Table 2.

Literature Review Describing Interaction Between Aspirin and NSAIDs.

Authors	Method	Conclusions
Lawson et al33	Coadministration of aspirin 81 mg once daily with acetaminophen (1000 mg), ibuprofen (400 mg), diclofenac (75 mg), or rofecoxib (25 mg). The NSAIDs were administered either 2 hours before or 2 hours after the aspirin.	The concomitant administration of ibuprofen, but not rofecoxib, acetaminophen, or diclofenac antagonized the irreversible platelet inhibition induced by aspirin. The effect of ibuprofen could be bypassed by administering aspirin 2 hours before a single dose of ibuprofen; however, when multiple doses of ibuprofen were given, these competitive effects were seen.
MacDonald and Wei34	Review of an anonymous database for 7107 patients who received low-dose aspirin (<325 mg) alone, aspirin plus ibuprofen, aspirin plus diclofenac, aspirin plus other NSAID	Statistically and clinically significant increased risk of mortality in users of aspirin plus ibuprofen compared with users of aspirin alone. No such increased risk was noted in users of aspirin plus diclofenac or other NSAIDS.
Capone et al26	Interaction between aspirin 100 mg and naproxen 500 mg twice daily in healthy patients in vitro and ex vivo	Naproxen interfered with the irreversible inhibitory effect of aspirin on platelet COX-1. Naproxen combined with aspirin might undermine the sustained inhibition of platelet COX-1 necessary for cardioprotection by aspirin.
Gladding et al29	Interaction between aspirin 300 mg and naproxen, tiaprofenic acid, ibuprofen, indomethacin, sulindac, and celecoxib. NSAIDS were given 2 hours prior to the aspirin.	Ibuprofen, indomethacin, naproxen, or tiaprofenic acid all block the antiplatelet effect of aspirin. Sulindac and celecoxib did not demonstrate any significant antiplatelet effect or reduce the antiplatelet effect of aspirin.
Wilner et al30	Healthy volunteers received celecoxib (400 mg/d) or placebo for 4 days. On day 5, they also received a single 325 mg dose of aspirin with either 200 mg celecoxib or placebo.	There was also no significant difference in the effect of aspirin on platelet aggregation due to ADP, collagen, or arachidonic acid between the groups. Therefore, these data indicate that celecoxib does not alter the effects of aspirin on platelet function.
Renda et al31	Twenty-four patients who were undergoing long-term treatment with aspirin (100 mg daily) for cardioprotection were coadministered celecoxib 200 mg twice daily, ibuprofen 600 mg 3 times daily, or placebo for 7 days	Unlike ibuprofen, celecoxib did not interfere with the inhibition of platelet COX-1 activity and function by aspirin despite a comparable suppression of COX-2 ex vivo in patients with osteoarthritis and stable ischemic heart disease.
Rimon et al35	In vitro and in vivo analysis (in dogs) of the effect of celecoxib administered at 8 am and 5 pm with aspirin 81 mg administered at 12 pm	In vivo results indicated that celecoxib could interfere with the action of aspirin on COX-1 in vivo, and in the dog model, celecoxib did interfere with the effect of low-dose aspirin.
Saxena et al32	In vitro analysis in healthy volunteers. Aspirin either alone or in combination with ibuprofen, naproxen, oxaprozin, diclofenac, ketorolac, flufenamic acid, piroxicam, dipyrone, and celecoxib.	Ibuprofen, naproxen, oxaprozin, flufenamic acid, piroxicam, celecoxib, and dipyrone led to potent interference with the platelet inhibitory action of aspirin. Oxprazosin and celecoxib showed a decline of platelet aggregation at their highest concentrations. Ketorolac, diclofenac, and acetaminophen did not interfere with aspirin at all.
Ruzov et al36	Ex vivo interaction between celecoxib and aspirin for COX-1 binding and measured resulting antiplatelet effects. Data were then analyzed using PK/PD modeling to predict in vivo platelet aggregation for different doses and administration schedules for aspirin and celecoxib.	Celecoxib (100 mg twice daily) can attenuate to a limited extent the in vivo antiplatelet effects of low-dose aspirin. This interaction can be substantial during the first few days of aspirin initiation in patients already treated with celecoxib and cannot be prevented by separating administration times. However, at high doses celecoxib will compete efficiently with low-dose aspirin and may be mitigated by changing administration times.

Abbreviations: ADP, adenosine 5'-diphosphate; COX-1, cyclooxygenase 1; NSAIDs, nonsteroidal anti-inflammatory drugs; PK/PD, pharmacokinetics/pharmacodynamics.