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CYP2C19 Genotype, Clopidogrel Metabolism, Platelet Function, and Cardiovascular Events, December 28, 2011, Holmes et al. 306 (24): 2704 � JAMA Genetic Epidemiology Group, Department of Epidemiology and Public Health, University College London, London, United Kingdom (Drs Holmes, Shah, Hingorani, and Casas); Faculty of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, London (Drs Perel and Casas); and Centre for Clinical Pharmacology, Division of Medicine, University College London (Drs Shah and Hingorani). Review: Proton pump inhibitor and clopidogrel interaction - NeLM Find key information about medicines by name (prototype) The authors conclude �the current evidence does not justify the conclusion that PPIs decrease the clinical efficacy of clopidogrel. Nonetheless, until further reliable data become available, wide separation of PPI and clopidogrel dosing should in theory minimise any potential, though unproven, clinical interaction between these two widely used medications.�Review Article: Combination of Clopidogrel and Proton Pump Inhibitors: Implications for Clinicians Loma Linda University School of Pharmacy and Loma Linda University Medical Center, Loma Linda, CA, USA 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 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.

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