Objective: To quantify the rate of adverse events reported with naproxen compared with placebo, ibuprofen and acetaminophen at non-prescription doses in multiple-dose, multi-day (7-10 days) duration clinical trials and further contribute towards current knowledge regarding the safety profile of naproxen. Methods: Safety data were retrospectively collected from eight randomized, controlled trials that included subjects exposed to a fixed dosing regimen of 220-750 mg naproxen per day over 7-10 days. All data on adverse events and their duration, severity and possible relationship to the study drug were taken from the clinical study reports. The data were used in a post-hoc pooled analysis of participants exposed to naproxen 220-750 mg/day (N = 1494) and grouped according to age (<65 and ≥65 years), daily dose, race and gender. Results: The safety profile of naproxen closely resembled that of placebo, with similar rates of adverse events across treatment groups as the active comparators. There was no dose effect of naproxen, and there were no differences in older versus younger participants. Most events were mild to moderate. The most frequently reported adverse events in all groups were related to the gastrointestinal system (most commonly dyspepsia with naproxen), with no differences between groups. Conclusions: Our pooled analysis did not find an increased risk of adverse events with short-term use of non-prescription doses of naproxen compared with placebo, or compared to other common analgesics.
Keywords: NSAID; Naproxen; non-prescription; randomized controlled trials; safety.