Efficacy and Safety of Single and Multiple Doses of a Fixed-dose Combination of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain Results From 2 Phase 3, Randomized, Parallel-group, Double-blind, Placebo-controlled Studies

Objectives: A previous pilot study demonstrated that various fixed-dose combinations (FDCs) of ibuprofen (IBU) and acetaminophen (APAP) provided analgesic efficacy comparable to a higher dose of IBU, with the same safety profile. These studies further evaluated the chosen FDC IBU/APAP 250/500 mg formulation. Materials and Methods: Two phase 3 dental pain studies enrolled healthy young patients with >= moderate pain after >= 3 third molar extractions who received single-dose FDC IBU/APAP 250/500 mg, IBU 250 mg, APAP 650 mg, or placebo evaluated over 12 hours (study 1) or multiple-dose FDC or placebo every 8 hours, evaluated over 48 hours (study 2). Time-weighted sum of pain intensity differences over 8 (SPID[11](0-8)) and 24 (SPID[11](0-24)) hours were primary outcomes, respectively. Time to meaningful pain relief and duration of pain relief were assessed; tolerability was evaluated by adverse events. Results: Five hundred sixty-eight patients were randomized in study 1; 123 in study 2. Study 1: SPID[11](0-8)favored FDC significantly over placebo, IBU, and APAP (P<0.001,P=0.008, andP<0.001, respectively); study 2: SPID[11](0-24)significantly favored FDC over placebo (P<0.001), with sustained efficacy during multiple dosing. Time to meaningful pain relief occurred within 1 hour; pain relief duration was >8 hours in both studies. Adverse event rates were lowest with the FDC. Discussion: FDC IBU/APAP 250/500 mg provides superior analgesic efficacy to individual monocomponents (IBU 250 mg and APAP 650 mg), a rapid onset of action, >8-hour duration of pain relief, is generally well tolerated, and may provide an additional nonopioid treatment option for acute pain.