chemical	gene	url	type	summary	phenotype	recommendation
abacavir	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166104997	case1	In individuals with the HLA-B*57:01 variant allele ("HLA-B*57:01-positive"), abacavir is not recommended and should be considered only under exceptional circumstances. See full guideline for disclaimers, further details and supporting evidence.	Very low risk of hypersensitivity (constitutes ~94% of patients)	Recommendations for abacavir therapy: Use abacavir per standard dosing guidelines Classification of recommendation for abacavir therapy: Strong
abacavir	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166104997	case1	In individuals with the HLA-B*57:01 variant allele ("HLA-B*57:01-positive"), abacavir is not recommended and should be considered only under exceptional circumstances. See full guideline for disclaimers, further details and supporting evidence.	High risk of hypersensitivity (~6% of patients)	Recommendations for abacavir therapy: Abacavir is not recommended Classification of recommendation for abacavir therapy: Strong
allopurinol	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166105003	case1	Allopurinol is contraindicated in individuals with the HLA-B*58:01 variant allele ("HLA-B*58:01-positive") due to significantly increased risk of allopurinol-induced SCAR.	Low or reduced risk of allopurinol SCAR	Recommendations for allopurinol therapy: Use allopurinol per standard dosing guidelines Classification of recommendation for allopurinol therapy: Strong
allopurinol	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166105003	case1	Allopurinol is contraindicated in individuals with the HLA-B*58:01 variant allele ("HLA-B*58:01-positive") due to significantly increased risk of allopurinol-induced SCAR.	Significantly increased risk of allopurinol SCAR	Recommendations for allopurinol therapy: Allopurinol is contraindicated Classification of recommendation for allopurinol therapy: Strong
amitriptyline	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105006	case5	The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Ultrarapid metabolizer (~2-5% of patients)	Therapeutic recommendations: 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 of recommendations for amitriptyline: Optional
amitriptyline	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105006	case5	The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Rapid metabolizer (~2-30% of patients)	Therapeutic recommendations: 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 of recommendations for amitriptyline: Optional
amitriptyline	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105006	case5	The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Normal metabolizer (~35-50% of patients)	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of recommendations for amitriptyline: Strong
amitriptyline	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105006	case5	The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Intermediate metabolizer (~18-45% of patients)	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of recommendations for amitriptyline: Strong
amitriptyline	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105006	case5	The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Poor metabolizer (~2-15% of patients)	Therapeutic recommendations: 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. Classification of recommendations for amitriptyline: Moderate
amitriptyline	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105006	case5	The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Ultrarapid metabolizer (~1-20% of patients)	Therapeutic Recommendations: 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. Classification of recommendation for amitriptyline and nortriptyline: Strong
amitriptyline	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105006	case5	The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Normal metabolizer (~72-88% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendation for amitriptyline and nortriptyline: Strong
amitriptyline	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105006	case5	The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Intermediate metabolizer (~1-13% of patients)	Therapeutic Recommendations: Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for amitriptyline and nortriptyline: Moderate
amitriptyline	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105006	case5	The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Poor metabolizer (~1-10% of patients)	Therapeutic Recommendations: Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6.If a TCA is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for amitriptyline and nortriptyline: Strong
atazanavir	UGT1A1	https://pharmgkb.org/guidelineAnnotation/PA166128738	case1	The CPIC dosing guideline recommends considering advising individuals who carry two decreased function UGT1A1 alleles about a substantial likelihood of developing jaundice, which may cause non-adherence. The dosing guideline recommends that alternative agents be considered if the risk of non-adherence due to jaundice is high. The risk of discontinuation is low and very low for individuals carrying one, or no decreased function UGT1A1 alleles, respectively.	Extensive Metabolizer	Recommendations for atazanavir therapy: There is no need to avoid prescribing of atazanavir based on UGT1A1 genetic test result. Classification of recommendation for atazanavir therapy: Strong
atazanavir	UGT1A1	https://pharmgkb.org/guidelineAnnotation/PA166128738	case1	The CPIC dosing guideline recommends considering advising individuals who carry two decreased function UGT1A1 alleles about a substantial likelihood of developing jaundice, which may cause non-adherence. The dosing guideline recommends that alternative agents be considered if the risk of non-adherence due to jaundice is high. The risk of discontinuation is low and very low for individuals carrying one, or no decreased function UGT1A1 alleles, respectively.	Intermediate Metabolizer	Recommendations for atazanavir therapy: 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 Classification of recommendation for atazanavir therapy: Strong
atazanavir	UGT1A1	https://pharmgkb.org/guidelineAnnotation/PA166128738	case1	The CPIC dosing guideline recommends considering advising individuals who carry two decreased function UGT1A1 alleles about a substantial likelihood of developing jaundice, which may cause non-adherence. The dosing guideline recommends that alternative agents be considered if the risk of non-adherence due to jaundice is high. The risk of discontinuation is low and very low for individuals carrying one, or no decreased function UGT1A1 alleles, respectively.	Poor Metabolizer	Recommendations for atazanavir therapy: Consider an alternative agent particularly where jaundice would be of concern to the patient. Classification of recommendation for atazanavir therapy: Strong
atomoxetine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166181885	case7	The CPIC Dosing Guideline for atomoxetine provides therapeutic recommendations for CYP2D6 ultrarapid, normal, intermediate, and poor metabolizer, which includes guidance for plasma drug concentration testing, as a means to estimate atomoxetine exposure, if no clinical response and in the absence of adverse events after 2 weeks of therapy.	CYP2D6 Ultrarapid Metabolizer	Therapeutic recommendations: 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 of recommendations: Moderate
atomoxetine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166181885	case7	The CPIC Dosing Guideline for atomoxetine provides therapeutic recommendations for CYP2D6 ultrarapid, normal, intermediate, and poor metabolizer, which includes guidance for plasma drug concentration testing, as a means to estimate atomoxetine exposure, if no clinical response and in the absence of adverse events after 2 weeks of therapy.	CYP2D6 Normal metabolizer	Therapeutic recommendations: 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 of recommendations: Moderate
atomoxetine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166181885	case7	The CPIC Dosing Guideline for atomoxetine provides therapeutic recommendations for CYP2D6 ultrarapid, normal, intermediate, and poor metabolizer, which includes guidance for plasma drug concentration testing, as a means to estimate atomoxetine exposure, if no clinical response and in the absence of adverse events after 2 weeks of therapy.	CYP2D6 Normal metabolizer or Intermediate metabolizer (controversy remains)	Therapeutic recommendations: 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 of recommendations: Moderate
atomoxetine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166181885	case7	The CPIC Dosing Guideline for atomoxetine provides therapeutic recommendations for CYP2D6 ultrarapid, normal, intermediate, and poor metabolizer, which includes guidance for plasma drug concentration testing, as a means to estimate atomoxetine exposure, if no clinical response and in the absence of adverse events after 2 weeks of therapy.	CYP2D6 Intermediate metabolizer	Therapeutic recommendations: 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 of recommendations: Moderate
atomoxetine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166181885	case7	The CPIC Dosing Guideline for atomoxetine provides therapeutic recommendations for CYP2D6 ultrarapid, normal, intermediate, and poor metabolizer, which includes guidance for plasma drug concentration testing, as a means to estimate atomoxetine exposure, if no clinical response and in the absence of adverse events after 2 weeks of therapy.	CYP2D6 Poor metabolizer	Therapeutic recommendations: 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 of recommendations: Moderate
azathioprine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104933	case5	Consider an alternate agent or extreme dose reduction of azathioprine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Normal Metabolizer	Dosing recommendations: Start with normal starting dose (e.g., 2-3 mg/kg/day) and adjust doses of azathioprine based on disease-specific guidelines. Allow 2 weeks to reach steady state after each dose adjustment. Classification of recommendations: Strong
azathioprine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104933	case5	Consider an alternate agent or extreme dose reduction of azathioprine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Intermediate Metabolizer	Dosing recommendations: Start with reduced starting doses (30-80% of normal dose) if normal starting dose is 2-3 mg/kg/day, (e.g. 0.6-2.4 mg/kg/day), and adjust doses of azathioprine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. Classification of recommendations: Strong
azathioprine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104933	case5	Consider an alternate agent or extreme dose reduction of azathioprine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Possible Intermediate Metabolizer	Dosing recommendations: Start with reduced starting doses (30-80% of normal dose) if normal starting dose is 2-3 mg/kg/day, (e.g. 0.6-2.4 mg/kg/day), and adjust doses of azathioprine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. Classification of recommendations: Strong
azathioprine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104933	case5	Consider an alternate agent or extreme dose reduction of azathioprine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Poor Metabolizer	Dosing recommendations: For non-malignant conditions, consider alternative non-thiopurine immunosuppressant therapy. For malignant conditions, start with drastically reduced normal daily doses (reduce dose by 10-fold) and adjust doses of azathioprine based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady-state after each dose adjustment. Classification of recommendations: Strong
azathioprine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104933	case5	Consider an alternate agent or extreme dose reduction of azathioprine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Indeterminate	Dosing recommendations: None Classification of recommendations: None
azathioprine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104933	case5	Consider an alternate agent or extreme dose reduction of azathioprine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Normal Metabolizer	Dosing recommendations: Start with normal starting dose (e.g., 2-3 mg/kg/day) and adjust doses of azathioprine based on disease-specific guidelines. Allow 2 weeks to reach steady state after each dose adjustment. Classification of recommendations: Strong
azathioprine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104933	case5	Consider an alternate agent or extreme dose reduction of azathioprine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Intermediate Metabolizer	Dosing recommendations: Start with reduced starting doses (30-80% of normal dose) if normal starting dose is 2-3 mg/kg/day, (e.g. 0.6-2.4 mg/kg/day), and adjust doses of azathioprine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. Classification of recommendations: Strong
azathioprine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104933	case5	Consider an alternate agent or extreme dose reduction of azathioprine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Possible Intermediate Metabolizer	Dosing recommendations: Start with reduced starting doses (30-80% of normal dose) if normal starting dose is 2-3 mg/kg/day, (e.g. 0.6-2.4 mg/kg/day), and adjust doses of azathioprine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. Classification of recommendations: Strong
azathioprine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104933	case5	Consider an alternate agent or extreme dose reduction of azathioprine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Poor Metabolizer	Dosing recommendations: For non-malignant conditions, consider alternative non-thiopurine immunosuppressant therapy. For malignancy, start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily) and adjust doses of azathioprine based on degree of myelosuppression and disease-specific guidelines Allow 4-6 weeks to reach steady-state after each dose adjustment. Classification of recommendations: Strong
azathioprine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104933	case5	Consider an alternate agent or extreme dose reduction of azathioprine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Indeterminate	Dosing recommendations: None Classification of recommendations: None
