Drug Interactions between clopidogrel and dexlansoprazole

Coadministration of clopidogrel with dexlansoprazole does not appear to significantly alter the systemic exposure to the active metabolite of clopidogrel or the drug's effect on platelet inhibition. The bioactivation of clopidogrel is mediated in part by CYP450 2C19. Since dexlansoprazole is also a substrate of CYP450 2C19, competitive inhibition could theoretically occur, which may lead to reduced formation of the active metabolite of clopidogrel and reduced therapeutic efficacy. In a study of 40 healthy subjects who were CYP450 2C19 extensive metabolizers, administration of clopidogrel 75 mg once daily in combination with dexlansoprazole 60 mg for 9 days resulted in an approximately 9% decrease in mean systemic exposure (AUC) to the active metabolite compared to administration of clopidogrel alone. Pharmacodynamic parameters were also measured and demonstrated that the change in inhibition of platelet aggregation (induced by 5 mcM ADP) was related to the change in exposure to clopidogrel active metabolite. The clinical significance of this finding is not clear. No dosage adjustment of clopidogrel is necessary when administered with an approved dosage of dexlansoprazole.