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

Background: Current outpatient management of postoperative pain includes the use of oral opioid analgesics or nonsteroidal anti-inflammatory drugs; however, 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 multiple-dose analgesic efficacy and tolerability of celecoxib, a specific cyclooxygenase-2 inhibitor, in the treatment of acute pain after orthopedic surgery. Methods: These were multicenter, randomized. placebo- and active-controlled, double-blind, parallel-group trials conducted between January and June 1998. Both consisted of a single-dose assessment period (SDAP) and a multiple-dose assessment period (MDAP). In the SDAP, patients who had undergone orthopedic surgery received a single oral dose of celecoxib 200 mg, hydrocodone 10 mg/acetaminophen 1000 mg, or placebo within 24 hours after the end of anesthesia, with pain assessments conducted over the following 8-hour period. In the MDAP, extending from 8 hours after the first dose of study medication 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 recipients were rerandomized to active treatment), which could be taken up to 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/acetaminophen. and 141 received placebo. During the MDAP, 185 patients received celecoxib and 181 received hydrocodone/ acetaminophen. When the combined data were analyzed, mean pain intensity difference (PID) scores generally favored the 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 celecoxib 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 medication (P < 0.05). During the MDAP, more hydrocodone/acetaminophen-treated patients (20%) than celecoxib-treated patients (12%) required rescue medication (P < 0.05), and the celecoxib group had significantly lower maximum pain intensity scores (P < 0.001, days 2-5), required fewer doses of study medication (P < 0.01, days 3-5), and had superior scores on a modified American Pain 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-treated patients (89%; P < 0.001). Conclusions: Over 8 hours, patients with moderate to severe pain after orthopedic surgery experienced comparable analgesia with single doses of celecoxib and hydrocodone/acetaminophen. Over a 5-day period, oral doses of celecoxib 200 mg taken 3 times a day demonstrated superior analgesia and tolerability 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.