capecitabine	DPYD	https://pharmgkb.org/guidelineAnnotation/PA166109594	case1	The CPIC Dosing Guideline for 5-fluorouracil and capecitabine recommends an alternative drug for patients who are DPYD poor metabolizers with an activity score of 0. In those who are poor metabolizers with an activity score of 0.5, an alternative drug is also recommended, but if this is not considered a suitable therapeutic option, 5-fluorouracil or capecitabine should be administered at a strongly reduced dose with early therapeutic drug monitoring. Patients who are intermediate metabolizers with an activity score of 1 or 1.5 should receive a dose reduction of 50%. Patients with the c.[2846A>T];[2846A>T] genotype may require a >50% dose reduction.	DPYD Normal Metabolizer	Dosing recommendations: Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration Classification of recommendations: Strong
capecitabine	DPYD	https://pharmgkb.org/guidelineAnnotation/PA166109594	case1	The CPIC Dosing Guideline for 5-fluorouracil and capecitabine recommends an alternative drug for patients who are DPYD poor metabolizers with an activity score of 0. In those who are poor metabolizers with an activity score of 0.5, an alternative drug is also recommended, but if this is not considered a suitable therapeutic option, 5-fluorouracil or capecitabine should be administered at a strongly reduced dose with early therapeutic drug monitoring. Patients who are intermediate metabolizers with an activity score of 1 or 1.5 should receive a dose reduction of 50%. Patients with the c.[2846A>T];[2846A>T] genotype may require a >50% dose reduction.	DPYD Intermediate Metabolizer	Dosing recommendations: 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];[2846A>T] genotype may require >50% reduction in starting dose. Classification of recommendations: Activity score 1: StrongActivity score 1.5: Moderate
capecitabine	DPYD	https://pharmgkb.org/guidelineAnnotation/PA166109594	case1	The CPIC Dosing Guideline for 5-fluorouracil and capecitabine recommends an alternative drug for patients who are DPYD poor metabolizers with an activity score of 0. In those who are poor metabolizers with an activity score of 0.5, an alternative drug is also recommended, but if this is not considered a suitable therapeutic option, 5-fluorouracil or capecitabine should be administered at a strongly reduced dose with early therapeutic drug monitoring. Patients who are intermediate metabolizers with an activity score of 1 or 1.5 should receive a dose reduction of 50%. Patients with the c.[2846A>T];[2846A>T] genotype may require a >50% dose reduction.	DPYD Poor Metabolizer	Dosing recommendations: Activity score 0.5: 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.Activity score 0: Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens. Classification of recommendations: Strong
carbamazepine	HLA-A	https://pharmgkb.org/guidelineAnnotation/PA166105008	case2	The CPIC Dosing Guideline update for carbamazepine recommends an alternative drug for carbamazepine-naive patients carrying at least one copy of either HLA-B*15:02 or HLA-A*31:01 due to the association of those alleles with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In addition, HLA-A*31:01 is associated with an increased risk of drug reaction with eosinophilia and systemic symptoms (DRESS) and maculopapular exanthema (MPE).	Homozygous for alleles other than HLA-B*15:02 and HLA-A*31:01	Therapeutic Recommendations: Use carbamazepine per standard dosing guidelines. Classification of Recommendation: Strong
carbamazepine	HLA-A	https://pharmgkb.org/guidelineAnnotation/PA166105008	case2	The CPIC Dosing Guideline update for carbamazepine recommends an alternative drug for carbamazepine-naive patients carrying at least one copy of either HLA-B*15:02 or HLA-A*31:01 due to the association of those alleles with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In addition, HLA-A*31:01 is associated with an increased risk of drug reaction with eosinophilia and systemic symptoms (DRESS) and maculopapular exanthema (MPE).	Heterozygote or homozygous for HLA-A*31:01 and homozygous for HLA-B alleles other than *15:02	Therapeutic Recommendations: A. If patient is carbamazepine-naive and alternative agents are available, do not use carbamazepine.B. If patient is carbamazepine-naive 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.C. The latency period for cutaneous adverse drug reactions is variable depending on phenotype; however, all usually occur within 3 months of regular dosing. Therefore, if patient has previously used carbamazepine for longer than 3 months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine. Classification of Recommendation: A. StrongB. OptionalC. Optional
carbamazepine	HLA-A	https://pharmgkb.org/guidelineAnnotation/PA166105008	case2	The CPIC Dosing Guideline update for carbamazepine recommends an alternative drug for carbamazepine-naive patients carrying at least one copy of either HLA-B*15:02 or HLA-A*31:01 due to the association of those alleles with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In addition, HLA-A*31:01 is associated with an increased risk of drug reaction with eosinophilia and systemic symptoms (DRESS) and maculopapular exanthema (MPE).	Heterozygote or homozygous for HLA-B*15:02 and any HLA-A*31:01 genotype (or HLA-A*31:01 genotype unknown)	Therapeutic Recommendations: A. If patient is carbamazepine-naive, do not use carbamazepine.B. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherance to therapy (~4-28 days), and cases usually occur within 3 months of dosing; therefore, if the patient has previously used carbamazepine consistently for longer than 3 months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine in the future. Classification of Recommendation: A. StrongB. Optional
carbamazepine	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166105008	case2	The CPIC Dosing Guideline update for carbamazepine recommends an alternative drug for carbamazepine-naive patients carrying at least one copy of either HLA-B*15:02 or HLA-A*31:01 due to the association of those alleles with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In addition, HLA-A*31:01 is associated with an increased risk of drug reaction with eosinophilia and systemic symptoms (DRESS) and maculopapular exanthema (MPE).	Homozygous for alleles other than HLA-B*15:02 and HLA-A*31:01	Therapeutic Recommendations: Use carbamazepine per standard dosing guidelines. Classification of Recommendation: Strong
carbamazepine	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166105008	case2	The CPIC Dosing Guideline update for carbamazepine recommends an alternative drug for carbamazepine-naive patients carrying at least one copy of either HLA-B*15:02 or HLA-A*31:01 due to the association of those alleles with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In addition, HLA-A*31:01 is associated with an increased risk of drug reaction with eosinophilia and systemic symptoms (DRESS) and maculopapular exanthema (MPE).	Heterozygote or homozygous for HLA-A*31:01 and homozygous for HLA-B alleles other than *15:02	Therapeutic Recommendations: A. If patient is carbamazepine-naive and alternative agents are available, do not use carbamazepine.B. If patient is carbamazepine-naive 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.C. The latency period for cutaneous adverse drug reactions is variable depending on phenotype; however, all usually occur within 3 months of regular dosing. Therefore, if patient has previously used carbamazepine for longer than 3 months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine. Classification of Recommendation: A. StrongB. OptionalC. Optional
carbamazepine	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166105008	case2	The CPIC Dosing Guideline update for carbamazepine recommends an alternative drug for carbamazepine-naive patients carrying at least one copy of either HLA-B*15:02 or HLA-A*31:01 due to the association of those alleles with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In addition, HLA-A*31:01 is associated with an increased risk of drug reaction with eosinophilia and systemic symptoms (DRESS) and maculopapular exanthema (MPE).	Heterozygote or homozygous for HLA-B*15:02 and any HLA-A*31:01 genotype (or HLA-A*31:01 genotype unknown)	Therapeutic Recommendations: A. If patient is carbamazepine-naive, do not use carbamazepine.B. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherance to therapy (~4-28 days), and cases usually occur within 3 months of dosing; therefore, if the patient has previously used carbamazepine consistently for longer than 3 months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine in the future. Classification of Recommendation: A. StrongB. Optional
celecoxib	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Normal metabolizer	Therapeutic recommendations: 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 of recommendations: Strong
celecoxib	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Intermediate metabolizer	Therapeutic recommendations: 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 of recommendations: Moderate
celecoxib	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Poor metabolizer	Therapeutic recommendations: 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 and 5 days for ibuprofen, flurbiprofen and lornoxicam 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 of recommendations: Moderate
celecoxib	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	Indeterminate	Therapeutic recommendations: No recommendation. Classification of recommendations: nan
citalopram	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127638	case3	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitors citalopram and escitalopram recommends an alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 ultrarapid metabolizers. For CYP2C19 poor metabolizers, consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19.	Ultrarapid metabolizer (~5-30% of patients)	Therapeutic Recommendations: Consider an alternative drug not predominantly metabolized by CYP2C19. Classification of recommendations: Moderate
citalopram	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127638	case3	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitors citalopram and escitalopram recommends an alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 ultrarapid metabolizers. For CYP2C19 poor metabolizers, consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19.	Extensive metabolizer (~35-50% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendations: Strong
citalopram	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127638	case3	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitors citalopram and escitalopram recommends an alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 ultrarapid metabolizers. For CYP2C19 poor metabolizers, consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19.	Intermediate metabolizer (~18-45% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendations: Strong
citalopram	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127638	case3	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitors citalopram and escitalopram recommends an alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 ultrarapid metabolizers. For CYP2C19 poor metabolizers, consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19.	Poor metabolizer (~2-15% of patients)	Therapeutic Recommendations: Consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19. Classification of recommendations: Moderate
clomipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105007	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including clomipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Ultrarapid metabolizer (~2-5% of patients)	Therapeutic recommendations: 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 of recommendations for amitriptyline: Optional
clomipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105007	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including clomipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Rapid metabolizer (~2-30% of patients)	Therapeutic recommendations: 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 of recommendations for amitriptyline: Optional
clomipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105007	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including clomipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Normal metabolizer (~35-50% of patients)	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of recommendations for amitriptyline: Strong
clomipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105007	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including clomipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Intermediate metabolizer (~18-45% of patients)	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of recommendations for amitriptyline: Optional
clomipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105007	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including clomipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Poor metabolizer (~2-15% of patients)	Therapeutic recommendations: 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. Classification of recommendations for amitriptyline: Optional
clomipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105007	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including clomipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Ultrarapid metabolizer (~1-20% of patients)	Therapeutic Recommendations: 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. Classification of recommendation for other TCAs: Optional
clomipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105007	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including clomipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Normal metabolizer (~72-88% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendation for other TCAs: Strong
clomipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105007	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including clomipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Intermediate metabolizer (~1-13% of patients)	Therapeutic Recommendations: Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for other TCAs: Optional
clomipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105007	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including clomipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Poor metabolizer (~1-10% of patients)	Therapeutic Recommendations: Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6.If a TCA is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for other TCAs: Optional
