI includes patients undergoing PCI for an ACS or non-ACS (elective) indication."},{"lookupkey":{"CYP2C19":"Indeterminate"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Indeterminate"},"activityscore":{},"population":"CVI ACS PCI ","comments":"n/a"},{"lookupkey":{"CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Increased clopidogrel active metabolite formation; lower on-treatment platelet reactivity; no association with higher bleeding risk"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{},"population":"CVI non-ACS non-PCI","comments":"For non-acute coronary syndrome (non-ACS) and non-percutaneous coronary intervention (non-PCI) cardiovascular indications. Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI."},{"lookupkey":{"CYP2C19":"Rapid Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Normal or increased clopidogrel active metabolite formation; normal or lower on-treatment platelet reactivity; no association with higher bleeding risk"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Rapid Metabolizer"},"activityscore":{},"population":"CVI non-ACS non-PCI","comments":"For non-acute coronary syndrome (non-ACS) and non-percutaneous coronary intervention (non-PCI) cardiovascular indications. Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI."},{"lookupkey":{"CYP2C19":"Normal Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity"},"drugrecommendation":"If considering clopidogrel, use at standard dose (75 mg/day)","classification":"Strong","phenotypes":{"CYP2C19":"Normal Metabolizer"},"activityscore":{},"population":"CVI non-ACS non-PCI","comments":"For non-acute coronary syndrome (non-ACS) and non-percutaneous coronary intervention (non-PCI) cardiovascular indications. Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI."},{"lookupkey":{"CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{},"population":"CVI non-ACS non-PCI","comments":"For non-acute coronary syndrome (non-ACS) and non-percutaneous coronary intervention (non-PCI) cardiovascular indications. Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI. The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Intermediate Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Intermediate Metabolizer"},"activityscore":{},"population":"CVI non-ACS non-PCI","comments":"For non-acute coronary syndrome (non-ACS) and non-percutaneous coronary intervention (non-PCI) cardiovascular indications. Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI."},{"lookupkey":{"G6PD":"Deficient"},"drugname":"dapsone","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute hemolytic anemia"},"drugrecommendation":"Avoid use","classification":"Strong","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"dapsone","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute eacerbation of chronic hemolysis"},"drugrecommendation":"Avoid use","classification":"Strong","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"Although there are not published data in individuals with the G6PD Deficient with CNSHA phenotype, there is a strong rationale to avoid these drugs based on evidence in G6PD Deficient individuals."},{"lookupkey":{"CYP2C19":"Likely Poor Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication.","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Poor Metabolizer"},"activityscore":{},"population":"CVI non-ACS non-PCI","comments":"For non-acute coronary syndrome (non-ACS) and non-percutaneous coronary intervention (non-PCI) cardiovascular indications. Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI. The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Poor Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication.","classification":"Moderate","phenotypes":{"CYP2C19":"Poor Metabolizer"},"activityscore":{},"population":"CVI non-ACS non-PCI","comments":"For non-acute coronary syndrome (non-ACS) and non-percutaneous coronary intervention (non-PCI) cardiovascular indications. Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI."},{"lookupkey":{"CYP2C19":"Indeterminate"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Indeterminate"},"activityscore":{},"population":"CVI non-ACS non-PCI","comments":"n/a"},{"lookupkey":{"CYP2C19":"Ultrarapid Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Increased clopidogrel active metabolite formation; lower on-treatment platelet reactivity"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{},"population":"NVI","comments":"For neurovascular indications. Neurovascular disease includes acute ischemic stroke or transient ischemic attack, secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms."},{"lookupkey":{"CYP2C19":"Rapid Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Normal or increased clopidogrel active metabolite formation; normal or lower on-treatment platelet reactivity"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Rapid Metabolizer"},"activityscore":{},"population":"NVI","comments":"For neurovascular indications. Neurovascular disease includes acute ischemic stroke or transient ischemic attack, secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms."},{"lookupkey":{"CYP2C19":"Normal Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity"},"drugrecommendation":"If considering clopidogrel, use at standard dose (75 mg/day)","classification":"Strong","phenotypes":{"CYP2C19":"Normal Metabolizer"},"activityscore":{},"population":"NVI","comments":"For neurovascular indications. Neurovascular disease includes acute ischemic stroke or transient ischemic attack, secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms."},{"lookupkey":{"CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication.","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{},"population":"NVI","comments":"For neurovascular indications. Neurovascular disease includes acute ischemic stroke or transient ischemic attack, secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms. Alternative P2Y12 inhibitors not impacted by CYP2C19 genetic variants include ticagrelor and ticlopidine. Prasugrel is contraindicated in patients with a history of stroke or TIA. Given limited outcomes data for genotype-guided anti-platelet therapy for neurovascular indications, selection of therapy should depend on individual patient treatment goals and risks for adverse events. The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Intermediate Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication.","classification":"Moderate","phenotypes":{"CYP2C19":"Intermediate Metabolizer"},"activityscore":{},"population":"NVI","comments":"For neurovascular indications. Neurovascular disease includes acute ischemic stroke or transient ischemic attack, secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms. Alternative P2Y12 inhibitors not impacted by CYP2C19 genetic variants include ticagrelor and ticlopidine. Prasugrel is contraindicated in patients with a history of stroke or TIA. Given limited outcomes data for genotype-guided anti-platelet therapy for neurovascular indications, selection of therapy should depend on individual patient treatment goals and risks for adverse events."},{"lookupkey":{"CYP2C19":"Likely Poor Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"Avoid clopidogrel if possible. Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication.","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Poor Metabolizer"},"activityscore":{},"population":"NVI","comments":"For neurovascular indications. Neurovascular disease includes acute ischemic stroke or transient ischemic attack, secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms. Alternative P2Y12 inhibitors not impacted by CYP2C19 genetic variants include ticagrelor and ticlopidine. Prasugrel is contraindicated in patients with a history of stroke or TIA. Given limited outcomes data for genotype-guided anti-platelet therapy for neurovascular indications, selection of therapy should depend on individual patient treatment goals and risks for adverse events. The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Poor Metabolizer"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events"},"drugrecommendation":"Avoid clopidogrel if possible. Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication.","classification":"Moderate","phenotypes":{"CYP2C19":"Poor Metabolizer"},"activityscore":{},"population":"NVI","comments":"For neurovascular indications. Neurovascular disease includes acute ischemic stroke or transient ischemic attack, secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms. Alternative P2Y12 inhibitors not impacted by CYP2C19 genetic variants include ticagrelor and ticlopidine. Prasugrel is contraindicated in patients with a history of stroke or TIA. Given limited outcomes data for genotype-guided anti-platelet therapy for neurovascular indications, selection of therapy should depend on individual patient treatment goals and risks for adverse events."},{"lookupkey":{"CYP2C19":"Indeterminate"},"drugname":"clopidogrel","guidelinename":"CYP2C19 and Clopidogrel","implications":{"CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Indeterminate"},"activityscore":{},"population":"NVI","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Reduced morphine formation"},"drugrecommendation":"Use codeine label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider a non-tramadol opioid.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Reduced morphine formation"},"drugrecommendation":"Use codeine label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider a non-tramadol opioid.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Reduced morphine formation"},"drugrecommendation":"Use codeine label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider a non-tramadol opioid.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Reduced morphine formation"},"drugrecommendation":"Use codeine label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider a non-tramadol opioid.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Expected morphine formation"},"drugrecommendation":"Use codeine label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Expected morphine formation"},"drugrecommendation":"Use codeine label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Expected morphine formation"},"drugrecommendation":"Use codeine label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Expected morphine formation"},"drugrecommendation":"Use codeine label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Expected morphine formation"},"drugrecommendation":"Use codeine label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Greatly reduced morphine formation leading to diminished analgesia."},"drugrecommendation":"Avoid codeine use because of possibility of diminished analgesia. If opioid use is warranted, consider a non-tramadol opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of morphine leading to higher risk of toxicity"},"drugrecommendation":"Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of morphine leading to higher risk of toxicity"},"drugrecommendation":"Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of morphine leading to higher risk of toxicity"},"drugrecommendation":"Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of morphine leading to higher risk of toxicity"},"drugrecommendation":"Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of morphine leading to higher risk of toxicity"},"drugrecommendation":"Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of morphine leading to higher risk of toxicity"},"drugrecommendation":"Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of morphine leading to higher risk of toxicity"},"drugrecommendation":"Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"codeine","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of morphine leading to higher risk of toxicity"},"drugrecommendation":"Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"G6PD":"Normal"},"drugname":"dapsone","guidelinename":"G6PD","implications":{"G6PD":"Low risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Variable"},"drugname":"dapsone","guidelinename":"G6PD","implications":{"G6PD":"Variable risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype; an enzyme activity test is needed to assign G6PD phenotype in such cases."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"dapsone","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"pegloticase","guidelinename":"G6PD","implications":{"G6PD":"Low risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"pegloticase","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute hemolytic anemia"},"drugrecommendation":"Avoid use","classification":"Strong","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"pegloticase","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute eacerbation of chronic hemolysis"},"drugrecommendation":"Avoid use","classification":"Strong","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"Although there are not published data in individuals with the G6PD Deficient with CNSHA phenotype, there is a strong rationale to avoid these drugs based on evidence in G6PD Deficient individuals."},{"lookupkey":{"G6PD":"Variable"},"drugname":"pegloticase","guidelinename":"G6PD","implications":{"G6PD":"Variable risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype; an enzyme activity test is needed to assign G6PD phenotype in such cases."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"pegloticase","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"rasburicase","guidelinename":"G6PD","implications":{"G6PD":"Low risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"rasburicase","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute hemolytic anemia"},"drugrecommendation":"Avoid use","classification":"Strong","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"rasburicase","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute eacerbation of chronic hemolysis"},"drugrecommendation":"Avoid use","classification":"Strong","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"Although there are not published data in individuals with the G6PD Deficient with CNSHA phenotype, there is a strong rationale to avoid these drugs based on evidence in G6PD Deficient individuals."},{"lookupkey":{"G6PD":"Variable"},"drugname":"rasburicase","guidelinename":"G6PD","implications":{"G6PD":"Variable risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype; an enzyme activity test is needed to assign G6PD phenotype in such cases."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"rasburicase","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"desflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"drugname":"desflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"n/a"},"drugrecommendation":"No CACNA1S genotype is available. Based on RYR1 status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"desflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"desflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"desflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 or CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"drugname":"desflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"n/a"},"drugrecommendation":"Based on RYR1 status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"desflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Based on CACNA1S status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"drugname":"desflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"No RYR1 genotype is available. Based on CACNA1S status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"enflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"enflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"enflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"enflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 or CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"drugname":"halothane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"n/a"},"drugrecommendation":"No CACNA1S genotype is available. Based on RYR1 status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"drugname":"enflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"n/a"},"drugrecommendation":"Based on RYR1 status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"enflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Based on CACNA1S status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"drugname":"enflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"n/a"},"drugrecommendation":"No CACNA1S genotype is available. Based on RYR1 status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"drugname":"enflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"No RYR1 genotype is available. Based on CACNA1S status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"halothane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"drugname":"halothane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"No RYR1 genotype is available. Based on CACNA1S status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"drugname":"sevoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"n/a"},"drugrecommendation":"No CACNA1S genotype is available. Based on RYR1 status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"halothane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"halothane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"halothane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 or CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"drugname":"halothane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"n/a"},"drugrecommendation":"Based on RYR1 status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"halothane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Based on CACNA1S status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"G6PD":"Deficient"},"drugname":"sulfisoxazole","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Optional","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs."},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"isoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"isoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"isoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"isoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 or CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"drugname":"isoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"n/a"},"drugrecommendation":"Based on RYR1 status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"isoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Based on CACNA1S status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"drugname":"isoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"n/a"},"drugrecommendation":"No CACNA1S genotype is available. Based on RYR1 status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"drugname":"isoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"No RYR1 genotype is available. Based on CACNA1S status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"methoxyflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"methoxyflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"methoxyflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"n/a"},"drugname":"piroxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"methoxyflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 or CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"drugname":"methoxyflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"n/a"},"drugrecommendation":"Based on RYR1 status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"methoxyflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Based on CACNA1S status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"drugname":"methoxyflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"n/a"},"drugrecommendation":"No CACNA1S genotype is available. Based on RYR1 status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"drugname":"methoxyflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"No RYR1 genotype is available. Based on CACNA1S status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"sevoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Based on CACNA1S status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"sevoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"sevoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"sevoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"sevoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 or CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"drugname":"sevoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"n/a"},"drugrecommendation":"Based on RYR1 status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"drugname":"sevoflurane","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"No RYR1 genotype is available. Based on CACNA1S status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"succinylcholine","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"succinylcholine","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"drugname":"succinylcholine","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"succinylcholine","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 or CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"drugname":"succinylcholine","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine","CACNA1S":"n/a"},"drugrecommendation":"Based on RYR1 status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"Malignant Hyperthermia Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in RYR1 generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"drugname":"succinylcholine","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"Individuals are at increased risk of developing malignant hyperthermia if administered halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine"},"drugrecommendation":"Based on CACNA1S status, halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Malignant Hyperthermia Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"A list of unsafe halogenated volatile anesthetics or depolarizing muscle relaxants and alternative anesthetics can be found at http://www.mhaus.org/healthcare-professionals/be-prepared/safe-and-unsafe-anesthetics. Individuals who have biallelic (homozygous or compound heterozygous) pathogenic variants in CACNA1S generally will have autosomal recessive myopathies and should be managed according to the standard of care for those disorders. Although some may, indeed, have susceptibility to anesthetic agents, the recommendations described here cannot adequately address such patients, and they should be managed by a physician who is knowledgeable regarding those disorders."},{"lookupkey":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"drugname":"succinylcholine","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).","CACNA1S":"n/a"},"drugrecommendation":"No CACNA1S genotype is available. Based on RYR1 status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"Uncertain Susceptibility","CACNA1S":"No Result"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"drugname":"succinylcholine","guidelinename":"RYR1, CACNA1S and Volatile anesthetic agents and Succinylcholine","implications":{"RYR1":"n/a","CACNA1S":"These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675)."},"drugrecommendation":"No RYR1 genotype is available. Based on CACNA1S status, clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.","classification":"Strong","phenotypes":{"RYR1":"No Result","CACNA1S":"Uncertain Susceptibility"},"activityscore":{"RYR1":"n/a","CACNA1S":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Reduced O-desmethyltramadol (active metabolite) formation"},"drugrecommendation":"Use tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects."},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects."},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects."},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects."},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects."},"drugrecommendation":"Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider a 50% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"desipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Ultrarapid Metabolizer"},"drugname":"dexlansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Decreased plasma concentrations of PPIs compared to CYP2C19 NMs; increased risk of therapeutic failure"},"drugrecommendation":"Increase starting daily dose by 100%. Daily dose may be given in divided doses. Monitor for efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Rapid Metabolizer"},"drugname":"dexlansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Decreased plasma concentrations of PPIs compared to CYP2C19 NMs; increased risk of therapeutic failure"},"drugrecommendation":"Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses.\nMonitor for efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Normal Metabolizer"},"drugname":"dexlansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs"},"drugrecommendation":"Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses.\nMonitor for efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"dexlansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Likely increased plasma concentration of PPI compared to CYP2C19 NMs; likely increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Intermediate Metabolizer"},"drugname":"dexlansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2C19":"Likely Poor Metabolizer"},"drugname":"dexlansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Likely increased plasma concentration of PPI compared to CYP2C19 NMs; likely increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Poor Metabolizer"},"drugname":"dexlansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Indeterminate"},"drugname":"dexlansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Indeterminate"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Reduced O-desmethyltramadol (active metabolite) formation"},"drugrecommendation":"Use tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"SLCO1B1":"Normal Function"},"drugname":"lovastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses based on disease-specific guidelines.","classification":"Strong","phenotypes":{"SLCO1B1":"Normal Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"G6PD":"Deficient"},"drugname":"methylene blue","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute hemolytic anemia"},"drugrecommendation":"Avoid use","classification":"Moderate","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Expected O-desmethyltramadol (active metabolite) formation"},"drugrecommendation":"Use tramadol label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Expected O-desmethyltramadol (active metabolite) formation"},"drugrecommendation":"Use tramadol label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use. If doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use. If doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use. If doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use. If doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use. If doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Expected O-desmethyltramadol (active metabolite) formation"},"drugrecommendation":"Use tramadol label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Expected O-desmethyltramadol (active metabolite) formation"},"drugrecommendation":"Use tramadol label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use. If doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use. If doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use. If doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use. If doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use. If doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use. If a doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use. If a doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use. If a doxepin is warranted, consider a 50% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"DPYD":"2.0"},"drugname":"capecitabine","guidelinename":"DPYD and Fluoropyrimidines","implications":{"DPYD":"Normal DPD activity and \"normal\" risk for fluoropyrimidine toxicity"},"drugrecommendation":"Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration.","classification":"Strong","phenotypes":{"DPYD":"Normal Metabolizer"},"activityscore":{"DPYD":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"DPYD":"1.5"},"drugname":"capecitabine","guidelinename":"DPYD and Fluoropyrimidines","implications":{"DPYD":"Decreased DPD activity (leukocyte DPD activity at 30% to 70% that of the normal population) and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs"},"drugrecommendation":"Reduce starting dose by 50% followed by titration of dose based on toxicity or therapeutic drug monitoring (if available).","classification":"Moderate","phenotypes":{"DPYD":"Intermediate Metabolizer"},"activityscore":{"DPYD":"1.5"},"population":"general","comments":"Increase the dose in patients experiencing no or clinically tolerable toxicity in the first two cycles to maintain efficacy; decrease the dose in patients who do not tolerate the starting dose to minimize toxicities."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. 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Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2C9":"2.0","SLCO1B1":"Increased Function"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Normal exposure.","SLCO1B1":"Typical myopathy risk and statin exposure."},"drugrecommendation":"Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer","SLCO1B1":"Increased Function"},"activityscore":{"CYP2C9":"2.0"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. 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Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid doxepin use; If doxepin is warranted, utilize therapeutic drug monitoring to guide dose adjustment. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. 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Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"2.0","SLCO1B1":"Indeterminate"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Normal exposure.","SLCO1B1":"n/a"},"drugrecommendation":"Based on CYP2C9 status, prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines. SLCO1B1 phenotype could not be assigned based on genotyping.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer","SLCO1B1":"Indeterminate"},"activityscore":{"CYP2C9":"2.0"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"No Result"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Normal Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Rapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Indeterminate"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2C9":"2.0","SLCO1B1":"No Result"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Normal exposure.","SLCO1B1":"n/a"},"drugrecommendation":"Based on CYP2C9 status, prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines. SLCO1B1 genotype result is not available.