Do Aspirin and Ibuprofen Interact?

Joanna M. Pangilinan, PharmD, BCOP


August 08, 2014


How does aspirin interact with ibuprofen? What are alternatives to ibuprofen?

Response from Joanna M. Pangilinan, PharmD, BCOP
Pharmacist, Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan

In 2006, the US Food and Drug Administration (FDA) alerted healthcare professionals about the potential for ibuprofen to interfere with the antiplatelet effect of low-dose aspirin (81 mg daily). Ibuprofen (a reversible inhibitor) may interact with aspirin (an irreversible inhibitor) by competitive inhibition of the acetylation site of platelet cyclooxygenase (COX). As ibuprofen and aspirin occupy nearby sites on COX, ibuprofen may prevent access and binding of aspirin. Consequently, irreversible inhibition of thromboxane B2 production by aspirin and inhibition of platelet aggregation may be reduced.[1]

Risks With Other NSAIDs

What are the risks with other nonsteroidal anti-inflammatory drugs (NSAIDs)? Data are conflicting.

Studies evaluated ex vivo antiplatelet effects of commonly prescribed NSAIDs in combination with aspirin. Ibuprofen, indomethacin, and naproxen were found to interfere with the antiplatelet effect of aspirin.[2]Celecoxib, sulindac,[2] and meloxicam[3] were found not to interfere with aspirin.

The effect of NSAIDs on antiplatelet activity of aspirin was evaluated in donor plasma. NSAIDs including, but not limited to, celecoxib, ibuprofen, naproxen, oxaprozin, and piroxicam interfered with the antiplatelet effect of aspirin. Diclofenac, ketorolac, and acetaminophen did not.[4]

Another study measured thromboxane B2 production in patients taking 80 mg aspirin daily and concomitant ibuprofen (800 mg, 3 times daily) or diclofenac (50 mg, 3 times daily) for 7 days. Aspirin 30 mg, the lowest dose with thromboprophylactic effects, was used as a reference. Thromboxane B2 level inhibition associated with diclofenac was 98.1%, whereas inhibition with ibuprofen was 86.6%. Inhibition associated with ibuprofen/aspirin resulted in a level less than that produced by 30 mg of aspirin.[5]

Timing Considerations

How does administration timing affect the interaction? Research evaluating in vitro antiplatelet effects of NSAIDs and aspirin found that the antiplatelet effect of aspirin was significantly reduced when aspirin was taken after ibuprofen or mefenamic acid. The effect was not reduced when aspirin was taken before.[6]

A pharmacokinetics/pharmacodynamics model was used to predict the time-dependent interaction of aspirin with ibuprofen. The antiplatelet effect of aspirin 81 mg was predicted not to be decreased when ibuprofen 200 mg was administered over 2 hours after aspirin. However, the antiplatelet effect was predicted to be markedly reduced when ibuprofen was administered up to 12 hours before aspirin. The antiplatelet effect of aspirin was predicted to be reduced upon repeated coadministration of ibuprofen 3 times daily.[7]

The FDA recommends that single-dose ibuprofen 400 mg should be taken over 8 hours before or at least 30 minutes after immediate-release aspirin.[1] Timing recommendations are not available for coadministration of ibuprofen and enteric-coated aspirin. Finally, occasional ibuprofen use is not expected to decrease cardioprotective effects of daily low-dose aspirin.[1]


According to Horn and Hansten[8]:

  • Expect that ibuprofen can decrease the efficacy of aspirin.

  • Avoid ibuprofen if possible or give it 2 hours after aspirin.

  • Consider that the interaction may be unavoidable if ibuprofen is administered more than once daily.

  • Avoid celecoxib, naproxen, and indomethacin if possible because of the potential for an interaction with aspirin.

  • Evidence suggests that acetaminophen, diclofenac, sulindac, and meloxicam may not interact.

An alternative to ibuprofen should be considered for patients requiring low-dose aspirin for cardioprotection. However, some NSAIDs may be associated with increased cardiovascular risk, making determination of an alternative even more challenging. Patients taking low-dose aspirin should be instructed to avoid over-the-counter use of ibuprofen unless directed to do so by their healthcare professional.


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