Table 2. Examples of drug label recommendations

Gene	Example drugs	Effect of polymorphism	Regulatory recommendation
*CYP2C19*	Clopidogrel	Reduced metabolism of clopidogrel, lower exposure to active metabolite and, thus, higher cardiovascular risk	Warning of potential effect; consider alternative treatment
	Voriconazole	Reduced metabolism of voriconazole, thus increased drug exposure	Warning of potential effect
*CYP2C9*	Warfarin	Reduced metabolism resulting in higher bleeding risk	Warning of potential effect; reduced dose may be required
*CYP2D6*	Codeine	Leads to ultra-rapid metabolism to active metabolite	Warning of potential effect; use lowest effective dose
	Tamoxifen	Poor metabolisers have higher plasma concentrations	Warning of potential effect
*EGFR*	Gefitinib	Effectiveness depends on EGFR status of tumour in nonsmall cell lung cancer	Tumour profiling to guide therapy
	Erlotinib
*ELM4-ALK*	Crizotinib	Effectiveness depends on ELM4-ALK status of tumour in nonsmall cell lung cancer	Tumour profiling to guide therapy
*G6PD*	Rasburicase	G6PD deficiency leads to severe haemolysis with several drugs	Screen patients in high-risk ethnic groups to exclude risk genotype before commencement
*HER 2*	Trastuzimab	Effect depends on HER2 expression levels in breast cancer	Screen for HER2 expression before treatment
**HLA-B1502***	Carbamazepine	Greatly increased risk of severe dermatological hypersensitivity reaction	Screen patients in high-risk ethnic groups to exclude genotype before commencement
	Abacavir	Greatly increased risk of generalised hypersensitivity reaction	Screen all patients prior to drug commencement
*LDLR*	Atorvastatin	LDL receptor deficiency or absence leads to familial hypercholesterolaemia	Dose adjustments in genetic risk groups
*NAT*	Rifampicin	Slow metabolism and greater drug exposure	Warning of potential effect
*TPMT*	Azathioprine	Slower metabolism and greater resultant risk of myelotoxicity	Screen all patients prior to drug commencement
*UGT1A1*	Irinotecan	Reduced metabolism and increased neutropenia risk	Reduce initial dose in those known to be homozygous for UGT1A*28
	Nilotinib	Exacerbation of jaundice caused by drug	Warning of potential effects
Urea cycle disorders	Valproate	Six potential culprit genes	Evaluate for UCD before commencement
*VKORC1*	Warfarin	SNPs associated with lower dose requirements	Warning of potential effects

EGFR: epidermal growth factor receptor; LDL: low-density lipoprotein; UCD: urea cycle disorders; SNP: single nucleotide polymorphism. Adapted from [16].