Naproxen may interfere with aspirin benefit

NSAIDs should be administered short term until the parameters of safety for extended dosing are established.

Patients should stop taking naproxen if aspirin treatment has been recommended for cardioprotection.

“They should switch to another pain killer, such as acetaminophen or diclofenac, that does not interact with the irreversible inhibition of platelet COX-1 by aspirin,” Paola Patrignani, MD, professor of clinical pharmacology, Università “G. d’Annunzio” in Chieti, Italy, told Cardiology Today.

Naproxen may interfere with the persistent inhibition of platelet COX-1 activity and function by aspirin, an effect necessary for cardioprotection.

Uncertainty about the cardioprotective effects of nonaspirin nonsteroidal antiinflammatory drugs has encouraged physicians to combine these agents with aspirin in patients with both musculoskeletal disorders and vascular disease, researchers reported in the Journal of the American College of Cardiology.

Recent data, however, have shown that ibuprofen would inhibit the protective effects of aspirin, and researchers suspected the same interaction would be observed with naproxen.

Four patients in trial

Researchers recruited four healthy volunteers and assigned them 100 mg aspirin daily for six days. Combination treatment then began with a 100-mg dose of aspirin, followed two hours later by 500 mg naproxen twice a day.

After a 14-day washout period, the naproxen dose was assigned first, followed by the aspirin two hours later.

Serum TXB₂ production was measured and used as an index of platelet COX-1 activity. Aspirin use over the first six-day period caused a 99% inhibition of COX-1 activity and 95% inhibition of platelet aggregation that persisted up to 26 hours following the last dose.

Co-administration of single doses of the two drugs — 100 mg aspirin and 500 mg naproxen — caused a time-dependent inhibition of platelet COX-1 activity and function.

“Interestingly, at one hour after dosing, serum TXB₂ and platelet aggregation were not significantly affected (92% +/- 5% and 99% +/- 0.1% of pre-drug values, respectively), which suggests that naproxen concentrations lower than those inhibiting platelet COX-1 activity interfered with the irreversible inhibition of aspirin,” researchers wrote.

Undetectable effect

“This effect was undetectable during the continuous and regular administration of an antiinflammatory dose of naproxen and low-dose aspirin because naproxen can mimic the inhibitory effect of aspirin on platelet TXA₂ generation, Patrignani told Cardiology Today.

“However, this interaction indeed occurred, as suggested by the results obtained in vitro and after the administration with single doses of the two drugs.”

In fact, the pharmacodynamic interaction was confirmed by the rapid recovery of COX-1 activity and function. At 72 hours after dosing, serum TXB₂ and platelet aggregation values did not differ significantly from those assessed before or 14 days after treatment.

“Until the parameters of safety for extended dosing are established, all NSAIDs — selective and nonselective for COX-2 — should be administered for short periods of treatment,” Patrignani said. – by Jeremy Moore

For more information:

• Capone ML, Sciulli MG, Tacconelli S, et al. Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects. J Am Coll Cardiol. 2005;45:1295-301.