Co-administration of clopidogrel with omeprazole, a proton pump inhibitor that is an inhibitor of CYP2C19, reduces the pharmacological activity of clopidogrel if given concomitantly or if given 12 hrs apart. There is no evidence that other drugs that reduce stomach acid eg, most H2 blockers (except cimetidine, which is a CYP2C19 inhibitor) or antacids interfere with the antiplatelet activity of clopidogrel.
Aspirin: In clinical studies, aspirin did not modify the clopidogrel-mediated inhibition of ADP-induced platelet aggregation. Concomitant administration of aspirin 500 mg twice a day for 1 day did not significantly increase the prolongation of bleeding time induced by clopidogrel. Clopidogrel potentiated the effect of aspirin on collagen-induced platelet aggregation. Clopidogrel and aspirin have been administered together for up to 1 year.
Heparin: Co-administration of heparin had no effect on inhibition of platelet aggregation induced by clopidogrel.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): NSAIDs and clopidogrel should be co-administered with caution.
Warfarin: Because of the increased risk of bleeding, the concomitant administration of warfarin with clopidogrel should be undertaken with caution.
Other Concomitant Therapy: No clinically significant pharmacodynamic interactions were observed when clopidogrel was co-administered with atenolol, nifedipine or both atenolol and nifedipine. The pharmacodynamic activity of clopidogrel was also not significantly influenced by the co-administration of phenobarbital or estrogen.
The pharmacokinetics of digoxin or theophylline was not modified by the co-administration of clopidogrel bisulfate.
Clopidogrel is metabolized to its active metabolite in part by CYP2C19. Concomitant use of drugs that inhibit the activity of this enzyme results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition. Avoid concomitant use of drugs that inhibit CYP2C19, including omeprazole, esomeprazole, cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine and ticlopidine.