clopidogrel	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166104948	case1	The CPIC Dosing Guideline for clopidogrel recommends an alternative antiplatelet therapy (e.g., prasugrel, ticagrelor) for CYP2C19 poor or intermediate metabolizers if there is no contraindication.	Ultrarapid metabolizer (UM) (~5-30% of patients)	Therapeutic recommendations: Clopidogrel - label recommended dosage and administration Classification of recommendations: Strong
clopidogrel	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166104948	case1	The CPIC Dosing Guideline for clopidogrel recommends an alternative antiplatelet therapy (e.g., prasugrel, ticagrelor) for CYP2C19 poor or intermediate metabolizers if there is no contraindication.	Extensive metabolizer (EM) (~35-50% of patients)	Therapeutic recommendations: Clopidogrel - label recommended dosage and administration Classification of recommendations: Strong
clopidogrel	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166104948	case1	The CPIC Dosing Guideline for clopidogrel recommends an alternative antiplatelet therapy (e.g., prasugrel, ticagrelor) for CYP2C19 poor or intermediate metabolizers if there is no contraindication.	Intermediate metabolizer (IM) (~18-45% of patients)	Therapeutic recommendations: Alternative antiplatelet therapy (if no contraindication); e.g., prasugrel, ticagrelor Classification of recommendations: Moderate
clopidogrel	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166104948	case1	The CPIC Dosing Guideline for clopidogrel recommends an alternative antiplatelet therapy (e.g., prasugrel, ticagrelor) for CYP2C19 poor or intermediate metabolizers if there is no contraindication.	Poor metabolizer (PM) (~2-15% of patients)	Therapeutic recommendations: Alternative antiplatelet therapy (if no contraindication); e.g., prasugrel, ticagrelor Classification of recommendations: Strong
codeine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104996	case1	Alternate analgesics are recommended for CYP2D6 ultrarapid and poor metabolizers. A label recommended age- or weight-specific codeine dose is warranted for CYP2D6 extensive and intermediate metabolizers.	Ultrarapid metabolizer (~1-2% of patients)	Recommendations for codeine therapy.: Avoid codeine use due to potential for toxicity. Classification of recommendation for codeine therapy: Strong
codeine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104996	case1	Alternate analgesics are recommended for CYP2D6 ultrarapid and poor metabolizers. A label recommended age- or weight-specific codeine dose is warranted for CYP2D6 extensive and intermediate metabolizers.	Extensive metabolizer (~77-92% of patients)	Recommendations for codeine therapy.: Use label recommended age- or weight-specific dosing. Classification of recommendation for codeine therapy: Strong
codeine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104996	case1	Alternate analgesics are recommended for CYP2D6 ultrarapid and poor metabolizers. A label recommended age- or weight-specific codeine dose is warranted for CYP2D6 extensive and intermediate metabolizers.	Intermediate metabolizer (~2-11% of patients)	Recommendations for codeine therapy.: Use label recommended age- or weight-specific dosing. If no response, consider alternative analgesics such as morphine or a non-opioid. Classification of recommendation for codeine therapy: Moderate
codeine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104996	case1	Alternate analgesics are recommended for CYP2D6 ultrarapid and poor metabolizers. A label recommended age- or weight-specific codeine dose is warranted for CYP2D6 extensive and intermediate metabolizers.	Poor metabolizer (~5-10% of patients)	Recommendations for codeine therapy.: Avoid codeine use due to lack of efficacy. Classification of recommendation for codeine therapy: Strong
desflurane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
desflurane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
desflurane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
desflurane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
desipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105002	case1	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline/nortriptyline and CYP2C19, CYP2D6 to other tricyclics including desipramine. The CPIC Dosing Guideline update for nortriptyline recommends a 25% dose reduction for CYP2D6 intermediate metabolizers. For CYP2D6 ultrarapid or poor metabolizers, an alternative drug should be considered. If nortriptyline is warranted, consider a 50% dose reduction in CYP2D6 poor metabolizers.	CYP2D6 Ultrarapid metabolizer (~1-20% of patients)	Therapeutic Recommendations: 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. Classification of recommendation for other TCAs: Optional
desipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105002	case1	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline/nortriptyline and CYP2C19, CYP2D6 to other tricyclics including desipramine. The CPIC Dosing Guideline update for nortriptyline recommends a 25% dose reduction for CYP2D6 intermediate metabolizers. For CYP2D6 ultrarapid or poor metabolizers, an alternative drug should be considered. If nortriptyline is warranted, consider a 50% dose reduction in CYP2D6 poor metabolizers.	CYP2D6 Normal metabolizer (~72-88% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendation for other TCAs: Strong
desipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105002	case1	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline/nortriptyline and CYP2C19, CYP2D6 to other tricyclics including desipramine. The CPIC Dosing Guideline update for nortriptyline recommends a 25% dose reduction for CYP2D6 intermediate metabolizers. For CYP2D6 ultrarapid or poor metabolizers, an alternative drug should be considered. If nortriptyline is warranted, consider a 50% dose reduction in CYP2D6 poor metabolizers.	CYP2D6 Intermediate metabolizer (~1-13% of patients)	Therapeutic Recommendations: Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for other TCAs: Optional
desipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105002	case1	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline/nortriptyline and CYP2C19, CYP2D6 to other tricyclics including desipramine. The CPIC Dosing Guideline update for nortriptyline recommends a 25% dose reduction for CYP2D6 intermediate metabolizers. For CYP2D6 ultrarapid or poor metabolizers, an alternative drug should be considered. If nortriptyline is warranted, consider a 50% dose reduction in CYP2D6 poor metabolizers.	CYP2D6 Poor metabolizer (~1-10% of patients)	Therapeutic Recommendations: Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6.If a TCA is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for other TCAs: Optional
doxepin	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105000	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including doxepin. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Ultrarapid metabolizer (~2-5% of patients)	Therapeutic recommendations: 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 of recommendations for amitriptyline: Optional
doxepin	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105000	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including doxepin. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Rapid metabolizer (~2-30% of patients)	Therapeutic recommendations: 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 of recommendations for amitriptyline: Optional
doxepin	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105000	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including doxepin. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Normal metabolizer (~35-50% of patients)	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of recommendations for amitriptyline: Strong
doxepin	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105000	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including doxepin. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Intermediate metabolizer (~18-45% of patients)	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of recommendations for amitriptyline: Optional
doxepin	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105000	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including doxepin. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Poor metabolizer (~2-15% of patients)	Therapeutic recommendations: 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. Classification of recommendations for amitriptyline: Optional
doxepin	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105000	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including doxepin. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Ultrarapid metabolizer (~1-20% of patients)	Therapeutic Recommendations: 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. Classification of recommendation for other TCAs: Optional
doxepin	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105000	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including doxepin. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Normal metabolizer (~72-88% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendation for other TCAs: Strong
doxepin	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105000	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including doxepin. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Intermediate metabolizer (~1-13% of patients)	Therapeutic Recommendations: Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for other TCAs: Optional
doxepin	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105000	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including doxepin. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Poor metabolizer (~1-10% of patients)	Therapeutic Recommendations: Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6.If a TCA is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for other TCAs: Optional
efavirenz	CYP2B6	https://pharmgkb.org/guidelineAnnotation/PA166182603	case1	Consider initiating efavirenz with a decreased dose of either 400 or 200 mg/day for patients who are CYP2B6 poor metabolizers. Consider initiating efavirenz with a decreased dose of 400 mg/day for patients who are CYP2B6 intermediate metabolizers.	Ultra Rapid Metabolizer	Dosing recommendations: Initiate efavirenz with standard dosing (600 mg/day) Classification of recommendations: Strong
efavirenz	CYP2B6	https://pharmgkb.org/guidelineAnnotation/PA166182603	case1	Consider initiating efavirenz with a decreased dose of either 400 or 200 mg/day for patients who are CYP2B6 poor metabolizers. Consider initiating efavirenz with a decreased dose of 400 mg/day for patients who are CYP2B6 intermediate metabolizers.	Rapid Metabolizer	Dosing recommendations: Initiate efavirenz with standard dosing (600 mg/day) Classification of recommendations: Strong
efavirenz	CYP2B6	https://pharmgkb.org/guidelineAnnotation/PA166182603	case1	Consider initiating efavirenz with a decreased dose of either 400 or 200 mg/day for patients who are CYP2B6 poor metabolizers. Consider initiating efavirenz with a decreased dose of 400 mg/day for patients who are CYP2B6 intermediate metabolizers.	Normal Metabolizer	Dosing recommendations: Initiate efavirenz with standard dosing (600 mg/day) Classification of recommendations: Strong
efavirenz	CYP2B6	https://pharmgkb.org/guidelineAnnotation/PA166182603	case1	Consider initiating efavirenz with a decreased dose of either 400 or 200 mg/day for patients who are CYP2B6 poor metabolizers. Consider initiating efavirenz with a decreased dose of 400 mg/day for patients who are CYP2B6 intermediate metabolizers.	Intermediate Metabolizer	Dosing recommendations: Consider initiating efavirenz with decreased dose of 400 mg/day. Classification of recommendations: Moderate
efavirenz	CYP2B6	https://pharmgkb.org/guidelineAnnotation/PA166182603	case1	Consider initiating efavirenz with a decreased dose of either 400 or 200 mg/day for patients who are CYP2B6 poor metabolizers. Consider initiating efavirenz with a decreased dose of 400 mg/day for patients who are CYP2B6 intermediate metabolizers.	Poor Metabolizer	Dosing recommendations: Consider initiating efavirenz with decreased dose of 400 or 200 mg/day. Classification of recommendations: Moderate
enflurane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
enflurane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
enflurane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
enflurane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
escitalopram	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127638	case3	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitors citalopram and escitalopram recommends an alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 ultrarapid metabolizers. For CYP2C19 poor metabolizers, consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19.	Ultrarapid metabolizer (~5-30% of patients)	Therapeutic Recommendations: Consider an alternative drug not predominantly metabolized by CYP2C19. Classification of recommendations: Moderate
escitalopram	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127638	case3	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitors citalopram and escitalopram recommends an alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 ultrarapid metabolizers. For CYP2C19 poor metabolizers, consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19.	Extensive metabolizer (~35-50% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendations: Strong
escitalopram	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127638	case3	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitors citalopram and escitalopram recommends an alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 ultrarapid metabolizers. For CYP2C19 poor metabolizers, consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19.	Intermediate metabolizer (~18-45% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendations: Strong
escitalopram	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127638	case3	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitors citalopram and escitalopram recommends an alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 ultrarapid metabolizers. For CYP2C19 poor metabolizers, consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19.	Poor metabolizer (~2-15% of patients)	Therapeutic Recommendations: Consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19. Classification of recommendations: Moderate
