Literature Review

Literature Review: FDA: Early Communication about an Ongoing Safety Review of clopidogrel bisulfate (marketed as Plavix).

Peter R. McNally, DO, FACP, FACG
University of Colorado School of Medicine
Center for Human Simulation
Aurora, Colorado

VHJOE Editor:

John Deutsch, MD
St. Mary's Duluth Clinic

International Editor :

Manoop S. Bhutani, MD
MD Anderson Cancer Center
Houston, TX

Editorial Board:

William R. Brugge, MD
Massachusetts General Hospital

Peter R. McNally, DO
Denver, CO

Thomas J. Savides, MD
University of California,
San Diego

C. Mel Wilcox, MD
University of Alabama, Birmingham

NOTE: Included with the literature review on this page is a corresponding PowerPoint presentation of the review. Just click on the link to open the presentation.

Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study.

Gilard M, Arnaud B, Cornily JC, Le Gal G, Lacut K, Le Calvez G, Mansourati J, Mottier D, Abgrall JF, Boschat J.
J Am Coll Cardiol 2008;51:256-60.

Click here to open PowerPoint presentation

INTRODUCTION

In this edition of VHJOE, Literature in Review, we highlight the important FDA: Early Communication about an Ongoing Safety Review of clopidogrel bisulfate (marketed as Plavix). http://www.fda.gov/Cder/drug/early_comm/clopidogrel_bisulfate.htm

This widespread FDA communication warns of the potential serious drug interaction between clopidogrel and proton pump inhibitors (PPIs). Both of these medicines are “prodrugs” requiring hepatic metabolism for activation. Unfortunately, each medicine is metabolized through the same hepatic CYP450 pathway, and competitive inhibition by each leads to decreased activation for both. We have chosen the article by Gilard, et al, to review, because it offers an objective, readily available, and validated measurement (Platelet Reactivity Index, PRI) of this drug interaction and the significant increased risk of Acute Coronary Syndrome for persons simultaneously prescribed clopidogrel and omeprazole. The article by Gilard, et al, specifically examines the effect of omeprazole on the effect of clopidogrel on PRI, but can be extrapolated to evaluation of the effect of all available PPIs on the platelet inhibitor effects of clopidogrel.

References:

1. Frere C et al, Effect of cytochrome P450 polymorphisms on platelet reactivity after treatment with clopidogrel in acute coronary syndrome. Am J Cardiol 2008; 101:1088-93.
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2. Trenk et al. Cytochrome P450 2C19 681G A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug eluting or bare-metal stents. J Am Coll Cardiol 2008; 51: 1925-34. <PubMed>

3. Gilard M et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole Clopidogrel Aspirin) Study. J Am Coll Cardiol 2008: 51:256-60. <PubMed>

4. Gilard M et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated to aspirin. J Thromb Haemost 2006; 4:2508-9. <PubMed>

5. Small DS et al. Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. J Clin Pharmacol 2008; 48: 475-484. <PubMed>

6. Siller-Matula JM et al. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J 2009; 157:148e1-148.e5 <PubMed>