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer","SLCO1B1":"No Result"},"activityscore":{"CYP2C9":"2.0"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Likely Poor Metabolizer"},"drugname":"doxepin","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2B6":"Ultrarapid Metabolizer"},"drugname":"efavirenz","guidelinename":"CYP2B6 and efavirenz","implications":{"CYP2B6":"Slightly lower dose-adjusted trough concentrations of efavirenz compared with normal metabolizers"},"drugrecommendation":"Initiate efavirenz with standard dosing (600 mg/day)","classification":"Strong","phenotypes":{"CYP2B6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2B6":"n/a"},"population":"child >40kg_adult","comments":"n/a"},{"lookupkey":{"CYP2B6":"Rapid Metabolizer"},"drugname":"efavirenz","guidelinename":"CYP2B6 and efavirenz","implications":{"CYP2B6":"Slightly lower dose-adjusted trough concentrations of efavirenz compared with normal metabolizers"},"drugrecommendation":"Initiate efavirenz with standard dosing (600 mg/day)","classification":"Strong","phenotypes":{"CYP2B6":"Rapid Metabolizer"},"activityscore":{"CYP2B6":"n/a"},"population":"child >40kg_adult","comments":"n/a"},{"lookupkey":{"CYP2B6":"Normal Metabolizer"},"drugname":"efavirenz","guidelinename":"CYP2B6 and efavirenz","implications":{"CYP2B6":"Normal efavirenz metabolism"},"drugrecommendation":"Initiate efavirenz with standard dosing (600 mg/day)","classification":"Strong","phenotypes":{"CYP2B6":"Normal Metabolizer"},"activityscore":{"CYP2B6":"n/a"},"population":"child >40kg_adult","comments":"The ENCORE study showed that in treatment-naïve patients randomized to initiate efavirenz-based regimens (combined with tenofovir and emtricitabine), 400 mg/day was non-inferior to 600 mg/day regardless of CYP2B6 genotype (PMID 24522178)."},{"lookupkey":{"CYP2B6":"Intermediate Metabolizer"},"drugname":"efavirenz","guidelinename":"CYP2B6 and efavirenz","implications":{"CYP2B6":"Higher dose-adjusted trough concentrations of efavirenz compared with normal metabolizers; increased risk of CNS adverse events"},"drugrecommendation":"Consider initiating efavirenz with decreased dose of 400 mg/day","classification":"Moderate","phenotypes":{"CYP2B6":"Intermediate Metabolizer"},"activityscore":{"CYP2B6":"n/a"},"population":"child >40kg_adult","comments":"If therapeutic drug monitoring is available and a decreased efavirenz dose is prescribed, consider obtaining steady-state plasma efavirenz concentrations to ensure concentrations are in the suggested therapeutic range (~1 to 4 μg/mL). To prescribe efavirenz at a decreased dose of 400 mg/day or 200 mg/day in a multidrug regimen may require prescribing more than one pill once daily. If so, the provider should weigh the potential benefit of reduced dose against the potential detrimental impact of increased pill number."},{"lookupkey":{"CYP2B6":"Poor Metabolizer"},"drugname":"efavirenz","guidelinename":"CYP2B6 and efavirenz","implications":{"CYP2B6":"Higher dose-adjusted trough concentrations of efavirenz compared with normal metabolizers; significantly increased risk of CNS adverse events and treatment discontinuation"},"drugrecommendation":"Consider initiating efavirenz with decreased dose of 400 or 200 mg/day","classification":"Moderate","phenotypes":{"CYP2B6":"Poor Metabolizer"},"activityscore":{"CYP2B6":"n/a"},"population":"child >40kg_adult","comments":"If therapeutic drug monitoring is available and a decreased efavirenz dose is prescribed, consider obtaining steady-state plasma efavirenz concentrations to ensure concentrations are in the suggested therapeutic range (~1 to 4 μg/mL). To prescribe efavirenz at a decreased dose of 400 mg/day or 200 mg/day in a multidrug regimen may require prescribing more than one pill once daily. If so, the provider should weigh the potential benefit of reduced dose against the potential detrimental impact of increased pill number."},{"lookupkey":{"CYP2B6":"Indeterminate"},"drugname":"efavirenz","guidelinename":"CYP2B6 and efavirenz","implications":{"CYP2B6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2B6":"Indeterminate"},"activityscore":{"CYP2B6":"n/a"},"population":"child >40kg_adult","comments":"n/a"},{"lookupkey":{"DPYD":"2.0"},"drugname":"fluorouracil","guidelinename":"DPYD and Fluoropyrimidines","implications":{"DPYD":"Normal DPD activity and \"normal\" risk for fluoropyrimidine toxicity"},"drugrecommendation":"Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration.","classification":"Strong","phenotypes":{"DPYD":"Normal Metabolizer"},"activityscore":{"DPYD":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"DPYD":"1.5"},"drugname":"fluorouracil","guidelinename":"DPYD and Fluoropyrimidines","implications":{"DPYD":"Decreased DPD activity (leukocyte DPD activity at 30% to 70% that of the normal population) and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs"},"drugrecommendation":"Reduce starting dose by 50% followed by titration of dose based on toxicity or therapeutic drug monitoring (if available).","classification":"Moderate","phenotypes":{"DPYD":"Intermediate Metabolizer"},"activityscore":{"DPYD":"1.5"},"population":"general","comments":"Increase the dose in patients experiencing no or clinically tolerable toxicity in the first two cycles to maintain efficacy; decrease the dose in patients who do not tolerate the starting dose to minimize toxicities."},{"lookupkey":{"DPYD":"1.0"},"drugname":"fluorouracil","guidelinename":"DPYD and Fluoropyrimidines","implications":{"DPYD":"Decreased DPD activity (leukocyte DPD activity at 30% to 70% that of the normal population) and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs"},"drugrecommendation":"Reduce starting dose by 50% followed by titration of dose based on toxicity or therapeutic drug monitoring (if available). Patients with the c.2846A>T/c.2846A>T genotype may require >50% reduction in starting dose.","classification":"Strong","phenotypes":{"DPYD":"Intermediate Metabolizer"},"activityscore":{"DPYD":"1.0"},"population":"general","comments":"Increase the dose in patients experiencing no or clinically tolerable toxicity in the first two cycles to maintain efficacy; decrease the dose in patients who do not tolerate the starting dose to minimize toxicities."},{"lookupkey":{"DPYD":"0.5"},"drugname":"fluorouracil","guidelinename":"DPYD and Fluoropyrimidines","implications":{"DPYD":"Complete DPD deficiency and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs."},"drugrecommendation":"Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens. In the event, based on clinical advice, alternative agents are not considered a suitable therapeutic option, 5-fluorouracil should be administered at a strongly reduced dose with early therapeutic drug monitoring.","classification":"Strong","phenotypes":{"DPYD":"Poor Metabolizer"},"activityscore":{"DPYD":"0.5"},"population":"general","comments":"If available, a phenotyping test (see main text for further details) should be considered to estimate the starting dose. In absence of phenotyping data, a dose of <25% of the normal starting dose is estimated assuming additive effects of alleles on 5-FU clearance. Therapeutic drug monitoring should be done at the earliest time point possible (e.g., minimum time point in steady state) in order to immediately discontinue therapy if the drug level is too high."},{"lookupkey":{"DPYD":"0.0"},"drugname":"fluorouracil","guidelinename":"DPYD and Fluoropyrimidines","implications":{"DPYD":"Complete DPD deficiency and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs."},"drugrecommendation":"Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens.","classification":"Strong","phenotypes":{"DPYD":"Poor Metabolizer"},"activityscore":{"DPYD":"0.0"},"population":"general","comments":"n/a"},{"lookupkey":{"DPYD":"1.0"},"drugname":"capecitabine","guidelinename":"DPYD and Fluoropyrimidines","implications":{"DPYD":"Decreased DPD activity (leukocyte DPD activity at 30% to 70% that of the normal population) and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs"},"drugrecommendation":"Reduce starting dose by 50% followed by titration of dose based on toxicity or therapeutic drug monitoring (if available). Patients with the c.2846A>T/c.2846A>T genotype may require >50% reduction in starting dose.","classification":"Strong","phenotypes":{"DPYD":"Intermediate Metabolizer"},"activityscore":{"DPYD":"1.0"},"population":"general","comments":"Increase the dose in patients experiencing no or clinically tolerable toxicity in the first two cycles to maintain efficacy; decrease the dose in patients who do not tolerate the starting dose to minimize toxicities."},{"lookupkey":{"DPYD":"0.5"},"drugname":"capecitabine","guidelinename":"DPYD and Fluoropyrimidines","implications":{"DPYD":"Complete DPD deficiency and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs."},"drugrecommendation":"Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens. In the event, based on clinical advice, alternative agents are not considered a suitable therapeutic option, 5-fluorouracil should be administered at a strongly reduced dose with early therapeutic drug monitoring.","classification":"Strong","phenotypes":{"DPYD":"Poor Metabolizer"},"activityscore":{"DPYD":"0.5"},"population":"general","comments":"If available, a phenotyping test (see main text for further details) should be considered to estimate the starting dose. In absence of phenotyping data, a dose of <25% of the normal starting dose is estimated assuming additive effects of alleles on 5-FU clearance. Therapeutic drug monitoring should be done at the earliest time point possible (e.g., minimum time point in steady state) in order to immediately discontinue therapy if the drug level is too high."},{"lookupkey":{"DPYD":"0.0"},"drugname":"capecitabine","guidelinename":"DPYD and Fluoropyrimidines","implications":{"DPYD":"Complete DPD deficiency and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs."},"drugrecommendation":"Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens.","classification":"Strong","phenotypes":{"DPYD":"Poor Metabolizer"},"activityscore":{"DPYD":"0.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"1.0","SLCO1B1":"Possible Decreased Function"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Increased fluvastatin exposure as compared to normal metabolizer which may translate to increased myopathy risk.","SLCO1B1":"Increased fluvastatin exposure as compared to normal function; Typical myopathy risk with ≤40 mg."},"drugrecommendation":"Prescribe ≤20mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Optional","phenotypes":{"CYP2C9":"Intermediate Metabolizer","SLCO1B1":"Possible Decreased Function"},"activityscore":{"CYP2C9":"1.0"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2C9":"1.0","SLCO1B1":"Decreased Function"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Increased fluvastatin exposure as compared to normal metabolizer which may translate to increased myopathy risk.","SLCO1B1":"Increased fluvastatin exposure as compared to normal function; Typical myopathy risk with ≤40 mg."},"drugrecommendation":"Prescribe ≤20mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Optional","phenotypes":{"CYP2C9":"Intermediate Metabolizer","SLCO1B1":"Decreased Function"},"activityscore":{"CYP2C9":"1.0"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2C9":"1.5","SLCO1B1":"Possible Decreased Function"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Increased fluvastatin exposure as compared to normal metabolizer which may translate to increased myopathy risk.","SLCO1B1":"Increased fluvastatin exposure as compared to normal function; Typical myopathy risk with ≤40 mg."},"drugrecommendation":"Prescribe ≤20mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. 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If patient is tolerating 40mg per day but higher potency is needed, a higher dose (>40mg) or an alternative statin (see Figure 1 of PMID: 35152405 for recommendations for alternative statins) or combination therapy (i.e. fluvastatin plus non-statin guideline directed medical therapy)(PMID: 30423391) could be considered. Prescriber should be aware of possible increased risk for myopathy with fluvastatin especially with doses >40mg per day. CYP2C9 phenotype could not be assigned based on genotyping.","classification":"Moderate","phenotypes":{"CYP2C9":"Indeterminate","SLCO1B1":"Poor Function"},"activityscore":{"CYP2C9":"n/a"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2C9":"1.0","SLCO1B1":"Indeterminate"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Increased fluvastatin exposure as compared to normal metabolizer which may translate to increased myopathy risk.","SLCO1B1":"n/a"},"drugrecommendation":"Based on CYP2C9 status, prescribe ≤40mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >40mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391). SLCO1B1 phenotype could not be assigned based on genotyping.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer","SLCO1B1":"Indeterminate"},"activityscore":{"CYP2C9":"1.0"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of fluvoxamine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"1.5","SLCO1B1":"Indeterminate"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Increased fluvastatin exposure as compared to normal metabolizer which may translate to increased myopathy risk.","SLCO1B1":"n/a"},"drugrecommendation":"Based on CYP2C9 status, prescribe ≤40mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >40mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391). SLCO1B1 phenotype could not be assigned based on genotyping.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer","SLCO1B1":"Indeterminate"},"activityscore":{"CYP2C9":"1.5"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2C9":"1.0","SLCO1B1":"No Result"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Increased fluvastatin exposure as compared to normal metabolizer which may translate to increased myopathy risk.","SLCO1B1":"n/a"},"drugrecommendation":"Based on CYP2C9 status, prescribe ≤40mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >40mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391). SLCO1B1 genotype result is not available.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer","SLCO1B1":"No Result"},"activityscore":{"CYP2C9":"1.0"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2C9":"1.5","SLCO1B1":"No Result"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Increased fluvastatin exposure as compared to normal metabolizer which may translate to increased myopathy risk.","SLCO1B1":"n/a"},"drugrecommendation":"Based on CYP2C9 status, prescribe ≤40mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >40mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391). SLCO1B1 genotype result is not available.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer","SLCO1B1":"No Result"},"activityscore":{"CYP2C9":"1.5"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2C9":"No Result","SLCO1B1":"Decreased Function"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"n/a","SLCO1B1":"Increased fluvastatin exposure as compared to normal function; Typical myopathy risk with ≤40 mg."},"drugrecommendation":"Based on SLCO1B1 status, prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >40mg per day. CYP2C9 genotype result is not available.","classification":"Moderate","phenotypes":{"CYP2C9":"No Result","SLCO1B1":"Decreased Function"},"activityscore":{"CYP2C9":"No Result"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2C9":"No Result","SLCO1B1":"Increased Function"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"n/a","SLCO1B1":"Typical myopathy risk and statin exposure."},"drugrecommendation":"Based on SLCO1B1 status, prescribe desired starting dose and adjust doses based on disease-specific guidelines. CYP2C9 genotype result is not available.","classification":"Strong","phenotypes":{"CYP2C9":"No Result","SLCO1B1":"Increased Function"},"activityscore":{"CYP2C9":"No Result"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"CYP2C9":"No Result","SLCO1B1":"Indeterminate"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"n/a","SLCO1B1":"n/a"},"drugrecommendation":"n/a","classification":"n/a","phenotypes":{"CYP2C9":"No Result","SLCO1B1":"Indeterminate"},"activityscore":{"CYP2C9":"No Result"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"No Result","SLCO1B1":"Normal Function"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"n/a","SLCO1B1":"Typical myopathy risk and statin exposure."},"drugrecommendation":"Based on SLCO1B1 status, prescribe desired starting dose and adjust doses based on disease-specific guidelines. CYP2C9 genotype result is not available.","classification":"Strong","phenotypes":{"CYP2C9":"No Result","SLCO1B1":"Normal Function"},"activityscore":{"CYP2C9":"No Result"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"CYP2C9":"No Result","SLCO1B1":"Poor Function"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"n/a","SLCO1B1":"Increased fluvastatin exposure as compared to normal and decreased function; Typical myopathy risk with doses less ≤40 mg."},"drugrecommendation":"Based on SLCO1B1 status, prescribe ≤40mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If patient is tolerating 40mg per day but higher potency is needed, a higher dose (>40mg) or an alternative statin (see Figure 1 of PMID: 35152405 for recommendations for alternative statins) or combination therapy (i.e. fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391) could be considered. Prescriber should be aware of possible increased risk for myopathy with fluvastatin especially with doses >40mg per day. CYP2C9 genotype result is not available.","classification":"Moderate","phenotypes":{"CYP2C9":"No Result","SLCO1B1":"Poor Function"},"activityscore":{"CYP2C9":"No Result"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2C9":"No Result","SLCO1B1":"Possible Decreased Function"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"n/a","SLCO1B1":"Increased fluvastatin exposure as compared to normal function; Typical myopathy risk with ≤40 mg."},"drugrecommendation":"Based on SLCO1B1 status, prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >40mg per day. CYP2C9 genotype result is not available.","classification":"Moderate","phenotypes":{"CYP2C9":"No Result","SLCO1B1":"Possible Decreased Function"},"activityscore":{"CYP2C9":"No Result"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of fluvoxamine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"0.0","SLCO1B1":"Indeterminate"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Increased fluvastatin exposure as compared to normal and intermediate metabolizer which may translate to increased myopathy risk.","SLCO1B1":"n/a"},"drugrecommendation":"Based on CYP2C9 status, prescribe ≤20mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391). SLCO1B1 phenotype could not be assigned based on genotyping.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer","SLCO1B1":"Indeterminate"},"activityscore":{"CYP2C9":"0.0"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2C9":"0.5","SLCO1B1":"Indeterminate"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Increased fluvastatin exposure as compared to normal and intermediate metabolizer which may translate to increased myopathy risk.","SLCO1B1":"n/a"},"drugrecommendation":"Based on CYP2C9 status, prescribe ≤20mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391). SLCO1B1 phenotype could not be assigned based on genotyping.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer","SLCO1B1":"Indeterminate"},"activityscore":{"CYP2C9":"0.5"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2C9":"0.0","SLCO1B1":"No Result"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Increased fluvastatin exposure as compared to normal and intermediate metabolizer which may translate to increased myopathy risk.","SLCO1B1":"n/a"},"drugrecommendation":"Based on CYP2C9 status, prescribe ≤20mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391). SLCO1B1 genotype result is not available.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer","SLCO1B1":"No Result"},"activityscore":{"CYP2C9":"0.0"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2C9":"0.5","SLCO1B1":"No Result"},"drugname":"fluvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"CYP2C9":"Increased fluvastatin exposure as compared to normal and intermediate metabolizer which may translate to increased myopathy risk.","SLCO1B1":"n/a"},"drugrecommendation":"Based on CYP2C9 status, prescribe ≤20mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391). SLCO1B1 genotype result is not available.","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer","SLCO1B1":"No Result"},"activityscore":{"CYP2C9":"0.5"},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"No data available for CYP2D6 ultrarapid metabolizers"},"drugrecommendation":"No recommendation due to lack of evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"No data available for CYP2D6 ultrarapid metabolizers"},"drugrecommendation":"No recommendation due to lack of evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"No data available for CYP2D6 ultrarapid metabolizers"},"drugrecommendation":"No recommendation due to lack of evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"No data available for CYP2D6 ultrarapid metabolizers"},"drugrecommendation":"No recommendation due to lack of evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"No data available for CYP2D6 ultrarapid metabolizers"},"drugrecommendation":"No recommendation due to lack of evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"No data available for CYP2D6 ultrarapid metabolizers"},"drugrecommendation":"No recommendation due to lack of evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"No data available for CYP2D6 ultrarapid metabolizers"},"drugrecommendation":"No recommendation due to lack of evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"No data available for CYP2D6 ultrarapid metabolizers"},"drugrecommendation":"No recommendation due to lack of evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"No data available for CYP2D6 ultrarapid metabolizers"},"drugrecommendation":"No recommendation due to lack of evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"No data available for CYP2D6 ultrarapid metabolizers"},"drugrecommendation":"No recommendation due to lack of evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"No data available for CYP2D6 ultrarapid metabolizers"},"drugrecommendation":"No recommendation due to lack of evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of fluvoxamine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Consider a 25-50% lower starting dose and slower titration schedule as compared to normal metabolizers or consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2D6.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"fluvoxamine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"NAT2":"Rapid Metabolizer"},"drugname":"hydralazine","guidelinename":"NAT2 and Hydralazine","implications":{"NAT2":"Predicted to have reduced plasma concentrations and efficacy of hydralazine compared to NAT2 poor metabolizers."},"drugrecommendation":"Consider a starting total daily dose of at least 75 mg. Titrate up to 300 mg total daily hydralazine dose as tolerated. NAT2 rapid metabolizers typically require a 50-100% higher maintenance dose compared to poor metabolizers.","classification":"Moderate","phenotypes":{"NAT2":"Rapid Metabolizer"},"activityscore":{},"population":"general","comments":"n/a"},{"lookupkey":{"NAT2":"Intermediate Metabolizer"},"drugname":"hydralazine","guidelinename":"NAT2 and Hydralazine","implications":{"NAT2":"Predicted to have reduced plasma concentrations and efficacy of hydralazine compared to NAT2 poor metabolizers."},"drugrecommendation":"Consider a starting total daily dose of at least 75 mg. Titrate up to 300 mg total daily hydralazine dose as tolerated. NAT2 intermediate metabolizers typically require a 50-100% higher maintenance dose compared to poor metabolizers.","classification":"Moderate","phenotypes":{"NAT2":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"n/a"},{"lookupkey":{"NAT2":"Poor Metabolizer"},"drugname":"hydralazine","guidelinename":"NAT2 and Hydralazine","implications":{"NAT2":"Predicted to have increased hydralazine plasma concentrations compared to NAT2 rapid and intermediate metabolizers, which may lead to both increased efficacy and adverse effects, including drug-induced systemic lupus erythematosus."},"drugrecommendation":"Initiate therapy at a total daily dose of 40 to 75 mg. Carefully titrate dose upward to clinical effect or guideline-recommended dose; use caution with total daily hydralazine doses of 200 mg or more.","classification":"Moderate","phenotypes":{"NAT2":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"n/a"},{"lookupkey":{"NAT2":"Indeterminate"},"drugname":"hydralazine","guidelinename":"NAT2 and Hydralazine","implications":{"NAT2":"n/a"},"drugrecommendation":"No Recommendation","classification":"No Recommendation","phenotypes":{"NAT2":"Indeterminate"},"activityscore":{},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"Use hydrocodone label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine or non-tramadol opioid.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"Use hydrocodone label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine or non-tramadol opioid.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"Use hydrocodone label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine or non-tramadol opioid.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"Use hydrocodone label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine or non-tramadol opioid.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Normal hydromorphone formation"},"drugrecommendation":"Use hydrocodone label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Normal hydromorphone formation"},"drugrecommendation":"Use hydrocodone label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Normal hydromorphone formation"},"drugrecommendation":"Use hydrocodone label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Normal hydromorphone formation"},"drugrecommendation":"Use hydrocodone label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Normal hydromorphone formation"},"drugrecommendation":"Use hydrocodone label recommended age- or weight-specific dosing.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Decreased metabolism of hydrocodone to active metabolite, hydromorphone, but there is insufficient evidence to determine if these effects on pharmacokinetics translate into decreased analgesia or side effects."},"drugrecommendation":"Use hydrocodone label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine and non-tramadol opioid.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"hydrocodone","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Minimal evidence for pharmacokinetic or clinical effect."},"drugrecommendation":"No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use. If a imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"methylene blue","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Avoid use","classification":"Strong","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"Although there are not published data in individuals with the G6PD Deficient with CNSHA phenotype, there is a strong rationale to avoid these drugs based on evidence in G6PD Deficient individuals."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid imipramine use. If a imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. 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Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. 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Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). 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Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Normal Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Normal metabolism of metoprolol"},"drugrecommendation":"Initiate standard dosing","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use. If imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use. If imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use. If imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use. If imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use. If imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Rapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Normal metabolism of metoprolol"},"drugrecommendation":"Initiate standard dosing","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate, or poor metabolism in combination with CYP2C19 ultrarapid, intermediate, or poor metabolism is strongly recommended"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"G6PD":"Deficient"},"drugname":"nitrofurantoin","guidelinename":"G6PD","implications":{"G6PD":"Medium risk of acute hemolytic anemia"},"drugrecommendation":"Use at standard doses with caution and with close monitoring for anemia","classification":"Optional","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Close monitoring may be more important at higher or more chronic dosage schedules, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Indeterminate"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use. If a imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2C19":"Indeterminate"},"drugname":"omeprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Indeterminate"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use. If imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use. If imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"SLCO1B1":"Increased Function"},"drugname":"lovastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses based on disease-specific guidelines.","classification":"Strong","phenotypes":{"SLCO1B1":"Increased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use. If imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use. If imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use. If imipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2C19":"Ultrarapid Metabolizer"},"drugname":"lansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Decreased plasma concentrations of PPIs compared to CYP2C19 NMs; increased risk of therapeutic failure"},"drugrecommendation":"Increase starting daily dose by 100%. Daily dose may be given in divided doses. Monitor for efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid imipramine use; If imipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Likely Poor Metabolizer"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"No Result"},"drugname":"imipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CFTR":"ivacaftor non-responsive in CF patients"},"drugname":"ivacaftor","guidelinename":"CFTR and Ivacaftor","implications":{"CFTR":"An individual diagnosed with cystic fibrosis (CF) and negative for a CFTR variant listed in the FDA-approved drug label as being responsive to ivacaftor."