Review Article: Combination of Clopidogrel and Proton Pump Inhibitors: Implications for Clinicians

Abstract

Objectives: To evaluate the existing literature on a proposed interaction between clopidogrel and proton pump inhibitors (PPIs) and discuss its implications for clinicians treating patients with this combination therapy. Background: Each year millions of patients receive antiplatelet therapy. A number of these patients are prescribed PPIs concomitantly to reduce the risk of gastrointestinal side effects associated with antiplatelet therapy. Several studies have been published recently addressing a potential adverse drug-drug interaction between clopidogrel and PPIs. Methods: Literature was evaluated through Pubmed using the terms clopidogrel, PPI, prasugrel, cytochrome P450, genetic polymorphisms, H ₂ blockers, famotidine, genetic cytochrome P450 polymorphisms, and drug interaction. Articles with these terms were considered for evaluation. In addition, reference citations from publications identified in the searches were further reviewed and analyzed. Results: None of the currently published studies were specifically designed to evaluate this drug-drug interaction or address the clinical relevance of this interaction prospectively. Conflicting evidence raised concerns but the information did not conclude with certainty a cause-and-effect relationship between concomitant use of the drugs and emerging safety issues. However, the Food and Drug Administration issued a public-health warning on the possible interaction between clopidogrel and PPIs, predominantly with omeprazole, in November 2009. Conclusions: Controversies exist on a potential drug-drug interaction between clopidogrel and PPIs. Although further studies are warranted, several studies indicated that there was a drug-drug interaction through this combination therapy with detrimental clinical outcomes and increased costs. Studies suggested that the use of a PPI may make clopidogrel less effective resulting in a higher risk of myocardial infarction, stroke, or death. Until additional information becomes available clinicians should consider discontinuing PPI use if no clear indication is documented. Alternative options like H₂-receptor antagonists should be considered. Upon availability, genetic testing may provide additional valuable information.