Korean J Med.  2011 Jul;81(1):34-39.

Concerns on Drug Interactions between Proton Pump Inhibitors and Clopidogrel: Unsafe Perspective

  • 1Division of Cardiology, Department of Internal Medicine, Gachon University of Medicine and Science, Incheon, Korea. shhan@gilhospital.com


Clopidogrel is a prodrug that is converted in the liver to an active thiol metabolite, which irreversibly inhibits the platelet P2Y12 adenosine diphosphate receptor. This mechanism requires cytochrome P450 2C19 (CYP 2C19) enzyme. Proton pump inhibitors (PPIs) competes against CYP 2C19 and inhibits the conversion of clopidogrel into its active metabolite, therefore, clopidogrel-PPIs drugs interaction may exist. These interactions could result in competitive inhibition decreasing the conversion of the clopidogrel pro-drug to the active metabolite and could potentially translate into an increased risk for cardiovascular events by inadequate platelet P2Y12 receptor inhibition. Many studies including retrospective cohort studies and studies using platelet function tests demonstrated the possible interactions between clopidogrel and PPIs leading to a decrease in the antiplatelet efficacy of clopidogrel and worse cardiovascular clinical outcomes than clopidogrel alone. In contrast, few comparative trials using clinical outcomes found no serious drug interactions between them. In this review, we introduce possible harmful effects of combined use of clopidogrel and PPIs on platelet function. In addition, we suggest how to overcome clopidogrel-PPIs interactions.


Clopidogrel; Proton pump inhibitor; Drug interactions
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