Moderate
clopidogrel × omeprazole
Antiplatelet agents – P2Y12 receptor inhibitors×Proton pump inhibitors
Mechanism
Omeprazole is a potent CYP2C19 inhibitor, the key enzyme for clopidogrel bioactivation. The active thiol metabolite concentration drops, weakening the antiplatelet effect. The FDA issued a black-box warning in 2010 about increased cardiovascular events on dual antiplatelet therapy.
Management
Avoid the combination. If gastric protection is needed, choose pantoprazole or rabeprazole (less CYP2C19 inhibition) or an H2-blocker (famotidine). Esomeprazole is as risky as omeprazole.
Sources
- FDA: FDA Drug Safety Communication: Reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug (2010)— FDA Drug Safety Communication, November 17, 2010
- COGENT Investigators: Clopidogrel with or without Omeprazole in Coronary Artery Disease (2010)— N Engl J Med 2010;363(20):1909–1917
- Lexicomp: Lexicomp Drug Interactions (2024)— Wolters Kluwer Clinical Drug Information, Inc. Lexi-Interact Online, 2024
- FDA: FDA Drug Safety Communication: Reduced effectiveness of Plavix in CYP2C19 poor metabolizers (2010)