Comparison of rofecoxib and celecoxib, two cyclooxygenase-2 inhibitors, in postoperative dental pain: a randomized, placebo- and active-comparator-controlled clinical trial

Pain is a common complaint, often occurring in conjunction with inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used analgesic agents in ambulatory patients. In recent studies, the cyclooxygenase-2 (COX-2) inhibitor rofecoxib demonstrated analgesic effects similar to those of NSAIDs in the treatment of acute pain and primary dysmenorrhea. The present randomized, single-dose, double-blind, double-dummy, placebo- and active-comparator-controlled, parallel-group study was undertaken to compare the analgesic efficacy of the COX-2 inhibitors rofecoxib 50 mg and celecoxib 200 mg with that of ibuprofen 400 mg and placebo in patients with postoperative dental pain. Two hundred and seventy-two patients experiencing pain after the removal of > or =2 third molars were randomized according to pain severity (moderate vs severe) to receive a single dose of placebo (n = 45), rofecoxib 50 mg (n = 90), celecoxib 200 mg (n = 91), or ibuprofen 400 mg (n = 46). Using a patient diary, patients recorded pain intensity, pain relief, and global evaluations throughout the 24-hour period after dosing. The overall analgesic effect, onset of action, peak effect, and duration of effect were evaluated, with the primary end point being total pain relief over 8 hours (TOPAR8). The safety profile was assessed on the basis of physical findings, laboratory results, and spontaneous reports of adverse experiences. The results showed that compared with celecoxib, rofecoxib had superior analgesic effects on all measures of analgesic efficacy, including overall analgesic effect (TOPAR8, 18.3 vs. 12.5; P<0.001), time to onset of effect (30 vs. 60 minutes; P = 0.003), peak pain relief (score, 2.8 vs 2.3; P<0.05), and duration of effect (>24 vs. 5.1 hours; P<0.001). In addition, rofecoxib's analgesic efficacy was similar to that of ibuprofen (TOPAR8, 18.3 vs. 17.0; P = 0.460), but the duration was longer (P<0.05); with ibuprofen, the time to on set was 24 minutes, peak pain relief score was 2.9, and duration of analgesic effect was 8.9 hours. The safety profile was similar across all treatment groups. Thus rofecoxib provided analgesic efficacy superior to that of celecoxib and comparable to that of ibuprofen in the treatment of patients with acute postoperative dental pain.     

Comparison of rofecoxib and oxycodone plus acetaminophen in the treatment of acute pain: a randomized, double-blind, placebo-controlled study in patients with moderate to severe postoperative pain in the third molar extraction model

BACKGROUND: Opiates, acetaminophen, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2-selective inhibitors such as rofecoxib are used in the treatment of acute pain because of their anti-inflammatory and/or analgesic properties. Rofecoxib has demonstrated an improved gastrointestinal safety profile compared with nonselective NSAIDs. OBJECTIVE: The aim of this study was to compare the analgesic efficacy and tolerability profile of rofecoxib 50 mg with those of the centrally acting, nonsalicylate, opiate/nonopiate analgesic combination oxycodone/acetominophen 5/325 in patients with pain after dental surgery. METHODS: In this randomized, double-blind, placebo- and active comparator-controlled study, patients experiencing moderate to severe postoperative pain after extraction of > or =2 third molars (including > or =1 mandibular impaction) received a single oral dose of rofecoxib 50 mg, oxycodone/acetaminophen 5/325 mg, or placebo. End points included total pain relief over 6 hours (TOPAR6, the primary end point) and 4 hours (TOPAR4), patient's global assessment of treatment at 6 hours (GLOBAL6) and 24 hours (GLOBAL24), summed pain intensity difference over 6 hours (SPID6), onset of analgesic effect (time to perceptible/meaningful pain relief, using a 2-stopwatch method), peak pain relief (PEAKPR), peak pain intensity difference (PEAKPID), and duration of analgesic effect (time to use of rescue analgesia). RESULTS: Two hundred twelve patients (63% female, 37% male; 76% white, 24% other; mean [SD] age, 20.9 [4.4] years; age range, 16-41 years) were enrolled in the study and received a single oral dose of rofecoxib 50 mg (n = 90), oxycodone/acetaminophen 5/325 mg (n = 91), or placebo (n = 31). The analgesic effect of rofecoxib was significantly greater than that of oxycodone/acetaminophen at P < 0.001 for TOPAR6, TOPAR4, GLOBAL6, GLOBAL24, and SPID6; at P < 0.010 for PEAKPR and PEAKPID; and at P < 0.001 for median time to use of rescue analgesia. Significantly fewer patients in the rofecoxib group (72.2%) took rescue analgesia within 24 hours postdose compared with the oxycodone/acetaminophen group (94.5%; P < 0.001) and the placebo group (96.8%; P < 0.02). Both active treatments were similar with respect to onset of analgesic effect. Both were generally well tolerated; the overall incidence of adverse experiences in the rofecoxib, oxycodone/acetaminophen, and placebo groups was 51.1%, 64.8%, and 48.4%, respectively. Rofecoxib was associated with a significantly lower incidence of nausea (18.9% vs 39.6%; P < 0.001) and vomiting (6.7% vs 23.1%; P < 0.001) compared with oxycodone/acetaminophen. CONCLUSIONS: In study patients with moderate to severe pain after dental surgery, rofecoxib 50 mg had a greater analgesic effect than oxycodone/acetaminophen 5/325 mg and was associated with less nausea and vomiting.     