},"drugrecommendation":"Ivacaftor is not recommended","classification":"Moderate","phenotypes":{"CFTR":"ivacaftor non-responsive in CF patients"},"activityscore":{"CFTR":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CFTR":"ivacaftor responsive in CF patients"},"drugname":"ivacaftor","guidelinename":"CFTR and Ivacaftor","implications":{"CFTR":"An individual diagnosed with cystic fibrosis (CF) and CFTR variants listed in the FDA-approved drug label as being responsive to ivacaftor"},"drugrecommendation":"Use ivacaftor according to the product label","classification":"Moderate","phenotypes":{"CFTR":"ivacaftor responsive in CF patients"},"activityscore":{"CFTR":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"SLCO1B1":"Possible Decreased Function"},"drugname":"lovastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased lovastatin acid exposure as compared to normal function which may translate to increased myopathy risk"},"drugrecommendation":"Prescribe an alternative statin depending on the desired potency (see Figure 1 of PMID: 35152405 for recommendations for alternative statins). If lovastatin therapy is warranted, limit dose to ≤20mg/day.","classification":"Moderate","phenotypes":{"SLCO1B1":"Possible Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Decreased Function"},"drugname":"lovastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased lovastatin acid exposure as compared to normal function which may translate to increased myopathy risk"},"drugrecommendation":"Prescribe an alternative statin depending on the desired potency (see Figure 1 of PMID: 35152405 for recommendations for alternative statins). If lovastatin therapy is warranted, limit dose to ≤20mg/day.","classification":"Moderate","phenotypes":{"SLCO1B1":"Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Poor Function"},"drugname":"lovastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased lovastatin acid exposure as compared to normal and decreased function which may translate to increased myopathy risk"},"drugrecommendation":"Prescribe an alternative statin depending on the desired potency (see Figure 1 of PMID: 35152405 for recommendations for alternative statins).","classification":"Moderate","phenotypes":{"SLCO1B1":"Poor Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Indeterminate"},"drugname":"lovastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"SLCO1B1":"Indeterminate"},"activityscore":{},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"2.0"},"drugname":"meloxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"1.5"},"drugname":"meloxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Mildly reduced metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the meloxicam prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age."},{"lookupkey":{"CYP2C9":"1.0"},"drugname":"meloxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities"},"drugrecommendation":"Initiate therapy with 50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 50% of the maximum recommended dose with caution. In accordance with the meloxicam prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady state is reached (at least 7 days). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider alternative therapy. Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"0.5"},"drugname":"meloxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"0.0"},"drugname":"meloxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"n/a"},"drugname":"meloxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites and higher concentrations of MeMPNs compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with standard starting dose of mecaptopurine (e.g., 75 mg/m2/day for malignancy or 1.5 mg/kg/day for nonmalignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"n/a"},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose. TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose. TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Poor Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Greatly reduced O-desmethyltramadol (active metabolite) formation leading to diminished analgesia."},"drugrecommendation":"Avoid tramadol use because of possibility of diminished analgesia. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"n/a"},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Indeterminate"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"G6PD":"Variable"},"drugname":"methylene blue","guidelinename":"G6PD","implications":{"G6PD":"Variable risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype; an enzyme activity test is needed to assign G6PD phenotype in such cases."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with decreased starting doses (20-50% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with decreased starting doses (20-50% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with decreased starting doses (20-50% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with decreased starting doses (20-50% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Indeterminate"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites and higher concentrations of MeMPNs compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with standard starting dose of mecaptopurine (e.g., 75 mg/m2/day for malignancy or 1.5 mg/kg/day for nonmalignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"methylene blue","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Indeterminate"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Indeterminate"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Normal Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with standard starting dose of mecaptopurine (e.g., 75 mg/m2/day for malignancy or 1.5 mg/kg/day for nonmalignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Indeterminate"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"n/a"},"drugrecommendation":"Neither TPMT or NUDT15 phenotype could be assigned based on genotyping performed. Consider evaluating TPMT erythrocyte activity to assess TPMT phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"TPMT":"No Result","NUDT15":"Normal Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with standard starting dose of mecaptopurine (e.g., 75 mg/m2/day for malignancy or 1.5 mg/kg/day for nonmalignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"No Result","NUDT15":"Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"No Result","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"No Result","NUDT15":"Poor Metabolizer"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"No Result","NUDT15":"Indeterminate"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"n/a"},"drugrecommendation":"Neither TPMT or NUDT15 phenotype could be assigned based on genotyping performed. Consider evaluating TPMT erythrocyte activity to assess TPMT phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"No Result"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites and higher concentrations of MeMPNs compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with standard starting dose of mecaptopurine (e.g., 75 mg/m2/day for malignancy or 1.5 mg/kg/day for nonmalignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"No Result"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"No Result"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"No Result"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"No Result"},"drugname":"mercaptopurine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"n/a"},"drugrecommendation":"Neither TPMT or NUDT15 phenotype could be assigned based on genotyping performed. Consider evaluating TPMT erythrocyte activity to assess TPMT phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"methylene blue","guidelinename":"G6PD","implications":{"G6PD":"Low risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid ased on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Normal metabolism of metoprolol"},"drugrecommendation":"Initiate standard dosing","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Normal metabolism of metoprolol"},"drugrecommendation":"Initiate standard dosing","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Decreased metabolism of metoprolol leading to increased drug concentrations; however, this does not appear to translate into clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"Initiate standard dosing","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Decreased metabolism of metoprolol leading to increased drug concentrations; however, this does not appear to translate into clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"Initiate standard dosing","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Decreased metabolism of metoprolol leading to increased drug concentrations; however, this does not appear to translate into clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"Initiate standard dosing","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Decreased metabolism of metoprolol leading to increased drug concentrations; however, this does not appear to translate into clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"Initiate standard dosing","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Decreased metabolism of metoprolol leading to markedly increased drug concentrations; this leads to greater heart rate and blood pressure reductions, but the effect on clinical outcomes is unclear"},"drugrecommendation":"Initiate therapy with lowest recommended starting dose. Carefully titrate dose upward to clinical effect or guideline-recommended dose; monitor more closely for bradycardia. Alternatively, consider selecting another beta-blocker.","classification":"Moderate","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes"},"drugrecommendation":"No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"metoprolol","guidelinename":"CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 and Beta-Blockers","implications":{"CYP2D6":"Normal metabolism of metoprolol"},"drugrecommendation":"Initiate standard dosing","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"n/a"},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"nitrofurantoin","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Avoid","classification":"Moderate","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype to rate as \"strong,\" but all medium risk drugs should be avoided in these rare patients due to the underlying pathophysiology that confers high risk for acute exacerbation of chronic hemolysis."},{"lookupkey":{"G6PD":"Variable"},"drugname":"nitrofurantoin","guidelinename":"G6PD","implications":{"G6PD":"Variable risk of acute hemolytic anemia"},"drugrecommendation":"If deemed necessary to ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype; an enzyme activity test is needed to assign G6PD phenotype in such cases."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"nitrofurantoin","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure."},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of tricyclic antidepressants"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of tricyclic antidepressants"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of tricyclic antidepressants"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of tricyclic antidepressants"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of tricyclic antidepressants"},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects."},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of tricyclic antidepressants for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects."},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of tricyclic antidepressants for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2C19":"Rapid Metabolizer"},"drugname":"lansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Decreased plasma concentrations of PPIs compared to CYP2C19 NMs; increased risk of therapeutic failure"},"drugrecommendation":"Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses.\nMonitor for efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Normal Metabolizer"},"drugname":"lansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs"},"drugrecommendation":"Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses.\nMonitor for efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects."},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of tricyclic antidepressants for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects."},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of tricyclic antidepressants for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects."},"drugrecommendation":"Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a tricyclic antidepressant is warranted, consider a 50% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of tricyclic antidepressants for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"nortriptyline","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"Because CYP2D6 phenotype could not be assigned based on genotyping performed, therapuetic monitoring should be considered. If therapuetic monitoring cannot be performed, monitor closely for toxicity and/or efficacy."},{"lookupkey":{"CYP2C19":"Ultrarapid Metabolizer"},"drugname":"omeprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Decreased plasma concentrations of PPIs compared to CYP2C19 NMs; increased risk of therapeutic failure"},"drugrecommendation":"Increase starting daily dose by 100%. Daily dose may be given in divided doses. Monitor for efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Rapid Metabolizer"},"drugname":"omeprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Decreased plasma concentrations of PPIs compared to CYP2C19 NMs; increased risk of therapeutic failure"},"drugrecommendation":"Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses.\nMonitor for efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Normal Metabolizer"},"drugname":"omeprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs"},"drugrecommendation":"Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses.\nMonitor for efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"omeprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Likely increased plasma concentration of PPI compared to CYP2C19 NMs; likely increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Intermediate Metabolizer"},"drugname":"omeprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Likely Poor Metabolizer"},"drugname":"omeprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Likely increased plasma concentration of PPI compared to CYP2C19 NMs; likely increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Poor Metabolizer"},"drugname":"omeprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"lansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Likely increased plasma concentration of PPI compared to CYP2C19 NMs; likely increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Intermediate Metabolizer"},"drugname":"lansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Likely Poor Metabolizer"},"drugname":"lansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Likely increased plasma concentration of PPI compared to CYP2C19 NMs; likely increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Poor Metabolizer"},"drugname":"lansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Indeterminate"},"drugname":"lansoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Indeterminate"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Ultrarapid Metabolizer"},"drugname":"pantoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Decreased plasma concentrations of PPIs compared to CYP2C19 NMs; increased risk of therapeutic failure"},"drugrecommendation":"Increase starting daily dose by 100%. Daily dose may be given in divided doses. Monitor for efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Rapid Metabolizer"},"drugname":"pantoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Decreased plasma concentrations of PPIs compared to CYP2C19 NMs; increased risk of therapeutic failure"},"drugrecommendation":"Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses.\nMonitor for efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Normal Metabolizer"},"drugname":"pantoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs"},"drugrecommendation":"Initiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses.\nMonitor for efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"pantoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Likely increased plasma concentration of PPI compared to CYP2C19 NMs; likely increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Intermediate Metabolizer"},"drugname":"pantoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Optional","phenotypes":{"CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Likely Poor Metabolizer"},"drugname":"pantoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Likely increased plasma concentration of PPI compared to CYP2C19 NMs; likely increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"The strength of recommendation for \"likely\" phenotypes are the same as their respective confirmed phenotypes. \"Likely\" indicates the uncertainty in the phenotype assignment, but it is reasonable to apply the recommendation for the confirmed phenotype to the corresponding \"likely\" phenotype."},{"lookupkey":{"CYP2C19":"Poor Metabolizer"},"drugname":"pantoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity"},"drugrecommendation":"Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.","classification":"Moderate","phenotypes":{"CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Indeterminate"},"drugname":"pantoprazole","guidelinename":"CYP2C19 and Proton Pump Inhibitors","implications":{"CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Indeterminate"},"activityscore":{"CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug."},{"lookupkey":{"HLA-B":"*15:02 negative"},"drugname":"oxcarbazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-B":"Normal risk of oxcarbazepine-induced SJS/TEN"},"drugrecommendation":"Use oxcarbazepine per standard dosing guidelines.","classification":"Strong","phenotypes":{},"activityscore":{"HLA-B":"n/a"},"population":"OXC use >3 mos","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug."},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug."},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug."},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug."},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Insufficient evidence demonstrating clinical impact"},"drugrecommendation":"No recommendation based on insufficient evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy."},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Insufficient evidence demonstrating clinical impact"},"drugrecommendation":"No recommendation based on insufficient evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy."},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Insufficient evidence demonstrating clinical impact"},"drugrecommendation":"No recommendation based on insufficient evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy."},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Insufficient evidence demonstrating clinical impact"},"drugrecommendation":"No recommendation based on insufficient evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy."},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Insufficient evidence demonstrating clinical impact"},"drugrecommendation":"No recommendation based on insufficient evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy."},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"ondansetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative"},"drugname":"oxcarbazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-B":"Normal risk of oxcarbazepine-induced SJS/TEN"},"drugrecommendation":"Use oxcarbazepine per standard dosing guidelines.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"OXC naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 positive"},"drugname":"oxcarbazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-B":"Greater risk of oxcarbazepine-induced SJS/TEN"},"drugrecommendation":"If patient is oxcarbazepine-naïve, do not use oxcarbazepine.","classification":"Strong","phenotypes":{},"activityscore":{},"population":"OXC naive","comments":"Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital."},{"lookupkey":{"HLA-B":"*15:02 positive"},"drugname":"oxcarbazepine","guidelinename":"HLA-A, HLA-B and Carbamazepine and Oxcarbazepine","implications":{"HLA-B":"Greater risk of oxcarbazepine-induced SJS/TEN"},"drugrecommendation":"The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (~4-28 days), and cases usually occur within three months of dosing; therefore, if the patient has previously used oxcarbazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of oxcarbazepine in the future.","classification":"Optional","phenotypes":{},"activityscore":{"HLA-B":"n/a"},"population":"OXC use >3 mos","comments":"Previous tolerance of oxcarbazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital."},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit. The extent to which ultrarapid metabolizers phenoconvert to normal, intermediate, or poor metabolizers due to paroxetine autoinhibition of CYP2D6 is unclear."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit. The extent to which ultrarapid metabolizers phenoconvert to normal, intermediate, or poor metabolizers due to paroxetine autoinhibition of CYP2D6 is unclear."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit. The extent to which ultrarapid metabolizers phenoconvert to normal, intermediate, or poor metabolizers due to paroxetine autoinhibition of CYP2D6 is unclear."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit. The extent to which ultrarapid metabolizers phenoconvert to normal, intermediate, or poor metabolizers due to paroxetine autoinhibition of CYP2D6 is unclear."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit. The extent to which ultrarapid metabolizers phenoconvert to normal, intermediate, or poor metabolizers due to paroxetine autoinhibition of CYP2D6 is unclear."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit. The extent to which ultrarapid metabolizers phenoconvert to normal, intermediate, or poor metabolizers due to paroxetine autoinhibition of CYP2D6 is unclear."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit. The extent to which ultrarapid metabolizers phenoconvert to normal, intermediate, or poor metabolizers due to paroxetine autoinhibition of CYP2D6 is unclear."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit. The extent to which ultrarapid metabolizers phenoconvert to normal, intermediate, or poor metabolizers due to paroxetine autoinhibition of CYP2D6 is unclear."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit. The extent to which ultrarapid metabolizers phenoconvert to normal, intermediate, or poor metabolizers due to paroxetine autoinhibition of CYP2D6 is unclear."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity"},"drugrecommendation":"Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit. The extent to which ultrarapid metabolizers phenoconvert to normal, intermediate, or poor metabolizers due to paroxetine autoinhibition of CYP2D6 is unclear."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit. The extent to which ultrarapid metabolizers phenoconvert to normal, intermediate, or poor metabolizers due to paroxetine autoinhibition of CYP2D6 is unclear."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism of paroxetine to less active compounds. Paroxetine-associated phenoconversion of normal metabolizers to intermediate or poor metabolizers due to CYP2D6 autoinhibition may occur and is dose-dependent and greater at steady state concentrations."},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism of paroxetine to less active compounds. Paroxetine-associated phenoconversion of normal metabolizers to intermediate or poor metabolizers due to CYP2D6 autoinhibition may occur and is dose-dependent and greater at steady state concentrations."},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism of paroxetine to less active compounds. Paroxetine-associated phenoconversion of normal metabolizers to intermediate or poor metabolizers due to CYP2D6 autoinhibition may occur and is dose-dependent and greater at steady state concentrations."},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism of paroxetine to less active compounds. Paroxetine-associated phenoconversion of normal metabolizers to intermediate or poor metabolizers due to CYP2D6 autoinhibition may occur and is dose-dependent and greater at steady state concentrations."},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism of paroxetine to less active compounds. Paroxetine-associated phenoconversion of normal metabolizers to intermediate or poor metabolizers due to CYP2D6 autoinhibition may occur and is dose-dependent and greater at steady state concentrations."},"drugrecommendation":"Initiate therapy with recommended starting dose","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers when starting treatment or at lower doses. Higher plasma concentrations may increase the probability of side\neffects. Paroxetine-associated phenoconversion of intermediate metabolizers to poor metabolizers due to CYP2D6 autoinhibition may occur and is dose-dependent and greater at steady state concentrations."},"drugrecommendation":"Consider a lower starting dose and slower titration schedule as compared to normal metabolizers.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers when starting treatment or at lower doses. Higher plasma concentrations may increase the probability of side\neffects. Paroxetine-associated phenoconversion of intermediate metabolizers to poor metabolizers due to CYP2D6 autoinhibition may occur and is dose-dependent and greater at steady state concentrations."},"drugrecommendation":"Consider a lower starting dose and slower titration schedule as compared to normal metabolizers.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers when starting treatment or at lower doses. Higher plasma concentrations may increase the probability of side\neffects. Paroxetine-associated phenoconversion of intermediate metabolizers to poor metabolizers due to CYP2D6 autoinhibition may occur and is dose-dependent and greater at steady state concentrations."},"drugrecommendation":"Consider a lower starting dose and slower titration schedule as compared to normal metabolizers.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of paroxetine to less active compounds when compared to CYP2D6 normal metabolizers when starting treatment or at lower doses. Higher plasma concentrations may increase the probability of side\neffects. Paroxetine-associated phenoconversion of intermediate metabolizers to poor metabolizers due to CYP2D6 autoinhibition may occur and is dose-dependent and greater at steady state concentrations."},"drugrecommendation":"Consider a lower starting dose and slower titration schedule as compared to normal metabolizers.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"G6PD":"Deficient"},"drugname":"sulfadimidine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Optional","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs."},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects. The impact of paroxetine-associated autoinhibition of CYP2D6 is minimal in poor metabolizers."},"drugrecommendation":"Consider a 50% reduction in recommended starting dose, slower titration schedule, and a 50% lower maintenance dose as compared to normal metabolizers.","classification":"Moderate","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"paroxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"G6PD":"Normal"},"drugname":"phenazopyridine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"phenazopyridine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Optional","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs."},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"phenazopyridine","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for for acute exacerbation of chronic hemolysis."},{"lookupkey":{"G6PD":"Variable"},"drugname":"phenazopyridine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"phenazopyridine","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"quinine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"quinine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Optional","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs."},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"quinine","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for for acute exacerbation of chronic hemolysis."},{"lookupkey":{"G6PD":"Variable"},"drugname":"quinine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"quinine","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"sulfadiazine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"sulfadiazine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Optional","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs."},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"sulfadiazine","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for for acute exacerbation of chronic hemolysis."},{"lookupkey":{"G6PD":"Variable"},"drugname":"sulfadiazine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"sulfadiazine","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"sulfadimidine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"sulfadimidine","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for for acute exacerbation of chronic hemolysis."},{"lookupkey":{"G6PD":"Variable"},"drugname":"sulfadimidine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"sulfadimidine","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"sulfamethoxazole / trimethoprim","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"sulfamethoxazole / trimethoprim","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Optional","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs."},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"sulfamethoxazole / trimethoprim","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for for acute exacerbation of chronic hemolysis."},{"lookupkey":{"G6PD":"Variable"},"drugname":"sulfamethoxazole / trimethoprim","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"sulfamethoxazole / trimethoprim","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"sulfanilamide","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"sulfanilamide","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Optional","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs."},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"sulfanilamide","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for for acute exacerbation of chronic hemolysis."},{"lookupkey":{"G6PD":"Variable"},"drugname":"sulfanilamide","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"sulfanilamide","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"sulfasalazine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"sulfasalazine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Optional","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs."},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"sulfasalazine","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for for acute exacerbation of chronic hemolysis."},{"lookupkey":{"G6PD":"Variable"},"drugname":"sulfasalazine","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Normal"},"drugname":"sulfisoxazole","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"sulfisoxazole","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for for acute exacerbation of chronic hemolysis."},{"lookupkey":{"G6PD":"Variable"},"drugname":"sulfisoxazole","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"sulfisoxazole","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"tolbutamide","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient"},"drugname":"tolbutamide","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Optional","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Closer monitoring may be indicated higher-than-normal dosages, and in the setting of infection or other oxidative stress including concomitant use of multiple medium and low-to-no risk drugs."},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"tolbutamide","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Use drug cautiously; if used, close monitoring for acute exacerbation of chronic hemolysis is recommended","classification":"Optional","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for for acute exacerbation of chronic hemolysis."},{"lookupkey":{"G6PD":"Variable"},"drugname":"tolbutamide","guidelinename":"G6PD","implications":{"G6PD":"Low-to-no risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status at standard doses","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"tolbutamide","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"2.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"1.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"1.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"0.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"0.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"n/a"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"n/a","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"SLCO1B1":"Increased Function"},"drugname":"pitavastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses based on disease-specific guidelines.","classification":"Strong","phenotypes":{"SLCO1B1":"Increased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"2.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"1.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"1.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"0.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"0.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"n/a"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"n/a"},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"2.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"1.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"1.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"0.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"0.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"n/a"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"n/a","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"No Result"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"No Result"},"activityscore":{"CYP2C9":"No Result"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"No Result"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"n/a"},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"No Result"},"activityscore":{"CYP2C9":"No Result"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"2.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"1.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"1.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"0.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"0.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"n/a"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"n/a","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"2.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"1.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"1.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity"},"drugrecommendation":"Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"0.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"0.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"n/a"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"n/a"},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"2.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"1.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"1.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"0.5"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"0.0"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"n/a"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"n/a","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"No Result"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"No Result"},"activityscore":{"CYP2C9":"No Result"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"No Result"},"drugname":"phenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"n/a"},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"No Result"},"activityscore":{"CYP2C9":"No Result"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity"},"drugrecommendation":"Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"2.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"1.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"1.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"0.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"0.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"n/a"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"n/a","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"2.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"1.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"1.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"0.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"0.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"SLCO1B1":"Normal Function"},"drugname":"pitavastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses based on disease-specific guidelines.","classification":"Strong","phenotypes":{"SLCO1B1":"Normal Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"n/a"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"n/a"},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"2.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"1.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"1.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"0.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"0.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"n/a"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"n/a","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"No Result"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"No Result"},"activityscore":{"CYP2C9":"No Result"},"population":"PHT naive","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"No Result"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"n/a"},"drugrecommendation":"If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine.","classification":"Strong","phenotypes":{"CYP2C9":"No Result"},"activityscore":{"CYP2C9":"No Result"},"population":"PHT naive","comments":"Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent."},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"2.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"1.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"1.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"0.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"0.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"n/a"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"n/a","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"2.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"1.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"1.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"0.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"0.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"n/a"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"n/a"},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"2.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Normal phenytoin metabolism"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"CYP2B6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Normal metabolism of sertraline to less active compounds.","CYP2C19":"Reduced metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose.","classification":"Moderate","phenotypes":{"CYP2B6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"1.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects."},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"1.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"0.5"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"0.0"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities."},"drugrecommendation":"For first dose, use typical initial or loading dose. For subsequent doses use approximately 50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"No Result","CYP2C9":"n/a"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No recommendation","classification":"n/a","phenotypes":{"CYP2C9":"Indeterminate"},"activityscore":{"CYP2C9":"n/a"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 negative","CYP2C9":"No Result"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"n/a","CYP2C9":"n/a"},"drugrecommendation":"No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN and patients should be carefully monitored according to a usual standard.","classification":"Strong","phenotypes":{"CYP2C9":"No Result"},"activityscore":{"CYP2C9":"No Result"},"population":"PHT use >3mos","comments":"n/a"},{"lookupkey":{"HLA-B":"*15:02 positive","CYP2C9":"No Result"},"drugname":"fosphenytoin","guidelinename":"CYP2C9, HLA-B and Phenytoin","implications":{"HLA-B":"Increased risk of phenytoin-induced SJS/TEN","CYP2C9":"n/a"},"drugrecommendation":"If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing.","classification":"Optional","phenotypes":{"CYP2C9":"No Result"},"activityscore":{"CYP2C9":"No Result"},"population":"PHT use >3mos","comments":"Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants."},{"lookupkey":{"CYP2C9":"2.0"},"drugname":"piroxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"1.5"},"drugname":"piroxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Mildly reduced metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age."},{"lookupkey":{"CYP2C9":"1.0"},"drugname":"piroxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities"},"drugrecommendation":"Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"0.5"},"drugname":"piroxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"0.0"},"drugname":"piroxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).","classification":"Moderate","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"SLCO1B1":"Possible Decreased Function"},"drugname":"pitavastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased pitavastatin exposure as compared to normal function which may translate to increased myopathy risk"},"drugrecommendation":"Prescribe ≤ 2mg as a starting dose and adjust doses of pitavastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >1mg. If dose >2mg needed for desired efficacy, consider an alternative statin (see Figure 1 of PMID: 35152405 for recommendations for alternative statins) or combination therapy (i.e. pitavastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Moderate","phenotypes":{"SLCO1B1":"Possible Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Decreased Function"},"drugname":"pitavastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased pitavastatin exposure as compared to normal function which may translate to increased myopathy risk"},"drugrecommendation":"Prescribe ≤ 2mg as a starting dose and adjust doses of pitavastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >1mg. If dose >2mg needed for desired efficacy, consider an alternative statin (see Figure 1 of PMID: 35152405 for recommendations for alternative statins) or combination therapy (i.e. pitavastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Moderate","phenotypes":{"SLCO1B1":"Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Poor Function"},"drugname":"pitavastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased pitavastatin exposure as compared to normal and decreased function which may translate to increased myopathy risk."},"drugrecommendation":"Prescribe ≤1mg as a starting dose and adjust doses of pitavastatin based on disease-specific guidelines. If dose >1mg needed for desired efficacy, consider an alternative statin (see Figure 1 of PMID: 35152405 for recommendations for alternative statins) or combination therapy (i.e. pitavastatin plus non-statin guideline directed medical therapy)(PMID: 30423391).","classification":"Moderate","phenotypes":{"SLCO1B1":"Poor Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Indeterminate"},"drugname":"pitavastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"SLCO1B1":"Indeterminate"},"activityscore":{},"population":"general","comments":"n/a"},{"lookupkey":{"SLCO1B1":"Increased Function"},"drugname":"pravastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses based on disease-specific guidelines.","classification":"Strong","phenotypes":{"SLCO1B1":"Increased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"SLCO1B1":"Normal Function"},"drugname":"pravastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses based on disease-specific guidelines.","classification":"Strong","phenotypes":{"SLCO1B1":"Normal Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"SLCO1B1":"Possible Decreased Function"},"drugname":"pravastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased pravastatin exposure as compared to normal function; Typical myopathy risk with doses ≤40 mg."},"drugrecommendation":"Prescribe desired starting dose and adjust doses of pravastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy with pravastatin especially with doses >40mg per day.","classification":"Moderate","phenotypes":{"SLCO1B1":"Possible Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Decreased Function"},"drugname":"pravastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased pravastatin exposure as compared to normal function; Typical myopathy risk with doses ≤40 mg."},"drugrecommendation":"Prescribe desired starting dose and adjust doses of pravastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy with pravastatin especially with doses >40mg per day.","classification":"Moderate","phenotypes":{"SLCO1B1":"Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Poor Function"},"drugname":"pravastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased pravastatin statin exposure as compared to normal and decreased function; Typical myopathy risk with doses ≤40 mg."},"drugrecommendation":"Prescribe ≤40mg as a starting dose and adjust doses of pravastatin based on disease-specific guidelines. If patient is tolerating 40mg dose but higher potency is needed, a higher dose (>40mg) or an alternative statin (see Figure 1 of of PMID: 35152405 for recommendations for alternative statins) or combination therapy (i.e. pravastatin plus non-statin guideline directed medical therapy)(PMID: 30423391) could be considered. Prescriber should be aware of possible increased risk for myopathy especially with pravastatin doses >40mg.","classification":"Moderate","phenotypes":{"SLCO1B1":"Poor Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Indeterminate"},"drugname":"pravastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"SLCO1B1":"Indeterminate"},"activityscore":{},"population":"general","comments":"n/a"},{"lookupkey":{"G6PD":"Normal"},"drugname":"primaquine","guidelinename":"G6PD","implications":{"G6PD":"Low risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"ABCG2":"Normal Function","SLCO1B1":"Possible Decreased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Typical myopathy risk and rosuvastatin exposure","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >20mg.","classification":"Strong","phenotypes":{"ABCG2":"Normal Function","SLCO1B1":"Possible Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"G6PD":"Deficient"},"drugname":"primaquine","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute hemolytic anemia with standard (or higher than standard) anti-relapse dosages for Plasmodium vivax or Plasmodium ovale of 0.25-0.5 mg/kg daily for 14 days"},"drugrecommendation":"Avoid primaquine, except in the following cases where established expert consensus guidelines for the treatment of malaria should be followed: (1) Treating Plasmodium vivax or Plasmodium ovale malaria for radical cure of liver-stage infections: 0.75 mg/kg once weekly x8 weeks (WHO) or 45 mg once weekly x8 weeks (CDC) - with close monitoring for hemolysis; (2) Treating Plasmodium falciparum malaria by using primaquine single dose as a gametocytocide at 0.25 mg/kg (WHO) - without need for monitoring for hemolysis.","classification":"Strong","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Dosing recommendations for primaquine in patients with G6PD deficiency are derived from the malaria treatment guidelines issued by the World Health Organization and the U.S. Centers for Disease Control and Prevention."},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"primaquine","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Avoid primaquine","classification":"Strong","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"The strength of evidence among patients with the G6PD Deficient phenotype provides strong rationale to also avoid primaquine in the setting of the more severe G6PD Deficient with CNSHA phenotype."},{"lookupkey":{"G6PD":"Variable"},"drugname":"primaquine","guidelinename":"G6PD","implications":{"G6PD":"Variable risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one nondeficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype; an enzyme activity test is needed to guide treatment in such cases."},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"primaquine","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"ABCG2":"Poor Function","SLCO1B1":"Decreased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure compared to normal and decreased function; unknown myopathy risk; increased lipid-lowering effects","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Prescribe ≤10mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose >10mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Optional","phenotypes":{"ABCG2":"Poor Function","SLCO1B1":"Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Poor Function","SLCO1B1":"Possible Decreased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure compared to normal and decreased function; unknown myopathy risk; increased lipid-lowering effects","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Prescribe ≤10mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose >10mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Optional","phenotypes":{"ABCG2":"Poor Function","SLCO1B1":"Possible Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Poor Function","SLCO1B1":"Poor Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure compared to normal and decreased function; unknown myopathy risk; increased lipid-lowering effects","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function and decreased function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Prescribe ≤10mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose >10mg needed for desired efficacy, consider combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Optional","phenotypes":{"ABCG2":"Poor Function","SLCO1B1":"Poor Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Normal Function","SLCO1B1":"Poor Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Typical myopathy risk and rosuvastatin exposure","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function and decreased function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Prescribe ≤20mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose > 20mg needed for desired efficacy, consider combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Moderate","phenotypes":{"ABCG2":"Normal Function","SLCO1B1":"Poor Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Poor Function","SLCO1B1":"Increased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure compared to normal and decreased function; unknown myopathy risk; increased lipid-lowering effects","SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe ≤20mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Optional","phenotypes":{"ABCG2":"Poor Function","SLCO1B1":"Increased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Poor Function","SLCO1B1":"Normal Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure compared to normal and decreased function; unknown myopathy risk; increased lipid-lowering effects","SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe ≤20mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Optional","phenotypes":{"ABCG2":"Poor Function","SLCO1B1":"Normal Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Decreased Function","SLCO1B1":"Poor Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure as compared to normal function; unknown risk for myopathy; increased lipid lowering effects","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function and decreased function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Prescribe ≤20mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose >20mg needed for desired efficacy, consider combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).","classification":"Moderate","phenotypes":{"ABCG2":"Decreased Function","SLCO1B1":"Poor Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Decreased Function","SLCO1B1":"Increased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure as compared to normal function; unknown risk for myopathy; increased lipid lowering effects","SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines.","classification":"Moderate","phenotypes":{"ABCG2":"Decreased Function","SLCO1B1":"Increased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Normal Function","SLCO1B1":"Increased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Typical myopathy risk and rosuvastatin exposure","SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines.","classification":"Strong","phenotypes":{"ABCG2":"Normal Function","SLCO1B1":"Increased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin."},{"lookupkey":{"ABCG2":"Decreased Function","SLCO1B1":"Normal Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure as compared to normal function; unknown risk for myopathy; increased lipid lowering effects","SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines.","classification":"Moderate","phenotypes":{"ABCG2":"Decreased Function","SLCO1B1":"Normal Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Normal Function","SLCO1B1":"Normal Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Typical myopathy risk and rosuvastatin exposure","SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines.","classification":"Strong","phenotypes":{"ABCG2":"Normal Function","SLCO1B1":"Normal Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin."},{"lookupkey":{"ABCG2":"Decreased Function","SLCO1B1":"Decreased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure as compared to normal function; unknown risk for myopathy; increased lipid lowering effects","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >20mg.","classification":"Moderate","phenotypes":{"ABCG2":"Decreased Function","SLCO1B1":"Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Decreased Function","SLCO1B1":"Possible Decreased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure as compared to normal function; unknown risk for myopathy; increased lipid lowering effects","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >20mg.","classification":"Moderate","phenotypes":{"ABCG2":"Decreased Function","SLCO1B1":"Possible Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Normal Function","SLCO1B1":"Decreased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Typical myopathy risk and rosuvastatin exposure","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >20mg.","classification":"Strong","phenotypes":{"ABCG2":"Normal Function","SLCO1B1":"Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"No Result","SLCO1B1":"Decreased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"n/a","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Based on SLCO1B1 status, prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >20mg. ABCG2 genotype result is not available.","classification":"Strong","phenotypes":{"ABCG2":"No Result","SLCO1B1":"Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"No Result","SLCO1B1":"Increased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"n/a","SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Based on SLCO1B1 status, prescribe desired starting dose and adjust doses based on disease-specific guidelines. ABCG2 genotype result is not available.","classification":"Strong","phenotypes":{"ABCG2":"No Result","SLCO1B1":"Increased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"ABCG2":"Decreased Function","SLCO1B1":"Indeterminate"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure as compared to normal function; unknown risk for myopathy; increased lipid lowering effects","SLCO1B1":"n/a"},"drugrecommendation":"Based on ABCG2 status, prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific guidelines and specific population guidelines. SLCO1B1 phenotype could not be assigned based on genotyping.","classification":"Moderate","phenotypes":{"ABCG2":"Decreased Function","SLCO1B1":"Indeterminate"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"No Result","SLCO1B1":"Indeterminate"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"n/a","SLCO1B1":"n/a"},"drugrecommendation":"n/a","classification":"n/a","phenotypes":{"ABCG2":"No Result","SLCO1B1":"Indeterminate"},"activityscore":{},"population":"general","comments":"n/a"},{"lookupkey":{"ABCG2":"Normal Function","SLCO1B1":"Indeterminate"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Typical myopathy risk and rosuvastatin exposure","SLCO1B1":"n/a"},"drugrecommendation":"Based on ABCG2 status, prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. SLCO1B1 phenotype could not be assigned based on genotyping.","classification":"Strong","phenotypes":{"ABCG2":"Normal Function","SLCO1B1":"Indeterminate"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin."},{"lookupkey":{"ABCG2":"Poor Function","SLCO1B1":"Indeterminate"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure compared to normal and decreased function; unknown myopathy risk; increased lipid-lowering effects","SLCO1B1":"n/a"},"drugrecommendation":"Based on ABCG2 status, prescribe ≤20mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391). SLCO1B1 phenotype could not be assigned based on genotyping.","classification":"Moderate","phenotypes":{"ABCG2":"Poor Function","SLCO1B1":"Indeterminate"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Decreased Function","SLCO1B1":"No Result"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure as compared to normal function; unknown risk for myopathy; increased lipid lowering effects","SLCO1B1":"n/a"},"drugrecommendation":"Based on ABCG2 status, prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific guidelines and specific population guidelines. SLCO1B1 genotype result is not available.","classification":"Moderate","phenotypes":{"ABCG2":"Decreased Function","SLCO1B1":"No Result"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"Normal Function","SLCO1B1":"No Result"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Typical myopathy risk and rosuvastatin exposure","SLCO1B1":"n/a"},"drugrecommendation":"Based on ABCG2 status, prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. SLCO1B1 genotype result is not available.","classification":"Strong","phenotypes":{"ABCG2":"Normal Function","SLCO1B1":"No Result"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin."},{"lookupkey":{"ABCG2":"Poor Function","SLCO1B1":"No Result"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"Increased rosuvastatin exposure compared to normal and decreased function; unknown myopathy risk; increased lipid-lowering effects","SLCO1B1":"n/a"},"drugrecommendation":"Based on ABCG2 status, prescribe ≤20mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391). SLCO1B1 genotype result is not available.","classification":"Moderate","phenotypes":{"ABCG2":"Poor Function","SLCO1B1":"No Result"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"No Result","SLCO1B1":"Normal Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"n/a","SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Based on SLCO1B1 status, prescribe desired starting dose and adjust doses based on disease-specific guidelines. ABCG2 genotype result is not available.","classification":"Strong","phenotypes":{"ABCG2":"No Result","SLCO1B1":"Normal Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"CYP2B6":"Rapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"Reduced metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2B6":"Rapid Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"ABCG2":"No Result","SLCO1B1":"Poor Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"n/a","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function and decreased function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Based on SLCO1B1 status, prescribe ≤20mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines If dose >20mg needed for desired efficacy, consider combination therapy (i.e. rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391). ABCG2 genotype result is not available.","classification":"Moderate","phenotypes":{"ABCG2":"No Result","SLCO1B1":"Poor Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"ABCG2":"No Result","SLCO1B1":"Possible Decreased Function"},"drugname":"rosuvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"ABCG2":"n/a","SLCO1B1":"Increased rosuvastatin exposure as compared to normal function; Typical myopathy risk with doses ≤20 mg."