Significant, long-lasting pain relief in primary dysmenorrhea with low-dose naproxen sodium compared with acetaminophen: a double-blind, randomized, single-dose, crossover study.

Objectives: Many women experience menstrual cramps, which adversely affects quality-of-life. Both naproxen and acetaminophen are indicated to relieve menstrual pain. This study assessed the analgesic efficacy of a single, maximum non-prescription dose of naproxen sodium compared with that of acetaminophen in the treatment of primary dysmenorrhea. Methods: Healthy females with primary dysmenorrhea were included in our double-blind, randomized, crossover study (trial registration no. NCT03448536). When pain was moderate (≥5 on 0-10 numerical rating scale), subjects took a single dose of naproxen sodium (440 mg) and crossed over to acetaminophen (1000 mg) in the next cycle, or vice versa. Total pain relief over 12 h (TOTPAR0-12) was the primary outcome, while secondary outcomes included summed pain intensity differences (SPID) and TOTPAR scores throughout 12 h, and subject overall evaluation of treatment. Results: The per protocol population ( n  = 189) used naproxen sodium ( n  = 170) and acetaminophen ( n  = 160). TOTPAR0-12 was significantly greater with naproxen sodium than acetaminophen (least-squares (LS) mean difference = 4.31; p  < .001), and pain intensity was significantly lower (SPID0-12 LS mean difference = 9.80; p  < .001). Some measures of pain intensity favoring naproxen sodium became significant at earlier time points (e.g. SPID4-6 LS mean difference = 1.49; p  = .02). After 6 h post-dose, naproxen sodium was significantly more effective than acetaminophen, maintained for 12 h (SPID6-12 LS mean difference = 8.27; TOTPAR6-12 LS mean difference = 3.75; both p  < .001). Significantly more subjects rated naproxen sodium as good-to-excellent (70.6%) vs acetaminophen (63.1%) ( p  = .002). Conclusions: A single, maximum non-prescription dose of naproxen sodium was more effective than acetaminophen over 12 h.