Comparison of the analgesic efficacy of rofecoxib and enteric-coated diclofenac sodium in the treatment of postoperative dental pain: a randomized,placebo-controlled clinical trial

BACKGROUND: Rofecoxib is a selective cyclooxygenase-2 inhibitor indicated for the treatment of acute pain, with similar analgesic efficacy to ibuprofen and naproxen sodium. Diclofenac sodium is the most commonly prescribed nonsteroidal anti-inflammatory drug worldwide; it is effective for the treatment of pain as well as the signs and symptoms associated with the painful conditions of osteoarthritis and rheumatoid arthritis. OBJECTIVE: The aim of this study was to compare the analgesic efficacy and tolerability of a single dose of rofecoxib 50 mg, 3 doses of enteric-coated diclofenac sodium 50 mg, and placebo over 8-hour and 24-hour periods in patients with moderate to severe pain after oral surgery. METHODS: In this double-blind, placebo- and active comparator-controlled, parallel-group study, patients experiencing moderate to severe pain after the surgical extraction of > or = 2 third molars were randomized to receive a single dose of rofecoxib 50 mg, 3 doses of enteric-coated diclofenac sodium 50 mg (50 mg given every 8 hours), or placebo. Patients rated pain intensity, pain relief, and global assessments at prespecified times throughout the 24-hour period after initial dosing. Overall analgesic efficacy was determined by total pain relief over 8 hours (TOPAR8) and 24 hours (TOPAR24) and patient global assessments at 8 and 24 hours. Onset of analgesic effect was determined by using the 2-stopwatch method for confirmed perceptible pain relief. Peak analgesic effect was the maximum pain relief attained during the first 8 hours. The duration of analgesic effect was determined by median time to rescue analgesia use. RESULTS: A total of 305 patients were randomized to treatment: 121 received rofecoxib, 121 received diclofenac sodium, and 63 received placebo. The baseline demographics were similar among the groups. Overall, 61.3% experienced moderate pain and 38.7% experienced severe pain; 53.1% were female; and the mean age was 23.4 years. The overall analgesic efficacy, as assessed by TOPAR8, of a single dose of rofecoxib 50 mg was significantly greater than a single dose of enteric-coated diclofenac sodium 50 mg (20.5 vs 8.2) and placebo (20.5 vs 5.9). Patient global assessment at 8 hours was also significantly better for rofecoxib compared with enteric-coated diclofenac sodium and placebo. TOPAR24 was significantly greater for a single dose of rofecoxib 50 mg compared with 3 doses of enteric-coated diclofenac sodium 50 mg (64.1 vs 25.1) and placebo (64.1 vs 19.2). At 24 hours, the patient global assessment for rofecoxib was significantly better than that achieved with enteric-coated diclofenac sodium and placebo. The onset of analgesic effect was significantly more rapid for rofecoxib than for enteric-coated diclofenac sodium and placebo (median times: 31 minutes, >4 hours, and >4 hours, respectively). The peak analgesic effect was significantly greater for rofecoxib compared with enteric-coated diclofenac sodium (3.2 vs 1.5) and placebo (3.2 vs 1.1). The duration of analgesia was significantly longer for rofecoxib than enteric-coated diclofenac sodium (median times: >24 hours vs 1 hour and 37 minutes) and placebo (>24 hours vs 1 hour and 37 minutes). Enteric-coated diclofenac sodium was numerically greater than placebo for the key end points measuring overall efficacy (total pain relief and patient global assessment), but diclofenac sodium did not provide as much analgesic effect as expected for a drug effective for pain, osteoarthritis, and rheumatoid arthritis and did not differ significantly from placebo. Overall, both rofecoxib and enteric-coated diclofenac sodium were generally well tolerated, although the rofecoxib group had a significantly lower incidence of clinical and drug-related adverse events than the enteric-coated diclofenac sodium group. CONCLUSIONS: A single 50-mg dose of rofecoxib provided greater overall analgesic efficacy over 8 hours, more rapid onset of analgesia, greater maximum analgesic effect, and longer duration of effect than a single 50-mg dose of enteric-coated diclofenac sodium in patients with moderate to severe pain associated with oral surgery. Compared with 3 doses of enteric-coated diclofenac sodium 50 mg (50 mg every 8 hours), a single dose of rofecoxib 50 mg provided greater overall analgesic efficacy over 24 hours.     

Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial

BACKGROUND: In recent studies of acute pain and primary dysmenorrhea, rofecoxib, a nonsteroidal anti-inflammatory drug that selectively targets the cyclooxygenase-2 enzyme, was found to be similar in efficacy to ibuprofen and naproxen sodium. OBJECTIVE: The purpose of this study was to determine the analgesic efficacy of a single oral dose of rofecoxib 50 mg compared with the combination of codeine 60 mg/acetaminophen 600 mg in a model of postsurgical dental pain. METHODS: In this double-blind, placebo- and active comparator-controlled, parallel-group study, patients experiencing moderate or severe pain after the surgical extraction of > or = 2 third molars, at least 1 of which was a mandibular impaction, were randomized to receive placebo, rofecoxib 50 mg, or codeine 60 mg/acetaminophen 600 mg. Patient evaluations of pain intensity, pain relief, and global assessments were recorded throughout the 24-hour period after dosing. The 2-stopwatch method was used to determine time to confirmed perceptible pain relief. The primary end point assessing overall analgesic effect was total pain relief over 6 hours (TOPAR6). Secondary end points were patient global assessment of response to therapy (PGART) at 6 hours, onset of analgesia, peak analgesic effect, and duration of analgesia. RESULTS: A total of 393 patients were enrolled; 182 received rofecoxib, 180 received codeine/acetaminophen, and 31 received placebo. The overall analgesic effect of rofecoxib 50 mg was greater than that of codeine 60 mg/acetaminophen 600 mg for TOPAR6 (12.4 vs 7.0; P < 0.001) and PGART at 6 hours (P < 0.001). The onset of analgesic effect was similar for rofecoxib and codeine/acetaminophen. Peak analgesic effect as measured by peak pain relief scores during the first 6 hours was significantly greater in the rofecoxib group compared with the codeine/acetaminophen group (P < 0.001), as was the duration of analgesic effect measured by the time to rescue analgesia (9.6 hours vs 2.3 hours, P < 0.001). Adverse events were reported in 33.0%, 46.1%, and 32.3% of patients treated with rofecoxib, codeine/acetaminophen, and placebo, respectively. The most common adverse events were nausea (6.0%, 25.0%, and 9.7%, respectively) and vomiting (3.8%, 18.3%, and 6.5%, respectively). Significantly more patients in the codeine/acetaminophen group than in the rofecoxib group experienced adverse events overall (P < 0.050) and nausea in particular (P < 0.001). CONCLUSION: In this study of moderate to severe postoperative dental pain, the analgesic efficacy of rofecoxib 50 mg was greater than that of codeine/acetaminophen, with a lower incidence of adverse events and nausea.     

A randomized, double-blind, parallel-group study comparing the analgesic effect of etoricoxib to placebo, naproxen sodium, and acetaminophen with codeine using the dental impaction pain model

OBJECTIVE: To compare the overall analgesic effect, including time to onset, peak and duration of effect for etoricoxib 120 mg, a new COX-2 selective inhibitor, in patients with acute pain to that of placebo. Naproxen sodium 550 mg and acetaminophen/codeine 600/60 mg were the active comparators. METHODS: A total of 201 patients with moderate to severe pain following surgical extraction of > or = 2 third molars, of which at least the mandibular tooth was impacted, were randomly allocated to receive single oral doses of placebo (n = 50), etoricoxib 120 mg (n = 50), naproxen sodium 550 mg (n = 51), or acetaminophen/codeine 600/60 mg (n = 50). The endpoints included total pain relief over 8 hours (TOPAR8, primary end point), sum of pain intensity difference over 8 hours, patient's global evaluation, onset, peak, and duration of analgesia. RESULTS: Etoricoxib 120 mg had a significantly greater least squares (LS) mean TOPAR8 score than placebo (20.9 vs 5.4; P < 0.001) and acetaminophen/codeine 600/60 mg (20.9 vs 11.5; P < 0.001), and a similar LS mean TOPAR8 score to naproxen sodium 550 mg (20.9 vs 21.3). All three active treatments had rapid onset of analgesia, median time approximately 30 minutes. The duration of analgesic effect, defined as median time to rescue medication use, was >24 hours for etoricoxib, 20.8 hours for naproxen sodium, 3.6 hours for acetaminophen/codeine, and 1.6 hours for placebo. DISCUSSION: Etoricoxib is a new COX-2 selective inhibitor under development for treatment of osteoarthritis, rheumatoid arthritis, and acute pain. In this study, etoricoxib 120 mg provided rapid and long-lasting pain relief to patients with moderate-to-severe postdental surgery pain. Etoricoxib was generally well tolerated.     

A randomized, double-blind, celecoxib- and placebo-controlled study of the effectiveness of CS-706 in acute postoperative dental pain

