MedGen

Clopidogrel is a thienopyridine antiplatelet agent that prevents platelet activation and aggregation by irreversibly inhibiting the P2Y12 ADP receptors. As a prodrug, clopidogrel requires hepatic biotransformation to form an active metabolite. This conversion is composed of two sequential oxidative steps, which involve cytochrome P450-2C19 (CYP2C19) and other enzymes. Genetic variants in CYP2C19, along with other genetic and non-genetic factors, are known to influence variability in clopidogrel response. Specific CYP2C19 variants impair formation of active clopidogrel metabolites, which results in reduced platelet inhibition. CYP2C19 intermediate and poor metabolizers who receive clopidogrel experience an increased risk for major adverse cardiovascular and cerebrovascular events. Therapeutic recommendations for clopidogrel based on an individual’s CYP2C19 genotype have been published by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the 2022 guideline update includes new recommendations for CYP2C19 genotype-guided antiplatelet therapy. [from PharmGKB]