Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of postoperative obstetric or gynecologic pain. Combination oxycodone 5 mg/ibuprofen 400 mg for the treatment of pain after abdominal or pelvic surgery in women: a randomized, double-blind, placebo- and active-controlled parallel-group study. Combination oxycodone 5 mg/ibuprofen 400 mg for the treatment of postoperative pain: a double-blind, placebo- and active-controlled parallel-group study. Bromfenac sodium, acetaminophen/oxycodone, ibuprofen, and placebo for relief of postoperative pain. 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. Analgesic efficacy of a hydrocodone with ibuprofen combination compared with ibuprofen alone for the treatment of acute postoperative pain. The analgesic efficacy of valdecoxib vs. oxycodone/acetaminophen after oral surgery. Ketoprofen, acetaminophen plus oxycodone, and acetaminophen in the relief of postoperative pain. Analgesic efficacy of a combination of hydrocodone with ibuprofen in postoperative pain.
The objective of this study was to compare the effectiveness of combination hydrocodone and ibuprofen with that of combination oxycodone and acetaminophen in the treatment of moderate to severe postoperative obstetric or gynecologic pain.
                Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen.
                This randomized, double-blind, parallel-group, single-dose, active-comparator, placebo-controlled study compared the effects of a 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg with those of a 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg and placebo. Analgesia was assessed over 8 hours.
                Mean pain relief (PR) scores were similar for the hydrocodone with ibuprofen and oxycodone with acetaminophen groups (n = 61 and 59, respectively) at 0.5, 1, 1.5, 2, 2.5, 3, 4, and 7 hours and significantly greater for the hydrocodone with ibuprofen group at 5, 6, and 8 hours (P < or = 0.05). Mean pain intensity difference (PID) scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen at 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours and significantly greater for hydrocodone with ibuprofen at 5, 6, 7, and 8 hours (P < or = 0.05). Total PR scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3- and 0- to 4-hour intervals and significantly greater for hydrocodone with ibuprofen for the 0- to 6- and 0- to 8-hour intervals (P < 0.05). The sum of the PID scores was similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3-, 0- to 4-, 0- to 6-, and 0- to 8-hour intervals. The median estimated time to onset of analgesia, mean peak PR score, median time to remedication, and mean global assessment score were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen. Assay sensitivity was demonstrated by the presence of statistically significant differences between both active treatments and placebo (n = 60). The number of patients experiencing adverse events was similar for each of the 3 groups (11 [18.0%], hydrocodone with ibuprofen; 7 [11.9%], oxycodone with acetaminophen; and 6 [10.0%], placebo).
                In this study, a 2-tablet dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg was as effective as a 2-tablet dose of combination oxycodone 5 mg and acetaminophen 325 mg in the treatment of moderate to severe postoperative obstetric or gynecologic pain. Both treatments were superior to placebo. The results of this study suggest that the combination of hydrocodone 7.5 mg and ibuprofen 200 mg may offer prescribers an additional option in combination pain therapy. The sensation of pain arises from both central and peripheral sites, and inflammation may be one of its underlying causes. Combination therapy with analgesic agents having multimodal mechanisms of action and complementary pharmacokinetic properties enhances pain relief by addressing the different pathways of pain while limiting individual drug doses and, therefore, the potential for adverse effects caused by any single agent. Oxycodone and ibuprofen each have been used effectively as monotherapy and in other combinations for the treatment of acute pain; a fixed combination of these analgesics may improve pain relief in the setting of abdominal or pelvic surgery, where trauma and any resultant inflammation may be present at the same time.
                This study evaluated and compared the analgesic efficacy and tolerability of a single-dose combination tablet containing oxycodone 5 mg/ibuprofen 400 mg with either agent alone and with placebo in women who had undergone abdominal or pelvic surgery.
                In this multicenter, randomized, double-blind,placebo- and active-controlled, parallel-group trial, women experiencing moderate to severe pain between 14 and 48 hours after surgery were randomized per protocol to receive a single dose of study medication in a 3:3:1:1 ratio (combination oxycodone/ibuprofen, ibuprofen, oxycodone, and placebo, in that order). Over a 6-hour study period, patients recorded their assessments of pain intensity (100-mm visual analog scale and 4-point scale), relief from starting pain, and overall evaluation of study drug based on prespecified definitions and rating scales. Based on these data, the following primary efficacy end points were determined: total pain relief 6 hours after dosing (TOTPAR6) and sum of pain intensity differences 6 hours after dosing (SPID6). Other end points included the time to onset of pain relief, time to use of rescue medication, and patient's global rating of analgesic effectiveness. Tolerability was evaluated on the basis of observed and patient-reported adverse events and findings on physical examination.
