Summit, N.J. – – September 11, 2026 -- A new over-the-counter pain reliever combining acetaminophen and naproxen sodium in a single pill has cleared two Phase 3 clinical trials, with data presented this week at the 20th Annual PAINWeek Conference in Las Vegas, running September 8-11, 2026.
TYLENOL with Naproxen pairs 650 mg of acetaminophen with 220 mg of naproxen sodium, a combination the FDA approved in July 2026 as the first and only OTC product of its kind. The formula starts working in under 30 minutes and delivers relief for up to 12 hours, according to Kenvue, the brand's parent company.
Trial data show the combo outperforms single-ingredient painkillers
In a Phase 3 study of patients with moderate-to-severe post-operative dental pain, the fixed-dose combination outperformed both acetaminophen alone and naproxen sodium alone (220 mg, comparable to Aleve) over a 12-hour period. It also relieved pain faster than naproxen sodium alone and lasted longer than acetaminophen alone.
Bunionectomy study cuts opioid rescue medication by nearly 40%
A separate Phase 3 trial tested the drug in patients recovering from bunionectomy surgery, a rigorous pain model typically used to evaluate prescription therapies. Compared with placebo, TYLENOL with Naproxen reduced total opioid rescue medication used over 48 hours by nearly 40%. Researchers say this marks the first time an OTC-intended pain medicine has been tested in this surgical pain model.
Earlier Phase 2 data found it beat a prescription opioid combo
A previously reported Phase 2 study in post-operative dental pain found that acetaminophen dosed alongside naproxen sodium provided more effective and longer-lasting relief than a hydrocodone-acetaminophen combination, an opioid-based prescription painkiller.
"Across these clinical studies, the fixed-dose combination consistently provided 12 hours of potent pain relief, in two distinct and well-validated pain models,