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Title : Interaction between clopidogrel and proton pump inhibitors: A clinical overview
Authors : Jinesh B. Nagavi*, B.M. Gurupadayya
Abstract : Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown. Over recent years there has been much debate about whether some or all proton pump inhibitors might reduce the effectiveness of clopidogrel because of a drug interaction at the cytochrome P450 2C19 enzyme. Clopidogrel is a prodrug that is metabolized to an active form, and this process occur primarily via cytochrome P450 2C19. Proton pump inhibitors inhibit cytochrome P450 enzyme to varying degrees, and the studies showed that the combined use of clopidogrel with omeprazole or lansoprazole leads to reduction in activity of clopidogrel as measured by platelet aggregation and associated biomarkers. This suggests that there is a potentially important pharmacokinetic interaction between these drugs when used at therapeutic doses. Evidence to date has been conflicting; some studies have observed an increased risk of vascular events in patients receiving clopidogrel and proton pump inhibitors, while others, including an underpowered randomized trial, found no increased risk.

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