                Four hundred fifty-six women participated in the study. They were primarily white and had a mean age of 41.6 years and a mean body weight of 171.5 pounds. Combination treatment was associated with significantly better TOTPAR6 and SPID6 scores compared with ibuprofen alone (P < 0.02 and P < 0.015, respectively), oxycodone alone (P < 0.009 and P < 0.001), or placebo (both, P < 0.001). Fewer patients receiving combination treatment required rescue medication, and the time to use of rescue medication was significantly longer in the combination-treatment group compared with the other groups (P < 0.05). Patients' global ratings of analgesic efficacy were significantly higher in the combination-treatment group compared with all other groups (P < 0.044 vs ibuprofen alone; P < 0.001 vs oxycodone alone and placebo). The onset of pain relief occurred within 15 minutes of dosing with all 4 regimens. Nausea was the most frequently reported treatment-emergent adverse event in all 4 groups. The incidence of treatment-emergent adverse events was highest with placebo (55.0%), followed by oxycodone alone (44.2%), ibuprofen alone (42.3%), and combination treatment (40.8%).
                In this population of women who had undergone abdominal or pelvic surgery, the combination of oxycodone 5 mg/ibuprofen 400 mg was significantly more effective than either agent alone or placebo in the treatment of moderate to severe postoperative pain. 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 objective of this double-masked, parallel-group, multicenter, inpatient study was to compare bromfenac with an acetaminophen/oxycodone combination and ibuprofen in patients who had pain due to abdominal gynecologic surgery. In the 8-hour, single-dose phase, 238 patients received single oral doses of bromfenac (50 or 100 mg), acetaminophen 650 mg/oxycodone 10 mg, ibuprofen 400 mg, or placebo. In the multiple-dose phase, 204 patients received bromfenac, acetaminophen/oxycodone, or ibuprofen for up to 5 days. In the single-dose phase, both bromfenac doses produced peak analgesic responses equivalent to acetaminophen/oxycodone, but the responses to bromfenac were longer lasting. Bromfenac produced significantly better overall (8-hour) analgesic summed scores than acetaminophen/oxycodone. Ibuprofen was less efficacious than the other analgesics. The remedication rate was lower in both bromfenac groups than in the other treatment groups. The acetaminophen/oxycodone group reported more somnolence and vomiting. Single doses of bromfenac provided analgesia at least equivalent to that of the acetaminophen/oxycodone combination, with a longer duration of action. Both doses of bromfenac and acetaminophen/oxycodone were superior to ibuprofen in this 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. Hydrocodone is a semisynthetic opioid with analgesic and antitussive properties qualitatively similar to other opioid agonists. Ibuprofen is a nonsteroidal antiinflammatory agent with analgesic and antipyretic activity and is an effective, primarily peripheral-acting antiinflammatory analgesic. The objective of this clinical trial was to determine the additive analgesic effect of the combination of 15 mg hydrocodone bitartrate with 400 mg ibuprofen, relative to 400 mg ibuprofen alone and placebo, in the treatment of postoperative pain. The single-dose analgesic efficacy of the combination of hydrocodone bitartrate with ibuprofen was compared with ibuprofen alone and placebo in 120 patients with moderate or severe postoperative pain after abdominal surgery. Analgesia was measured during the 6-hour period after dosing based on onset of relief, hourly and summary variables, and duration of effect. A significantly greater proportion of patients treated with the hydrocodone/ibuprofen combination reported onset of relief compared with ibuprofen or placebo; however, the distribution functions for time to onset of relief did not differ among treatments. Hydrocodone with ibuprofen and ibuprofen alone were significantly more effective than placebo for all measures of analgesia. The combination of hydrocodone with ibuprofen was significantly superior to ibuprofen for all hourly analgesic evaluations, weighted sum of pain intensity differences (SPID), total pain relief (TOTPAR), and global rating of study medication. No patients in the hydrocodone with ibuprofen group required analgesic remedication during the 6-hour study period, compared with 25% and 82% in the ibuprofen and placebo groups, respectively. The analgesic superiority of 15 mg hydrocodone bitartrate combined with 400 mg ibuprofen compared with 400 mg ibuprofen alone was demonstrated across many efficacy variables. The authors conducted two studies to compare the analgesic efficacy and safety of the cyclooxygenase, or COX, -2-specific inhibitor, valdecoxib, with oxycodone/ acetaminophen in patients who have undergone oral surgery.
