Table 1.

Selected Guidelines from the Clinical Pharmacogenetics Implementation Consortium

Drug	Gene	Risk variant alleles or genotypes	Recommendation
allopurinol62,63	HLA-B	HLA-B*58:01	Contraindicated in individuals with one or more HLA-B*58:01 variant alleles due to increased risk of allopurinol-induced severe cutaneous adverse reaction.
azathioprine64,65	TPMT	Intermediate enzyme activity- *1/*2, *1/*3A, *1/*3B, *1/*3C, *1/*4.	Intermediate activity - start at 30–70% of target dose.
		Low or deficient enzyme activity *3A/*3A, *2/*3A, *3C/*3A, *3C/*4, *3C/*2, *3A/*4.	Low or deficient - consider an alternate agent or extreme dose reduction of azathioprine.
clopidogrel66,67	CYP2C19	Intermediate metabolizer *1/*2, *1/*3, *2/*17 (~18–45% of patients)	Intermediate or poor activity - alternative antiplatelet therapy (if no contraindication); e.g., prasugrel, ticagrelor.
		Poor metabolizer *2/*2, *2/*3, *3/*3 (~2–15% of patients)
citalopram/escitalopram68	CYP2C19	Ultrarapid metabolizer *17/*17, *1/*17 (~5–30% of patients).	Ultra-rapid - Consider an alternative drug not predominantly metabolized by CYP2C19.
		Poor metabolizer *2/*2, *2/*3, *3/*3 (~2–15% of patients).	Poor - Consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19.
phenytoin69	HLA-B	HLA-B*15:02	Increased risk of phenytoin- induced SJS/TEN in individuals with one or more alleles.
phenytoin69	CYP2C9	Intermediate metabolizer *1/*3, *1/*2 (~8% of patients)	Intermediate - consider 25% reduction of recommended starting maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring and response.
		Poor metabolizer *2/*2, *3/*3, *2/*3 (~1% of patients)	Poor - Consider 50% reduction of recommended starting maintenance dose. Subsequent maintenance doses should be adjusted according to therapeutic drug monitoring and response.
simvastatin70,71	SLCO1B1	Intermediate function *1a/*5, *1a/*15, *1a/*17, *1b/*5, *1b/*15, *1b/*17.	Intermediate myopathy risk, prescribe a lower dose or consider an alternative statin (e.g. pravastatin or rosuvastatin); consider routine CK surveillance.
		Low function *5/*5, *5/*15, *5/*17, *15/*15, *15/*17, *17/*17	High myopathy risk, prescribe a lower dose or consider an alternative statin (e.g. pravastatin or rosuvastatin); consider routine CK surveillance.
tacrolimus61	CYP3A5	Extensive metabolizer *1/*1	Extensive or intermediate - 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.
		Intermediate metabolizer *1/*3, *1/*6, *1/*7
voriconazole72	CYP2C19	Ultrarapid metabolizer *17/*17 (~2–5% of patients).	Ultrarapid and rapid at risk for low blood concentrations. 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.
		Rapid metabolizer *1/*17 (~2–30% of patients).
		Poor metabolizer *2/*2, *2/*3, *3/*3 (~2–15% of patients).	Poor metabolizer are at risk for adverse events. 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.