Analgesic efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg compared with those of oxycodone 5 mg/acetaminophen 325 mg and hydrocodone 7.5 mg/acetaminophen 500 mg in patients with moderate to severe postoperative pain: a randomized, double-blind, placebo-controlled, single-dose, parallel-group study in a dental pain model. Combination oxycodone 5 mg/ibuprofen 400 mg for the treatment of postoperative pain: a double-blind, placebo- and active-controlled parallel-group study.
Combination therapy has been widely used for the clinical management of acute pain. By combining 2 drugs with different mechanisms of action, such therapy provides additive analgesic effects while reducing the risk for adverse effects.
                This study compared the efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg with those of oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, and placebo in a dental pain model.
                This was a multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group, single-dose study in patients experiencing moderate to severe pain after surgical removal of > or = 2 ipsilateral impacted third molars. Patients were randomly assigned to receive oxycodone 5 mg/ibuprofen 400 mg, oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, or placebo. The primary outcome measures were total pain relief through 6 hours after dosing (TOTPAR6), sum of pain intensity differences through 6 hours (SPID6), and adverse events. Secondary efficacy measures included SPID3 and TOTPAR3, peak pain relief, peak pain intensity difference, time to onset of pain relief, time to use of rescue medication, proportion of patients reporting pain half gone, and the patient's global evaluation.
                Two hundred forty-nine patients (43.5% male; 87.5% white; mean age, 19.1 years; mean body weight, 153.6 pounds) were randomized to treatment as follows: 62 to oxycodone 5 mg/ibuprofen 400 mg, 61 to oxycodone 5 mg/acetaminophen 325 mg, 63 to hydrocodone 7.5 mg/acetaminophen 500 mg, and 63 to placebo. Oxycodone 5 mg/ibuprofen 400 mg provided significantly greater analgesia compared with oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, and placebo (mean [SD] TOTPAR6, 14.98 [5.37], 9.53 [6.77], 8.36 [6.68], and 5.05 [6.49], respectively; P < 0.001, oxycodone 5 mg/ibuprofen 400 mg vs all other treatments). SPID6 values also differed significantly for oxycodone 5 mg/ibuprofen 400 mg compared with all other treatments (mean: 7.78 [4.11], 3.58 [4.64], 3.32 [4.73], and 0.69 [4.85]; P < 0.001). Oxycodone 5 mg/ibuprofen 400 mg was significantly more effective compared with the other treatments on all secondary end points (P < 0.001, all variables except peak PID vs oxycodone 5 mg/acetaminophen 325 mg [P = 0.006]), with the exception of the time to onset of analgesia. The lowest frequency of nausea and vomiting occurred in the groups that received oxycodone 5 mg/ibuprofen 400 mg (6.5% and 3.2%, respectively) and placebo (3.2% and 1.6%). Rates of nausea and vomiting were significantly lower with oxycodone 5 mg/ibuprofen 400 mg compared with oxycodone 5 mg/acetaminophen 325 mg (P = 0.011 and P = 0.009, respectively) but not with hydrocodone 7.5 mg/acetaminophen 500 mg.
                In this study in patients with moderate to severe pain after surgery to remove impacted third molars, oxycodone 5 mg/ibuprofen 400 mg provided significantly better analgesia throughout the 6-hour study compared with the other opioid/nonopioid combinations tested, and was associated with fewer adverse events. This study compared the efficacy and safety of a single dose of oxycodone 5 mg/ibuprofen 400 mg versus its individual components and placebo in a third-molar extraction model.
                In this multicenter, double-blind, double-dummy, parallel-group investigation, subjects with moderate to severe pain within 5 hours after extraction of > or =2 ipsilateral bony impacted third molars were randomized to single doses of oxycodone 5 mg/ibuprofen 400 mg, ibuprofen 400 mg, oxycodone 5 mg, or placebo. Primary efficacy variables were the sum of pain intensity difference over 6 hours (SP1D6) and total pain relief through 6 hours (TOTPAR6). The pharmacokinetics of oxycodone and ibuprofen, alone and in combination, were also determined in a subset of patients.
                A total of 498 subjects were randomized to treatment (187 to oxycodone 5 mg/ibuprofen 400 mg, 186 to ibuprofen 400 mg, 63 to oxycodone 5 mg, and 62 to placebo). Baseline demographics were generally similar among treatment groups, despite differences in sex (P = 0.041) and race (P = 0.023). Combination therapy was associated with greater analgesia than ibuprofen alone, oxycodone alone, or placebo (mean [SE] TOTPAR6: 13.3 [0.52], 12.2 [0.52], 4.3 [0.82], and 4.2 [0.83], respectively [P < 0.001 vs oxycodone or placebo, P = 0.012 vs ibuprofen]; mean [SE] SP1D6: 6.54 [0.42], 5.41 [0.44], 0.14 [0.60], and 0.32 [0.59], respectively [P < 0.001 vs oxycodone or placebo, P = 0.002 vs ibuprofen]). Combination therapy was well tolerated. Pharmacokinetic results implied no interaction between oxycodone and ibuprofen.
                In this study, a single dose of oxycodone 5 mg/ibuprofen 400 mg was fast-acting, effective, and well tolerated in subjects with moderate to severe pain after dental surgery. Oxycodone 5 mg alone did not provide an efficacy benefit over placebo in this study.
The combination of ibuprofen 400mg + oxycodone 5mg provided analgesia for longer than oxycodone alone, but not ibuprofen alone (at the same dose). There was also a smaller chance of needing additional analgesia over about eight hours, and with no greater chance of experiencing an adverse event.