fluorouracil	DPYD	https://pharmgkb.org/guidelineAnnotation/PA166122686	case1	The CPIC Dosing Guideline for 5-fluorouracil and capecitabine recommends an alternative drug for patients who are DPYD poor metabolizers with an activity score of 0. In those who are poor metabolizers with an activity score of 0.5, an alternative drug is also recommended, but if this is not considered a suitable therapeutic option, 5-fluorouracil or capecitabine should be administered at a strongly reduced dose with early therapeutic drug monitoring. Patients who are intermediate metabolizers with an activity score of 1 or 1.5 should receive a dose reduction of 50%. Patients with the c.[2846A>T];[2846A>T] genotype may require a >50% dose reduction.	DPYD Normal Metabolizer	Dosing recommendations: Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration Classification of recommendations: Strong
fluorouracil	DPYD	https://pharmgkb.org/guidelineAnnotation/PA166122686	case1	The CPIC Dosing Guideline for 5-fluorouracil and capecitabine recommends an alternative drug for patients who are DPYD poor metabolizers with an activity score of 0. In those who are poor metabolizers with an activity score of 0.5, an alternative drug is also recommended, but if this is not considered a suitable therapeutic option, 5-fluorouracil or capecitabine should be administered at a strongly reduced dose with early therapeutic drug monitoring. Patients who are intermediate metabolizers with an activity score of 1 or 1.5 should receive a dose reduction of 50%. Patients with the c.[2846A>T];[2846A>T] genotype may require a >50% dose reduction.	DPYD Intermediate Metabolizer	Dosing recommendations: 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];[2846A>T] genotype may require >50% reduction in starting dose. Classification of recommendations: Activity score 1: StrongActivity score 1.5: Moderate
fluorouracil	DPYD	https://pharmgkb.org/guidelineAnnotation/PA166122686	case1	The CPIC Dosing Guideline for 5-fluorouracil and capecitabine recommends an alternative drug for patients who are DPYD poor metabolizers with an activity score of 0. In those who are poor metabolizers with an activity score of 0.5, an alternative drug is also recommended, but if this is not considered a suitable therapeutic option, 5-fluorouracil or capecitabine should be administered at a strongly reduced dose with early therapeutic drug monitoring. Patients who are intermediate metabolizers with an activity score of 1 or 1.5 should receive a dose reduction of 50%. Patients with the c.[2846A>T];[2846A>T] genotype may require a >50% dose reduction.	DPYD Poor Metabolizer	Dosing recommendations: Activity score 0.5: 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.Activity score 0: Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens. Classification of recommendations: Strong
flurbiprofen	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Normal metabolizer	Therapeutic recommendations: 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 of recommendations: Strong
flurbiprofen	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Intermediate metabolizer	Therapeutic recommendations: 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 of recommendations: Moderate
flurbiprofen	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Poor metabolizer	Therapeutic recommendations: 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 and 5 days for ibuprofen, flurbiprofen and lornoxicam 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 of recommendations: Moderate
flurbiprofen	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	Indeterminate	Therapeutic recommendations: No recommendation. Classification of recommendations: nan
fluvoxamine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166127637	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor fluvoxamine recommends to consider a 25-50% reduction of recommended starting dose and titrate to response or use an alternative drug not metabolized by CYP2D6 for CYP2D6 poor metabolizers.	Ultrarapid metabolizer (~1-2% of patients)	Therapeutic Recommendations: No recommendation due to lack of evidence. Classification of recommendations: Optional
fluvoxamine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166127637	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor fluvoxamine recommends to consider a 25-50% reduction of recommended starting dose and titrate to response or use an alternative drug not metabolized by CYP2D6 for CYP2D6 poor metabolizers.	Extensive metabolizer (~77-92% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendations: Strong
fluvoxamine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166127637	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor fluvoxamine recommends to consider a 25-50% reduction of recommended starting dose and titrate to response or use an alternative drug not metabolized by CYP2D6 for CYP2D6 poor metabolizers.	Intermediate metabolizer (~2-11% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendations: Moderate
fluvoxamine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166127637	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor fluvoxamine recommends to consider a 25-50% reduction of recommended starting dose and titrate to response or use an alternative drug not metabolized by CYP2D6 for CYP2D6 poor metabolizers.	Poor metabolizers (~5-10% of patients)	Therapeutic Recommendations: Consider a 25-50% reduction of recommended starting dose and titrate to response or use an alternative drug not metabolized by CYP2D6. Classification of recommendations: Optional
halothane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
halothane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
halothane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
halothane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
ibuprofen	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Normal metabolizer	Therapeutic recommendations: 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 of recommendations: Strong
ibuprofen	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Intermediate metabolizer	Therapeutic recommendations: 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 of recommendations: Moderate
ibuprofen	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Poor metabolizer	Therapeutic recommendations: 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 and 5 days for ibuprofen, flurbiprofen and lornoxicam 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 of recommendations: Moderate
ibuprofen	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	Indeterminate	Therapeutic recommendations: No recommendation. Classification of recommendations: nan
imipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166104999	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including imipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Ultrarapid metabolizer (~2-5% of patients)	Therapeutic recommendations: 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 of recommendations for amitriptyline: Optional
imipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166104999	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including imipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Rapid metabolizer (~2-30% of patients)	Therapeutic recommendations: 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 of recommendations for amitriptyline: Optional
imipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166104999	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including imipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Normal metabolizer (~35-50% of patients)	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of recommendations for amitriptyline: Strong
imipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166104999	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including imipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Intermediate metabolizer (~18-45% of patients)	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of recommendations for amitriptyline: Optional
imipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166104999	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including imipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Poor metabolizer (~2-15% of patients)	Therapeutic recommendations: 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. Classification of recommendations for amitriptyline: Optional
imipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104999	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including imipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Ultrarapid metabolizer (~1-20% of patients)	Therapeutic Recommendations: 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. Classification of recommendation for other TCAs: Optional
imipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104999	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including imipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Normal metabolizer (~72-88% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendation for other TCAs: Strong
imipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104999	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including imipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Intermediate metabolizer (~1-13% of patients)	Therapeutic Recommendations: Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for other TCAs: Optional
imipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104999	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including imipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Poor metabolizer (~1-10% of patients)	Therapeutic Recommendations: Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6.If a TCA is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for other TCAs: Optional
isoflurane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
isoflurane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
isoflurane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
isoflurane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
ivacaftor	CFTR	https://pharmgkb.org/guidelineAnnotation/PA166114461	case1	Ivacaftor treatment is recommended only in cystic fibrosis (CF) patients that are either homozygous or heterozygous for certain CFTR variants.  See full guideline for disclaimers, further details and supporting evidence.	Homozygous or Heterozygous G551D-CFTR, rs75527207 genotype AA or AG	Recommendations for ivacaftor therapy: Use ivacaftor according to the product label Classification of recommendation for ivacaftor therapy: Strong
ivacaftor	CFTR	https://pharmgkb.org/guidelineAnnotation/PA166114461	case1	Ivacaftor treatment is recommended only in cystic fibrosis (CF) patients that are either homozygous or heterozygous for certain CFTR variants.  See full guideline for disclaimers, further details and supporting evidence.	Homozygous for F508del-CFTR, rs113993960 or rs199826652 genotype del/del	Recommendations for ivacaftor therapy: Ivacaftor is not recommended Classification of recommendation for ivacaftor therapy: Moderate
ivacaftor	CFTR	https://pharmgkb.org/guidelineAnnotation/PA166114461	case1	Ivacaftor treatment is recommended only in cystic fibrosis (CF) patients that are either homozygous or heterozygous for certain CFTR variants.  See full guideline for disclaimers, further details and supporting evidence.	Homozygous or heterozygous for one of the following CFTR variants: E56K, P67L, R74W, D110E, D110H, R117C, R117H, G178R, E193K, L206W, R347H, R352Q, A455E, S549N, S549R, G551D, G551S, D579G, S945L, S997F, F1052V, K1060T, A1067T, G1069R, R1070Q, R1070W, F1074L, D1152H, G1244E, S1251N, S1255P, D1270N, G1349D, 2789+5G->A, 3272-26A->G, 3849+10kbC->T, 711+1G->T and E831X	Recommendations for ivacaftor therapy: Use ivacaftor according to the product label Classification of recommendation for ivacaftor therapy: Moderate
lornoxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Normal metabolizer	Therapeutic recommendations: 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 of recommendations: Strong
lornoxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Intermediate metabolizer	Therapeutic recommendations: 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 of recommendations: Moderate
lornoxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Poor metabolizer	Therapeutic recommendations: 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 and 5 days for ibuprofen, flurbiprofen and lornoxicam 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 of recommendations: Moderate
lornoxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166191841	case3	The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	Indeterminate	Therapeutic recommendations: No recommendation. Classification of recommendations: nan
meloxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192301	case1	The CPIC Dosing Guideline for meloxicam recommends alternative therapy for CYP2C9 poor metabolizers due to markedly prolonged half-life, and initiating therapy with 50% of the lowest recommended starting dose or choose an alternative therapy for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Normal metabolizer	Therapeutic recommendations: 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 of recommendations: Strong
meloxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192301	case1	The CPIC Dosing Guideline for meloxicam recommends alternative therapy for CYP2C9 poor metabolizers due to markedly prolonged half-life, and initiating therapy with 50% of the lowest recommended starting dose or choose an alternative therapy for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Intermediate metabolizer	Therapeutic recommendations: 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 (Table 2). Classification of recommendations: Moderate
meloxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192301	case1	The CPIC Dosing Guideline for meloxicam recommends alternative therapy for CYP2C9 poor metabolizers due to markedly prolonged half-life, and initiating therapy with 50% of the lowest recommended starting dose or choose an alternative therapy for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	CYP2C9 Poor metabolizer	Therapeutic recommendations: 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 (Table 2). Classification of recommendations: Moderate
meloxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192301	case1	The CPIC Dosing Guideline for meloxicam recommends alternative therapy for CYP2C9 poor metabolizers due to markedly prolonged half-life, and initiating therapy with 50% of the lowest recommended starting dose or choose an alternative therapy for CYP2C9 intermediate metabolizers with activity score of 1. See full guideline for further details and supporting evidence.	Indeterminate	Therapeutic recommendations: No recommendation. Classification of recommendations: nan
mercaptopurine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104945	case5	Consider an alternate agent or extreme dose reduction of mercaptopurine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Normal Metabolizer	Dosing recommendations: Start with normal starting dose (e.g., 75 mg/m/day or 1.5 mg/kg/day) and adjust doses of mercaptopurine (and of any other myelosuppressive therapy) without any special emphasis on mercaptopurine compared to other agents. Allow at least 2 weeks to reach steady-state after each dose adjustment. Classification of recommendations: Strong
mercaptopurine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104945	case5	Consider an alternate agent or extreme dose reduction of mercaptopurine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Intermediate Metabolizer	Dosing recommendations: Start with reduced starting doses (30-80% of normal dose) if normal starting dose is > or = 75 mg/m/day or > or = 1.5 mg/kg/day (e.g. start at 25-60 mg/m/day or 0.45-1.2 mg/kg/day) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs and depending on other therapy, emphasis should be on reducing mercaptopurine over other agents. If normal starting dose is already < 75 mg/m/day or 1.5 mg/kg/day, dose reduction may not be recommended. Classification of recommendations: Strong
mercaptopurine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104945	case5	Consider an alternate agent or extreme dose reduction of mercaptopurine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Possible Intermediate Metabolizer	Dosing recommendations: Start with reduced starting doses (30-80% of normal dose) if normal starting dose is > or = 75 mg/m/day or > or = 1.5 mg/kg/day (e.g. start at 25-60 mg/m/day or 0.45-1.2 mg/kg/day) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs and depending on other therapy, emphasis should be on reducing mercaptopurine over other agents. If normal starting dose is already < 75 mg/m/day or 1.5 mg/kg/day, dose reduction may not be recommended. Classification of recommendations: Strong
mercaptopurine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104945	case5	Consider an alternate agent or extreme dose reduction of mercaptopurine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Poor Metabolizer	Dosing recommendations: For malignancy, initiate dose at 10 mg/m/day and adjust dose based on myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For non-malignant conditions, consider alternative non-thiopurine immunosuppressant therapy. Classification of recommendations: Strong
mercaptopurine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104945	case5	Consider an alternate agent or extreme dose reduction of mercaptopurine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Indeterminate	Dosing recommendations: None Classification of recommendations: None
mercaptopurine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104945	case5	Consider an alternate agent or extreme dose reduction of mercaptopurine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Normal Metabolizer	Dosing recommendations: Start with normal starting dose (e.g., 75 mg/m/day or 1.5 mg/kg/day) and adjust doses of mercaptopurine (and of any other myelosuppressive therapy) without any special emphasis on mercaptopurine compared to other agents. Allow at least 2 weeks to reach steady-state after each dose adjustment. Classification of recommendations: Strong
mercaptopurine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104945	case5	Consider an alternate agent or extreme dose reduction of mercaptopurine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Intermediate Metabolizer	Dosing recommendations: Start with reduced starting doses (30-80% of normal dose) if normal starting dose is > or = 75 mg/m/day or > or = 1.5 mg/kg/day (e.g. start at 25-60 mg/m/day or 0.45-1.2 mg/kg/day) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing mercaptopurine over other agents. If normal starting dose is already < 75 mg/m/day or < 1.5 mg/kg/day, dose reduction may not be recommended. Classification of recommendations: Strong
mercaptopurine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104945	case5	Consider an alternate agent or extreme dose reduction of mercaptopurine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Possible Intermediate Metabolizer	Dosing recommendations: Start with reduced starting doses (30-80% of normal dose) if normal starting dose is > or = 75 mg/m/day or > or = 1.5 mg/kg/day (e.g. start at 25-60 mg/m/day or 0.45-1.2 mg/kg/day) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing mercaptopurine over other agents. If normal starting dose is already < 75 mg/m/day or < 1.5 mg/kg/day, dose reduction may not be recommended. Classification of recommendations: Strong
mercaptopurine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104945	case5	Consider an alternate agent or extreme dose reduction of mercaptopurine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Poor Metabolizer	Dosing recommendations: For malignancy, start with drastically reduced doses (reduce daily dose by 10-fold and reduce frequency to thrice weekly instead of daily, e.g. 10 mg/m/day given just 3 days/week) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For non-malignant conditions, consider alternative non-thiopurine immunosuppressant therapy. Classification of recommendations: Strong
mercaptopurine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104945	case5	Consider an alternate agent or extreme dose reduction of mercaptopurine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 30-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Indeterminate	Dosing recommendations: None Classification of recommendations: None
methoxyflurane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
methoxyflurane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
methoxyflurane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
methoxyflurane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
nortriptyline	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104998	case1	The CPIC Dosing Guideline update for nortriptyline recommends a 25% dose reduction for CYP2D6 intermediate metabolizers. For CYP2D6 ultrarapid or poor metabolizers, an alternative drug should be considered. If nortriptyline is warranted, consider a 50% dose reduction in CYP2D6 poor metabolizers.	CYP2D6 Ultrarapid metabolizer (~1-20% of patients)	Therapeutic Recommendations: 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. Classification of recommendation for amitriptyline and nortriptyline: Strong
nortriptyline	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104998	case1	The CPIC Dosing Guideline update for nortriptyline recommends a 25% dose reduction for CYP2D6 intermediate metabolizers. For CYP2D6 ultrarapid or poor metabolizers, an alternative drug should be considered. If nortriptyline is warranted, consider a 50% dose reduction in CYP2D6 poor metabolizers.	CYP2D6 Normal metabolizer (~72-88% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendation for amitriptyline and nortriptyline: Strong
nortriptyline	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104998	case1	The CPIC Dosing Guideline update for nortriptyline recommends a 25% dose reduction for CYP2D6 intermediate metabolizers. For CYP2D6 ultrarapid or poor metabolizers, an alternative drug should be considered. If nortriptyline is warranted, consider a 50% dose reduction in CYP2D6 poor metabolizers.	CYP2D6 Intermediate metabolizer (~1-13% of patients)	Therapeutic Recommendations: Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for amitriptyline and nortriptyline: Moderate
nortriptyline	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166104998	case1	The CPIC Dosing Guideline update for nortriptyline recommends a 25% dose reduction for CYP2D6 intermediate metabolizers. For CYP2D6 ultrarapid or poor metabolizers, an alternative drug should be considered. If nortriptyline is warranted, consider a 50% dose reduction in CYP2D6 poor metabolizers.	CYP2D6 Poor metabolizer (~1-10% of patients)	Therapeutic Recommendations: Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6.If a TCA is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for amitriptyline and nortriptyline: Strong
ondansetron	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166161954	case1	The CPIC dosing guideline for ondansetron recommends selecting an alternate drug for CYP2D6 ultrarapid metabolizers.  It is recommended that the alternate drug not be predominantly metabolized by CYP2D6 (eg. granisetron).	Ultrarapid metabolizer	Therapeutic recommendations: Select and alternative drug not predominantly metabolized by CYP2D6 (i.e. granisetron). Classification of Recommendations: Moderate
ondansetron	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166161954	case1	The CPIC dosing guideline for ondansetron recommends selecting an alternate drug for CYP2D6 ultrarapid metabolizers.  It is recommended that the alternate drug not be predominantly metabolized by CYP2D6 (eg. granisetron).	Normal metabolizer	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of Recommendations: Strong
ondansetron	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166161954	case1	The CPIC dosing guideline for ondansetron recommends selecting an alternate drug for CYP2D6 ultrarapid metabolizers.  It is recommended that the alternate drug not be predominantly metabolized by CYP2D6 (eg. granisetron).	Intermediate metabolizer	Therapeutic recommendations: Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose. Classification of Recommendations: No recommendation
ondansetron	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166161954	case1	The CPIC dosing guideline for ondansetron recommends selecting an alternate drug for CYP2D6 ultrarapid metabolizers.  It is recommended that the alternate drug not be predominantly metabolized by CYP2D6 (eg. granisetron).	Poor metabolizer	Therapeutic recommendations: Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose. Classification of Recommendations: No recommendation
oxcarbazepine	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166176623	case1	The CPIC Dosing Guideline for oxcarbazepine recommends an alternative drug for oxcarbazepine-naive patients carrying at least one copy of HLA-B*15:02 due to the association of this allele with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).	Homozygous for alleles other than HLA-B*15:02	Therapeutic Recommendations: Use oxcarbazepine per standard dosing guidelines. Classification of Recommendation: Strong
oxcarbazepine	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166176623	case1	The CPIC Dosing Guideline for oxcarbazepine recommends an alternative drug for oxcarbazepine-naive patients carrying at least one copy of HLA-B*15:02 due to the association of this allele with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).	Heterozygote or homozygous for HLA-B*15:02	Therapeutic Recommendations: A. If patient is oxcarbazepine-naive, do not use oxcarbazepine.B. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherance to therapy (~4-28 days), and cases usually occur within 3 months of dosing; therefore, if the patient has previously used oxcarbazepine consistently for longer than 3 months without incidence of cutaneous adverse reactions, cautiously consider use of oxcarbazepine in the future. Classification of Recommendation: A. StrongB. Optional
paroxetine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166127636	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor paroxetine recommends an alternative drug not predominantly metabolized by CYP2D6 for CYP2D6 ultrarapid metabolizers and for CYP2D6 poor metabolizers. For CYP2D6 poor metabolizers, if paroxetine use is warranted, consider a 50% reduction of recommended starting dose and titrate to response.	Ultrarapid metabolizer (~1-2% of patients)	Therapeutic Recommendations: Select alternative drug not predominantly metabolized by CYP2D6. Classification of recommendations: Strong
paroxetine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166127636	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor paroxetine recommends an alternative drug not predominantly metabolized by CYP2D6 for CYP2D6 ultrarapid metabolizers and for CYP2D6 poor metabolizers. For CYP2D6 poor metabolizers, if paroxetine use is warranted, consider a 50% reduction of recommended starting dose and titrate to response.	Extensive metabolizer (~77-92% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendations: Strong
paroxetine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166127636	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor paroxetine recommends an alternative drug not predominantly metabolized by CYP2D6 for CYP2D6 ultrarapid metabolizers and for CYP2D6 poor metabolizers. For CYP2D6 poor metabolizers, if paroxetine use is warranted, consider a 50% reduction of recommended starting dose and titrate to response.	Intermediate metabolizer (~2-11% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendations: Moderate
paroxetine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166127636	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor paroxetine recommends an alternative drug not predominantly metabolized by CYP2D6 for CYP2D6 ultrarapid metabolizers and for CYP2D6 poor metabolizers. For CYP2D6 poor metabolizers, if paroxetine use is warranted, consider a 50% reduction of recommended starting dose and titrate to response.	Poor metabolizers (~5-10% of patients)	Therapeutic Recommendations: Select alternative drug not predominantly metabolized by CYP2D6 or if paroxetine use warranted, consider a 50% reduction of recommended starting dose and titrate to response. Classification of recommendations: Optional
peginterferon alfa-2a	IFNL3	https://pharmgkb.org/guidelineAnnotation/PA166110235	case3	IFNL3 (IL28B) variation (rs12979860) is the strongest baseline predictor of response to PEG-interferon-alpha-containing regimens in HCV genotype 1 patients.  Patients with the favorable response genotype (rs12979860 CC) have increased likelihood of response (higher SVR rate) to PEG-interferon-alpha-containing regimens as compared to patients with unfavorable response genotype (rs12979860 CT or TT). Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	CC	Classification of recommendations: Strong
