Rofecoxib versus codeine/acetaminophen in postoperative dental pain: A double-blind, randomized, placebo- and active comparator-controlled clinical trial

Background: In recent studies of acute pain and primary dysmenorrhea, rofec oxib, a nonsteroidal anti-inflammatory drug that selectively targets the cy clooxyoenase-2 enzyme, was found to be similar in efficacy to ibuprofen and naproxen sodium. Objective: The purpose of this study was to determine the analgesic efficac y of a single oral dose of rofecoxib 50 mg compared with the combination of codeine 60 mg/acetaminophen 600 mg in a model of postsurgical dental pain. Methods: In this double-blind, placebo- and active comparator-controlled, p arallel-group study, patients experiencing moderate or severe pain after th e surgical extraction of greater than or equal to2 third molars, at least 1 of which was a mandibular impaction, were randomized to receive placebo, r ofecoxib 50 mg, or codeine 60 mg/acetaminophen 600 mg. Patient evaluations of pain intensity, pain relief, and global assessments were recorded throug hout the 24-hour period after dosing. The 2-stopwatch method was used to de termine time to confirmed perceptible pain relief. The primary end point as sessing overall analgesic effect was total pain relief over 6 hours (TOPAR6 ). Secondary end points were patient global assessment of response to thera py (PGART) at 6 hours, onset of analgesia, peak analgesic effect, and durat ion of analgesia. Results: A total of 393 patients were enrolled; 182 received rofecoxib, 180 received codeine/acetaminophen, and 31 received placebo. The overall analg esic effect of rofecoxib 50 mg was greater than that of codeine 60 mg/aceta minophen 600 mg for TOPAR6 (12.4 vs 7.0; P<0.001) and PGART at 6 hours (P<0 .001). The onset of analgesic effect was similar for rofecoxib and codeine/ acetaminophen. Peak analgesic effect as measured by peak pain relief scores during the first 6 hours was significantly greater in the rofecoxib group compared with the codeine/acetaminophen, group (P<0.001), as was the durati on of analgesic effect measured by the time to rescue analgesia (9.6 hours vs 2.3 hours, P<0.001). Adverse events were reported in 33.0%, 46.1%, and 3 2.3% of patients treated with rofecoxib, codeine/acetaminophen, and placebo , respectively. The most common adverse events were nausea (6.0%, 25.0%, an d 9.7%, respectively) and vomiting (3.8%, 18.3%, and 6.5%, respectively). S ignificantly more patients in the codeine/acetaminophen group than in the r ofecoxib group experienced adverse events overall (P<0.050) and nausea in p articular (P<0.001). Conclusion: In this study of moderate to severe postoperative dental pain, the analgesic efficacy of rofecoxib, 50 mg was greater than that of codeine /acetaminophen, with a lower incidence of adverse events and nausea.