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The antiplatelet drug clopidogrel (Plavix, and others) reduces major cardiovascular events, but can cause bleeding. Proton pump inhibitors (PPIs) are often used with clopidogrel to prevent gastrointestinal bleeding, however, some evidence suggests that PPIs may interfere with the activation of clopidogrel and diminish its antiplatelet effect.1 FDA-approved labeling recommends avoiding concurrent use of the PPIs omeprazole and esomeprazole with clopidogrel.
POSSIBLE MECHANISM — Clopidogrel is a prodrug; the CYP2C19 isozyme appears to be mainly responsible for its bioactivation.2 Concurrent use of clopidogrel and drugs that inhibit CYP2C19 could inhibit conversion of clopidogrel to its active form. Among the PPIs, omeprazole and esomeprazole appear to be the strongest inhibitors of CYP2C19 and pantoprazole appears to be the... more
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