Drug Interactions Newsletter

Volume 1, Issue 24, 06/30/2009

Question

Are there any differences among the proton pump inhibitors (PPI) in their ability to inhibit the activation of clopidogrel (Plavix®) through the cytochrome P450 (CYP) enzyme system?

Answer

This is part 1 of a 3 part series related to the drug interaction between proton pump inhibitors (PPI) and clopidogrel (Plavix®).  This short series is important given the growing number of studies being done that have now revealed the impact that the PPI class of medications can have on the ability of clopidogrel to adequately inhibit platelet aggregation for the purposes of preventing stent thrombosis.(1-5)  The current PPIs on the market include dexlansoprazole (Kapidex®), esomeprazole (Nexium®), omeprazole (Prilosec®; Zegerid®), lansoprazole (Prevacid®), pantoprazole (Protonix®), and rabeprazole (AcipHex®),  Their influences on the metabolism of clopidogrel are reflected in figure 1 and influences on the cytochrome P450 (CYP) enzymes in the table below.(6-17) 

The use of both aspirin and clopidogrel are increasing due to their proven benefits in both primary and secondary prevention of cardiovascular disease (CVD) and now more importantly in patients who have received drug eluting stents.(18-20)  Unfortunately, this combination of antiplatelet drug therapy is also known to increase the patient's risk for clinically relevant gastrointestinal (GI) bleeding.(21)  The potential for this adverse event has become increasingly important since the publication of a position statement sponsored by the American Heart Association (AHA) stating that....

There is a figure outlining the mechanism for the drug interaction between PPIs and clopidogrel as well as a table available that outlines the CYP450 enzyme profile for all of the available PPIs.

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