US FDA warns against use of PPI Prilosec with Plavix

Article | 18 November 2009

The US Food and Drug Administration has notified health care professionals of what it says is new safety information concerning an interaction between clopidogrel (Plavix), an anti-clotting medication, and omeprazole (Prilosec/Prilosec OTC), a proton pump inhibitor (PPI) used to reduce stomach acid. New data show that when clopidogrel and omeprazole are taken together, the effectiveness of clopidogrel is reduced by almost half; the effectiveness of clopidogrel is reduced by 45% with the effect of the drug on platelets reduced by as much as 47%.

Global sales of the antiplatelet agent Plavix, the world’s second biggest selling drug after Pfizer’s cholesterol lowerer Lipitor (atorvastatin), rose 17% last year to $9.5 billion. The drug is co-marketed by drug majors Sanofi-Aventis of France and the USA’s Bristol-Myers Squibb. Procter & Gamble's Prilosec OTC is available over-the-counter, while AstraZeneca's Nexium (esomeprazole) is only available with a prescription. Heartburn drugs are sometimes recommended to ease digestive side effects of Plavix, and regulators began probing the safety of the combination in January.

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“Bristol-Myers Squibb and Sanofi are continuing to conduct research on this topic and will provide updates as soon as they become available,” said Laura Hortas, a spokeswoman for B-MS, in a phone interview with Bloomberg. “The goal of the research is to provide information on specific factors that may affect patients’ response to Plavix,” she added.

The FDA stated that patients at risk for heart attacks or strokes who use clopidogrel to prevent blood clots will not get the full effect of this medicine if they are also taking omeprazole. Separating the dose of clopidogrel and omeprazole in time will not reduce this drug interaction.

Other drugs that are expected to have a similar effect and should be avoided in combination with clopidogrel, according to the regulatory agency, include: cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine and ticlopidine.

WBB Securities analyst Steven Brozak said the news would put pressure on Paris-based Sanofi and New York-based B-MS to provide more safety data on their best-selling product, reported The Associated Press. "This is going to create a chain reaction as patients start calling their physicians, and they are forced to make a spot decision on limited information. That's not gonna help either company's bottom line," he opined.

ACC/AHC question data novelty

Responding to the FDA announcement, the American College of Cardiology and American Heart Association argued that the data are not yet peer-reviewed and published. Moreover, they say that the FDA's statement is not based on any new published, peer-reviewed clinical trials showing changes in cardiovascular outcomes.

Clopidogrel is often prescribed to people who have chest pain, have had a heart attack or undergone an artery-opening procedure such as angioplasty or stenting. Effective anti-clotting therapy is proven to reduce the risk of another heart event, the associations explained. Since clopidogrel can cause bleeding in the stomach, medications like omeprazole may be used in combination to reduce stomach acid and prevent stomach bleeding, they noted.