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, rofecoxib, a nonsteroidal anti-inflammatory drug that selectively targets the cyclooxygenase-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 efficacy 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, parallel-group study, patients experiencing moderate or severe pain after the surgical extraction of > or = 2 third molars, at least 1 of which was a mandibular impaction, were randomized to receive placebo, rofecoxib 50 mg, or codeine 60 mg/acetaminophen 600 mg. Patient evaluations of pain intensity, pain relief, and global assessments were recorded throughout the 24-hour period after dosing. The 2-stopwatch method was used to determine time to confirmed perceptible pain relief. The primary end point assessing overall analgesic effect was total pain relief over 6 hours (TOPAR6). Secondary end points were patient global assessment of response to therapy (PGART) at 6 hours, onset of analgesia, peak analgesic effect, and duration of analgesia.


RESULTS
A total of 393 patients were enrolled; 182 received rofecoxib, 180 received codeine/acetaminophen, and 31 received placebo. The overall analgesic effect of rofecoxib 50 mg was greater than that of codeine 60 mg/acetaminophen 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 duration 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 32.3% of patients treated with rofecoxib, codeine/acetaminophen, and placebo, respectively. The most common adverse events were nausea (6.0%, 25.0%, and 9.7%, respectively) and vomiting (3.8%, 18.3%, and 6.5%, respectively). Significantly more patients in the codeine/acetaminophen group than in the rofecoxib group experienced adverse events overall (P < 0.050) and nausea in particular (P < 0.001).


CONCLUSIONS
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.
Chang
D J
DJ
Merck & Co, Inc, West Point, Pennsylvania 19486-0004, USA. david_chang@merck.com
Fricke
J R
JR
Bird
S R
SR
Bohidar
N R
NR
Dobbins
T W
TW
Geba
G P
GP
D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003061:Codeine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000627:therapeutic use*; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D013450:Sulfones; D013997:Time Factors; D014081:Tooth Extraction; D016896:Treatment Outcome
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D000082:Acetaminophen; D006853:Hydrocodone; D003061:Codeine