peginterferon alfa-2a	IFNL3	https://pharmgkb.org/guidelineAnnotation/PA166110235	case3	IFNL3 (IL28B) variation (rs12979860) is the strongest baseline predictor of response to PEG-interferon-alpha-containing regimens in HCV genotype 1 patients.  Patients with the favorable response genotype (rs12979860 CC) have increased likelihood of response (higher SVR rate) to PEG-interferon-alpha-containing regimens as compared to patients with unfavorable response genotype (rs12979860 CT or TT). Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	CT or TT	Classification of recommendations: Strong
peginterferon alfa-2b	IFNL3	https://pharmgkb.org/guidelineAnnotation/PA166110235	case3	IFNL3 (IL28B) variation (rs12979860) is the strongest baseline predictor of response to PEG-interferon-alpha-containing regimens in HCV genotype 1 patients.  Patients with the favorable response genotype (rs12979860 CC) have increased likelihood of response (higher SVR rate) to PEG-interferon-alpha-containing regimens as compared to patients with unfavorable response genotype (rs12979860 CT or TT). Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	CC	Classification of recommendations: Strong
peginterferon alfa-2b	IFNL3	https://pharmgkb.org/guidelineAnnotation/PA166110235	case3	IFNL3 (IL28B) variation (rs12979860) is the strongest baseline predictor of response to PEG-interferon-alpha-containing regimens in HCV genotype 1 patients.  Patients with the favorable response genotype (rs12979860 CC) have increased likelihood of response (higher SVR rate) to PEG-interferon-alpha-containing regimens as compared to patients with unfavorable response genotype (rs12979860 CT or TT). Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	CT or TT	Classification of recommendations: Strong
phenytoin	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166122806	case2	Phenytoin is contraindicated in individuals with the HLA-B*15:02 variant allele ("HLA-B*15:02-positive") due to significantly increased risk of phenytoin-induced cutaneous adverse reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).  Additionally, patients with the CYP2C9 poor metabolizer phenotype may require reduced doses of phenytoin. This guideline is currently being updated by CPIC. We will make the genotype picker tool available again as soon as the updated guideline has been finalized.	CYP2C9 Extensive Metabolizer	HLA-B*15:02 "positive" - Therapeutic recommendation: If patient is phenytoin-naive , do not use phenytoin/fosphenytoin. HLA-B*15:02 "positive" - Classification of recommendation: STRONG HLA-B*15:02 "negative"-Therapeutic recommendation: Initiate therapy with recommended maintenance dose . HLA-B*15:02 "negative"-Classification of Recommendation: STRONG
phenytoin	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166122806	case2	Phenytoin is contraindicated in individuals with the HLA-B*15:02 variant allele ("HLA-B*15:02-positive") due to significantly increased risk of phenytoin-induced cutaneous adverse reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).  Additionally, patients with the CYP2C9 poor metabolizer phenotype may require reduced doses of phenytoin. This guideline is currently being updated by CPIC. We will make the genotype picker tool available again as soon as the updated guideline has been finalized.	CYP2C9 Intermediate Metabolizer	HLA-B*15:02 "positive" - Therapeutic recommendation: If patient is phenytoin-naive , do not use phenytoin/fosphenytoin. HLA-B*15:02 "positive" - Classification of recommendation: STRONG HLA-B*15:02 "negative"-Therapeutic recommendation: Consider 25% reduction of recommended starting maintenance dose . Subsequent doses should be adjusted according to therapeutic drug monitoring and response. HLA-B*15:02 "negative"-Classification of Recommendation: MODERATE
phenytoin	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166122806	case2	Phenytoin is contraindicated in individuals with the HLA-B*15:02 variant allele ("HLA-B*15:02-positive") due to significantly increased risk of phenytoin-induced cutaneous adverse reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).  Additionally, patients with the CYP2C9 poor metabolizer phenotype may require reduced doses of phenytoin. This guideline is currently being updated by CPIC. We will make the genotype picker tool available again as soon as the updated guideline has been finalized.	CYP2C9 Poor Metabolizer	HLA-B*15:02 "positive" - Therapeutic recommendation: If patient is phenytoin-naive , do not use phenytoin/fosphenytoin. HLA-B*15:02 "positive" - Classification of recommendation: STRONG HLA-B*15:02 "negative"-Therapeutic recommendation: Consider 50% reduction of recommended starting maintenance dose . Subsequent maintenance doses should be adjusted according to therapeutic drug monitoring and response. HLA-B*15:02 "negative"-Classification of Recommendation: STRONG
phenytoin	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166122806	case2	Phenytoin is contraindicated in individuals with the HLA-B*15:02 variant allele ("HLA-B*15:02-positive") due to significantly increased risk of phenytoin-induced cutaneous adverse reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).  Additionally, patients with the CYP2C9 poor metabolizer phenotype may require reduced doses of phenytoin. This guideline is currently being updated by CPIC. We will make the genotype picker tool available again as soon as the updated guideline has been finalized.	CYP2C9 Extensive Metabolizer	HLA-B*15:02 "positive" - Therapeutic recommendation: If patient is phenytoin-naive , do not use phenytoin/fosphenytoin. HLA-B*15:02 "positive" - Classification of recommendation: STRONG HLA-B*15:02 "negative"-Therapeutic recommendation: Initiate therapy with recommended maintenance dose . HLA-B*15:02 "negative"-Classification of Recommendation: STRONG
phenytoin	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166122806	case2	Phenytoin is contraindicated in individuals with the HLA-B*15:02 variant allele ("HLA-B*15:02-positive") due to significantly increased risk of phenytoin-induced cutaneous adverse reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).  Additionally, patients with the CYP2C9 poor metabolizer phenotype may require reduced doses of phenytoin. This guideline is currently being updated by CPIC. We will make the genotype picker tool available again as soon as the updated guideline has been finalized.	CYP2C9 Intermediate Metabolizer	HLA-B*15:02 "positive" - Therapeutic recommendation: If patient is phenytoin-naive , do not use phenytoin/fosphenytoin. HLA-B*15:02 "positive" - Classification of recommendation: STRONG HLA-B*15:02 "negative"-Therapeutic recommendation: Consider 25% reduction of recommended starting maintenance dose . Subsequent doses should be adjusted according to therapeutic drug monitoring and response. HLA-B*15:02 "negative"-Classification of Recommendation: MODERATE
phenytoin	HLA-B	https://pharmgkb.org/guidelineAnnotation/PA166122806	case2	Phenytoin is contraindicated in individuals with the HLA-B*15:02 variant allele ("HLA-B*15:02-positive") due to significantly increased risk of phenytoin-induced cutaneous adverse reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).  Additionally, patients with the CYP2C9 poor metabolizer phenotype may require reduced doses of phenytoin. This guideline is currently being updated by CPIC. We will make the genotype picker tool available again as soon as the updated guideline has been finalized.	CYP2C9 Poor Metabolizer	HLA-B*15:02 "positive" - Therapeutic recommendation: If patient is phenytoin-naive , do not use phenytoin/fosphenytoin. HLA-B*15:02 "positive" - Classification of recommendation: STRONG HLA-B*15:02 "negative"-Therapeutic recommendation: Consider 50% reduction of recommended starting maintenance dose . Subsequent maintenance doses should be adjusted according to therapeutic drug monitoring and response. HLA-B*15:02 "negative"-Classification of Recommendation: STRONG
piroxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192321	case1	The CPIC Dosing Guideline for piroxicam recommends that CYP2C9 poor metabolizers and intermediate metabolizers with activity score of 1 should 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 full guideline for further details and supporting evidence.	CYP2C9 Normal metabolizer	Therapeutic recommendations: 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 of recommendations: Strong
piroxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192321	case1	The CPIC Dosing Guideline for piroxicam recommends that CYP2C9 poor metabolizers and intermediate metabolizers with activity score of 1 should 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 full guideline for further details and supporting evidence.	CYP2C9 Intermediate metabolizer	Therapeutic recommendations: 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 (Table 2). Classification of recommendations: Moderate
piroxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192321	case1	The CPIC Dosing Guideline for piroxicam recommends that CYP2C9 poor metabolizers and intermediate metabolizers with activity score of 1 should 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 full guideline for further details and supporting evidence.	CYP2C9 Poor metabolizer	Therapeutic recommendations: 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 (Table 2). Classification of recommendations: Moderate
piroxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192321	case1	The CPIC Dosing Guideline for piroxicam recommends that CYP2C9 poor metabolizers and intermediate metabolizers with activity score of 1 should 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 full guideline for further details and supporting evidence.	Indeterminate	Therapeutic recommendations: No recommendation. Classification of recommendations: nan
rasburicase	G6PD	https://pharmgkb.org/guidelineAnnotation/PA166119846	case1	Rasburicase is contraindicated in G6PD deficient patients with or without chronic non-spherocytic hemolytic anemia (CNSHA). In patients with a negative or inconclusive genetic test result an enzyme activity test is recommended prior to rasburicase treatment to determine whether a patient is G6PD deficient. The G6PD gene is X-linked and therefore males only have one copy, whereas females have two copies. See full guideline for disclaimers, further details and supporting evidence.	Normal . A male carrying a non-deficient (class IV) allele or a female carrying two non-deficient (class IV) alleles.	Dosing recommendations for rasburicase: No reason to withhold rasburicase based on G6PD status . Classification of recommendations: Strong
rasburicase	G6PD	https://pharmgkb.org/guidelineAnnotation/PA166119846	case1	Rasburicase is contraindicated in G6PD deficient patients with or without chronic non-spherocytic hemolytic anemia (CNSHA). In patients with a negative or inconclusive genetic test result an enzyme activity test is recommended prior to rasburicase treatment to determine whether a patient is G6PD deficient. The G6PD gene is X-linked and therefore males only have one copy, whereas females have two copies. See full guideline for disclaimers, further details and supporting evidence.	Deficient or Deficient with CNSHA. A male carrying a class I, II or III allele, a female carrying two deficient class I-III alleles.	Dosing recommendations for rasburicase: Rasburicase is contraindicated; alternatives include allopurinol . Classification of recommendations: Strong
rasburicase	G6PD	https://pharmgkb.org/guidelineAnnotation/PA166119846	case1	Rasburicase is contraindicated in G6PD deficient patients with or without chronic non-spherocytic hemolytic anemia (CNSHA). In patients with a negative or inconclusive genetic test result an enzyme activity test is recommended prior to rasburicase treatment to determine whether a patient is G6PD deficient. The G6PD gene is X-linked and therefore males only have one copy, whereas females have two copies. See full guideline for disclaimers, further details and supporting evidence.	Variable . A female carrying one non-deficient (class IV) and one deficient (class I-III variants) allele.	Dosing recommendations for rasburicase: To ascertain that G6PD status is normal, enzyme activity must be measured; alternatives include allopurinol . Classification of recommendations: Moderate
ribavirin	IFNL3	https://pharmgkb.org/guidelineAnnotation/PA166110235	case3	IFNL3 (IL28B) variation (rs12979860) is the strongest baseline predictor of response to PEG-interferon-alpha-containing regimens in HCV genotype 1 patients.  Patients with the favorable response genotype (rs12979860 CC) have increased likelihood of response (higher SVR rate) to PEG-interferon-alpha-containing regimens as compared to patients with unfavorable response genotype (rs12979860 CT or TT). Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	CC	Classification of recommendations: Strong
ribavirin	IFNL3	https://pharmgkb.org/guidelineAnnotation/PA166110235	case3	IFNL3 (IL28B) variation (rs12979860) is the strongest baseline predictor of response to PEG-interferon-alpha-containing regimens in HCV genotype 1 patients.  Patients with the favorable response genotype (rs12979860 CC) have increased likelihood of response (higher SVR rate) to PEG-interferon-alpha-containing regimens as compared to patients with unfavorable response genotype (rs12979860 CT or TT). Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	CT or TT	Classification of recommendations: Strong
sertraline	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127639	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor sertraline recommends to consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 poor metabolizers.	Ultrarapid metabolizer (~5-30% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. If patient does not respond to recommended maintenance dosing, consider alternative drug not predominantly metabolized by CYP2C19. Classification of recommendations: Optional
sertraline	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127639	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor sertraline recommends to consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 poor metabolizers.	Extensive metabolizer (~35-50% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendations: Strong