BACKGROUND: CS-706 is a cyclooxygenase-2 (COX-2)-selective inhibitor with an in vitro selectivity ratio (COX-1:COX-2) similar to that of celecoxib. It has exhibited analgesic, anti-inflammatory, and antitumor properties in animal models. OBJECTIVES: This study evaluated the tolerability of single doses of CS-706 and compared the analgesic efficacy of CS-706 with that of celecoxib and placebo in the dental pain model. METHODS: This was a randomized, double-blind, double-dummy, active- and placebo-controlled study. Healthy male and female subjects with moderate to severe pain intensity (PI) after dental surgery were randomized ( approximately 50 per group) to receive a single oral dose of CS-706 10, 50, 100, or 200 mg; celecoxib 400 mg; or placebo. PI and pain relief (PR) were measured on categorical and visual analog scales through 24 hours after the dose. The primary efficacy variable was the time-weighted sum of PR scores at 4 hours after the dose (TOPAR4). The onset of analgesia was assessed by calculating the pain intensity difference (PID). Perceptible and meaningful pain relief were assessed using a 2-stopwatch method. RESULTS: The majority of subjects were female (62.0%) and white (59.5%). Subjects' mean (SD) age was 22.6 (3.9) years, and their mean body mass index was 25.3 (5.1) kg/m(2). All doses of CS-706 were associated with significant analgesic efficacy compared with placebo based on the primary end point, TOPAR4 (P<0.001), and on all secondary end points (P<0.05, comparisons of all CS-706 doses vs placebo) with the exception of time to 100% PR for CS-706 10 mg. Single 50-, 100-, and 200-mg doses of CS-706 also were significantly more effective than celecoxib for TOPAR4 (P=0.036, P=0.004, and P=0.006, respectively). The onset of analgesia (PID >or= 1) for all CS-706 doses occurred within 1 hour after dosing (P<0.001 vs placebo). The median duration of analgesia, measured as the time to administration of rescue medication, was significantly greater for all doses of CS-706 compared with placebo (5.7 hours for CS-706 10 mg, >24 hours for CS-706 50, 100, and 200 mg, and 1.7 hours for placebo; P<0.001 for CS-706 50, 100, and 200 mg). These data suggest that once-daily administration of CS-706 may be effective in providing relief of acute pain. The incidence of adverse events was similar among all treatment groups. Adverse events occurring in >or= 5 % of subjects in any treatment group were nausea, vomiting, dry socket, dizziness, headache, and paresthesia. CONCLUSION: Single doses of CS-706 had significant analgesic efficacy compared with celecoxib and placebo in the relief of postoperative dental pain in the healthy subjects enrolled in this study.     

Etoricoxib in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled dose-ranging study

BACKGROUND: Patients experiencing acute pain after surgery, including dental surgery, often require analgesia. Ideally, the chosen analgesic should have a rapid onset and sustained effect. Etoricoxib is a new cyclooxygenase-2-selective inhibitor that has demonstrated analgesic efficacy in the treatment of acute pain with a rapid onset and long-lasting pain relief. OBJECTIVE: The goal of this study was to determine the analgesic effect of single oral doses of etoricoxib 60, 120, 180, and 240 mg compared with placebo in the treatment of pain after dental surgery. Ibuprofen was used as an active control. METHODS: This was a randomized, double-blind, parallel-group, single-dose, placebo- and active comparator-controlled study performed at a single center. It consisted of 3 visits (prestudy, treatment, and poststudy). Eligible patients were aged > or =16 years with moderate or severe pain after surgical extraction of > or =2 third molars, of which > or =1 was an impacted mandibular molar. Patients were assessed over 24 hours and reported pain intensity and pain relied at 14 predefined time points. Plasma samples for a pharmacokinetic/pharmacodynamic analysis were collected from a subset of patients at baseline and the 14 predefined time points. The end points included total pain relief over 8 hours (TOPAR8, the primary end point), sum of pain intensity difference over 8 hours, patient's global evaluation of treatment, median time to onset of pain relief (2-stopwatch method), peak pain relief, and duration of analgesic effect (median time to use of rescue medication). Adverse events were collected up to 14 days postdose. RESULTS: Three hundred ninety-eight (63.1% women, 36.9% men; mean age, 21.1 years; 72.1% white, 27.9% other; mean number of third molars removed, 3.5; 65.2% experiencing moderate pain) were randomly allocated to receive etoricoxib 60 mg (n = 75), etoricoxib 120 mg (n = 76), etoricoxib 180 mg (n = 74), etoricoxib 240 mg (n = 76), ibuprofen 400 mg (n = 48), and placebo (n = 49). All active treatments had significantly greater overall analgesic effect (TOPAR8) compared with placebo (P < or 0.001). Patients who received etoricoxib 120 and 180 mg had significantly higher TOPAR8 scores than those who received etoricoxib 60 mg ( P < = 0.001) and ibuprofen (P < 0.05 etoricoxib 120 mg; P < or = 0.001 etoricoxib 180 mg). Least-squares mean TOPAR8 scores for etoricoxib 60, 120, 180, and 240 mg, ibuprofen, and placebo were 16.0, 22.0, 23.5, 20.7, 18.6, and 5.2, respectively. The median time to onset of analgesia was 24 minutes for etoricoxib 120, 180, and 240 mg, and 30 minutes for etoricoxib 60 mg and ibuprofen. There were no significant differences in the onset of analgesia between etoricoxib 120, 180, and 240 mg and ibuprofen. The duration of analgesic effect was >24 hours for etoricoxib 120, 180, and 240 mg, and 12.1 hours for etoricoxib 60 mg. The duration of effect was significantly longer with all 4 etoricoxib doses compared with ibuprofen (10.1 hours; P < 0.05 etoricoxib 60 mg; < or = 0.001etoricoxib 120, 180, and 240 mg) and compared with placebo (2.1 hours; P < = 0.001). In the pharmacokinetic/pharmacodynamic analysis (n approximately 120), there was a linear relationship between plasma etoricoxib concentrations and pain relief scores up to the maximum observed concentration, followed by a decline in plasma concentrations with persistent analgesia. The most common adverse events were postextraction alveolitis and nausea. Conclusions: In this dose-ranging study, etoricoxib 120 mg was determined to be the minimum dose that had maximal efficacy in patients with moderate to severe acute pain associated with dental surgery. Both etoricoxib and ibuprofen were generally well tolerated.     