},"drugrecommendation":"Based on SLCO1B1 status, prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >20mg. ABCG2 genotype result is not available.","classification":"Strong","phenotypes":{"ABCG2":"No Result","SLCO1B1":"Possible Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"CYP2B6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"n/a","CYP2C19":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2B6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"CYP2B6 metabolizer status, drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be also considered."},{"lookupkey":{"CYP2B6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Increase in metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose. If patient does not adequately respond to recommended maintenance dosing, consider titrating to a higher\nmaintenance dose or switching to a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19 or CYP2B6.","classification":"Optional","phenotypes":{"CYP2B6":"Ultrarapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Rapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose. If patient does not adequately respond to recommended maintenance dosing, consider titrating to a higher\nmaintenance dose or switching to a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19 or CYP2B6.","classification":"Optional","phenotypes":{"CYP2B6":"Rapid Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Normal metabolism of sertraline to less active compounds.","CYP2C19":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2B6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Reduced metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2B6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Poor Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Greatly reduced metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.","CYP2C19":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2B6":"Poor Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Indeterminate","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"n/a","CYP2C19":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2B6":"Indeterminate","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"No Result","CYP2C19":"Rapid Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"n/a","CYP2C19":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2B6":"No Result","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"CYP2B6 metabolizer status, drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be also considered."},{"lookupkey":{"CYP2B6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Increase in metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose. If patient does not adequately respond to recommended maintenance dosing, consider titrating to a higher\nmaintenance dose or switching to a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19 or CYP2B6.","classification":"Optional","phenotypes":{"CYP2B6":"Ultrarapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Rapid Metabolizer","CYP2C19":"Rapid Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers."},"drugrecommendation":"Initiate therapy with recommended starting dose. 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Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19.","classification":"Optional","phenotypes":{"CYP2B6":"Ultrarapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Rapid Metabolizer","CYP2C19":"Poor Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"Greatly reduced metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19.","classification":"Optional","phenotypes":{"CYP2B6":"Rapid Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Reduced metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"Greatly reduced metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19.","classification":"Moderate","phenotypes":{"CYP2B6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Poor Metabolizer","CYP2C19":"Poor Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Greatly reduced metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.","CYP2C19":"Greatly reduced metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Select an alternative antidepressant not primarily metabolized by CYP2C19 or CYP2B6.","classification":"Optional","phenotypes":{"CYP2B6":"Poor Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Indeterminate","CYP2C19":"Poor Metabolizer"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"n/a","CYP2C19":"Greatly reduced metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19.","classification":"Moderate","phenotypes":{"CYP2B6":"Indeterminate","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"No Result","CYP2C19":"Indeterminate"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2B6":"No Result","CYP2C19":"Indeterminate"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"CYP2B6 metabolizer status, drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be also considered."},{"lookupkey":{"CYP2B6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Increase in metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2B6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Rapid Metabolizer","CYP2C19":"Indeterminate"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2B6":"Rapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Normal metabolism of sertraline to less active compounds.","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2B6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Reduced metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose.","classification":"Moderate","phenotypes":{"CYP2B6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Poor Metabolizer","CYP2C19":"Indeterminate"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Greatly reduced metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.","CYP2C19":"n/a"},"drugrecommendation":"Consider a lower starting dose, slower titration schedule and 25% reduction of standard maintenance dose as CYP2B6 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2B6.","classification":"Optional","phenotypes":{"CYP2B6":"Poor Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Indeterminate","CYP2C19":"Indeterminate"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2B6":"Indeterminate","CYP2C19":"Indeterminate"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Increase in metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2B6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"CYPC19 metabolizer status, drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be also considered."},{"lookupkey":{"CYP2B6":"Rapid Metabolizer","CYP2C19":"No Result"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Small increase in metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2B6":"Rapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"CYPC19 metabolizer status, drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be also considered."},{"lookupkey":{"CYP2B6":"Normal Metabolizer","CYP2C19":"No Result"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Normal metabolism of sertraline to less active compounds.","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2B6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"CYPC19 metabolizer status, drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be also considered."},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2B6":"Intermediate Metabolizer","CYP2C19":"No Result"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Reduced metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than CYP2B6 normal metabolizers.","classification":"Optional","phenotypes":{"CYP2B6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"CYPC19 metabolizer status, drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be also considered."},{"lookupkey":{"CYP2B6":"Poor Metabolizer","CYP2C19":"No Result"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"Greatly reduced metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.","CYP2C19":"n/a"},"drugrecommendation":"Consider a lower starting dose, slower titration schedule and 25% reduction of standard maintenance dose as compared to CYP2B6 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2B6.","classification":"Optional","phenotypes":{"CYP2B6":"Poor Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"CYPC19 metabolizer status, drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be also considered."},{"lookupkey":{"CYP2B6":"Indeterminate","CYP2C19":"No Result"},"drugname":"sertraline","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2B6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2B6":"Indeterminate","CYP2C19":"No Result"},"activityscore":{"CYP2B6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"SLCO1B1":"Increased Function"},"drugname":"simvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses based on disease-specific guidelines.","classification":"Strong","phenotypes":{"SLCO1B1":"Increased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"SLCO1B1":"Normal Function"},"drugname":"simvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Typical myopathy risk and statin exposure"},"drugrecommendation":"Prescribe desired starting dose and adjust doses based on disease-specific guidelines.","classification":"Strong","phenotypes":{"SLCO1B1":"Normal Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin."},{"lookupkey":{"SLCO1B1":"Possible Decreased Function"},"drugname":"simvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased simvastatin acid exposure as compared to normal function; increased risk of myopathy"},"drugrecommendation":"Prescribe an alternative statin depending on the desired potency (see Figure 1 of PMID: 35152405 for recommendations for alternative statins). If simvastatin therapy is warranted, limit dose to <20mg/day.","classification":"Strong","phenotypes":{"SLCO1B1":"Possible Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Decreased Function"},"drugname":"simvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased simvastatin acid exposure as compared to normal function; increased risk of myopathy"},"drugrecommendation":"Prescribe an alternative statin depending on the desired potency (see Figure 1 of PMID: 35152405 for recommendations for alternative statins). If simvastatin therapy is warranted, limit dose to <20mg/day.","classification":"Strong","phenotypes":{"SLCO1B1":"Decreased Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Poor Function"},"drugname":"simvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"Increased simvastatin acid exposure compared to normal and decreased function; highly increased myopathy risk"},"drugrecommendation":"Prescribe an alternative statin depending on the desired potency (see Figure 1 of PMID: 35152405 for recommendations for alternative statins).","classification":"Strong","phenotypes":{"SLCO1B1":"Poor Function"},"activityscore":{},"population":"general","comments":"The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy."},{"lookupkey":{"SLCO1B1":"Indeterminate"},"drugname":"simvastatin","guidelinename":"SLCO1B1, ABCG2, CYP2C9, and Statins","implications":{"SLCO1B1":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"SLCO1B1":"Indeterminate"},"activityscore":{},"population":"general","comments":"n/a"},{"lookupkey":{"CYP3A5":"Normal Metabolizer"},"drugname":"tacrolimus","guidelinename":"CYP3A5 and Tacrolimus","implications":{"CYP3A5":"Lower dose-adjusted trough concentrations of tacrolimus and decreased chance of achieving target tacrolimus concentrations."},"drugrecommendation":"Increase starting dose 1.5 to 2 times recommended starting dose. Total starting dose should not exceed 0.3 mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP3A5":"Normal Metabolizer"},"activityscore":{"CYP3A5":"n/a"},"population":"general","comments":"This recommendation includes the use of tacrolimus in kidney, heart, lung and hematopoietic stem cell transplant patients, and liver transplant patients where the donor and recipient genotypes are identical. Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors (e.g., medication interactions, or hepatic function). Typically with other CYP enzymes, a normal metabolizer would be classified as having normal metabolism, and therefore, the drug dose would not change based on the patient's genotype. However, in the case of CYP3A5 and tacrolimus, a CYP3A5 expresser (i.e., CYP3A5 normal metabolizer or intermediate metabolizer) would require a higher recommended starting dose, and the CYP3A5 non-expresser (i.e., poor metabolizer) would require the standard recommended starting dose."},{"lookupkey":{"CYP3A5":"Possible Intermediate Metabolizer"},"drugname":"tacrolimus","guidelinename":"CYP3A5 and Tacrolimus","implications":{"CYP3A5":"Lower dose-adjusted trough concentrations of tacrolimus and decreased chance of achieving target tacrolimus concentrations."},"drugrecommendation":"Increase starting dose 1.5 to 2 times recommended starting dose. Total starting dose should not exceed 0.3 mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP3A5":"Possible Intermediate Metabolizer"},"activityscore":{"CYP3A5":"n/a"},"population":"general","comments":"This recommendation includes the use of tacrolimus in kidney, heart, lung and hematopoietic stem cell transplant patients, and liver transplant patients where the donor and recipient genotypes are identical. Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors (e.g., medication interactions, or hepatic function).Typically with other CYP enzymes, a normal metabolizer would be classified as having normal metabolism, and therefore, the drug dose would not change based on the patient's genotype. However, in the case of CYP3A5 and tacrolimus, a CYP3A5 expresser (i.e., CYP3A5 normal metabolizer or intermediate metabolizer) would require a higher recommended starting dose and the CYP3A5 non-expresser (i.e., poor metabolizer) would require the standard recommended starting dose."},{"lookupkey":{"CYP3A5":"Intermediate Metabolizer"},"drugname":"tacrolimus","guidelinename":"CYP3A5 and Tacrolimus","implications":{"CYP3A5":"Lower dose-adjusted trough concentrations of tacrolimus and decreased chance of achieving target tacrolimus concentrations."},"drugrecommendation":"Increase starting dose 1.5 to 2 times recommended starting dose. Total starting dose should not exceed 0.3 mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP3A5":"Intermediate Metabolizer"},"activityscore":{"CYP3A5":"n/a"},"population":"general","comments":"This recommendation includes the use of tacrolimus in kidney, heart, lung and hematopoietic stem cell transplant patients, and liver transplant patients where the donor and recipient genotypes are identical. Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors (e.g., medication interactions, or hepatic function).Typically with other CYP enzymes, a normal metabolizer would be classified as having normal metabolism, and therefore, the drug dose would not change based on the patient's genotype. However, in the case of CYP3A5 and tacrolimus, a CYP3A5 expresser (i.e., CYP3A5 normal metabolizer or intermediate metabolizer) would require a higher recommended starting dose and the CYP3A5 non-expresser (i.e., poor metabolizer) would require the standard recommended starting dose."},{"lookupkey":{"CYP3A5":"Poor Metabolizer"},"drugname":"tacrolimus","guidelinename":"CYP3A5 and Tacrolimus","implications":{"CYP3A5":"Higher (\"normal\") dose-adjusted trough concentrations of tacrolimus and increased chance of achieving target tacrolimus concentrations."},"drugrecommendation":"Initiate therapy with standard recommended dose. Use therapeutic drug monitoring to guide dose adjustments.","classification":"Strong","phenotypes":{"CYP3A5":"Poor Metabolizer"},"activityscore":{"CYP3A5":"n/a"},"population":"general","comments":"This recommendation includes the use of tacrolimus in kidney, heart, lung and hematopoietic stem cell transplant patients, and liver transplant patients where the donor and recipient genotypes are identical. Typically with other CYP enzymes, a normal metabolizer would be classified as having normal metabolism, and therefore, the drug dose would not change based on the patient's genotype. However, in the case of CYP3A5 and tacrolimus, a CYP3A5 expresser (i.e., CYP3A5 normal metabolizer or intermediate metabolizer) would require a higher recommended starting dose and the CYP3A5 non-expresser (i.e., poor metabolizer) would require the standard recommended starting dose."},{"lookupkey":{"CYP3A5":"Indeterminate"},"drugname":"tacrolimus","guidelinename":"CYP3A5 and Tacrolimus","implications":{"CYP3A5":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP3A5":"Indeterminate"},"activityscore":{"CYP3A5":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"G6PD":"Normal"},"drugname":"tafenoquine","guidelinename":"G6PD","implications":{"G6PD":"Low risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid based on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":"Tafenoquine's safety has been established for a G6PD enzyme activity ≥70% of normal. (Inclusion criteria for clinical trials involving tafenoquine included G6PD activity ≥70%.)"},{"lookupkey":{"G6PD":"Deficient"},"drugname":"tafenoquine","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute hemolytic anemia"},"drugrecommendation":"Avoid use","classification":"Strong","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"tafenoquine","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Avoid use","classification":"Strong","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"Although there are not published data in individuals with the G6PD Deficient with CNSHA phenotype, there is a strong rationale to avoid these drugs based on evidence in G6PD Deficient individuals."},{"lookupkey":{"G6PD":"Variable"},"drugname":"tafenoquine","guidelinename":"G6PD","implications":{"G6PD":"Variable risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype; an enzyme activity test is needed to assign G6PD phenotype in such cases. Tafenoquine's safety has been established for a G6PD enzyme activity ≥70% of normal. (Inclusion criteria for clinical trials involving tafenoquine included G6PD activity ≥70%.)"},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"tafenoquine","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Therapeutic endoxifen concentrations"},"drugrecommendation":"Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers."},"drugrecommendation":"Consider hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women, given that these approaches are superior to tamoxifen regardless of CYP2D6 genotype (PMID 26211827). If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose (40 mg/day)(PMID 27226358). Avoid CYP2D6 strong to weak inhibitors.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers."},"drugrecommendation":"Consider hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women, given that these approaches are superior to tamoxifen regardless of CYP2D6 genotype (PMID 26211827). If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose (40 mg/day)(PMID 27226358). Avoid CYP2D6 strong to weak inhibitors.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers."},"drugrecommendation":"Consider hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women, given that these approaches are superior to tamoxifen regardless of CYP2D6 genotype (PMID 26211827). If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose (40 mg/day)(PMID 27226358). Avoid CYP2D6 strong to weak inhibitors.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers."},"drugrecommendation":"Consider hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women, given that these approaches are superior to tamoxifen regardless of CYP2D6 genotype (PMID 26211827). If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose (40 mg/day)(PMID 27226358). Avoid CYP2D6 strong to weak inhibitors.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers."},"drugrecommendation":"Recommend alternative hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women given that these approaches are superior to tamoxifen regardless of CYP2D6 genotype (PMID 26211827) and based on knowledge that CYP2D6 poor metabolizers switched from tamoxifen to anastrozole do not have an increased risk of recurrence (PMID 23213055). Note, higher dose tamoxifen (40 mg/day) increases but does not normalize endoxifen concentrations and can be considered if there are contraindications to aromatase inhibitor therapy (PMID 27226358, 21768473).","classification":"Strong","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"tamoxifen","guidelinename":"CYP2D6 and Tamoxifen","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"2.0"},"drugname":"tenoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Strong","phenotypes":{"CYP2C9":"Normal Metabolizer"},"activityscore":{"CYP2C9":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C9":"1.5"},"drugname":"tenoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Mildly reduced metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.","classification":"Moderate","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.5"},"population":"general","comments":"IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age."},{"lookupkey":{"CYP2C9":"1.0"},"drugname":"tenoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities"},"drugrecommendation":"Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).","classification":"Optional","phenotypes":{"CYP2C9":"Intermediate Metabolizer"},"activityscore":{"CYP2C9":"1.0"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"0.5"},"drugname":"tenoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).","classification":"Optional","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.5"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"CYP2C9":"0.0"},"drugname":"tenoxicam","guidelinename":"CYP2C9 and NSAIDs","implications":{"CYP2C9":"Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities"},"drugrecommendation":"Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).","classification":"Optional","phenotypes":{"CYP2C9":"Poor Metabolizer"},"activityscore":{"CYP2C9":"0.0"},"population":"general","comments":"Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity."},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with standard starting dose of thioguanine (e.g., 40 mg/m2/day for malignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern. TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern. TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Poor Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Indeterminate"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Normal Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"Poor Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity"},"drugrecommendation":"Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity"},"drugrecommendation":"Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with decreased starting doses (20%-50% of standard starting dose) if standard starting dose is ≥ 40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with decreased starting doses (20%-50% of standard starting dose) if standard starting dose is ≥ 40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with decreased starting doses (20%-50% of standard starting dose) if standard starting dose is ≥ 40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Higher risk of toxicity compared to single IM."},"drugrecommendation":"Initiate therapy with decreased starting doses (20%-50% of standard starting dose) if standard starting dose is ≥ 40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"Indeterminate"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with standard starting dose of thioguanine (e.g., 40 mg/m2/day for malignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"Indeterminate"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"No Result","NUDT15":"Poor Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Poor Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Indeterminate"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Normal Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with standard starting dose of thioguanine (e.g., 40 mg/m2/day for malignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"Indeterminate"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"n/a"},"drugrecommendation":"Neither TPMT or NUDT15 phenotype could be assigned based on genotyping performed. Consider evaluating TPMT erythrocyte activity to assess TPMT phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"TPMT":"No Result","NUDT15":"Normal Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with standard starting dose of thioguanine (e.g., 40 mg/m2/day for malignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Normal Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"No Result","NUDT15":"Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"No Result","NUDT15":"Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"No Result","NUDT15":"Possible Intermediate Metabolizer"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on NUDT15, initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"No Result","NUDT15":"Possible Intermediate Metabolizer"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"No Result","NUDT15":"Indeterminate"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"n/a"},"drugrecommendation":"Neither TPMT or NUDT15 phenotype could be assigned based on genotyping performed. Consider evaluating TPMT erythrocyte activity to assess TPMT phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.","classification":"Strong","phenotypes":{"TPMT":"No Result","NUDT15":"Indeterminate"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"TPMT":"Normal Metabolizer","NUDT15":"No Result"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT NMs have lower erythrocyte concentrations of TGN metabolites compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.","NUDT15":"Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with standard starting dose of thioguanine (e.g., 40 mg/m2/day for malignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.","classification":"Strong","phenotypes":{"TPMT":"Normal Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Intermediate Metabolizer","NUDT15":"No Result"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Intermediate Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"No Result"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression."},"drugrecommendation":"Based on TPMT, initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.","classification":"Moderate","phenotypes":{"TPMT":"Possible Intermediate Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Poor Metabolizer","NUDT15":"No Result"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.","NUDT15":"Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease."},"drugrecommendation":"Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.","classification":"Strong","phenotypes":{"TPMT":"Poor Metabolizer","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":"Standard starting doses may vary by patient characteristics and/or treatment regimens and according to local clinical practice."},{"lookupkey":{"TPMT":"Indeterminate","NUDT15":"No Result"},"drugname":"thioguanine","guidelinename":"TPMT, NUDT15 and Thiopurines","implications":{"TPMT":"n/a","NUDT15":"n/a"},"drugrecommendation":"Neither TPMT or NUDT15 phenotype could be assigned based on genotyping performed. Consider evaluating TPMT erythrocyte activity to assess TPMT phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.","classification":"Strong","phenotypes":{"TPMT":"Indeterminate","NUDT15":"No Result"},"activityscore":{},"population":"general","comments":null},{"lookupkey":{"G6PD":"Normal"},"drugname":"toluidine blue","guidelinename":"G6PD","implications":{"G6PD":"Low risk of acute hemolytic anemia"},"drugrecommendation":"No reason to avoid ased on G6PD status","classification":"Strong","phenotypes":{"G6PD":"Normal"},"activityscore":{},"population":"general","comments":"Toluidine blue classification strength is based on extrapolation from methylene blue data"},{"lookupkey":{"G6PD":"Deficient"},"drugname":"toluidine blue","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute hemolytic anemia"},"drugrecommendation":"Avoid use","classification":"Moderate","phenotypes":{"G6PD":"Deficient"},"activityscore":{},"population":"general","comments":"Toluidine blue classification strength is based on extrapolation from methylene blue data"},{"lookupkey":{"G6PD":"Deficient with CNSHA"},"drugname":"toluidine blue","guidelinename":"G6PD","implications":{"G6PD":"High risk of acute exacerbation of chronic hemolysis"},"drugrecommendation":"Avoid use","classification":"Strong","phenotypes":{"G6PD":"Deficient with CNSHA"},"activityscore":{},"population":"general","comments":"Although there are not published data in individuals with the G6PD Deficient with CNSHA phenotype, there is a strong rationale to avoid these drugs based on evidence in G6PD Deficient individuals. Toluidine blue classification strength is based on extrapolation from methylene blue data"},{"lookupkey":{"G6PD":"Variable"},"drugname":"toluidine blue","guidelinename":"G6PD","implications":{"G6PD":"Variable risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Variable"},"activityscore":{},"population":"general","comments":"Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype; an enzyme activity test is needed to assign G6PD phenotype in such cases. Toluidine blue classification strength is based on extrapolation from methylene blue data"},{"lookupkey":{"G6PD":"Indeterminate"},"drugname":"toluidine blue","guidelinename":"G6PD","implications":{"G6PD":"Unknown risk of acute hemolytic anemia"},"drugrecommendation":"To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.","classification":"Moderate","phenotypes":{"G6PD":"Indeterminate"},"activityscore":{},"population":"general","comments":"Toluidine blue classification strength is based on extrapolation from methylene blue data"},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Reduced O-desmethyltramadol (active metabolite) formation"},"drugrecommendation":"Use tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Reduced O-desmethyltramadol (active metabolite) formation"},"drugrecommendation":"Use tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity"},"drugrecommendation":"Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity"},"drugrecommendation":"Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity"},"drugrecommendation":"Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity"},"drugrecommendation":"Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity"},"drugrecommendation":"Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"tramadol","guidelinename":"CYP2D6, OPRM1, COMT, and Opioids","implications":{"CYP2D6":"Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity"},"drugrecommendation":"Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.","classification":"Strong","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Rapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Rapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Rapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Rapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\nfor conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.25","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.5","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.75","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"0.