Potential interaction of Proton Pump Inhibitors (PPIs) with Plavix (clopidogrel) - For the Public

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Contact: Marketed Health Products Directorate (MHPD)

The Health Products and Food Branch (HPFB) posts on the Health Canada web site safety alerts, public health advisories, press releases and other notices as a service to health professionals, consumers, and other interested parties. These advisories may be prepared with Directorates in the HPFB which includes pre-market and post-market areas as well as market authorization holders and other stakeholders. Although the HPFB grants market authorizations or licenses for therapeutic products, we do not endorse either the product or the company. Any questions regarding product information should be discussed with your health professional.

This is duplicated text of a letter from sanofi-aventis Canada Inc. and Bristol-Myers Squibb.
Contact the company for a copy of any references, attachments or enclosures.

PUBLIC COMMUNICATION
Health Canada Endorsed Important Safety Information on Plavix
(clopidogrel)

August 20, 2009

Subject: Potential drug interaction between Proton Pump Inhibitors (PPIs) and Plavix^® (clopidogrel)

Sanofi-aventis Canada Inc. and Bristol Myers Squibb Canada Co., in collaboration with Health Canada, would like to inform you of a potential drug interaction between proton pump inhibitors (PPIs) and Plavix^®. PPIs are used to treat stomach ulcers and heartburn and Plavix^® is used to prevent blood clots that could lead to life-threatening events such as heart attack or stroke. This update is due to recent reports in the scientific literature suggesting a potential interaction that may reduce the effect of Plavix^®.

The Canadian prescribing information for Plavix^® is being revised to provide doctors, pharmacists and patients with updated information regarding this potential interaction. Patients should discuss all their current medications with their healthcare professionals.

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of serious drug interaction with a PPI or other serious or unexpected adverse reactions in patients taking Plavix^® should be reported to sanofi-aventis Canada Inc. or Health Canada at the following addresses:

sanofi-aventis Canada Inc.
2150 St. Elzear Blvd. West
Laval, Quebec, H7L 4A8
Telephone: 1-800-265-7927

The Product Monograph (prescribing information) and a copy of this Important Safety Information can be accessed online at sanofi-aventis Canada Inc. and at Bristol-Myers Squibb Canada Co. Web sites.

Any suspected adverse reaction can also be reported to:
Canada Vigilance Program
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0701C
Ottawa, Ontario, K1A 0K9
Telephone: 613-957-0337 or Fax: 613-957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Telephone: 866-234-2345
Fax: 866-678-6789
CanadaVigilance@hc-sc.gc.ca

The Adverse Reaction Reporting Form and the Adverse Reaction Guidelines can be found on the Health Canada Web site or in The Canadian Compendium of Pharmaceuticals and Specialties.

For other inquiries related to this communication, please contact Health Canada at: Marketed Health Products Directorate (MHPD)
E-mail: mhpd_dpsc@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738

For media enquiries:
Christian Marcoux, Director of Communications
1-877-904-2667 or 514-904-2667

original signed by

Laurent-Didier Jacobs, M.D.
Vice President, Medical Affairs
sanofi-aventis Canada Inc

original signed by

H. Mitchell Shulman, MDCM, FRCPC, CSPQ
Vice President, Medical
Bristol-Myers Squibb Canada Co.

References:

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2. Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. Epub 2009 Jan 28. PubMed PMID: 19176635; PubMed Central PMCID: PMC2659819.
3. 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 Clopidogrel Medco Outcomes Study" accessed on 2009-07-18
4. Siller-Matula JM, Spiel AO, Lang IM, Kreiner G, Christ G, Jilma B. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J. 2009 Jan;157(1):148.e1-5. Epub 2008 Nov 6. PubMed PMID: 19081411.
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6. Sibbing D, Morath T, Stegherr J, Braun S, Vogt W, Hadamitzky M, Schömig A, Kastrati A, von Beckerath N. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost. 2009 Apr;101(4):714-9. PubMed PMID: 19350116.
7. Ho PM, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, Rumsfeld JS. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009 Mar 4;301(9):937-44. PubMed PMID: 19258584.