Analgesic efficacy of the cyclooxygenase-2-specific inhibitor rofecoxib in post-dental surgery pain: a randomized, controlled trial.

Previous data have suggested that rofecoxib, a cyclooxygenase (COX)-2-specific inhibitor, had analgesic effects similar to those of the nonsteroidal anti-inflammatory drugs when tested in the post-dental surgery pain model. The objective of this parallel-group, double-masked, randomized, placebo- and active comparator-controlled clinical trial was to assess more fully the analgesic efficacy of rofecoxib in the treatment of postoperative dental pain. After dental surgery, 151 patients (50.3% women; mean age, 18.3 years; 93.4% white) experiencing moderate-to-severe pain were to receive a single dose of placebo, rofecoxib 50 mg, or ibuprofen 400 mg. Analgesic efficacy was assessed for up to 24 hours postdose using self-administered questionnaires. Tolerability was assessed using spontaneous reports of adverse experiences, physical findings, and laboratory measurements. The results of this study demonstrated that rofecoxib 50 mg was more effective than placebo on all measures of analgesic efficacy. Rofecoxib 50 mg exhibited overall analgesic effects, onset of analgesia, and peak analgesic effects that were not significantly different from those of ibuprofen 400 mg, with a significantly longer duration of action (P < 0.05). We concluded that rofecoxib was efficacious in the treatment of postoperative dental pain and that COX-2-derived prostanoids play a role in treatment of the pain associated with dental surgery.     

Analgesic efficacy of a single dose of lumiracoxib compared with rofecoxib, celecoxib and placebo in the treatment of post-operative dental pain

This randomised, double-blind, placebo-controlled, parallel-group study compared the efficacy and tolerability of lumiracoxib (a novel COX-2 selective inhibitor) with rofecoxib, celecoxib and placebo in patients with moderate-to-severe post-operative dental pain. Following third molar extraction, patients received single oral doses of lumiracoxib 400 mg, rofecoxib 50 mg, celecoxib 200 mg or placebo (n = 355). Additional patients from a similar study, assigned to lumiracoxib, rofecoxib or placebo (n = 155), were included for analysis of the primary variable, Summed Pain Intensity Difference over the first 8 h post dose (SPID-8). For SPID-8, lumiracoxib was superior to rofecoxib (p < 0.05), celecoxib (p < 0.001) and placebo (p < 0.001). Lumiracoxib demonstrated the fastest onset of analgesia and the longest time to rescue medication use. Patient global evaluation of lumiracoxib was comparable to rofecoxib and superior to celecoxib and placebo. All treatments were well tolerated. Lumiracoxib 400 mg provides rapid, effective and sustained relief of post-operative dental pain, comparable or superior to rofecoxib.     

Rofecoxib 50 mg and valdecoxib 20 or 40 mg in adults and adolescents with postoperative pain after third molar extraction: results of two randomized, double-blind, placebo-controlled, single-dose studies

OBJECTIVE: These studies assessed the comparative efficacy of rofecoxib and valdecoxib in the treatment of acute postoperative dental pain. METHODS: Two randomized, double-blind, placebo-controlled, single-dose studies were conducted in patients undergoing extraction of > or =2 third molars, with > or =1 mandibular impaction, who experienced moderate or severe pain after extraction. In study 1, patients were randomized in a 4:4:1 ratio to receive rofecoxib 50 mg, valdecoxib 20 mg, or placebo. In study 2, which was an exploratory study, patients were randomized in a 2:2:1 ratio to receive reofecoxib 50 mg, valdecoxib 40 mg, or palcebo. The primary efficacy end point was total pain relief at 12 hours (TOPAR12) for rofecoxib compared with valdecoxib 20 mg (study 1) or valdecoxib 40 mg (study 2). Tolerability was assessed based on clinical adverse experiences (AEs) and vital signs. These studies were performed before both agents were withdrawn from the market. RESULTS: In study 1, 200 patients were randomized to receive rofecoxib 50 mg, 201 to valdecoxib 20 mg, and 49 to placebo. In study 2, 51 patients were randomized to receive rofecoxib 50 mg, 50 to valdecoxib 40 mg, and 24 to placebo. The majority of patients in both studies were female (approximately 54%) and white ( approximately 66%), with a mean age of approximately 22 years and a mean weight of approximately 75 kg. Most (approximately 58%) patients reported experiencing moderate postoperative pain. In study 1, mean TOPAR12 scores were 30.7 for rofecoxib 50 mg, 28.9 for valdecoxib 20 mg, and 5.5 for placebo; in study 2, TOPAR12 scores were 27.0 for rofecoxib 50 mg, 28.6 for valdecoxib 40 mg, and 6.9 for placebo. In both studies, the active treatments were comparable in terms of the primary end point and were statistically superior to placebo (P<0.001). In study 1, rofecoxib was associated with a longer median time to use of rescue medication compared with valdecoxib 20 mg (>24 hours vs 23 hours 58 minutes; P=0.010) and a significantly smaller proportion of patients using rescue medication over 24 hours (35.0% vs 50.2%; P<0.001). In study 2, there were no significant differences in the median time to use of rescue medication or the proportion of patients using rescue medication between active treatments. There were no significant differences in total pain relief at 4 or 8 hours, patients' global assessment, onset of analgesia, or AEs between active treatments in either study. The incidence of clinical AEs in study 1 was similar for rofecoxib 50 mg, valdecoxib 20 mg, and placebo (39.5%, 36.8%, and 49.0%, respectively). In study 2, AEs occurred significantly less frequently with rofecoxib 50 mg compared with placebo (35.3% vs 70.8%, respectively; P<0.01); there was no significant difference between the rate of AEs with valdecoxib 40 mg (50.0%) and placebo. CONCLUSIONS: Rofecoxib 50 mg had comparable analgesic efficacy to valdecoxib 20 and 40 mg in these patients with pain after dental surgery. All active treatments were well tolerated.     

