Drug Interaction between Clopidogrel and Proton Pump Inhibitors

Antiplatelet therapy using both clopidogrel and aspirin has been shown to reduce recurrent cardiac events in patients with acute coronary syndromes or in patients who have undergone coronary artery stent placement. Clopidogrel is a prodrug that is transformed in the liver to an active metabolite by cytochrome P450 enzyme. Due to the concern of bleeding in patients on both clopidogrel and aspirin therapy, concomitant prophylaxis of gastrointestinal ulcer with a proton pump inhibitor (PPI) is occasionally prescribed. Data from recent studies have shown that PPIs, which are extensively metabolized by the cytochrome system, may decrease the antiplatelet activity of clopidogrel. This article reviews the metabolism of various PPIs and existing data regarding the drug-drug interaction between PPIs and clopidogrel.