                In total, 205 eligible subjects in Study A and 201 in Study B were randomized to receive a single oral dose of valdecoxib (20 or 40 milligrams), a combination of oxycodone 10 mg/acetaminophen 1,000 mg or placebo. Eligible subjects experienced moderate-to-severe pain within six hours of surgery during which two or more impacted third molars were extracted. Analgesic efficacy was assessed over 24 hours or until the patient required rescue analgesia.
                In both studies, subjects receiving either dose of valdecoxib experienced a rapid onset of analgesia and (among those who received valdecoxib 40 mg) a level of pain relief comparable with that of those who received oxycodone/ acetaminophen. Both valdecoxib doses had a significantly longer duration of analgesic effect than did oxycodone/acetaminophen. Pooled safety data demonstrated that each valdecoxib dose had a tolerability profile superior to that of oxycodone/ acetaminophen and similar to that of placebo.
                Orally administered valdecoxib is as rapidly acting and effective as oxycodone/acetaminophen, and it has a superior duration of analgesic effect in patients after oral surgery. Valdecoxib has a tolerability profile superior to that of oxycodone/acetaminophen.
                The current standard of care for alleviating acute pain after oral surgery has rested largely on conventional nonsteroidal anti-inflammatory drugs or opioid/analgesic combination products. The studies reported here suggest that the COX-2-specific inhibitor valdecoxib offers an efficacious and safe alternative to other analgesics used to treat pain after oral surgery. Ketoprofen (Orudis) is a nonsteroidal anti-inflammatory drug that is currently approved in the United States for the management of mild to moderate pain. The objective of this trial was to determine the effectiveness of orally administered ketoprofen in the management of severe postoperative pain. This randomized, double-blind parallel study compared the efficacy and safety of single doses of 100 mg or 50 mg ketoprofen, the combination of 650 mg acetaminophen plus 10 mg oxycodone hydrochloride, 650 mg acetaminophen, or placebo in 240 patients with severe postoperative pain after cesarean section. Analgesia for the first dose was assessed over an 8-hour period. Multiple doses of 100 mg or 50 mg ketoprofen and the combination at half the dose (325 mg acetaminophen plus 5 mg oxycodone) were also assessed for up to 7 days. The 100 and 50 mg doses of ketoprofen and the combination were statistically superior to acetaminophen and placebo for many analgesic measures. A dose response was observed between the two doses of ketoprofen, with the 100 mg dose providing significantly greater analgesia over the lower dose. Ketoprofen, 100 mg, was at least as effective as the combination and its effects lasted longer, with the exception of hour 1 when the combination was superior. Remedication time for the group receiving 100 mg ketoprofen was significantly longer than for the other treatment groups. Significantly more patients who took repeated doses of the combination (84%) than those who took either dose of ketoprofen (70%) had adverse effects. Ketoprofen at both dose levels was shown to be effective, long-lasting, and well tolerated, and it should be considered as a viable option for the management of moderate to severe postoperative pain. Two randomized, double-blind, parallel-group single-dose 2 x 2 factorial analgesic studies compared a single-dose or a 2-tablet dose of a combination of 7.5 mg hydrocodone bitartrate with 200 mg ibuprofen with each constituent alone and with a placebo in women with moderate or severe postoperative pain from abdominal or gynecologic surgery. A nurse-observer recorded patient reports of pain intensity and pain relief periodically for 8 hours. In both studies, the combination was significantly superior to placebo for sum of the pain intensity differences (SPID), total pain relief (TOTPAR), peak pain intensity difference (PID) and pain relief, global evaluation, and time to remedication. The combination was likewise significantly superior to both hydrocodone and ibuprofen for most of these summary measures of analgesia. In a factorial analysis, both the hydrocodone and ibuprofen effects were significant for most summary measures of analgesia, whereas results of the interaction contrast were consistent with the concept that the analgesic effect of the combination represents the additive analgesia of its 2 constituents.
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.