Table 2.

Examples of clinically actionable variants in pharmacogenomics and evidence supporting use in practice

Drug/drug class	Gene/mutation	Clinical recommendation (approved indication, CPIC, FDA label)	Clinical endorsement(s)	Major supporting evidence
abacavir	HLA-B*5701	test all abacavir-naïve patients and avoid drug to prevent ADR (standard of care)	clinical guidelines,38, 39 CPIC, FDA label	RCT,52 retrospective and prospective associations, replication in multiple populations/ethnicities
allopurinol	HLA-B*5801	alternative drug recommendation	CPIC	retrospective associations, replication in multiple populations/ethnicities
carbamazepine	HLA-B*1502	alternative drug recommendation	FDA label, CPIC	retrospective associations, replication in multiple populations/single ethnic group
clopidogrel	CYP2C19*2/*3	alternative drug recommendation	FDA label and Boxed Warning, CPIC	retrospective and prospective associations, replication in multiple populations/ethnicitiesa
codeine	CYP2D6b	alternative drug/dose recommendation	FDA label, CPIC	retrospective and prospective associations, replication in multiple populations/ethnicities
simvastatin	SLCO1B1*5	alternative drug/dose recommendation	CPIC	Retrospective study,53 replication
tacrolimus	CYP3A5b	dose modification	-	retrospective and prospective associations, replication in multiple populations/ethnicities
thiopurinesc	TPMTb	modify dose based on genotype	clinical guidelines,54 CPIC, FDA label	retrospective and prospective associations, replication in multiple populations/ethnicities
tricyclic antidepressantsd	CYP2D6b CYP2C19b	dose modification or use avoidance	FDA label, CPIC	retrospective and prospective associations, replication in multiple populations/ethnicities
warfarin	CYP2C9 *2/*3 VKORC1 -1639G>A	Dose modification based on pharmacogenomic algorithm	FDA label, CPIC	retrospective and prospective associations, replication in multiple populations/ethnicitiesa

CLIA indicates Clinical Laboratory Improvement Amendments, CPIC Clinical Pharmacogenomics Implementation Consortium, FDA Food and Drug Administration, TPMT thiopurine methyltransferase.

^aRCT currently in progress

^bmultiple variants within gene are potentially clinically actionable for relevant drug(s)

^cinclude azathioprine, mercaptopurine, and thioguanine

^dapply primarily to amitriptyline and nortriptyline, but may be extrapolated to other tricyclic antidepressants