The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
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Concerns on Drug Interactions between Proton Pump Inhibitors and Clopidogrel: Unsafe Perspective

항혈소판제제와 프로톤펌프억제제 간의 약물 상호 작용: Unsafe 측면과 대책

  • Lee, Kyoung-Hoon (Division of Cardiology, Department of Internal Medicine, Gachon University of Medicine and Science) ;
  • Han, Seung-Hwan (Division of Cardiology, Department of Internal Medicine, Gachon University of Medicine and Science)
  • 이경훈 (가천의과학대학교 의학전문대학원 내과학교실 심장내과) ;
  • 한승환 (가천의과학대학교 의학전문대학원 내과학교실 심장내과)
  • Published : 2011.07.01
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Abstract

Clopidogrel is a prodrug that is converted in the liver to an active thiol metabolite, which irreversibly inhibits the platelet $P2Y_{12}$ 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 $P2Y_{12}$ 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.

Keywords

References

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