M. Palangio et al., Dose-response effect of combination hydrocodone with ibuprofen in patientswith moderate to severe postoperative pain, CLIN THER, 22(8), 2000, pp. 990-1002
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
.