sertraline	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127639	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor sertraline recommends to consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 poor metabolizers.	Intermediate metabolizer (~18-45% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendations: Strong
sertraline	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166127639	case1	The CPIC Dosing Guideline for the selective serotonin reuptake inhibitor sertraline recommends to consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19 for CYP2C19 poor metabolizers.	Poor metabolizer (~2-15% of patients)	Therapeutic Recommendations: Consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19. Classification of recommendations: Optional
sevoflurane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
sevoflurane	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
sevoflurane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
sevoflurane	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
simvastatin	SLCO1B1	https://pharmgkb.org/guidelineAnnotation/PA166105005	case1	The FDA recommends against 80mg daily simvastatin dosage. In patients with the C allele at SLCO1B1 rs4149056, there are modest increases in myopathy risk even at lower simvastatin doses (40mg daily); if optimal efficacy is not achieved with a lower dose, alternate agents should be considered.	Normal function, Homozygous wild-type (two normal function alleles)	Dosing recommendations for simvastatin: Prescribe desired starting dose and adjust doses of simvastatin based on disease-specific guidelines. Classification of recommendations: Strong
simvastatin	SLCO1B1	https://pharmgkb.org/guidelineAnnotation/PA166105005	case1	The FDA recommends against 80mg daily simvastatin dosage. In patients with the C allele at SLCO1B1 rs4149056, there are modest increases in myopathy risk even at lower simvastatin doses (40mg daily); if optimal efficacy is not achieved with a lower dose, alternate agents should be considered.	Intermediate function, Heterozygous (one normal function allele plus one decreased function allele)	Dosing recommendations for simvastatin: Prescribe a lower dose or consider an alternative statin (e.g. pravastatin or rosuvastatin); consider routine CK surveillance. Classification of recommendations: Strong
simvastatin	SLCO1B1	https://pharmgkb.org/guidelineAnnotation/PA166105005	case1	The FDA recommends against 80mg daily simvastatin dosage. In patients with the C allele at SLCO1B1 rs4149056, there are modest increases in myopathy risk even at lower simvastatin doses (40mg daily); if optimal efficacy is not achieved with a lower dose, alternate agents should be considered.	Low function, Homozygous variant or mutant (two decreased function alleles)	Dosing recommendations for simvastatin: Prescribe a lower dose or consider an alternative statin (e.g. pravastatin or rosuvastatin); consider routine CK surveillance. Classification of recommendations: Strong
succinylcholine	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
succinylcholine	CACNA1S	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
succinylcholine	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Malignant Hyperthermia susceptible	Dosing recommendations for inhaled anesthetics or succinylcholine: Halogenated volatile anesthetics or depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with 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 of recommendations: Strong
succinylcholine	RYR1	https://pharmgkb.org/guidelineAnnotation/PA166180457	case8	The CPIC Dosing Guideline recommends that halogenated volatile anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and the depolarizing muscle relaxants succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). See full guideline for disclaimers, further details and supporting evidence.	Uncertain susceptibility	Dosing recommendations for inhaled anesthetics or succinylcholine: Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. Classification of recommendations: Strong
tacrolimus	CYP3A5	https://pharmgkb.org/guidelineAnnotation/PA166124619	case1	The CPIC dosing guideline for tacrolimus recommends increasing the starting dose by 1.5 to 2 times the recommended starting dose in patients who are CYP3A5 intermediate or extensive metabolizers, though total starting dose should not exceed 0.3 mg/kg/day. Therapeutic drug monitoring should also be used to guide dose adjustments.	Extensive metabolizer (CYP3A5 expresser)	Therapeutic Recommendations: Increase starting dose 1.5 to 2 times recommended starting dose . Total starting dose should not exceed 0.3mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments Classification of recommendations: Strong
tacrolimus	CYP3A5	https://pharmgkb.org/guidelineAnnotation/PA166124619	case1	The CPIC dosing guideline for tacrolimus recommends increasing the starting dose by 1.5 to 2 times the recommended starting dose in patients who are CYP3A5 intermediate or extensive metabolizers, though total starting dose should not exceed 0.3 mg/kg/day. Therapeutic drug monitoring should also be used to guide dose adjustments.	Intermediate metabolizer (CYP3A5 expresser)	Therapeutic Recommendations: Increase starting dose 1.5 to 2 times recommended starting dose . Total starting dose should not exceed 0.3mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments Classification of recommendations: Strong
tacrolimus	CYP3A5	https://pharmgkb.org/guidelineAnnotation/PA166124619	case1	The CPIC dosing guideline for tacrolimus recommends increasing the starting dose by 1.5 to 2 times the recommended starting dose in patients who are CYP3A5 intermediate or extensive metabolizers, though total starting dose should not exceed 0.3 mg/kg/day. Therapeutic drug monitoring should also be used to guide dose adjustments.	Poor metabolizer (CYP3A5 non-expresser)	Therapeutic Recommendations: Initiate therapy with standard recommended dose. Use therapeutic drug monitoring to guide dose adjustments Classification of recommendations: Strong
tamoxifen	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166176068	case1	The CPIC Dosing Guideline for tamoxifen recommends the use of alternative hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women for CYP2D6 poor metabolizer, if aromatase inhibitor use is not contraindicated. For CYP2D6 intermediate metabolizers and CYP2D6 allele combinations resulting in an activity score (AS) of 1 the recommendation is to consider the recommendations stated for the CYP2D6 poor metabolizer. If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose for CYP2D6 intermediate metabolizers and CYP2D6 allele combinations resulting in an AS of 1. For poor metabolizer, 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.	CYP2D6 Ultrarapid Metabolizer	Therapeutic recommendations: Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day). Classification of recommendations: Strong
tamoxifen	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166176068	case1	The CPIC Dosing Guideline for tamoxifen recommends the use of alternative hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women for CYP2D6 poor metabolizer, if aromatase inhibitor use is not contraindicated. For CYP2D6 intermediate metabolizers and CYP2D6 allele combinations resulting in an activity score (AS) of 1 the recommendation is to consider the recommendations stated for the CYP2D6 poor metabolizer. If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose for CYP2D6 intermediate metabolizers and CYP2D6 allele combinations resulting in an AS of 1. For poor metabolizer, 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.	CYP2D6 Normal metabolizer	Therapeutic recommendations: Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day). Classification of recommendations: Strong
tamoxifen	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166176068	case1	The CPIC Dosing Guideline for tamoxifen recommends the use of alternative hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women for CYP2D6 poor metabolizer, if aromatase inhibitor use is not contraindicated. For CYP2D6 intermediate metabolizers and CYP2D6 allele combinations resulting in an activity score (AS) of 1 the recommendation is to consider the recommendations stated for the CYP2D6 poor metabolizer. If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose for CYP2D6 intermediate metabolizers and CYP2D6 allele combinations resulting in an AS of 1. For poor metabolizer, 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.	CYP2D6 Normal metabolizer or Intermediate metabolizer (controversy remains)	Therapeutic recommendations: 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 [Articles:26211827, 24881463]. If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose (40 mg/day) [Article:27226358]. Avoid CYP2D6 strong to weak inhibitors. Classification of recommendations: Moderate
tamoxifen	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166176068	case1	The CPIC Dosing Guideline for tamoxifen recommends the use of alternative hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women for CYP2D6 poor metabolizer, if aromatase inhibitor use is not contraindicated. For CYP2D6 intermediate metabolizers and CYP2D6 allele combinations resulting in an activity score (AS) of 1 the recommendation is to consider the recommendations stated for the CYP2D6 poor metabolizer. If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose for CYP2D6 intermediate metabolizers and CYP2D6 allele combinations resulting in an AS of 1. For poor metabolizer, 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.	CYP2D6 Intermediate metabolizer	Therapeutic recommendations: 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 [Articles:26211827, 24881463]. If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose (40 mg/day) [Article:27226358]. Avoid CYP2D6 strong to weak inhibitors. Classification of recommendations: Moderate
tamoxifen	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166176068	case1	The CPIC Dosing Guideline for tamoxifen recommends the use of alternative hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women for CYP2D6 poor metabolizer, if aromatase inhibitor use is not contraindicated. For CYP2D6 intermediate metabolizers and CYP2D6 allele combinations resulting in an activity score (AS) of 1 the recommendation is to consider the recommendations stated for the CYP2D6 poor metabolizer. If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose for CYP2D6 intermediate metabolizers and CYP2D6 allele combinations resulting in an AS of 1. For poor metabolizer, 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.	CYP2D6 Poor metabolizer	Therapeutic recommendations: 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 [Articles:26211827, 24881463] and based on knowledge that CYP2D6 poor metabolizers switched from tamoxifen to anastrozole do not have an increased risk of recurrence [Article: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 [Articles:27226358, 21768473]. Classification of recommendations: Strong
tegafur	DPYD	https://pharmgkb.org/guidelineAnnotation/PA166122687	case1	As of the November 2017 update of CPIC guidelines regarding fluoropyrimidine dosing, there are no longer dosing recommendations for tegafur based on DPYD  genotype. This is due to limited evidence regarding the impact of DPYD variants on tegafur toxicity risk. The guidelines currently only apply to 5-fluorouracil and capecitabine dosing.	Homozygous wild-type or normal, high DPD activity (two or more functional *1 alleles)	Dosing recommendations: Use label-recommended dosage and administration Classification of recommendations: Moderate
tegafur	DPYD	https://pharmgkb.org/guidelineAnnotation/PA166122687	case1	As of the November 2017 update of CPIC guidelines regarding fluoropyrimidine dosing, there are no longer dosing recommendations for tegafur based on DPYD  genotype. This is due to limited evidence regarding the impact of DPYD variants on tegafur toxicity risk. The guidelines currently only apply to 5-fluorouracil and capecitabine dosing.	Heterozygous or intermediate activity (~3-5% of patients), may have partial DPD deficiency, at risk for toxicity with drug exposure (one functional allele *1, plus one nonfunctional allele - *2A, *13 or rs67376798A )	Dosing recommendations: Start with at least a 50% reduction in starting dose followed by titration of dose based on toxicity or pharmacokinetic test (if available) Classification of recommendations: Moderate
tegafur	DPYD	https://pharmgkb.org/guidelineAnnotation/PA166122687	case1	As of the November 2017 update of CPIC guidelines regarding fluoropyrimidine dosing, there are no longer dosing recommendations for tegafur based on DPYD  genotype. This is due to limited evidence regarding the impact of DPYD variants on tegafur toxicity risk. The guidelines currently only apply to 5-fluorouracil and capecitabine dosing.	Homozygous variant, DPD deficiency (~0.2% of patients), at risk for toxicity with drug exposure (2 nonfunctional alleles - *2A, *13 or rs67376798A )	Dosing recommendations: Select alternate drug Classification of recommendations: Strong
tenoxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192341	case1	The CPIC Dosing Guideline for tenoxicam recommends that CYP2C9 poor metabolizers and intermediate metabolizers with activity score of 1 should 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 full guideline for further details and supporting evidence.	CYP2C9 Normal metabolizer	Therapeutic recommendations: 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 of recommendations: Strong
tenoxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192341	case1	The CPIC Dosing Guideline for tenoxicam recommends that CYP2C9 poor metabolizers and intermediate metabolizers with activity score of 1 should 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 full guideline for further details and supporting evidence.	CYP2C9 Intermediate metabolizer	Therapeutic recommendations: 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 (Table 2). Classification of recommendations: Optional
tenoxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192341	case1	The CPIC Dosing Guideline for tenoxicam recommends that CYP2C9 poor metabolizers and intermediate metabolizers with activity score of 1 should 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 full guideline for further details and supporting evidence.	CYP2C9 Poor metabolizer	Therapeutic recommendations: 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 (Table 2). Classification of recommendations: Optional
