Drug–Drug Interaction Between Clopidogrel and the Proton Pump Inhibitors

OBJECTIVE: To evaluate the interaction between clopidogrel and proton pump inhibitors (PPIs). DATA SOURCES: Literature retrieval was accessed through PubMed (1980-January 2009), abstracts from 2008 American Heart Association and 2009 Society of Cardiovascular Angiography and Interventions Scientific Sessions, and media press releases using the terms clopidogrel, proton pump inhibitors, cytochrome 2C19, genetic cytochrome P450 polymorphisms, and drug interaction. In addition, reference citations from publications identified in the search were reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant original research articles and review articles were evaluated. Articles were selected if they were published in English and focused on any of the key words or appeared to have substantial content addressing the drug interaction. DATA SYNTHESIS: Recent attention has been placed on a potential interaction observed between clopidogrel and the widely used PPIs. Preliminary evidence suggests that omeprazole interacts with clopidogrel, reducing clopidogrel's antiplatelet effects as measured by various laboratory tests. Most data indicate that the interaction involves the competitive inhibition of the CYP2C19 isoenzyme. The interaction appears to be clinically significant, as several retrospective analyses have shown an increase in adverse cardiovascular outcomes when PPIs and clopidogrel are used concomitantly. However, this may not be a class effect. CONCLUSIONS: Available data suggest that omeprazole is the PPI most likely to have a significant interaction with clopidogrel. Further studies are needed to determine that an interaction between the other PPIs and clopidogrel does not exist. In situations in which both clopidogrel and a PPI are indicated, pantoprazole should be used since it is the PPI least likely to interact with clopidogrel.