Omeprazole and Clopidogrel Interaction

Introduction to Concomitant Use

The American College of Cardiology Foundation, American College of Gastroenterology, and American Heart Association expert consensus acknowledges that pharmacokinetic and pharmacodynamic studies consistently show reduced antiplatelet effects with the strongest evidence for interaction being between omeprazole and clopidogrel, though they note the clinical translation remains uncertain 2, 1
A large Asian cohort study found patients on clopidogrel plus omeprazole had significantly higher risk of subsequent myocardial infarction compared to clopidogrel alone, with an adjusted hazard ratio of 2.03 1

The American College of Cardiology and American Heart Association guidelines specifically recommend non-CYP2C19-interfering proton pump inhibitors, such as pantoprazole or dexlansoprazole, when gastroprotection is needed with clopidogrel 4
Pantoprazole, dexlansoprazole, or lansoprazole are preferred alternatives as they have less pronounced effects on CYP2C19 and clopidogrel's antiplatelet activity compared to omeprazole or esomeprazole 3

If a patient has a history of upper gastrointestinal bleeding or multiple risk factors for gastrointestinal bleeding, proton pump inhibitors are recommended, particularly those at elevated bleeding risk, according to the American College of Cardiology and American Heart Association guidelines 2, 4
The American College of Cardiology and American Heart Association guidelines state that proton pump inhibitors reduce the risk of gastrointestinal bleeding among patients receiving dual antiplatelet therapy or oral anticoagulants 4