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.0","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Intermediate Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use. If trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use. If trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use. If trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use. If trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use. If trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Rapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Rapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Rapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. 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The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Rapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. 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The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. 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The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Consider alternative drug not metabolized by CYP2C19; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use. If trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use. If trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use. If trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use. If trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use. If trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations\n for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.25","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.5","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.5","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"1.75","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"1.75","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.0","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Normal metabolism of TCAs","CYP2C19":"n/a"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.25","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use. If a trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid trimipramine use. If a trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Rapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider a 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use. If a trimipramine is warranted, consider a 50% reduction of recommended starting dose. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"0.0","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations \nfor conditions where lower initial doses are used, such as neuropathic pain. 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See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. Utilizing therapeutic drug monitoring to guide dose adjustments is strongly recommended.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"Utilizing therapeutic drug monitoring if a tricyclic is prescribed to a patient with CYP2D6 ultrarapid, intermediate or poor metabolism in combination with CYP2C19 ultrarapid, intermediate or poor metabolism is strongly recommended."},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). 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Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, consider titrating to a higher target dose (compared to normal metabolizers). 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Utilize therapeutic drug monitoring to guide dose adjustment.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. 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Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid trimipramine use; If trimipramine is warranted, utilize therapeutic drug monitoring to guide dose adjustment. 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Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"2.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"4.0","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.0","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.25","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.25","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.5","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥4.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥3.75","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥5.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"Increased metabolism of TCAs to less active compounds compared to normal metabolizers; Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure","CYP2C19":"n/a"},"drugrecommendation":"Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"≥6.0","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"No recommendation","classification":"Strong","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Rapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal metabolizers. There is insufficient evidence supporting the clinical impact of increased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 ultrarapid metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"n/a","CYP2C19":"No Result"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"Indeterminate","CYP2C19":"No Result"},"activityscore":{"CYP2D6":"n/a","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Normal Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Normal metabolism of tertiary amines"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Normal Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Poor Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Rapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Rapid Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal metabolizers. There is insufficient evidence supporting the clinical impact of increased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 ultrarapid metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Increased metabolism of tertiary amines compared to normal metabolizers; Greater conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Indeterminate"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Indeterminate"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Reduced metabolism of tertiary amines compared to normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"No Result","CYP2C19":"Likely Poor Metabolizer"},"drugname":"trimipramine","guidelinename":"CYP2D6, CYP2C19 and Tricyclic Antidepressants","implications":{"CYP2D6":"n/a","CYP2C19":"Greatly reduced metabolism of tertiary amines compared to normal metabolizers; Decreased conversion of tertiary amines to secondary amines may affect response or side effects"},"drugrecommendation":"Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.","classification":"Optional","phenotypes":{"CYP2D6":"No Result","CYP2C19":"Likely Poor Metabolizer"},"activityscore":{"CYP2D6":"No Result","CYP2C19":"n/a"},"population":"general","comments":"Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose."},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug."},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug."},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug."},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug."},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug."},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal metabolizers. There is insufficient evidence supporting the clinical impact of increased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 ultrarapid metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting)."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6 (i.e., granisetron).","classification":"Moderate","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"Drug-drug interactions, the involvement of other metabolizing enzymes and other patient characteristics (e.g., age, renal and hepatic function) should be considered when selecting alternative therapy, as emerging evidence may further clarify the role of enzymes beyond CYP2D6 in the metabolism of the drug. Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs."},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Insufficient evidence demonstrating clinical impact"},"drugrecommendation":"No recommendation based on insufficient evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy."},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Insufficient evidence demonstrating clinical impact"},"drugrecommendation":"No recommendation based on insufficient evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy."},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Insufficient evidence demonstrating clinical impact"},"drugrecommendation":"No recommendation based on insufficient evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy."},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Insufficient evidence demonstrating clinical impact"},"drugrecommendation":"No recommendation based on insufficient evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy."},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"Insufficient evidence demonstrating clinical impact"},"drugrecommendation":"No recommendation based on insufficient evidence","classification":"No Recommendation","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy."},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"tropisetron","guidelinename":"CYP2D6 and Ondansetron and Tropisetron","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal metabolizers. There is insufficient evidence supporting the clinical impact of increased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 ultrarapid metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal metabolizers. There is insufficient evidence supporting the clinical impact of increased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 ultrarapid metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal metabolizers. There is insufficient evidence supporting the clinical impact of increased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 ultrarapid metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal metabolizers. There is insufficient evidence supporting the clinical impact of increased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 ultrarapid metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal metabolizers. There is insufficient evidence supporting the clinical impact of increased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 ultrarapid metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal metabolizers. There is insufficient evidence supporting the clinical impact of increased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 ultrarapid metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal metabolizers. There is insufficient evidence supporting the clinical impact of increased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 ultrarapid metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal metabolizers. There is insufficient evidence supporting the clinical impact of increased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 ultrarapid metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism"},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Decreased metabolism of venlafaxine to active metabolite O-desmethylvenlafaxine (desvenlafaxine) and decreased O-desmethylvenlafaxine:venlafaxine ratio as compared to normal metabolizers. There is insufficient evidence supporting the clinical impact of the decreased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 intermediate metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Decreased metabolism of venlafaxine to active metabolite O-desmethylvenlafaxine (desvenlafaxine) and decreased O-desmethylvenlafaxine:venlafaxine ratio as compared to normal metabolizers. There is insufficient evidence supporting the clinical impact of the decreased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 intermediate metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Decreased metabolism of venlafaxine to active metabolite O-desmethylvenlafaxine (desvenlafaxine) and decreased O-desmethylvenlafaxine:venlafaxine ratio as compared to normal metabolizers. There is insufficient evidence supporting the clinical impact of the decreased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 intermediate metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Decreased metabolism of venlafaxine to active metabolite O-desmethylvenlafaxine (desvenlafaxine) and decreased O-desmethylvenlafaxine:venlafaxine ratio as compared to normal metabolizers. There is insufficient evidence supporting the clinical impact of the decreased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 intermediate metabolizers."},"drugrecommendation":"No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.","classification":"No Recommendation","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Decreased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and greatly decreased O-desmethylvenlafaxine:venlafaxine ratio as compared to CYP2D6 normal and intermediate metabolizers. The clinical impact of increased venlafaxine and decreased O-desmethylvenlafaxine:venlafaxine ratio in CYP2D6 poor metabolizers is unclear, but CYP2D6 PM genotype has been associated with adverse effects."},"drugrecommendation":"Consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2D6.","classification":"Optional","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"venlafaxine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2C19":"Rapid Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"In patients for whom a rapid metabolizer genotype (*1/*17) is identified, the probability of attainment of therapeutic concentrations is modest with standard dosing"},"drugrecommendation":"Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include isavuconazole, liposomal amphotericin B, and posaconazole.","classification":"Moderate","phenotypes":{"CYP2C19":"Rapid Metabolizer"},"activityscore":{},"population":"adults","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities."},{"lookupkey":{"CYP2C19":"Ultrarapid Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"In patients for whom an ultrarapid metabolizer genotype (*17/*17) is identified, the probability of attainment of therapeutic concentrations is small"},"drugrecommendation":"Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include liposomal amphotericin B and posaconazole.","classification":"Moderate","phenotypes":{"CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{},"population":"pediatrics","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities. Achieving voriconazole therapeutic concentrations in the pediatric population with ultrarapid and rapid metabolizer phenotypes in a timely manner is difficult. As critical time may be lost in achieving therapeutic concentrations, an alternative antifungal agent is recommended in order that the child receives effective antifungal therapy as soon as possible."},{"lookupkey":{"CYP2C19":"Rapid Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"In patients for whom a rapid metabolizer genotype (*1/*17) is identified, the probability of attainment of therapeutic concentrations is variable."},"drugrecommendation":"Initiate therapy with recommended standard of care dosing. Use therapeutic drug monitoring to titrate dose to therapeutic trough concentrations.","classification":"Moderate","phenotypes":{"CYP2C19":"Rapid Metabolizer"},"activityscore":{},"population":"pediatrics","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring (TDM), and comorbidities. Achieving voriconazole therapeutic concentrations in the pediatric population with ultrarapid and rapid metabolizer phenotypes in a timely manner is difficult. As critical time may be lost in achieving therapeutic concentrations, an alternative antifungal agent is recommended in order that the child receives effective antifungal therapy as soon as possible. Meticulous TDM is critical for rapid metabolizers. There is insufficient evidence to distinguish a CYP2C19*1/*17 and *1/*1 pediatric patient due to large variability in trough concentrations."},{"lookupkey":{"CYP2C19":"Normal Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"Normal voriconazole metabolism"},"drugrecommendation":"Initiate therapy with recommended standard of care dosing","classification":"Strong","phenotypes":{"CYP2C19":"Normal Metabolizer"},"activityscore":{},"population":"pediatrics","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities."},{"lookupkey":{"CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"Higher dose-adjusted trough concentrations of voriconazole compared with normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended standard of care dosing","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{},"population":"pediatrics","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities."},{"lookupkey":{"CYP2C19":"Intermediate Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"Higher dose-adjusted trough concentrations of voriconazole compared with normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended standard of care dosing","classification":"Moderate","phenotypes":{"CYP2C19":"Intermediate Metabolizer"},"activityscore":{},"population":"pediatrics","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities."},{"lookupkey":{"CYP2C19":"Likely Poor Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"Higher dose-adjusted trough concentrations of voriconazole and may increase probability of adverse events"},"drugrecommendation":"Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include liposomal amphotericin B and posaconazole. In the event that voriconazole is considered to be the most appropriate agent, based on clinical advice, for a patient with poor metabolizer genotype, voriconazole should be administered at a preferably lower than standard dosage with careful therapeutic drug monitoring.","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Poor Metabolizer"},"activityscore":{},"population":"pediatrics","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities. Recommendation based upon data extrapolated from adults."},{"lookupkey":{"CYP2C19":"Poor Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"Higher dose-adjusted trough concentrations of voriconazole and may increase probability of adverse events"},"drugrecommendation":"Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include liposomal amphotericin B and posaconazole. In the event that voriconazole is considered to be the most appropriate agent, based on clinical advice, for a patient with poor metabolizer genotype, voriconazole should be administered at a preferably lower than standard dosage with careful therapeutic drug monitoring.","classification":"Moderate","phenotypes":{"CYP2C19":"Poor Metabolizer"},"activityscore":{},"population":"pediatrics","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities. Recommendation based upon data extrapolated from adults."},{"lookupkey":{"CYP2C19":"Indeterminate"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Indeterminate"},"activityscore":{},"population":"pediatrics","comments":"n/a"},{"lookupkey":{"CYP2C19":"Ultrarapid Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"In patients for whom an ultrarapid metabolizer genotype (*17/*17) is identified, the probability of attainment of therapeutic voriconazole concentrations is small with standard dosing"},"drugrecommendation":"Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include isavuconazole, liposomal amphotericin B, and posaconazole.","classification":"Moderate","phenotypes":{"CYP2C19":"Ultrarapid Metabolizer"},"activityscore":{},"population":"adults","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities. Recommendations based upon data extrapolated from patients with CYP2C19*1/*17 genotype."},{"lookupkey":{"CYP2C19":"Normal Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"Normal voriconazole metabolism"},"drugrecommendation":"Initiate therapy with recommended standard of care dosing","classification":"Strong","phenotypes":{"CYP2C19":"Normal Metabolizer"},"activityscore":{},"population":"adults","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities."},{"lookupkey":{"CYP2C19":"Likely Intermediate Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"Higher dose-adjusted trough concentrations of voriconazole compared with normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended standard of care dosing","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Intermediate Metabolizer"},"activityscore":{},"population":"adults","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities."},{"lookupkey":{"CYP2C19":"Intermediate Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"Higher dose-adjusted trough concentrations of voriconazole compared with normal metabolizers"},"drugrecommendation":"Initiate therapy with recommended standard of care dosing","classification":"Moderate","phenotypes":{"CYP2C19":"Intermediate Metabolizer"},"activityscore":{},"population":"adults","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities."},{"lookupkey":{"CYP2C19":"Likely Poor Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"Higher dose-adjusted trough concentrations of voriconazole and may increase probability of adverse events"},"drugrecommendation":"Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include isavuconazole, liposomal amphotericin B, and posaconazole. In the event that voriconazole is considered to be the most appropriate agent, based on clinical advice, for a patient with poor metabolizer genotype, voriconazole should be administered at a preferably lower than standard dosage with careful therapeutic drug monitoring.","classification":"Moderate","phenotypes":{"CYP2C19":"Likely Poor Metabolizer"},"activityscore":{},"population":"adults","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities."},{"lookupkey":{"CYP2C19":"Poor Metabolizer"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"Higher dose-adjusted trough concentrations of voriconazole and may increase probability of adverse events"},"drugrecommendation":"Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include isavuconazole, liposomal amphotericin B, and posaconazole. In the event that voriconazole is considered to be the most appropriate agent, based on clinical advice, for a patient with poor metabolizer genotype, voriconazole should be administered at a preferably lower than standard dosage with careful therapeutic drug monitoring.","classification":"Moderate","phenotypes":{"CYP2C19":"Poor Metabolizer"},"activityscore":{},"population":"adults","comments":"Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities."},{"lookupkey":{"CYP2C19":"Indeterminate"},"drugname":"voriconazole","guidelinename":"CYP2C19 and Voriconazole","implications":{"CYP2C19":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2C19":"Indeterminate"},"activityscore":{},"population":"adults","comments":"n/a"},{"lookupkey":{"CYP2D6":"≥6.0"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥6.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥5.0"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥5.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥3.75"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.75"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥4.0"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥4.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥3.5"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.5"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥3.25"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.25"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"≥3.0"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"≥3.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"4.0"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"4.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"2.75"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.75"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"3.0"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"3.0"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"2.5"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Increased metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit."},"drugrecommendation":"Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.","classification":"Optional","phenotypes":{"CYP2D6":"Ultrarapid Metabolizer"},"activityscore":{"CYP2D6":"2.5"},"population":"general","comments":"Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"2.25"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"2.0"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"2.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.75"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.5"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.25"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Normal metabolism."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Strong","phenotypes":{"CYP2D6":"Normal Metabolizer"},"activityscore":{"CYP2D6":"1.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"1.0"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of vortioxetine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"1.0"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.75"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of vortioxetine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.75"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.5"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of vortioxetine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.5"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.25"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Reduced metabolism of vortioxetine to less active compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate therapy with recommended starting dose.","classification":"Moderate","phenotypes":{"CYP2D6":"Intermediate Metabolizer"},"activityscore":{"CYP2D6":"0.25"},"population":"general","comments":"n/a"},{"lookupkey":{"CYP2D6":"0.0"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"Greatly reduced metabolism of vortioxetine to inactive compounds when compared to CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects."},"drugrecommendation":"Initiate 50% of starting dose (e.g., 5 mg) and titrate to the maximum recommended dose of 10 mg or consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2D6.","classification":"Moderate","phenotypes":{"CYP2D6":"Poor Metabolizer"},"activityscore":{"CYP2D6":"0.0"},"population":"general","comments":"Drug-drug interactions, indication and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose or selecting an alternative therapy."},{"lookupkey":{"CYP2D6":"n/a"},"drugname":"vortioxetine","guidelinename":"CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants","implications":{"CYP2D6":"n/a"},"drugrecommendation":"No recommendation","classification":"No Recommendation","phenotypes":{"CYP2D6":"Indeterminate"},"activityscore":{"CYP2D6":"n/a"},"population":"general","comments":"n/a"}],"results":[{"genesymbol":"CYP2D6","result":"Ultrarapid Metabolizer","activityscore":"2.5","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)]. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.0022434974,"American":0.0005345896,"European":0.0003203256,"Oceanian":0.00024761492,"East Asian":0.00034846712,"Near Eastern":0.005864233,"Central/South Asian":0.00006554563,"Sub-Saharan African":0.015329994,"African American/Afro-Caribbean":0.01435911}},{"genesymbol":"CYP2D6","result":"Normal Metabolizer","activityscore":"2.0","ehrpriority":"Normal/Routine/ Low Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be a normal metabolizer of CYP2D6 substrates. There is no reason to selectively adjust the dose of most medications that are metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.42007107,"American":0.57988566,"European":0.32166475,"Oceanian":0.48931405,"East Asian":0.1527359,"Near Eastern":0.2670007,"Central/South Asian":0.34187043,"Sub-Saharan African":0.15406683,"African American/Afro-Caribbean":0.22171879}},{"genesymbol":"CYP2D6","result":"Normal Metabolizer","activityscore":"1.75","ehrpriority":"Normal/Routine/ Low Risk","consultationtext":"This result signifies that this patient has three copies of *41 (*41x3) and one copy of a normal function allele (*_) or [2 copies of a decreased function allele with an activity value of 0.5 (*_x2)]. Based on the genotype result this patient is predicted to be a normal metabolizer of CYP2D6 substrates. There is no reason to selectively adjust the dose of most medications that are metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0,"American":0,"European":0,"Oceanian":0,"East Asian":0,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0,"African American/Afro-Caribbean":0}},{"genesymbol":"CYP2D6","result":"Normal Metabolizer","activityscore":"1.25","ehrpriority":"Normal/Routine/ Low Risk","consultationtext":"This result signifies that this patient has [1 copy of a normal function allele (*_)] or [2 copies of a decreased function allele with an activity value of 0.5 (*_x2)] and [1 copy of a decreased function allele with an activity value of 0.25 (*_)] OR *41x3 and [1 copy of a decreased function allele with an activity value of 0.5 (*_)] or [2 copies of a decreased function allele with an activity value of 0.25 (*_x2)]. Based on the genotype result this patient is predicted to be a normal metabolizer of CYP2D6 substrates. There is no reason to selectively adjust the dose of most medications that are metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.11888533,"American":0.07351474,"European":0.15507403,"Oceanian":0.12359433,"East Asian":0.3547828,"Near Eastern":0.22410923,"Central/South Asian":0.23109229,"Sub-Saharan African":0.073030114,"African American/Afro-Caribbean":0.07348749}},{"genesymbol":"CYP2D6","result":"Intermediate Metabolizer","activityscore":"1.