Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen inthe treatment of pain after ambulatory orthopedic surgery in adults

Background: Current outpatient management of postoperative pain includes th e use of oral opioid analgesics or nonsteroidal anti-inflammatory drugs; ho wever, both types of medications are associated with side effects that can limit their usefulness in the outpatient setting. Objective: Two studies with identical protocols assessed the single- and mu ltiple-dose analgesic efficacy and tolerability of celecoxib, a specific cy clooxygenase-2 inhibitor, in the treatment of acute pain after orthopedic s urgery. Methods: These were multicenter, randomized. placebo- and active-controlled , double-blind, parallel-group trials conducted between January and June 19 98. Both consisted of a single-dose assessment period (SDAP) and a multiple -dose assessment period (MDAP). In the SDAP, patients who had undergone ort hopedic surgery received a single oral dose of celecoxib 200 mg, hydrocodon e 10 mg/acetaminophen 1000 mg, or placebo within 24 hours after the end of anesthesia, with pain assessments conducted over the following 8-hour perio d. In the MDAP, extending from 8 hours after the first dose of study medica tion up to 5 days, patients who had received less than or equal to1 dose of rescue medication during the SDAP continued on study medication (placebo r ecipients were rerandomized to active treatment), which could be taken up t o 3 times a day as needed. Results: A total of 418 patients were enrolled in the 2 trials. During the SDAP, 141 patients received celecoxib, 136 received hydrocodone/acetaminoph en. and 141 received placebo. During the MDAP, 185 patients received celeco xib and 181 received hydrocodone/ acetaminophen. When the combined data wer e analyzed, mean pain intensity difference (PID) scores generally favored t he active treatments over placebo from 1 to 6 hours (with the exception of 1.5 hours) after dosing (P less than or equal to 0.016) and favored celecox ib over the othertreatments at 7 and 8 hours after dosing (P < 0.001). Tne active treatments demonstrated superior summed PID scores through 8 hours ( P < 0.001), significantly shorter median times to onset of analgesia (P < 0 .05), and significantly longer median times to first use of rescue medicati on (P < 0.05). During the MDAP, more hydrocodone/acetaminophen-treated pati ents (20%) than celecoxib-treated patients (12%) required rescue medication (P < 0.05), and the celecoxib group had significantly lower maximum pain i ntensity scores (P < 0.001, days 2-5), required fewer doses of study medica tion (P < 0.01, days 3-5), and had superior scores on a modified American P ain Society Patient Outcome Questionnaire (P less than or equal to 0.013). In addition, a significantly lower proportion of celecoxib-treated patients experienced adverse events (43%) compared with hydrocodone/acetaminophen-t reated patients (89%; P < 0.001). Conclusions: Over 8 hours, patients with moderate to severe pain after orth opedic surgery experienced comparable analgesia with single doses of celeco xib and hydrocodone/acetaminophen. Over a 5-day period, oral doses of celec oxib 200 mg taken 3 times a day demonstrated superior analgesia and tolerab ility compared with hydrocodone 10 mg/acetaminophen 1000 mg taken 3 times a day. Most patients required no more than 2 daily doses of celecoxib 200 mg for the control of their postorthopedic surgical pain.