The FDA is aware of published reports that clopidogrel (marketed as Plavix) is less effective in some patients than it is in others. Differences in effectiveness may be due to genetic differences in the way the body metabolizes clopidogrel, or that using certain other drugs with clopidogrel can interfere with how the body metabolizes clopidogrel.

Clopidogrel is an antiplatelet drug that is used to prevent blood clots that could lead to heart attacks or strokes in patients at risk for these problems. The drug clopidogrel is a “pro-drug” which means that it has to be metabolized by the body before it can be biologically active and have the effect of preventing blood clots. Understanding that there are differences in how the body metabolizes clopidogrel and there are effects that other drugs may have on its metabolism is important because decreases in the effectiveness of clopidogrel might be avoided, in part, by using other drugs with clopidogrel that do not interfere with its metabolism.

One class of drugs commonly used with clopidogrel is proton pump inhibitors (PPIs). Some reports suggest that use of certain PPIs may make clopidogrel less effective by inhibiting the enzyme that converts clopidogrel to the active form of the drug. Other reports do not suggest this effect. Proton pump inhibitors decrease stomach acid and are used to treat frequent heartburn and stomach ulcers. Clopidogrel can irritate the stomach so PPIs are commonly used with clopidogrel to help reduce this irritation.

PPIs include omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole. The FDA note that they have no evidence that H2 blockers, such have ranitidine, or antacids have a similar effect, and are currently conducting a review with manufacturers. in the interim they have suggested the following:

• Healthcare providers should continue to prescribe and patients should continue to take clopidogrel as directed, because clopidogrel has demonstrated benefits in preventing blood clots that could lead to a heart attack or stroke.
• Healthcare providers should re-evaluate the need for starting or continuing treatment with a PPI, including Prilosec OTC, in patients taking clopidogrel.
• Patients taking clopidogrel should consult with their healthcare provider if they are currently taking or considering taking a PPI, including Prilosec OTC.

EMEA public statement