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [1 copy of a normal function allele (*_)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be an intermediate metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.2278144,"American":0.21460281,"European":0.28533316,"Oceanian":0.077126324,"East Asian":0.070599586,"Near Eastern":0.14959782,"Central/South Asian":0.17827679,"Sub-Saharan African":0.20079781,"African American/Afro-Caribbean":0.2080644}},{"genesymbol":"CYP2D6","result":"Intermediate Metabolizer","activityscore":"0.5","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [1 copy of a decreased function allele with an activity value of 0.5 (*_)] or [2 copies of a decreased function allele with an activity value of 0.25 (*_x2)] and one copy of a no function allele (*_) OR two copies for a decreased function allele with an activity value of 0.25 (*_/*_). Based on the genotype result this patient is predicted to be an intermediate metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.022830304,"American":0.0047207433,"European":0.023932345,"Oceanian":0.008138877,"East Asian":0.21193053,"Near Eastern":0.06410619,"Central/South Asian":0.040293686,"Sub-Saharan African":0.0954133,"African American/Afro-Caribbean":0.08539959}},{"genesymbol":"CYP3A5","result":"Indeterminate","activityscore":"n/a","ehrpriority":"none","consultationtext":"This result signifies that the patient has an allele combination with uncertain and/or unknown function alleles. The expected phenotype for this patient cannot be determined currently based on the CYP3A5 diplotype result. Please consult a clinical pharmacist for more specific information about how CYP3A5 function influences drug dosing.","frequency":{"Latino":0,"European":0,"East Asian":0,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0,"African American/Afro-Caribbean":0}},{"genesymbol":"DPYD","result":"Normal Metabolizer","activityscore":"2.0","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of normal function DPYD alleles. Based on the genotype result this patient is predicted to be DPYD Normal Metabolizer with a DPYD activity score of 2. For this genotype, no selective dose adjustment is indicated for medications that are metabolized by DPD. Please consult a clinical pharmacist for more information about how DPD metabolic status influences drug selection and dosing.","frequency":null},{"genesymbol":"DPYD","result":"Intermediate Metabolizer","activityscore":"1.5","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of a decreased function allele of the DPYD gene. Based on the genotype result this patient is predicted to be a DPYD Intermediate Metabolizer with a DPYD activity score of 1.5. This patient may be at risk for adverse drug reactions to medications that are metabolized by DPD (i.e. 5-fluorouracil, capecitabine, and tegafur) and a dose adjustment may be indicated. Please consult a clinical pharmacist for more information about how DPD metabolic status influences drug selection and dosing.","frequency":null},{"genesymbol":"DPYD","result":"Intermediate Metabolizer","activityscore":"1.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has either one copy of a normal function allele and one copy of a no function allele of the DPYD gene OR two copies of decreased function alleles of the DPYD gene. Based on the genotype result this patient is predicted to be a DPYD Intermediate Metabolizer with a DPYD activity score of 1. This patient may be at risk for adverse drug reactions to medications that are metabolized by DPD (i.e. 5-fluorouracil, capecitabine, and tegafur) and a dose adjustment may be indicated. Please consult a clinical pharmacist for more information about how DPD metabolic status influences drug selection and dosing.","frequency":null},{"genesymbol":"DPYD","result":"Poor Metabolizer","activityscore":"0.5","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a decreased function allele and one copy of a no function allele of the DPYD gene. Based on the genotype result this patient is predicted to be a DPYD Poor Metabolizer with a DPYD activity score of 0.5. This patient may be at risk for adverse drug reactions to medications that are metabolized by DPD (i.e. 5-fluorouracil, capecitabine, and tegafur) and a dose adjustment or alternative therapeutic agents may be indicated. Please consult a clinical pharmacist for more information about how DPD metabolic status influences drug selection and dosing.","frequency":null},{"genesymbol":"DPYD","result":"Poor Metabolizer","activityscore":"0.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of no function alleles of the DPYD gene. Based on the genotype result this patient is predicted to be a DPYD Poor Metabolizer with a DPYD activity score of 0. This patient may be at risk for adverse drug reactions to medications that are metabolized by DPD (i.e. 5-fluorouracil, capecitabine, and tegafur) and alternative therapeutic agents may be indicated. Please consult a clinical pharmacist for more information about how DPD metabolic status influences drug selection and dosing.","frequency":null},{"genesymbol":"CYP2B6","result":"Ultrarapid Metabolizer","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of increased function alleles. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2B6 substrates. There is no reason to selectively adjust the dose of most medications that are metabolized by CYP2B6. Please consult a clinical pharmacist for more information about how CYP2B6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.011284955,"European":0.0016704409,"Oceanian":0,"East Asian":0.007088209,"Near Eastern":0.010816,"Central/South Asian":0.009801,"Sub-Saharan African":0,"African American/Afro-Caribbean":0.000106068765}},{"genesymbol":"CYP2D6","result":"Poor Metabolizer","activityscore":"0.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of a no function allele (*_/*_). Based on the genotype result this patient is predicted to be a poor metabolizer of CYP2D6 substrates. This patient may be at a high risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by the CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.0311798,"American":0.020160662,"European":0.065024786,"Oceanian":0.0031239481,"East Asian":0.008123729,"Near Eastern":0.021957064,"Central/South Asian":0.023507897,"Sub-Saharan African":0.020398295,"African American/Afro-Caribbean":0.023474354}},{"genesymbol":"CYP2D6","result":"Ultrarapid Metabolizer","activityscore":"≥3.25","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.00018561553,"American":0.00009731066,"European":0.00046782166,"Oceanian":0,"East Asian":0.0009120896,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0.000952962,"African American/Afro-Caribbean":0}},{"genesymbol":"NAT2","result":"Poor Metabolizer","activityscore":"n/a","ehrpriority":"Priority/High Risk","consultationtext":"This result signifies that the patient has inherited two decreased function alleles. Based on the genotype result this patient is predicted to be a poor metabolizer of NAT2 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by NAT2. To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by NAT2. Please consult a clinical pharmacist for more information about how NAT2 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.46457,"European":0.59478,"East Asian":0.22421,"Central/South Asian":0.59796,"Sub-Saharan African":0.44457}},{"genesymbol":"G6PD","result":"Deficient","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"Based on the genotype result, this patient is predicted to be G6PD deficient and is at risk for developing hemolytic anemia when exposed to certain medications (such as dapsone, methylene blue, pegloticase, primaquine (at certain doses), rasburicase, tafenoquine, toluidine blue) or foods (such as fava beans). Please consult a clinical pharmacist for more information.","frequency":null},{"genesymbol":"G6PD","result":"Deficient with CNSHA","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"Based on the genotype result, this patient is predicted to be G6PD deficient with CNSHA and is at risk for developing or worsening hemolytic anemia when exposed to certain medications (such as dapsone, methylene blue, pegloticase, primaquine (at certain doses), rasburicase, tafenoquine, toluidine blue) or foods (such as fava beans). Please consult a clinical pharmacist for more information.","frequency":null},{"genesymbol":"G6PD","result":"Indeterminate","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has an allele combination with uncertain and/or unknown function alleles. The expected phenotype for this patient cannot be determined currently based on genotype alone. A G6PD enzyme activity test is recommended to assess for G6PD deficiency. Please consult a clinical pharmacist for more specific information about how G6PD function influences drug dosing.","frequency":null},{"genesymbol":"G6PD","result":"Normal","activityscore":"n/a","ehrpriority":"Normal Risk","consultationtext":"Based on the genotype result, this patient is predicted to have normal G6PD enzyme activity. This means there is no reason to selectively avoid G6PD associated medications based on the G6PD status alone. Please consult a clinical pharmacist for more information.","frequency":null},{"genesymbol":"G6PD","result":"Variable","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This patient carries one copy of a deficient G6PD allele and one copy of a normal G6PD allele. Due to X inactivation, patients who are heterozygous with one deficient allele and one normal allele may exhibit G6PD activity ranging from normal to deficient. A G6PD enzyme activity test is recommended to assess for G6PD deficiency. Please consult a clinical pharmacist for more information.","frequency":null},{"genesymbol":"CYP2C19","result":"Indeterminate","activityscore":"n/a","ehrpriority":"none","consultationtext":"This result signifies that the patient has an allele combination with uncertain and/or unknown function alleles. The expected phenotype for this patient cannot be determined currently based on the CYP2C19 diplotype result. Please consult a clinical pharmacist for more specific information about how CYP2C19 function influences drug dosing.","frequency":{"Latino":0,"American":0,"European":0,"Oceanian":0,"East Asian":0.0034064606,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0,"African American/Afro-Caribbean":0.0022393465}},{"genesymbol":"CYP2C19","result":"Intermediate Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of a no function allele OR one copy of an increased function and one copy of a no function allele. Based on the genotype result this patient is predicted to be an intermediate metabolizer of CYP2C19 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2C19. To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by CYP2C19. Please consult a clinical pharmacist for more information about how CYP2C19 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.19035932,"American":0.21383229,"European":0.26108757,"Oceanian":0.36902928,"East Asian":0.45928204,"Near Eastern":0.2354828,"Central/South Asian":0.40806636,"Sub-Saharan African":0.29945874,"African American/Afro-Caribbean":0.31398684}},{"genesymbol":"CYP2C19","result":"Poor Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of a no function allele. Based on the genotype result this patient is predicted to be a poor metabolizer of CYP2C19 substrates. This patient may be at a high risk for an adverse or poor response to medications that are metabolized by CYP2C19. To avoid an untoward drug response, dose adjustments or or alternative therapy may be necessary for medications metabolized by the CYP2C19. Please consult a clinical pharmacist for more information about how CYP2C19 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.011408395,"American":0.014819587,"European":0.02387743,"Oceanian":0.5713864,"East Asian":0.12978691,"Near Eastern":0.018584846,"Central/South Asian":0.08156806,"Sub-Saharan African":0.036714304,"African American/Afro-Caribbean":0.040512204}},{"genesymbol":"CYP3A5","result":"Normal Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of a normal function allele. Patients with this genotype are expected to require higher starting tacrolimus dosing (1.5 times to 2 times the standard dose-maximum starting dose not to exceed 0.3mg/kg/day). Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors (e.g., medication interactions, or hepatic function). Please consult a clinical pharmacist for more specific dosing information.","frequency":{"Latino":0.029857205,"European":0.005491413,"East Asian":0.064288594,"Near Eastern":0.014869832,"Central/South Asian":0.106746115,"Sub-Saharan African":0.22983262,"African American/Afro-Caribbean":0.20507748}},{"genesymbol":"CYP3A5","result":"Poor Metabolizer","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of a no function allele. Patients with this genotype are expected to require standard tacrolimus dosing. Please consult a clinical pharmacist for more specific dosing information.","frequency":{"Latino":0.68427247,"European":0.85728335,"East Asian":0.5571847,"Near Eastern":0.770986,"Central/South Asian":0.45330563,"Sub-Saharan African":0.2710154,"African American/Afro-Caribbean":0.2993679}},{"genesymbol":"CYP3A5","result":"Possible Intermediate Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of an uncertain or unknown function allele. Patients with this genotype are expected to require higher starting tacrolimus dosing (1.5 times to 2 times the standard dose-maximum starting dose not to exceed 0.3mg/kg/day). Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors (e.g., medication interactions, or hepatic function). Please consult a clinical pharmacist for more specific dosing information.","frequency":{"Latino":0,"European":0,"East Asian":0,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0,"African American/Afro-Caribbean":0}},{"genesymbol":"NUDT15","result":"Normal Metabolizer","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of a normal function allele OR one copy of a normal function allele and one copy of a decreased function allele. Based on the genotype result this patient is predicted to be a NUDT15 normal metabolizer. There is no reason to selectively adjust the dose of most medications that are metabolized by NUDT15. Please consult a clinical pharmacist for more information about how NUDT15 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.8768086,"European":0.98632336,"East Asian":0.79165995,"Central/South Asian":0.8657786}},{"genesymbol":"HLA-A","result":"*31:01 negative","activityscore":"n/a","ehrpriority":"Routine/Low-Risk","consultationtext":"The HLA-A*31:01 allele, which is associated with severe cutaneous adverse reactions among patients taking certain aromatic anticonvulsants, was not detected in this patient. No change in therapy is warranted based on these results. It should be noted that a negative HLA-A*31:01 result does not absolutely rule out the possibility of an adverse drug reaction. Please consult a clinical pharmacist for more information.","frequency":null},{"genesymbol":"HLA-A","result":"*31:01 positive","activityscore":"n/a","ehrpriority":"Priority/High-Risk","consultationtext":"This result signifies that the patient has one or two copies of HLA-A*31:01. Patients with this genotype are at increased risk of severe cutaneous adverse reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and maculopapular exanthema (MPE), with certain aromatic anticonvulsants (e.g., carbamazepine). Alternative therapy may be warranted. Please consult a clinical pharmacist for more information.","frequency":null},{"genesymbol":"MT-RNR1","result":"increased risk of aminoglycoside-induced hearing loss","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has a copy of the MT-RNR1 [variant]. Based on this genotype result, the patient is predicted to be at increased risk of aminoglycoside-induced hearing loss. This means that the patient is likely to develop irreversible hearing loss if aminoglycosides (e.g. amikacin, gentamicin, tobramycin) are prescribed. Please consult a clinical pharmacist or Infectious Diseases Service for help selecting alternative therapies.","frequency":null},{"genesymbol":"MT-RNR1","result":"normal risk of aminoglycoside-induced hearing loss","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that MT-RNR1 variants associated with aminoglycoside-induced hearing loss were not detected in this patient. Based on this genotype result, no change in aminoglycoside therapy is warranted. It should be noted that this result does not absolutely rule out the possibility of the patient developing ototoxicity with aminoglycoside use.","frequency":null},{"genesymbol":"MT-RNR1","result":"uncertain risk of aminoglycoside-induced hearing loss","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has a copy of MT-RNR1 [variant]. At this time, the association of this allele with aminoglycoside-induced hearing loss is unknown/uncertain. Based on this genotype result, no change in aminoglycoside therapy is warranted. It should be noted that this result does not absolutely rule out the possibility of the patient developing ototoxicity with aminoglycoside use.","frequency":null},{"genesymbol":"CYP2C9","result":"Normal Metabolizer","activityscore":"2.0","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of a normal function allele. Based on the genotype result, this patient is predicted to be a CYP2C9 Normal metabolizer. Based only on the CYP2C9 genotype, there is no reason to adjust the dose of most medications that are affected by CYP2C9. Please consult a clinical pharmacist for more specific information about how CYP2C9 function influences drug dosing.","frequency":{"Latino":0.74342215,"American":0.83149743,"European":0.62845254,"Oceanian":0.9122409,"East Asian":0.8378542,"Near Eastern":0.61125296,"Central/South Asian":0.5961676,"Sub-Saharan African":0.73114437,"African American/Afro-Caribbean":0.75866354}},{"genesymbol":"CYP2C9","result":"Intermediate Metabolizer","activityscore":"1.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of a no function allele OR two copies of decreased function alleles. Based on the genotype result, this patient is predicted to be a CYP2C9 intermediate metabolizer (activity score of 1). This patient may be at risk for an adverse response to medications that are affected by CYP2C9. Please consult a clinical pharmacist for more specific information about how CYP2C9 intermediate metabolizer status influences drug dosing.","frequency":{"Latino":0.08109343,"American":0.05818467,"European":0.13767911,"Oceanian":0.03061276,"East Asian":0.098925985,"Near Eastern":0.1494271,"Central/South Asian":0.18352722,"Sub-Saharan African":0.049747862,"African American/Afro-Caribbean":0.049812526}},{"genesymbol":"CYP2D6","result":"Ultrarapid Metabolizer","activityscore":"4.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.0007764387,"American":0.0010402872,"European":0.0003002313,"Oceanian":0.014133941,"East Asian":0.000063105406,"Near Eastern":0.0041771694,"Central/South Asian":0.00016144973,"Sub-Saharan African":0.0006431835,"African American/Afro-Caribbean":0.0007742127}},{"genesymbol":"NAT2","result":"Intermediate Metabolizer","activityscore":"n/a","ehrpriority":"Priority/High Risk","consultationtext":"This result signifies that the patient has inherited one increased function allele and one decreased function allele. Based on the genotype result this patient is predicted to be an intermediate metabolizer of NAT2 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by NAT2. To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by NAT2. Please consult a clinical pharmacist for more information about how NAT2 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.42782,"European":0.35087,"East Asian":0.5049600000000001,"Central/South Asian":0.34409999999999996,"Sub-Saharan African":0.41168}},{"genesymbol":"NUDT15","result":"Indeterminate","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of an uncertain function allele OR one copy of a decreased function allele and one copy of an uncertain function allele OR two copies of an uncertain function allele. The expected phenotype for this patient cannot be determined currently based on the NUDT15 diplotype result. If thiopurines are required and NUDT15 status is unknown, monitor closely for toxicity. Please consult a clinical pharmacist for more specific information about how NUDT15 function influences drug dosing.","frequency":{"Latino":0,"European":0,"East Asian":0,"Central/South Asian":0}},{"genesymbol":"SLCO1B1","result":"Normal Function","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of a normal function allele. Based on the genotype result, this patient is predicted to have normal SLCO1B1 function. This means that there is no reason to adjust the dose of most medications that are affected by SLCO1B1 on the basis of SLCO1B1 genetic status. Please consult a clinical pharmacist for more specific information about how SLCO1B1 function influences drug dosing.","frequency":{"American":0.5776,"European":0.6564144,"Oceanian":1,"East Asian":0.75683165,"Near Eastern":0.64000005,"Central/South Asian":0.8648222,"Sub-Saharan African":0.94491136,"African American/Afro-Caribbean":0.98010004}},{"genesymbol":"ABCG2","result":"Normal Function","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of a normal function allele. Based on the genotype result, this patient is predicted to have normal ABCG2 function. This means that there is no reason to adjust the dose of most medications that are affected by ABCG2 on the basis of ABCG2 genetic status. Please consult a clinical pharmacist for more specific information about how ABCG2 function influences drug dosing.","frequency":{"Latino":0.6015554,"American":0.64000005,"European":0.8035329,"Oceanian":0.63246274,"East Asian":0.4801104,"Near Eastern":0.87366414,"Central/South Asian":0.8222862,"Sub-Saharan African":0.9883421,"African American/Afro-Caribbean":0.9314832}},{"genesymbol":"CYP2D6","result":"Ultrarapid Metabolizer","activityscore":"2.75","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0,"American":0,"European":0,"Oceanian":0,"East Asian":0,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0,"African American/Afro-Caribbean":0}},{"genesymbol":"NAT2","result":"Rapid Metabolizer","activityscore":"n/a","ehrpriority":"Priority/High Risk","consultationtext":"This result signifies that the patient has inherited two increased function alleles. Based on the genotype result this patient is predicted to be a rapid metabolizer of NAT2 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by NAT2. To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by NAT2. Please consult a clinical pharmacist for more information about how NAT2 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.09974,"European":0.0538,"East Asian":0.26687,"Central/South Asian":0.054189999999999995,"Sub-Saharan African":0.09016}},{"genesymbol":"HLA-B","result":"*15:02 negative","activityscore":"n/a","ehrpriority":"Routine/Low-Risk","consultationtext":"The HLA-B*15:02 allele, which is associated with severe cutaneous adverse reactions among patients taking certain aromatic anticonvulsants, was not detected in this patient. No change in therapy is warranted based on these results. It should be noted that a negative HLA-B*15:02 result does not absolutely rule out the possibility of an adverse drug reaction. Please consult a clinical pharmacist for more information.","frequency":null},{"genesymbol":"HLA-B","result":"*15:02 positive","activityscore":"n/a","ehrpriority":"Priority/High-Risk","consultationtext":"This result signifies that the patient has one or two copies of HLA-B*15:02. Patients with this genotype are at increased risk of severe cutaneous adverse reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), with certain aromatic anticonvulsants (e.g., carbamazepine, oxcarbazepine, phenytoin/fosphenytoin). Alternative therapy may be warranted. Please consult a clinical pharmacist for more information.","frequency":null},{"genesymbol":"HLA-B","result":"*57:01 negative","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"The HLA-B*57:01 allele, associated with abacavir hypersensitivity, was not detected in this patient. The patient may be prescribed abacavir. Please refer to the hospital formulary guidelines for specific dosing information. It should be noted that a negative HLA-B*57:01 result does not absolutely rule out the possibility of some form of abacavir hypersensitivity. Administration of abacavir therapy requires close observation including immediate discontinuation of therapy should any signs or symptoms of hypersensitivity develop.","frequency":null},{"genesymbol":"HLA-B","result":"*57:01 positive","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"The HLA-B*57:01 allele, associated with abacavir hypersensitivity, was detected in this patient. HLA-B*5701 positive patients should NOT be prescribed abacavir.","frequency":null},{"genesymbol":"HLA-B","result":"*58:01 negative","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"The HLA-B*58:01 allele, associated with allopurinol hypersensitivity, was not detected in this patient. Allopurinol can be used per standard dosing guidelines. Patients should be monitored closely for any signs of sensitivity reactions, especially those patients receiving allopurinol (of >300 mg/day), concomitant medications (i.e. thiazide diuretics or penicillin/cephalosporin) or with medical conditions (i.e. chronic kidney disease) that increase the non-genetic risk for allopurinol-related hypersensitivity reactions.","frequency":null},{"genesymbol":"HLA-B","result":"*58:01 positive","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"The HLA-B*58:01 allele, associated with allopurinol hypersensitivity, was detected in this patient. Allopurinol is contraindicated.","frequency":null},{"genesymbol":"NAT2","result":"Indeterminate","activityscore":"n/a","ehrpriority":"none","consultationtext":"This result signifies that the patient has inhertied an allele combination with uncertain and/or unknown function alleles. The expected phenotype for this patient cannot be determined currently based on the NAT2 diplotype result. Please consult a clinical pharmacist for more specific information about how NAT2 function influences drug dosing.","frequency":{"Latino":0.00656,"European":0.00031,"East Asian":0,"Central/South Asian":0.00063,"Sub-Saharan African":0.0516}},{"genesymbol":"ABCG2","result":"Decreased Function","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of a no decreased allele . Based on the genotype result, this patient is predicted to have decreased ABCG2 function. This patient may be at risk for an adverse response to medications that are affected by ABCG2. To avoid an untoward drug response, dose adjustments may be necessary for medications affected by ABCG2 (i.e. statins). Please consult a clinical pharmacist for more specific information about how ABCG2 function influences drug dosing.","frequency":{"Latino":0.34808928,"American":0.32000002,"European":0.18573408,"Oceanian":0.32562497,"East Asian":0.4255792,"Near Eastern":0.122071825,"Central/South Asian":0.1690275,"Sub-Saharan African":0.011623656,"African American/Afro-Caribbean":0.06730118}},{"genesymbol":"CACNA1S","result":"Malignant Hyperthermia Susceptibility","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has one copy of a variant [variant] associated with malignant hyperthermia susceptibility. Halogenated volatile anesthetics or depolarizing muscle relaxants are relatively contraindicated in persons with MHS. They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. Please consult a MHS specialist or contact MHAUS (https://www.mhaus.org/healthcare-professionals/) for further information.","frequency":null},{"genesymbol":"CACNA1S","result":"Uncertain Susceptibility","activityscore":"n/a","ehrpriority":"Normal Risk","consultationtext":"Variation in RYR1 and/or CACNA1S genes is associated with increased risk of Malignant hyperthermia after administration of depolarizing muscle relaxants and potent volatile anesthetics. Although listed causative CACNA1S variants were NOT detected in this patient, it should be noted that this finding does not absolutely rule out the possibility of malignant hyperthermia. These results should be interpreted in the context of other genetic and clinical findings, family history and other laboratory data.","frequency":null},{"genesymbol":"NUDT15","result":"Intermediate Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of a no function allele OR two copies of a decreased function allele. Based on the genotype result this patient is predicted to be a NUDT15 intermediate metabolizer. This patient may be at risk for an adverse reactions to medications that are metabolized by NUDT15 (eg thiopurines). To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by NUDT15. Please consult a clinical pharmacist for more information about how NUDT15 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.11914396,"European":0.013629507,"East Asian":0.19375925,"Central/South Asian":0.12932494}},{"genesymbol":"NUDT15","result":"Possible Intermediate Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of an uncertain function allele and one copy of a no function allele. Based on the genotype result this patient is predicted to be a NUDT15 possible intermediate metabolizer. This patient may be at risk for an adverse reactions to medications that are metabolized by NUDT15 (eg thiopurines). To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by NUDT15. Please consult a clinical pharmacist for more information about how NUDT15 metabolic status influences drug selection and dosing.","frequency":{"Latino":0,"European":0,"East Asian":0,"Central/South Asian":0}},{"genesymbol":"NUDT15","result":"Poor Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of a no function allele OR one copy of a no function allele and one copy of a decreased function allele. Based on the genotype result this patient is predicted to be a NUDT15 poor metabolizer. This patient may be at a high risk for an adverse reactions to medications that are metabolized by NUDT15 (eg. thiopurines). To avoid an untoward drug response, dose adjustments or or alternative therapy may be necessary for medications metabolized by NUDT15. Please consult a clinical pharmacist for more information about how NUDT15 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.0040474297,"European":0.000047192545,"East Asian":0.014580801,"Central/South Asian":0.004896416}},{"genesymbol":"TPMT","result":"Possible Intermediate Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of an uncertain or unknown function allele and one copy of a no function allele OR one copy of a no function allele and one copy of a decreased function allele. Based on the genotype result this patient has a priority result (TPMT possible intermediate metabolizer) because their activity is not likely to be any higher than that of an intermediate metabolizer; if the uncertain/unknown function allele is also low, activity may be even lower than that of an intermediate metabolizer. This patient may be at risk for an adverse reactions to medications that are metabolized by TPMT (eg. thiopurines). To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by TPMT. However, thiopurines can be affected by a patient's TPMT and NUDT15 phenotype. Please consult a clinical pharmacist for more information about how TPMT and NUDT15metabolic status influences drug selection and dosing.","frequency":{"Latino":0.00018168772,"European":0.000062770196,"East Asian":0.0000021581852,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0,"African American/Afro-Caribbean":0.0024473174}},{"genesymbol":"CYP3A5","result":"Intermediate Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of a no function allele. Patients with this genotype are expected to require higher starting tacrolimus dosing (1.5 times to 2 times the standard dose-maximum starting dose not to exceed 0.3mg/kg/day). Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors (e.g., medication interactions, or hepatic function). Please consult a clinical pharmacist for more specific dosing information.","frequency":{"Latino":0.28587034,"European":0.13722531,"East Asian":0.37852672,"Near Eastern":0.21414419,"Central/South Asian":0.43994826,"Sub-Saharan African":0.499152,"African American/Afro-Caribbean":0.4955547}},{"genesymbol":"RYR1","result":"Malignant Hyperthermia Susceptibility","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has one copy of a variant [variant] associated with malignant hyperthermia susceptibility. Halogenated volatile anesthetics or depolarizing muscle relaxants are relatively contraindicated in persons with MHS. They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. Please consult a MHS specialist or contact MHAUS (https://www.mhaus.org/healthcare-professionals/) for further information.","frequency":null},{"genesymbol":"RYR1","result":"Uncertain Susceptibility","activityscore":"n/a","ehrpriority":"Normal Risk","consultationtext":"Variation in RYR1 and/or CACNA1S genes is associated with increased risk of Malignant hyperthermia after administration of depolarizing muscle relaxants and potent volatile anesthetics. Although listed causative RYR1 variants were NOT detected in this patient, it should be noted that this finding does not absolutely rule out the possibility of malignant hyperthermia. These results should be interpreted in the context of other genetic and clinical findings, family history and other laboratory data.","frequency":null},{"genesymbol":"ABCG2","result":"Poor Function","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of a decreased function allele. Based on the genotype result, this patient is predicted to have poor ABCG2 function. This patient may be at a high risk for an adverse response to medications that are affected by ABCG2 (i.e. statins). To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications affected by ABCG2. Please consult a clinical pharmacist for more specific information about how ABCG2 function influences drug dosing.","frequency":{"Latino":0.05035536,"American":0.040000003,"European":0.010732961,"Oceanian":0.0419122,"East Asian":0.09431041,"Near Eastern":0.00426409,"Central/South Asian":0.00868624,"Sub-Saharan African":0.000034175762,"African American/Afro-Caribbean":0.0012156549}},{"genesymbol":"CFTR","result":"ivacaftor responsive in CF patients","activityscore":"n/a","ehrpriority":null,"consultationtext":null,"frequency":null},{"genesymbol":"CFTR","result":"ivacaftor non-responsive in CF patients","activityscore":"n/a","ehrpriority":null,"consultationtext":null,"frequency":null},{"genesymbol":"CYP2D6","result":"Normal Metabolizer","activityscore":"2.25","ehrpriority":"Normal/Routine/ Low Risk","consultationtext":"This result signifies that this patient has two copies of a normal function allele (*_x2) and one copy of decreased function allele with an activity value of 0.25 (*_). Based on the genotype result this patient is predicted to be a normal metabolizer of CYP2D6 substrates. There is no reason to selectively adjust the dose of most medications that are metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.005172111,"American":0.0031386076,"European":0.004804125,"Oceanian":0.021296859,"East Asian":0.0072455397,"Near Eastern":0.029094387,"Central/South Asian":0.005050826,"Sub-Saharan African":0.0048336256,"African American/Afro-Caribbean":0.004428509}},{"genesymbol":"CYP2D6","result":"Normal Metabolizer","activityscore":"1.5","ehrpriority":"Normal/Routine/ Low Risk","consultationtext":"This result signifies that this patient has [1 copy of a normal function allele (*_)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be a normal metabolizer of CYP2D6 substrates. There is no reason to selectively adjust the dose of most medications that are metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.051568672,"American":0.012521543,"European":0.010339902,"Oceanian":0.00143701,"East Asian":0.017062929,"Near Eastern":0.045171212,"Central/South Asian":0.0029989334,"Sub-Saharan African":0.23161727,"African American/Afro-Caribbean":0.23827769}},{"genesymbol":"CYP2D6","result":"Intermediate Metabolizer","activityscore":"0.75","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has has three copies of *41 (*41x3) and one copy of a no function allele (*_) OR [1 copy of a decreased function allele with an activity value of 0.25 (*_)] and [1 copy of a decreased function allele with an activity value of 0.5 (*_)] or [2 copies of a decreased function allele with an activity value of 0.25 (*_x2)] . Based on the genotype result this patient is predicted to be an intermediate metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.0074723335,"American":0.00080644403,"European":0.0025628314,"Oceanian":0.00018655165,"East Asian":0.020004882,"Near Eastern":0.02042247,"Central/South Asian":0.0010252715,"Sub-Saharan African":0.05760366,"African American/Afro-Caribbean":0.041067164}},{"genesymbol":"CYP2D6","result":"Ultrarapid Metabolizer","activityscore":"≥6.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.0000010000001,"American":0.0000010000001,"European":0.0000028470035,"Oceanian":0,"East Asian":0.0000010000001,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0.000025000001,"African American/Afro-Caribbean":0}},{"genesymbol":"CYP2D6","result":"Ultrarapid Metabolizer","activityscore":"≥5.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.000055729302,"American":0.00006450697,"European":0.000058472542,"Oceanian":0,"East Asian":0.000015887783,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0.00025361063,"African American/Afro-Caribbean":0}},{"genesymbol":"CYP2B6","result":"Normal Metabolizer","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of normal function alleles. Based on the genotype result this patient is predicted to be an normal metabolizer of CYP2B6 substrates. There is no reason to selectively adjust the dose of most medications that are metabolized by CYP2B6. Please consult a clinical pharmacist for more information about how CYP2B6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.33582056,"European":0.42950228,"Oceanian":0.12960002,"East Asian":0.48562673,"Near Eastern":0.29052103,"Central/South Asian":0.42183065,"Sub-Saharan African":0.14307445,"African American/Afro-Caribbean":0.333572}},{"genesymbol":"CYP2B6","result":"Poor Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of a no function allele OR two copies of a decreased function allele OR one copy of a no function allele and one copy of a decreased function allele. Based on the genotype result this patient is predicted to be a poor metabolizer of CYP2B6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2B6. To avoid an untoward drug response, dose adjustments or or alternative therapy may be necessary for medications metabolized by CYP2B6. Please consult a clinical pharmacist for more information about how CYP2B6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.09452413,"European":0.07428478,"Oceanian":0.4096,"East Asian":0.0436291,"Near Eastern":0.127449,"Central/South Asian":0.059536003,"Sub-Saharan African":0.23673655,"African American/Afro-Caribbean":0.15714757}},{"genesymbol":"CYP2B6","result":"Rapid Metabolizer","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of an increased function allele. Based on the genotype result this patient is predicted to be a rapid metabolizer of CYP2B6 substrates. There is no reason to selectively adjust the dose of most medications that are metabolized by CYP2B6. Please consult a clinical pharmacist for more information about how CYP2B6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.1231214,"European":0.05357082,"Oceanian":0,"East Asian":0.11734093,"Near Eastern":0.112112,"Central/South Asian":0.12859802,"Sub-Saharan African":0,"African American/Afro-Caribbean":0.011896482}},{"genesymbol":"SLCO1B1","result":"Decreased Function","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele (*_) and one copy of a no function allele (*_). Based on the genotype result, this patient is predicted to have decreased SLCO1B1 function. This patient may be at risk for an adverse response to medications that are affected by SLCO1B1. To avoid an untoward drug response, dose adjustments may be necessary for medications affected by SLCO1B1 (i.e. statins). Please consult a clinical pharmacist for more specific information about how SLCO1B1 function influences drug dosing.","frequency":{"American":0.3648,"European":0.28296122,"Oceanian":0,"East Asian":0.21842287,"Near Eastern":0.32000002,"Central/South Asian":0.12971397,"Sub-Saharan African":0.054308295,"African American/Afro-Caribbean":0.0198}},{"genesymbol":"SLCO1B1","result":"Increased Function","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of an increased function allele. Based on the genotype result, this patient is predicted to have increased SLCO1B1 function. This means that there is no reason to adjust the dose of most medications that are affected by SLCO1B1 on the basis of SLCO1B1 genetic status at this time. Please consult a clinical pharmacist for more specific information about how SLCO1B1 function influences drug dosing.","frequency":{"American":0,"European":0.029916462,"Oceanian":0,"East Asian":0,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0,"African American/Afro-Caribbean":0}},{"genesymbol":"SLCO1B1","result":"Indeterminate","activityscore":"n/a","ehrpriority":"none","consultationtext":"This result signifies that the patient has an allele combination with unknown or uncertain function alleles. The expected phenotype for this patient cannot be determined currently based on the SLCO1B1 diplotype result. Please consult a clinical pharmacist for more specific information about how SLCO1B1 function influences drug dosing.","frequency":{"American":0,"European":0.001279436,"Oceanian":0,"East Asian":0.007855513,"Near Eastern":0,"Central/South Asian":0.0005580649,"Sub-Saharan African":0,"African American/Afro-Caribbean":0}},{"genesymbol":"SLCO1B1","result":"Poor Function","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of a no function allele. Based on the genotype result, this patient is predicted to have low SLCO1B1 function. This patient may be at a high risk for an adverse response to medications that are affected by SLCO1B1 (i.e. statins). To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications affected by SLCO1B1. Please consult a clinical pharmacist for more specific information about how SLCO1B1 function influences drug dosing.","frequency":{"American":0.0576,"European":0.02916489,"Oceanian":0,"East Asian":0.015759302,"Near Eastern":0.040000003,"Central/South Asian":0.004863923,"Sub-Saharan African":0.0007803353,"African American/Afro-Caribbean":0.0001}},{"genesymbol":"CYP2B6","result":"Indeterminate","activityscore":"n/a","ehrpriority":"none","consultationtext":"This result signifies that the patient has an allele combination with uncertain and/or unknown function alleles. The expected phenotype for this patient cannot be determined currently based on the CYP2B6 diplotype result. Please consult a clinical pharmacist for more specific information about how CYP2B6 function influences drug dosing.","frequency":{"Latino":0.013596146,"European":0.06145065,"Oceanian":0,"East Asian":0.020025712,"Near Eastern":0,"Central/South Asian":0.014973663,"Sub-Saharan African":0.25210795,"African American/Afro-Caribbean":0.031204166}},{"genesymbol":"CYP2C19","result":"Likely Intermediate Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of a decreased function allele OR one copy of an increased function allele and one copy of a decreased function allele OR two copies of a decreased function allele. Based on the genotype result this patient MAY be an intermediate metabolizer of CYP2C19 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2C19. To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by CYP2C19. Please consult a clinical pharmacist for more information about how CYP2C19 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.003709162,"American":0,"European":0.0011160374,"Oceanian":0,"East Asian":0.00076989824,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0.042863965,"African American/Afro-Caribbean":0.027788177}},{"genesymbol":"CYP2C19","result":"Likely Poor Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a decreased function allele and one copy of a no function allele. Based on the genotype result this patient MAY be a poor metabolizer of CYP2C19 substrates. This patient may be at a high risk for an adverse or poor response to medications that are metabolized by CYP2C19. To avoid an untoward drug response, dose adjustments or or alternative therapy may be necessary for medications metabolized by the CYP2C19. Please consult a clinical pharmacist for more information about how CYP2C19 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.0004440685,"American":0,"European":0.00020405183,"Oceanian":0,"East Asian":0.0004349198,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0.010332189,"African American/Afro-Caribbean":0.007090685}},{"genesymbol":"CYP2C19","result":"Normal Metabolizer","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of a normal function allele. Based on the genotype result this patient is predicted to be an normal metabolizer of CYP2C19 substrates. There is no reason to selectively adjust the dose of most medications that are metabolized by CYP2C19. Please consult a clinical pharmacist for more information about how CYP2C19 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.5249766,"American":0.62755567,"European":0.39611652,"Oceanian":0.035006005,"East Asian":0.38055435,"Near Eastern":0.45192146,"Central/South Asian":0.29552925,"Sub-Saharan African":0.36977687,"African American/Afro-Caribbean":0.32805592}},{"genesymbol":"CYP2C19","result":"Rapid Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of an increased function allele. Based on the genotype result this patient is predicted to be a rapid metabolizer of CYP2C19 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2C19. To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by CYP2C19. Please consult a clinical pharmacist for more information about how CYP2C19 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.24136075,"American":0.13638271,"European":0.2711846,"Oceanian":0.021329276,"East Asian":0.025343522,"Near Eastern":0.2573682,"Central/South Asian":0.18567303,"Sub-Saharan African":0.21080859,"African American/Afro-Caribbean":0.2373838}},{"genesymbol":"CYP2C19","result":"Ultrarapid Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of an increased function allele. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2C19 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2C19. To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by CYP2C19. Please consult a clinical pharmacist for more information about how CYP2C19 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.02774172,"American":0.0074097984,"European":0.04641379,"Oceanian":0.003249,"East Asian":0.00042194634,"Near Eastern":0.036642652,"Central/South Asian":0.029163336,"Sub-Saharan African":0.030045323,"African American/Afro-Caribbean":0.042943195}},{"genesymbol":"TPMT","result":"Intermediate Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of a no function allele OR two copies of a decreased function allele. Based on the genotype result this patient is predicted to be a TPMT intermediate metabolizer. This patient may be at risk for an adverse reactions to medications that are metabolized by TPMT (eg. thiopurines). To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by TPMT. However, thiopurines can be affected by a patient's TPMT and NUDT15 phenotype. Please consult a clinical pharmacist for more information about how TPMT and NUDT15 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.10138224,"European":0.087302946,"East Asian":0.039815668,"Near Eastern":0.06641302,"Central/South Asian":0.036385097,"Sub-Saharan African":0.10365061,"African American/Afro-Caribbean":0.069424435}},{"genesymbol":"TPMT","result":"Poor Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of a no function allele. Based on the genotype result this patient is predicted to be a TPMT poor metabolizer. This patient may be at a high risk for an adverse reactions to medications that are metabolized by TPMT (eg. thiopurines). To avoid an untoward drug response, dose adjustments or or alternative therapy may be necessary for medications metabolized by TPMT. However, thiopurines can be affected by a patient's TPMT and NUDT15 phenotype. Please consult a clinical pharmacist for more information about how TPMT and NUDT16 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.0028794738,"European":0.0020956735,"East Asian":0.00041297937,"Near Eastern":0.0011826118,"Central/South Asian":0.0003435882,"Sub-Saharan African":0.002971174,"African American/Afro-Caribbean":0.0013917874}},{"genesymbol":"CYP2C9","result":"Intermediate Metabolizer","activityscore":"1.5","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of a decreased function allele. Based on the genotype result, this patient is predicted to be a CYP2C9 intermediate metabolizer (activity score of 1.5). This patient may be at risk for an adverse response to medications that are affected by CYP2C9. Please consult a clinical pharmacist for more specific information about how CYP2C9 intermediate metabolizer status influences drug dosing.","frequency":{"Latino":0.1647683,"American":0.10592343,"European":0.20758142,"Oceanian":0.05599055,"East Asian":0.052658077,"Near Eastern":0.2097067,"Central/South Asian":0.17885593,"Sub-Saharan African":0.21372117,"African American/Afro-Caribbean":0.1863267}},{"genesymbol":"CYP2C9","result":"Poor Metabolizer","activityscore":"0.5","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a decreased function allele and one copy of a no function allele. Based on the genotype result, this patient is predicted to be a CYP2C9 poor metabolizer. This patient may be at high risk for an adverse response to medications that are affected by CYP2C9. Please consult a clinical pharmacist for more specific information about how CYP2C9 intermediate metabolizer status influences drug dosing.","frequency":{"Latino":0.007974847,"American":0.0034911723,"European":0.019907156,"Oceanian":0.0009130932,"East Asian":0.0030826868,"Near Eastern":0.022547128,"Central/South Asian":0.025517693,"Sub-Saharan African":0.0049882242,"African American/Afro-Caribbean":0.004712071}},{"genesymbol":"CYP2C9","result":"Poor Metabolizer","activityscore":"0.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of no function alleles. Based on the genotype result, this patient is predicted to be a CYP2C9 poor metabolizer. This patient may be at high risk for an adverse response to medications that are affected by CYP2C9. Please consult a clinical pharmacist for more specific information about how CYP2C9 intermediate metabolizer status influences drug dosing.","frequency":{"Latino":0.0017415384,"American":0.00090327376,"European":0.0057798154,"Oceanian":0.00024261088,"East Asian":0.0028714235,"Near Eastern":0.007066085,"Central/South Asian":0.012135133,"Sub-Saharan African":0.0003982905,"African American/Afro-Caribbean":0.00048520204}},{"genesymbol":"UGT1A1","result":"Indeterminate","activityscore":"n/a","ehrpriority":"none","consultationtext":"This result signifies that the patient has an allele combination with uncertain and/or unknown function alleles. The expected phenotype for this patient cannot be determined currently based on the UGT1A1 diplotype result. UGT1A1*80 is in very high linkage disequilibrium with *28 and *37. In the rare event that *80 is detected but *28 and *37 are not, there are not enough clinical data to predict metabolizer status with certainty. However, if only *80 is interrogated and the patient is heterozygous or homozygous for *80, an intermediate or poor metabolizer phenotype may be inferred, respectively. Please consult a clinical pharmacist for more specific information about how UGT1A1 function influences drug dosing.","frequency":null},{"genesymbol":"UGT1A1","result":"Intermediate Metabolizer","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele (*1) OR one copy of an increased function allele (*36), AND and one copy of a decreased function allele (*_). Based on the genotype result this patient is predicted to be an intermediate metabolizer of UGT1A1 substrates. There is no reason to selectively adjust the dose of most medications that inhibit or are inactivated by UGT1A1. Please consult a clinical pharmacist for more information about how UGT1A1 metabolic status influences drug selection and dosing.","frequency":null},{"genesymbol":"UGT1A1","result":"Normal Metabolizer","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of a normal function allele (*1) OR one copy of a normal function allele (*1) and one copy of an increased function allele (*36) OR two copies of an increased function allele (*36). Based on the genotype result this patient is predicted to be an normal metabolizer of UGT1A1 substrates. There is no reason to selectively adjust the dose of most medications that inhibit or are inactivated by UGT1A1. Please consult a clinical pharmacist for more information about how UGT1A1 metabolic status influences drug selection and dosing.","frequency":null},{"genesymbol":"UGT1A1","result":"Poor Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has two copies of decreased function alleles (*_ and *_). Based on the genotype result this patient is predicted to be a poor metabolizer of UGT1A1 substrates. This patient may be at risk for an adverse or poor response to medications that inhibit or are inactivated by UGT1A1. Based on the genotype result, this patient is predicted to have low UGT1A1 function, which is generally indicative of Gilbert syndrome. This patient may be at high risk for toxicity from select medications that inhibit or are inactivated by UGT1A1. Please consult a clinical pharmacist for more information about how UGT1A1 metabolic status influences drug selection and dosing.","frequency":null},{"genesymbol":"CYP2B6","result":"Intermediate Metabolizer","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of a no function allele OR one copy of a normal function allele and one copy of a decreased function allele OR one copy of an increased function allele and one copy of a no function allele OR one copy of an increased function allele and one copy of a decreased function allele. Based on the genotype result this patient is predicted to be an intermediate metabolizer of CYP2B6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2B6. To avoid an untoward drug response, dose adjustments or alternative therapeutic agents may be necessary for medications metabolized by CYP2B6. Please consult a clinical pharmacist for more information about how CYP2B6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.42165288,"European":0.37952113,"Oceanian":0.46080005,"East Asian":0.32628936,"Near Eastern":0.459102,"Central/South Asian":0.36526063,"Sub-Saharan African":0.36808127,"African American/Afro-Caribbean":0.4660738}},{"genesymbol":"CYP2C9","result":"Indeterminate","activityscore":"n/a","ehrpriority":"none","consultationtext":"This result signifies that the patient has an allele combination with uncertain and/or unknown function alleles. The expected phenotype for this patient cannot be determined currently based on the CYP2C9 diplotype result. Please consult a clinical pharmacist for more specific information about how CYP2C9 function influences drug dosing.","frequency":{"Latino":0.0009997501,"American":0,"European":0.00059991,"Oceanian":0,"East Asian":0.0046076896,"Near Eastern":0,"Central/South Asian":0.0037963898,"Sub-Saharan African":0,"African American/Afro-Caribbean":0}},{"genesymbol":"CYP2D6","result":"Ultrarapid Metabolizer","activityscore":"≥4.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.0012809848,"American":0.0015109289,"European":0.0018874556,"Oceanian":0,"East Asian":0.0007779561,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0.0038317435,"African American/Afro-Caribbean":0}},{"genesymbol":"CYP2D6","result":"Ultrarapid Metabolizer","activityscore":"≥3.75","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0,"American":0,"European":0,"Oceanian":0,"East Asian":0,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0,"African American/Afro-Caribbean":0}},{"genesymbol":"CYP2D6","result":"Ultrarapid Metabolizer","activityscore":"≥3.5","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.00008051411,"American":0.00001657463,"European":0.000031193038,"Oceanian":0,"East Asian":0.00004386605,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0.0030223487,"African American/Afro-Caribbean":0}},{"genesymbol":"CYP2D6","result":"Ultrarapid Metabolizer","activityscore":"≥3.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.00035315607,"American":0.0002839765,"European":0.0008605249,"Oceanian":0,"East Asian":0.00018026348,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0.001428226,"African American/Afro-Caribbean":0}},{"genesymbol":"CYP2D6","result":"Indeterminate","activityscore":"n/a","ehrpriority":"none","consultationtext":"This result signifies that the patient has an allele combination with uncertain and/or unknown function alleles. The expected phenotype for this patient cannot be determined currently based on the CYP2D6 diplotype result. Please consult a clinical pharmacist for more specific information about how CYP2D6 function influences drug dosing.","frequency":{"Latino":0.041558996,"American":0.02454997,"European":0.03725156,"Oceanian":0.087338224,"East Asian":0.066782884,"Near Eastern":0.03744279,"Central/South Asian":0.09993659,"Sub-Saharan African":0.09009597,"African American/Afro-Caribbean":0.038868744}},{"genesymbol":"CYP2D6","result":"Ultrarapid Metabolizer","activityscore":"3.0","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has [X copies of a normal function allele (*_xN)] [X copies of a decreased function allele (*_)] [X copies of a no function allele (*_)]. Based on the genotype result this patient is predicted to be an ultrarapid metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.035694193,"American":0.048732717,"European":0.019382542,"Oceanian":0.16405001,"East Asian":0.006179998,"Near Eastern":0.06435209,"Central/South Asian":0.014773737,"Sub-Saharan African":0.019435417,"African American/Afro-Caribbean":0.025694855}},{"genesymbol":"CYP2D6","result":"Intermediate Metabolizer","activityscore":"0.25","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that this patient has one copy of a decreased function allele with an activity value of 0.25 (*_) and one copy of a no function allele (*_). Based on the genotype result this patient is predicted to be an intermediate metabolizer of CYP2D6 substrates. This patient may be at risk for an adverse or poor response to medications that are metabolized by CYP2D6. To avoid an untoward drug response, dose adjustments may be necessary for medications metabolized by CYP2D6. Please consult a clinical pharmacist for more information about how CYP2D6 metabolic status influences drug selection and dosing.","frequency":{"Latino":0.03277562,"American":0.0138169695,"European":0.07070104,"Oceanian":0.010012345,"East Asian":0.08220821,"Near Eastern":0.06670452,"Central/South Asian":0.060946763,"Sub-Saharan African":0.027220901,"African American/Afro-Caribbean":0.024385082}},{"genesymbol":"SLCO1B1","result":"Possible Decreased Function","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a uncertain or unknown function allele (*_) and one copy of a no function allele (*_). Based on the genotype result, this patient is predicted to have possible decreased SLCO1B1 function. This patient may be at risk for an adverse response to medications that are affected by SLCO1B1. To avoid an untoward drug response, dose adjustments may be necessary for medications affected by SLCO1B1 (i.e. statins). Please consult a clinical pharmacist for more specific information about how SLCO1B1 function influences drug dosing.","frequency":{"American":0,"European":0.00026362084,"Oceanian":0,"East Asian":0.0011306308,"Near Eastern":0,"Central/South Asian":0.0000418451,"Sub-Saharan African":0,"African American/Afro-Caribbean":0}},{"genesymbol":"TPMT","result":"Indeterminate","activityscore":"n/a","ehrpriority":"Abnormal/Priority/High Risk","consultationtext":"This result signifies that the patient has one copy of a normal function allele and one copy of an uncertain or unknown function allele OR one copy of a decreased function allele and one copy of an uncertain or unknown function allele OR two copies of an uncertain or unknown function allele. The expected phenotype for this patient cannot be determined currently based on the TPMT diplotype result. Consider evaluating TPMT erythrocyte activity to assess TPMT phenotype. Erythrocyte TPMT activity test results can be falsely low at diagnosis of leukemia and is unreliable in the case of recent red blood cell transfusions. If thiopurines are required and TPMT status is unknown, monitor closely for toxicity. Please consult a clinical pharmacist for more specific information about how TPMT function influences drug dosing.","frequency":{"Latino":0.0032013063,"European":0.0013079308,"East Asian":0.000104039,"Near Eastern":0,"Central/South Asian":0,"Sub-Saharan African":0,"African American/Afro-Caribbean":0.06207684}},{"genesymbol":"TPMT","result":"Normal Metabolizer","activityscore":"n/a","ehrpriority":"Normal/Routine/Low Risk","consultationtext":"This result signifies that the patient has two copies of a normal function allele OR one copy of a normal function allele and one copy of a decreased function allele. Based on the genotype result this patient is predicted to be a TPMT normal metabolizer. There is no reason to selectively adjust the dose of most medications that are metabolized by TPMT. However, thiopurines can be affected by a patient's TPMT and NUDT15 phenotype. 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