Concomitant use of low-dose aspirin and ibuprofen may interfere with aspirin's antiplatelet effects, possibly attenuating its cardioprotective benefits, according to a recent statement by the Food and Drug Administration's arm responsible for compiling adverse drug events.
“Platelet function tests suggest there is a pharmacodynamic interaction between 400 mg of ibuprofen and low-dose aspirin when they are dosed concomitantly,” the FDA wrote in a statement posted on its MedWatch Web site in September.
Experts stress, however, that virtually all nonsteroidal anti-inflammatory drugs have the potential to interfere with aspirin's cardioprotective effects. Compared with ibuprofen, there may be fewer data on the other NSAIDs, but “if physicians only pay attention to the FDA statement” they're likely to miss the potential effects of these other NSAIDs on aspirin's antiplatelet properties, said rheumatologist Dr. Roy Altman, of the University of California, Los Angeles.
The FDA's statement reinforces the importance of asking patients about over-the-counter drug usage. “Some colleagues may have let that mind-set go by the wayside,” said family physician Thomas A. Kintanar of Indiana University School of Medicine's Fort Wayne branch. It also doesn't hurt to focus on ibuprofen, which is one of the most widely used OTC drugs on the market.
Nevertheless, clinical studies have yet to be conducted to evaluate and quantify the inhibitory effect of ibuprofen on aspirin.
Nor are enough data available to address the effect of taking less than 400 mg of ibuprofen on aspirin's cardioprotective effects. And there are “no clear data” on the potential antiplatelet effects associated with the chronic use of ibuprofen at doses above 400 mg.
The FDA advised health care professionals to counsel patients taking immediate-release low-dose (81 mg) aspirin (not enteric coated) and 400 mg of ibuprofen to take the ibuprofen at least 8 hours before or at least 30 minutes after taking the aspirin to minimize the pharmacodynamic interaction. Other analgesics that do not interfere with aspirin's antiplatelet effects “should be considered” for patients at high risk for cardiovascular events. However, other nonselective, over-the-counter NSAIDs should also be considered as having the potential to affect the antiplatelet benefits of aspirin “unless proven otherwise.”
The recommendation on timing of the ibuprofen dose does not apply to patients taking enteric-coated low-dose aspirin, as such an advisement cannot be made based on the data available. Only one study showed that when 400 mg of ibuprofen is administered 2, 7, and 12 hours after enteric-coated low-dose aspirin, the antiplatelet effects are attenuated.
The mechanism underlying the aspirin-ibuprofen interaction may be due to “competitive inhibition of the acetylation site of cyclooxygenase in the platelet,” according to the FDA. Occasional use of ibuprofen, it said, is unlikely to have a negative impact on aspirin's cardioprotective effects because of the long-lasting effects of daily aspirin.
Dr. Raymond Gibbons, president of the American Heart Association (AHA), said in an interview that although the potential interaction between ibuprofen and aspirin has been recognized as a concern in the past, the advisory is a useful reminder to health care professionals about this issue.
These concerns are based on science that dates back to 2001, he said, adding that an AHA scientific advisory in the spring of 2005 on cyclooxygenase-2 inhibitors noted that data showed that ibuprofen interfered with aspirin and could possibly reduce the protective effects of aspirin.
He stressed the importance of the recommendation that analgesics that do not interfere with the antiplatelet effects of aspirin should be considered for high-risk patients. The data on ibuprofen are “far more suggestive of a problem” than, for example, data on acetaminophen or diclofenac, which are not associated with this risk, said Dr. Gibbons, the Albert M. and Gladys Gray professor of medicine at the Mayo Medical School, Rochester, Minn.
As for the recommendation on timing the ibuprofen and aspirin doses to avoid the interaction, Dr. Gibbons said he would be “cautious” about relying on appropriate timing, “because we don't have a tremendous amount of evidence in the presence of all the confounders” in patients. “I'd feel more comfortable if we emphasize the importance of this potential interaction and avoid ibuprofen in high-risk patients.”
Dr. Kintanar said he'd be comfortable allowing a compliant patient to follow the FDA's advice. However, it is rare to have that comfort level about a patient's level of compliance, he said.
For more information, go to www.fda.gov/medwatch/safety/2006/safety06.htm#aspirin
The warning reinforces the importance of asking patients about over-the-counter drug usage. DR. KINTANAR