Concomitant Use of Ibuprofen and Aspirin

Maria Marzella Sulli, Pharm.D.

Daily aspirin therapy has been proven to prevent heart attacks, strokes, and other types of thromboses in patients with a previous history or in those at high risk for these events. The high prevalence of heart disease, combined with the fact that aspirin is widely available and inexpensive, makes it one of the most commonly used chronic medications. Millions of people take a daily aspirin to protect their heart. As with any medication, aspirin therapy does not come without risks, most notably the risk of bleeding. Several factors influence the effectiveness of aspirin to prevent blood clots, heart attacks, and strokes including adherence to the medication. One study found that the risk of recurrent stroke was about three times higher in the first four weeks following discontinuation of aspirin therapy.1 Aspirin and other NSAIDS are nonselective inhibitors of the enzyme cyclooxygenase (COX). There are two forms of COX in the body; COX-1 is found in the blood vessels, stomach, and kidneys and COX-2 is found wherever inflammation is present. Aspirin works to prevent blood clots by irreversibly inhibiting the enzyme COX-1. By inhibiting COX-1, it prevents the formation of thromboxane from arachidonic acid. Thromboxane induces platelet aggregation, and therefore aspirin inhibits platelet aggregation. The irreversible manner by which it inhibits COX-1 is unique to aspirin. Other non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX-1, but do so reversibly, so the inhibition only lasts as long as the effect of the drug. The irreversible binding of aspirin allows for lower, once-daily doses of the medication to be effective for prevention of blood clots. Inhibition of the COX enzyme is competitive, so it becomes an issue of “whoever gets there first.” Once aspirin inhibits COX-1, the inhibition lasts for the life of the platelet. If another NSAID wins the race to binding site and blocks aspirin from binding, the inhibition will be short-lived. Several studies have documented this interaction; however, there is controversy over its clinical implications.2 On September 8, 2006, the FDA released the Science Paper on Concomitant Use of Ibuprofen and Aspirin: Potential for Attenuation of the Anti-Platelet Effect of Aspirin, describing the interaction and providing recommendations for patients.3 The FDA recommends that patients be counseled to take their non-enteric-coated aspirin tablets 30 minutes before ibuprofen or 8 hours after their aspirin to preserve the antiplatelet effect of aspirin. However, several questions still remain. For example, patients are advised to separate doses of their aspirin and ibuprofen until more is known about the clinical significance of the interaction, but it is unclear how to avoid the interaction in patients taking enteric-coated aspirin tablets, the most common form used to prevent heart disease. One study showed an interaction with enteric-coated aspirin even when the ibuprofen was dosed 12 hours after the aspirin.4 It is unlikely that single, infrequent doses of ibuprofen have clinical significance, but patients should be advised to avoid the chronic use of ibuprofen for pain. Although evidence is lacking for NSAIDs other than ibuprofen, they may interact as well, as COX-1 inhibition is universal for NSAIDs. Pharmacists need to inform patients of the potential for the interaction and advise them accordingly. Patients may wish to use acetaminophen for the treatment of chronic pain, such as pain from osteoarthritis, particularly if they are at high risk for cardiovascular events. This potential interaction is yet another opportunity for pharmacists to talk with their patients about self-care. It is essential that pharmacists discuss the use of all over-the-counter products with their patients, and document the counseling in the patient profile. If we do not, we are missing an opportunity to make interventions that could potentially save a life. References: 1. Maulaz AB, Bezerra DC, Michel P, Bogousslavsky J. Effect of discontinuing aspirin therapy on the risk of brain ischemic stroke. Arch Neurol. 2005;62(8):1217-20. 2. Cheema AA. Should people on aspirin avoid Ibuprofen? A review of the literature. Cardiol Rev. 2004;12:174-6. 3. FDA. Science Paper on Concomitant Use of Ibuprofen and Aspirin: Potential for Attenuation of the Anti-Platelet Effect of Aspirin. http://www.fda.gov/cder/drug/infopage/ibuprofen/science_paper.htm Accessed: December 1, 2006. 4. Catella-Lawson et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. NEJM 2001; 345: 1809-17. 5. Patel TN and Goldberg KC. Use of Aspirin and Ibuprofen Compared With Aspirin Alone and the Risk of Myocardial Infarction. Arch Intern Med. 2004;164:852-6. Return to Top