tenoxicam	CYP2C9	https://pharmgkb.org/guidelineAnnotation/PA166192341	case1	The CPIC Dosing Guideline for tenoxicam recommends that CYP2C9 poor metabolizers and intermediate metabolizers with activity score of 1 should 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 full guideline for further details and supporting evidence.	Indeterminate	Therapeutic recommendations: No recommendation. Classification of recommendations: nan
thioguanine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104965	case5	Consider an alternate agent or extreme dose reduction of thioguanine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 50-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Normal Metabolizer	Dosing recommendations: Start with normal starting dose (40-60 mg/day). Adjust doses of thioguanine and of other myelosuppressive therapy without any special emphasis on thioguanine. Allow 2 weeks to reach steady-state after each dose adjustment. Classification of recommendations: Strong
thioguanine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104965	case5	Consider an alternate agent or extreme dose reduction of thioguanine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 50-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Intermediate Metabolizer	Dosing recommendations: Start with reduced doses (50% to 80% of normal dose) if normal starting dose is > or = 40-60 mg/m/day) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing thioguanine over other agents. Classification of recommendations: Moderate
thioguanine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104965	case5	Consider an alternate agent or extreme dose reduction of thioguanine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 50-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Possible Intermediate Metabolizer	Dosing recommendations: Start with reduced doses (50% to 80% of normal dose) if normal starting dose is > or = 40-60 mg/m/day) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing thioguanine over other agents. Classification of recommendations: Moderate
thioguanine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104965	case5	Consider an alternate agent or extreme dose reduction of thioguanine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 50-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Poor Metabolizer	Dosing recommendations: Reduce doses to 25% of normal dose and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady-state after each dose adjustment. In setting of myelosuppression, emphasis should be on reducing thioguanine over other agents. For non-malignant conditions, consider alternative non-thiopurine immunosuppressant therapy. Classification of recommendations: Strong
thioguanine	NUDT15	https://pharmgkb.org/guidelineAnnotation/PA166104965	case5	Consider an alternate agent or extreme dose reduction of thioguanine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 50-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Indeterminate	Dosing recommendations: None Classification of recommendations: None
thioguanine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104965	case5	Consider an alternate agent or extreme dose reduction of thioguanine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 50-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Normal Metabolizer	Dosing recommendations: Start with normal starting dose (e.g. 40-60 mg/m/day) and adjust doses of thioguanine and of other myelosuppressive therapy without any special emphasis on thioguanine. Allow 2 weeks to reach steady-state after each dose adjustment. Classification of recommendations: Strong
thioguanine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104965	case5	Consider an alternate agent or extreme dose reduction of thioguanine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 50-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Intermediate Metabolizer	Dosing recommendations: Start with reduced doses (50% to 80% of normal dose) if normal starting dose is > or = 40-60 mg/m/day (e.g. 20-48 mg/m/day) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing thioguanine over other agents. Classification of recommendations: Moderate
thioguanine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104965	case5	Consider an alternate agent or extreme dose reduction of thioguanine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 50-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Possible Intermediate Metabolizer	Dosing recommendations: Start with reduced doses (50% to 80% of normal dose) if normal starting dose is > or = 40-60 mg/m/day (e.g. 20-48 mg/m/day) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing thioguanine over other agents. Classification of recommendations: Moderate
thioguanine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104965	case5	Consider an alternate agent or extreme dose reduction of thioguanine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 50-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Poor Metabolizer	Dosing recommendations: Start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents. For non-malignant conditions, consider alternative non-thiopurine immunosuppressant therapy. Classification of recommendations: Strong
thioguanine	TPMT	https://pharmgkb.org/guidelineAnnotation/PA166104965	case5	Consider an alternate agent or extreme dose reduction of thioguanine for patients who are TPMT or NUDT15 poor metabolizers.  Start at 50-80% of target dose for patients who are TPMT or NUDT15 intermediate metabolizers.	Indeterminate	Dosing recommendations: None Classification of recommendations: None
trimipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105001	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including trimipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Ultrarapid metabolizer (~2-5% of patients)	Therapeutic recommendations: 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 of recommendations for amitriptyline: Optional
trimipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105001	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including trimipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Rapid metabolizer (~2-30% of patients)	Therapeutic recommendations: 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 of recommendations for amitriptyline: Optional
trimipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105001	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including trimipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Normal metabolizer (~35-50% of patients)	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of recommendations for amitriptyline: Strong
trimipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105001	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including trimipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Intermediate metabolizer (~18-45% of patients)	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of recommendations for amitriptyline: Optional
trimipramine	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166105001	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including trimipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2C19 Poor metabolizer (~2-15% of patients)	Therapeutic recommendations: 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. Classification of recommendations for amitriptyline: Optional
trimipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105001	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including trimipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Ultrarapid metabolizer (~1-20% of patients)	Therapeutic Recommendations: 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. Classification of recommendation for other TCAs: Optional
trimipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105001	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including trimipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Normal metabolizer (~72-88% of patients)	Therapeutic Recommendations: Initiate therapy with recommended starting dose. Classification of recommendation for other TCAs: Strong
trimipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105001	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including trimipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Intermediate metabolizer (~1-13% of patients)	Therapeutic Recommendations: Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for other TCAs: Optional
trimipramine	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166105001	case4	Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including trimipramine. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.	CYP2D6 Poor metabolizer (~1-10% of patients)	Therapeutic Recommendations: Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6.If a TCA is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Classification of recommendation for other TCAs: Optional
tropisetron	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166161955	case1	The CPIC dosing guideline for tropisetron recommends selecting an alternate drug for CYP2D6 ultrarapid metabolizers.  It is recommended that the alternate drug not be predominantly metabolized by CYP2D6 (eg. granisetron).	Ultrarapid metabolizer	Therapeutic recommendations: Select and alternative drug not predominantly metabolized by CYP2D6 (i.e. granisetron). Classification of Recommendations: Moderate
tropisetron	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166161955	case1	The CPIC dosing guideline for tropisetron recommends selecting an alternate drug for CYP2D6 ultrarapid metabolizers.  It is recommended that the alternate drug not be predominantly metabolized by CYP2D6 (eg. granisetron).	Normal metabolizer	Therapeutic recommendations: Initiate therapy with recommended starting dose. Classification of Recommendations: Strong
tropisetron	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166161955	case1	The CPIC dosing guideline for tropisetron recommends selecting an alternate drug for CYP2D6 ultrarapid metabolizers.  It is recommended that the alternate drug not be predominantly metabolized by CYP2D6 (eg. granisetron).	Intermediate metabolizer	Therapeutic recommendations: Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose. Classification of Recommendations: No recommendation
tropisetron	CYP2D6	https://pharmgkb.org/guidelineAnnotation/PA166161955	case1	The CPIC dosing guideline for tropisetron recommends selecting an alternate drug for CYP2D6 ultrarapid metabolizers.  It is recommended that the alternate drug not be predominantly metabolized by CYP2D6 (eg. granisetron).	Poor metabolizer	Therapeutic recommendations: Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose. Classification of Recommendations: No recommendation
voriconazole	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166161537	case6	The CPIC dosing guideline for voriconazole recommends selecting an alternative agent that is not dependent on CYP2C19 metabolism in adults who are CYP2C19 ultrarapid metabolizers, rapid metabolizers or poor metabolizers. In pediatric patients, an alternative agent should be used in patients who are ultrarapid metabolizers or poor metabolizers. In pediatric rapid metabolizers, therapy should be initiated at recommended standard case dosing, then therapeutic dosing monitoring should be used to titrate dose to therapeutic trough concentrations.	Ultrarapid metabolizer (~2-5% of patients)	Therapeutic recommendations: 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 of Recommendations: Moderate
voriconazole	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166161537	case6	The CPIC dosing guideline for voriconazole recommends selecting an alternative agent that is not dependent on CYP2C19 metabolism in adults who are CYP2C19 ultrarapid metabolizers, rapid metabolizers or poor metabolizers. In pediatric patients, an alternative agent should be used in patients who are ultrarapid metabolizers or poor metabolizers. In pediatric rapid metabolizers, therapy should be initiated at recommended standard case dosing, then therapeutic dosing monitoring should be used to titrate dose to therapeutic trough concentrations.	Rapid metabolizer (~2-30% of patients)	Therapeutic recommendations: 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 of Recommendations: Moderate
voriconazole	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166161537	case6	The CPIC dosing guideline for voriconazole recommends selecting an alternative agent that is not dependent on CYP2C19 metabolism in adults who are CYP2C19 ultrarapid metabolizers, rapid metabolizers or poor metabolizers. In pediatric patients, an alternative agent should be used in patients who are ultrarapid metabolizers or poor metabolizers. In pediatric rapid metabolizers, therapy should be initiated at recommended standard case dosing, then therapeutic dosing monitoring should be used to titrate dose to therapeutic trough concentrations.	Normal metabolizer (~35-50% of patients)	Therapeutic recommendations: Initiate therapy with recommended standard of care dosing. Classification of Recommendations: Strong
voriconazole	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166161537	case6	The CPIC dosing guideline for voriconazole recommends selecting an alternative agent that is not dependent on CYP2C19 metabolism in adults who are CYP2C19 ultrarapid metabolizers, rapid metabolizers or poor metabolizers. In pediatric patients, an alternative agent should be used in patients who are ultrarapid metabolizers or poor metabolizers. In pediatric rapid metabolizers, therapy should be initiated at recommended standard case dosing, then therapeutic dosing monitoring should be used to titrate dose to therapeutic trough concentrations.	Intermediate metabolizer (~18-45% of patients)	Therapeutic recommendations: Initiate therapy with recommended standard of care dosing. Classification of Recommendations: Moderate
voriconazole	CYP2C19	https://pharmgkb.org/guidelineAnnotation/PA166161537	case6	The CPIC dosing guideline for voriconazole recommends selecting an alternative agent that is not dependent on CYP2C19 metabolism in adults who are CYP2C19 ultrarapid metabolizers, rapid metabolizers or poor metabolizers. In pediatric patients, an alternative agent should be used in patients who are ultrarapid metabolizers or poor metabolizers. In pediatric rapid metabolizers, therapy should be initiated at recommended standard case dosing, then therapeutic dosing monitoring should be used to titrate dose to therapeutic trough concentrations.	Poor metabolizer (~2-15% of patients)	Therapeutic recommendations: 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 of Recommendations: Moderate
