• Clopidogrel is a prodrug; requires activation by CYP enzyme system (principally by CYP2C19) to produce its pharmacologically active metabolite.
• Genetic variations of CYP2C19 can result in impaired metabolism and reduced effectiveness of clopidogrel. (See Reduced Efficacy Associated with Impaired CYP2C19 Function under Cautions.) Higher rates of major adverse cardiovascular events (e.g., death, MI, stroke) have been reported in poor metabolizers of CYP2C19 receiving clopidogrel at recommended dosages following acute coronary syndrome or PCI compared with those who have normal CYP2C19 function.
• Genetic tests are available to determine a patient's CYP2C19 genotype; results of such tests may be used to guide treatment decisions.
• Consider use of other antiplatelet agents or alternative dosing strategies for clopidogrel in patients with variant CYP2C19 genotypes.

REMS:

FDA approved a REMS for clopidogrel to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page ([Web]) or the ASHP REMS Resource Center ([Web]).