Ibuprofen liquigel for oral surgery pain

BACKGROUND: Ibuprofen liquigel is a solubilized potassium ibuprofen 200-mg gelatin capsule formulation that was approved for over-the-counter use in 1995. OBJECTIVE: This study compared the analgesic efficacy and tolerability of ibuprofen liquigel 200 mg, ibuprofen liquigel 400 mg, acetaminophen caplets 1000 mg, and placebo in patients experiencing moderate or severe pain after surgical removal of impacted third molars. METHODS: This randomized, double-blind, parallel-group, 6-hour study was conducted in 210 patients experiencing moderate or severe postoperative pain. Ratings of pain intensity and pain relief were recorded every 15 minutes for the first hour, at 90 and 120 minutes, and then hourly through hour 6. The onsets of first perceptible relief and meaningful relief were recorded using 2 stopwatches. An analysis of variance model was employed to test for significant differences (P < or = 0.05) between treatment groups with respect to pain relief, pain intensity difference, total pain relief (TOTPAR), and summed pain intensity difference (SPID). Stopwatch measures were analyzed using the Cox proportional hazards model. Drug tolerability was assessed by monitoring the occurrence of adverse events. RESULTS: During the first 2 hours of the study (TOTPAR 2 and SPID 2), all active treatments were significantly more efficacious than placebo (P < 0.001), with ibuprofen liquigel 200 and 400 mg significantly more efficacious than acetaminophen 1000 mg (P < 0.05 and P < 0.01, respectively). For the entire duration of the study (TOTPAR 6 and SPID 6), only the 2 doses of ibuprofen liquigel were significantly more efficacious than placebo (P < 0.001). Ibuprofen liquigel 200 and 400 mg were also significantly more efficacious than acetaminophen 1000 mg on the summary measures TOTPAR 6 and SPID 6 (P < 0.01 and P < 0.001, respectively). Analysis of the stopwatch data revealed that all active treatments displayed significantly more rapid onsets to confirmed first perceptible relief (P < 0.001 to < 0.05) and meaningful relief (P < 0.001 to < 0.01) than did placebo, with ibuprofen liquigel 400 mg displaying a significantly more rapid onset to meaningful relief than acetaminophen 1000 mg (P < 0.05) and a significantly more rapid onset to confirmed first perceptible relief than acetaminophen 1000 mg (P < 0.001) and ibuprofen liquigel 200 mg (P < 0.01). All adverse events were considered mild or moderate, with an overall incidence of 11.5% in the ibuprofen liquigel 200-mg group, 6.8% in the ibuprofen liquigel 400-mg group, 19.0% in the acetaminophen 1000-mg group, and 25.9% in the placebo group. CONCLUSIONS: Ibuprofen liquigel provided greater peak and overall analgesic effects and a more rapid onset to analgesia than did acetaminophen 1000 mg.     

Characterization of rofecoxib as a cyclooxygenase-2 isoform inhibitor and demonstration of analgesia in the dental pain model

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and indomethacin (INN, indometacin) inhibit both the constitutive (COX-1) and inducible (COX-2) isoforms of cyclooxygenase. The induction of COX-2 after inflammatory stimuli has led to the hypothesis that COX-2 inhibition primarily accounts for the therapeutic properties of NSAIDs. METHODS: Chinese hamster ovary (CHO) cell lines that express each COX isoform were used to characterize the in vitro selectivity of rofecoxib. Single oral doses of rofecoxib and indomethacin were then assessed in subjects with use of ex vivo COX-isoform specific assays (serum thromboxane B2 [TXB2] and lipopolysaccharide [LPS]-stimulated whole blood prostaglandin E2 and assays of COX-1 and COX-2 activity, respectively). A double-blind, parallel-group study compared the analgesic efficacy of rofecoxib to placebo and ibuprofen in 102 patients with dental pain. RESULTS: Rofecoxib showed a >800-fold COX-2 selectivity with use of CHO cells that express human COX-1 and COX-2. In subjects, dose- and concentration-dependent inhibition of LPS-stimulated prostaglandin E2 was observed with both rofecoxib (IC50 [the concentration estimated to produce 50% inhibition], 0.77 micromol/L) and indomethacin (IC50, 0.33 micromol/L). Whereas indomethacin inhibited TXB2, (IC50, 0.14 micromol/L), no inhibition was observed with rofecoxib even at doses of up to 1000 mg. In the dental pain study, total pain relief (TOTPAR) over the 6 hours after dosing was similar between 50 mg and 500 mg rofecoxib and 400 mg ibuprofen (P > .20). All active treatments showed greater improvement than placebo (P < .001) CONCLUSIONS: Rofecoxib inhibited COX-2 without evidence of COX-1 inhibition, even at oral doses of up to 1000 mg. Nonetheless, rofecoxib showed analgesic activity indistinguishable from that observed with ibuprofen, a nonisoform-selective COX inhibitor. These results support the hypothesis that the analgesic effects of NSAIDs primarily derive from inhibition of COX-2.     

