FDA: Separate ibuprofen and aspirin
In September, the FDA distributed communication to health care providers related to a potential drug interaction between low-dose aspirin (81 mg daily) and ibuprofen. This interaction could render low-dose aspirin less effective as a cardioprotective agent in those requiring secondary prevention. Although there are not a lot of published data, there is sufficient information to warrant educating our patients about the need to separate the administration of these frequently used drugs.
The common mechanism of action for all NSAIDs is inhibition of the cyclooxygenase (COX) enzyme. There are two isoforms of COX: COX 1, which is found primarily in blood vessels, kidney and stomach, and COX 2, which is induced in the setting of inflammation. All over-the-counter NSAIDs inhibit both COX 1 and COX 2 to varying degrees. The anti-inflammatory and analgesic properties of NSAIDs are derived from COX-2 inhibition, and the common side effect properties (gastrointestinal bleeding) are derived from COX-1 inhibition.
Inhibition of COX-1 also prevents the formation of thromboxane from arachidonic acid, which ultimately prevents thromboxane-induced platelet aggregation. Aspirin irreversibly inhibits COX-1, and the cardioprotective effects of low-dose aspirin are a result of this antiplatelet activity. Other available NSAIDs have only reversible antiplatelet activity and therefore are not used for secondary prevention of cardiovascular events.
Available data nonconclusive
Since aspirin and ibuprofen both bind to similar and proximal areas of the COX enzyme, there is concern that taking these drugs together would diminish the desired antiplatelet activity of aspirin. Although there are no cardiovascular endpoint studies available, published and unpublished data available to the FDA indicate that a dose of ibuprofen 400 mg interferes with aspirins antiplatelet effect, as measured by thromboxane B2 levels and platelet activation studies.
This interference has been documented when ibuprofen was taken within 30 minutes after immediate release aspirin, and when a single dose of ibuprofen 400 mg was taken within eight hours before aspirin dosing. There are also data from a published multidose study indicating that when immediate release aspirin was taken at least one hour prior to ibuprofen 400 mg, three times daily, there was no thromboxane interaction. However when a similar experiment was conducted with enteric-coated low-dose aspirin, there was a thromboxane interaction.
Although the available data do not provide conclusive evidence related to ibuprofens interference with aspirins ability to protect against future cardiovascular events, heeding the FDA recommendation to separate low-dose aspirin and ibuprofen by at least 30 minutes is reasonable. Enteric-coated low-dose aspirin should be avoided in patients who use ibuprofen chronically.
Naproxen a problem, too?
Prior to the removal of selective COX-2 inhibitor rofecoxib (Vioxx, Merck) from the market in 2004, the prescription and OTC use of ibuprofen and other NSAIDs was fairly constant. Since then, based on data from IMS Healths Web site, prescription use of ibuprofen increased 10% (19 million prescriptions in 2005) and OTC sales of ibuprofen increased 9.6% in the last year to almost $56 million. OTC naproxen sodium sales increased 19% during the same period and totaled almost $15 million in the last year. There are limited data suggesting there may be a similar naproxen and low-dose aspirin interaction. Until additional data are available, similar caution should be taken when administering this combination.
Based on these data, plus recent data from the American Heart Association indicating that approximately 19 million people in the United States have either CHD or stroke and would be candidates for secondary prevention with low-dose aspirin, this drug interaction has the potential to affect a significant portion of the cardiovascular patient population.
Until additional data are available that unequivocally discount a drug interaction between low-dose aspirin and ibuprofen or naproxen sodium, the potential for an interaction should be considered. Although the clinical implications of this interaction are unclear at this time, patients should be cautioned about this interaction and should be educated to take their low-dose aspirin at least 30 minutes prior to their first daily dose of ibuprofen or other NSAID in the morning.
Rhonda Cooper-DeHoff, Pharm D, is Assistant Director of Clinical Programs and Research Assistant Professor in the Division of Cardiology at University of Florida College of Medicine, Gainesville. She is a member of Cardiology Todays Editorial Board.