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 < or =1 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 < or = 0.016) and favored celecoxib over the other treatments at 7 and 8 hours after dosing (P < 0.001). The 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 < or = 0.01, days 3-5), and had superior scores on a modified American Pain Society Patient Outcome Questionnaire (P < or = 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.
Gimbel
J S
JS
Arizona Research Center LLC, Phoenix 85023, USA. arizrc@aol.com
Brugger
A
A
Zhao
W
W
Verburg
K M
KM
Geis
G S
GS
D000082:Acetaminophen; D000328:Adult; D000556:Ambulatory Surgical Procedures; 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*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D000068579:Celecoxib; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009985:Orthopedics; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D011720:Pyrazoles; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D011720:Pyrazoles; D013449:Sulfonamides; D000082:Acetaminophen; D006853:Hydrocodone; D000068579:Celecoxib