Celecoxib in the treatment of primary dysmenorrhea: Results from two randomized,double-blind,active- and placebo-controlled,crossover studies

Background: Celecoxib, a cyclooxygenase-2 inhibitor, has established analgesic efficacy for the treatment of acute pain resulting from a variety of causes.Objective: This article describes 2 studies designed to assess the efficacy and tolerability of celecoxib in patients with primary dysmenorrhea.Methods: Two identical, 3-day, multiple-dose, randomized, double-blind, active- and placebo-controlled, crossover studies were carried out in women aged 18 to 44 years with primary dysmenorrhea (studies 1 and 2). The studies employed a 6-sequence, 3-period, complete-block crossover design over 3 menstrual cycles. Patients received celecoxib 400 mg, followed by celecoxib 200 mg no sooner than 12 hours after first dose (day 1), then celecoxib 200 mg q12h as necessary (days 2 and 3); naproxen sodium 550 mg followed by naproxen sodium 550 mg no sooner than 12 hours after first dose (day 1), then naproxen sodium 550 mg q12h as necessary (days 2 and 3); or placebo. Primary efficacy measures were time-weighted sum of total pain relief and time-weighted sum of pain intensity difference at 8 hours after administration of the first dose of study medication (TOTPAR[8] and SPID[8], respectively). Tolerability was assessed using routine physical examination, including vital sign measurements, and clinical laboratory analyses at screening and end of study.Results: In total, 149 and 154 patients were randomized to 1 of the 6 treatment sequences in studies 1 and 2, respectively. Across treatment sequences, mean age ranges were 23.4 to 26.9 years (study 1) and 28.3 to 34.1 years (study 2). Mean weight ranges were 62.7 to 74.5 kg (study 1) and 69.2 to 86.7 kg (study 2). Most patients (96.6% in study 1, 80.5% in study 2) were white. Mean TOTPAR[8] values with celecoxib (study 1/study 2, 18.28/17.98) and naproxen sodium (20.59/21.27) were significantly greater than with placebo (12.82/12.98) (all, P < 0.001). Mean SPID[8] values were significantly greater with celecoxib (10.06/9.60) and naproxen sodium (11.48/11.71) than with placebo (5.96/6.41) (all, P < 0.001). Naproxen sodium was significantly different from celecoxib in TOTPAR[8] (study 2 only) and SPID[8] (both studies) (all, P < 0.001). In both studies, the adverse-events (AEs) profile was not significantly different between treatments, with the majority of AEs being related to primary dysmenorrhea and not medication. Less than 10% of patients experienced severe AEs in any treatment period.Conclusions: In these 2 identically designed studies in women aged 18 to 44 years, celecoxib 400 mg (followed by 200 mg q12h) was more effective, as measured using pain scores, in the treatment of primary dysmenorrhea compared with placebo. In each study, the primary efficacy measures—TOTPAR[8] and SPID[8] scores—were significantly improved with celecoxib and naproxen sodium compared with placebo. SPID[8] in both studies and TOTPAR[8] in study 2 were significantly improved with naproxen sodium compared with celecoxib. Both celecoxib and naproxen sodium were well tolerated and provided relief from menstrual pain within 1 hour of administration.     

A double-blind,single-dose comparison of the analgesic efficacy of tramadol/acetaminophen combination tablets,hydrocodone/acetaminophen combination tablets,and placebo after oral surgery

