A combination of ibuprofen and acetaminophen can relieve chronic knee pain — including that caused by osteoarthritis — but at the cost of increased side effects, mainly GI bleeding.

Investigators conducted a randomized, double-blind trial to explore short-term (10-day) and long-term (13-week) benefits and side effects of four regimens, each taken t.i.d.: (1) ibuprofen 400 mg; (2) acetaminophen 1,000 mg; (3) one fixed-dose combination tablet of ibuprofen 200 mg and acetaminophen 500 mg; and (4) two fixed-dose combination tablets of ibuprofen 400 mg and acetaminophen 1,000 mg.

Of the 892 participants, 63% had radiographic knee osteoarthritis and 85% fulfilled American College of Rheumatology criteria for osteoarthritis. At day 10 of the study, the two-combination-tablet regimen proved to be superior to acetaminophen for pain relief. At 13 weeks, significantly more participants taking one or two combination tablets rated their treatment as excellent/good compared with those taking acetaminophen.

By 13 weeks, hemoglobin levels fell by at least 1 g/dL in some participants in all groups. The reduction occurred in twice as many participants taking two combination tablets compared with persons on monotherapy.

“Ibuprofen/[acetaminophen] combination analgesia, at nonprescription doses, confers modest short-term benefits for knee pain/osteoarthritis,” the authors concluded (Ann Rheum Dis. 2011;70:1534-1541). “In this population, [aceta­minophen] 3 g/day may cause similar degrees of blood loss as ibuprofen 1,200 mg/day, and the combination of the two appears to be additive.”