Dose-response effect of combination hydrocodone with ibuprofen in patientswith moderate to severe postoperative pain

Objective: The objective of this study was to demonstrate a dose-response e ffect with 1- and 2-tablet doses of combination hydrocodone 7.5 mg with ibu profen 200 mg and placebo in patients with moderate to severe postoperative abdominal or gynecologic pain. Background: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved f ixed-dose combination analgesic containing an opioid and ibuprofen. Previou s studies with this combination have demonstrated that the components have an additive analgesic effect as well as efficacy compared with other fixed- dose combination analgesics. Methods: This randomized, parallel-group, double-blind, single-dose, placeb o-controlled study compared 1 tablet of hydrocodone 7.5 mg with ibuprofen 2 00 mg (n = 60), 2 tablets of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), and placebo (n = 60) in patients with moderate or severe pain after ab dominal or gynecologic surgery. Analgesia was evaluated over 8 hours. Results: Mean pain relief (PR) scores were significantly greater for the 2- tablet dose than for the 1-tablet dose at 80 (P = 0.027) and 100 (P = 0.017 ) minutes and at 2 (P = 0.013), 2.5 (P = 0.012), 3 (P = 0.006), 4 (P = 0.02 9), 5 (P = 0.002), 6 (P = 0.032), 7 (P = 0.036), and 8 (P = 0.01) hours. Me an pain intensity difference scores were significantly greater for the 2-ta blet dose than for the 1-tablet dose at 80 (P = 0.013) and 100 (P = 0.007) minutes and at 2 (P = 0.003), 2.5 (P = 0.002), 3 (P = 0.002), 4 (P = 0.009) , 5 (P < 0.001), 6 (P = 0.004), 7 (P = 0.009) and 8 (P = 0.001) hours. Mean total PR scores were significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.01; 0 to 4 hours, P = 0.006; 0 to 6 hours, P = 0.003; 0 to 8 hours, P = 0.003). Mean sum of pain intensity differences was significantly greater for the 2 -tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.004; 0 to 4 hours, P < 0.001; 0 to 6 hours, P < 0.001; 0 to 8 hours, P < 0.001). Mean peak PR score and median time-to-remedication were significantly greater for the 2-tablet dose than for the 1-tablet dose (P < 0.029 and P = 0.017, respectively). Both doses were superior to place bo. There were no significant differences in the number of patients experie ncing adverse events between the 2-tablet dose (n = 6 [10.0%]), the 1-table t dose (n = 4 [6.7%]), and placebo (n = 1 [1.7%]). Adverse events were not serious, and none of the patients discontinued therapy because of side effe cts. Conclusions: This study demonstrated that a 2-tablet dose of hydrocodone wi th ibuprofen provided significantly more analgesia than a 1-tablet dose (a positive dose-response effect) and that both doses were superior to placebo .