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Clopidogrel (Plavix) with Use of PPIs (Proton Pump Inhibitors)

Clopidogrel (Plavix) is a prodrug that is metabo- lized in the liver to the active form that inhibits platelet activation by cytochrome P450 CYP2C19. Proton pump inhibitors (PPIs) are also metabolized by CYP2C19. The matter of which patients should receive a PPI, in light of the potential interaction, is controversial. There is pre- liminary evidence to suggest that PPIs may reduce clopidogrel's antiplatelet effect. The results of the Clopidogrel Medco Outcomes Study found that patients taking both clopidogrel and proton pump inhibitors experienced a 50 % increase in the combined risk of hospitalization for heart attack, stroke, unstable angina, or repeat revascularization. Based on this study, it is recommended that health care providers evaluate patients for the continued need for PPI therapy and consider prescribing a hista- minergic (H2) blocker or antacids instead of PPIs con- comitantly with clopidogrel, considering the high risk for adverse events.

Prospective data from the Clopidogrel and the Opti- mization of Gastrointestinal Events [COGENT] study suggest that adding a PPI to clopidogrel does not increase the risk for cardiac events. Based on this data, experts suggest giving the doses of clopidogrel and PPI at different times of day might be a good idea. It concluded taking the PPI 30 minutes before breakfast and clopidogrel at night might be most convenient for patients. In conclusion, it does not appear that a single PPI is less likely than others to result in the potential inter- action. Omperazole, esomeprazole, pantoprazole and lansoprazole were each associated with 39-61% greater risk of a CV event vs. clopidogrel alone. The FDA has issued a safety bulletin regarding this issue and is working with manufacturers to design a pro- spective trial to assess the interaction. The VHA Pharmacy Benefits Management Services and the Medical Advisory Panel recommends that patients who are currently receiving therapy with a PPI and clopidogrel should be evaluated for the continued need for PPI therapy.


VHA Pharmacy Benefits Management Service. Clopidogrel Criteria for use. http://vaww.national.cmop.va.gov/PBM/default.aspx


Antoinet Moore, PharmD successfully passed the examination to become a Board Certified Geriatric Pharmacist (BCGP).

Robin Townsend, RPh obtained her Doctorate of Pharmacy Degree (PharmD).

Do Proton Pump Inhibitors Decrease Clopidogrel (Plavix) Activity? Pharmacist's Letter/Prescriber's Letter 2008;24(11):241114.

Rx List The Internet Drug Index (www.rxlist.com/ plavix- drug.htm )

SCAI Statement on “A National Study of the Effect of Individual Proton Pump Inhibitors on Cardiovascular Outcomes in Patients Treated with Clopidogrel Following Coronary Stenting: The Clopido- grel Medco Outcomes Study”

Bhatt D. The Clopidogrel and the Optimization of Gastrointestinal Events [COGENT]. Presented at Transcatheter Cardiovascular Therapeutics 2009, September 23, 2009, San Francisco, CA. [Abstract].

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    submitted by

Alison James, PharmD VA CBOCPerry

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