BACKGROUND: Improved clinical outcomes have been documented with combinations of oral analgesic agents, particularly those with complementary activities. However, because not all combinations or dose ratios lead to enhanced analgesia or reduced adverse events (AEs), each combination and dose ratio must be evaluated individually in carefully designed preclinical and clinical trials. OBJECTIVE: The goal of the study was to compare the efficacy and safety of 37.5 mg tramadol/325 mg acetaminophen tablets (T/APAP), 10 mg hydrocodone bitartrate/650 mg acetaminophen tablets (HC/APAP), and placebo in the treatment of postoperative dental pain. METHODS: This was a single-center, double-blind, parallel-group, placebo- and active-controlled study in adults with at least moderate pain (score > or =50 on a 100-mm pain visual analog scale) after extraction of > or =2 impacted third molars. Patients were randomized to receive 1 or 2 T/APAP tablets, 1 HC/APAP tablet, or placebo. Scores for hourly pain relief (PAR), pain intensity difference (PID), and combined PAR and PID (PRID) were based on reported pain at 30 minutes and each successive hour for 8 hours. Primary efficacy measures were summary pain intensity and pain relief scores (total pain relief [TOTPAR], sum of pain intensity differences [SPID], and sum of pain relief and pain intensity differences [SPRIDI) for 0 to 4 hours, 4 to 8 hours, and 0 to 8 hours. Secondary efficacy measures were hourly PAR, PID, and PRID scores; onset and duration of pain relief; time to remedication with a supplemental analgesic agent; and patients' overall assessment of medication. RESULTS: Two hundred adults took part in the study (50 per treatment group) and were included in the efficacy and safety analyses. T/APAP 75/650 mg and HC/APAP were statistically superior to placebo on the primary efficacy measures of TOTPAR, SPID, and SPRID (P < or = 0.024), as well as on hourly PAR, PID, and PRID over 6 hours (P < or = 0.045). All active treatments were statistically superior to placebo in terms of onset of pain relief (P < or = 0.001), duration of pain relief (P < or = 0.024), time to remedication (P < 0.001), and patients' overall assessment of medication (P < 0.001). A statistically significant dose response with T/APAP (2 tablets > 1 tablet > placebo) was seen for TOTPAR, SPID, and SPRID (all, P < or = 0.018). The median time to onset of pain relief was approximately 34.0 minutes with 2 T/APAP tablets and 25.4 minutes with HC/APAP. Although the median time to onset of pain relief was shorter with HC/APAP, two T/APAP tablets had comparable efficacy to HC/APAP. The median time to remedication with a supplemental analgesic agent was 169.0 minutes in the T/APAP 75/650 mg group and 204.0 minutes in the HC/APAP group. However, the duration of pain relief, as defined by time to remedication, was not significantly different between these 2 groups. The overall incidence of AEs was lower with T/APAP (0% treatment-related AEs) than with HC/APAP (4%) or placebo (10%). The incidence of nausea (18% T/APAP, 36% HC/APAP) and vomiting (12% T/APAP, 30% HC/APAP) was approximately 50% lower with 2 T/APAP tablets than with HC/APAP (P < 0.05). CONCLUSIONS: T/APAP tablets provided effective, rapid (< or = 34 minutes), dose-dependent analgesia for the treatment of postoperative dental pain. Two T/APAP tablets provided analgesia comparable to that provided by HC/APAP with better tolerability.     

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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

A single-blind, randomized, controlled trial to assess the efficacy and tolerability of rofecoxib, diclofenac sodium, and meloxicam in patients with acute gouty arthritis

BACKGROUND: Acute attacks of gouty arthritis are characterized by the rapid onset of severe pain, swelling, and erythema of the affected joint. Nonsteroidal anti-inflammatory drugs are considered the drugs of first choice for treating acute gout. Rofecoxib is a specific cyclooxygenase-2 inhibitor, which has demonstrated analgesic efficacy in the setting of acute pain. Whether it is effective in the treatment of acute gouty arthritis remains to be evaluated. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of rofecoxib compared with diclofenac sodium sustained release (SR) and meloxicam in the treatment of acute gouty arthritis. METHODS: In this single-blind, randomized, controlled, parallel-group study, patients aged > or =18 years with acute gout within 48 hours of onset were randomized to receive oral treatment with 2 tablets of rofecoxib (25 mg), diclofenac (75 mg), or meloxicam (7.5 mg) once daily for 7 days. The primary outcome measures were patients global assessment of response to therapy and investigator assessment of response to therapy on days 3 and 8. Other efficacy measurements included investigator assessment of total inflammatory scores on days 3 and 8 and patient assessment of pain intensity during the first 12 hours of treatment. RESULTS: Sixty-two patients (53 men, 9 women; mean [SD] age, 51.1 [12.1] years) were assigned to receive rofexocib (n = 20), diclofenac (n = 21), or meloxicam (n = 21). For patient global response to therapy on days 3 and 8, rofecoxib was associated with analgesic efficacy in significantly more patients compared with meloxicam (84.2% vs 40.0% of patients [ P=0.005] and 94.7% vs 60.0% of patients [ P=0.02], respectively); no significant differences versus diclofenac were found. Similarly, for investigator global assessment of response to therapy, a greater percentage of responders was found in the rofecoxib group compared with the meloxicam group on day 3 (88.9% vs 40.0% of patients [ P=0.02 ]), but the difference was not significant on day 8. A greater percentage of responders was found in the rofecoxib group compared with the diclofenac group on day 3 (88.9% vs 47.3% [ P=0.007 ]), but the difference was not significant on day 8. Compared with baseline, all regimens showed significant improvement in total inflammatory scores on days 3 and 8 (all P<0.01 ). During the first 12 hours after dosing, pain intensity score was significantly reduced with rofecoxib starting at 0.5 hours ( P<0.05 ), but not with diclofenac or meloxicam. Clinical adverse events (AEs) were reported in 4 (20.0%), 7 (33.3%), and 6 (28.6%) patients in the rofecoxib, diclofenac, and meloxicam groups, respectively; the most common AEs reported were edema in 1 patient each in the rofecoxib (5.0%) and meloxicam (4.8%) groups and 2 patients (9.5%) in the diclofenac group and abdominal (1 [5.0%], 1 [4.8%], and 2 [9.5%], respectively). No significant differences in tolerability were found among the 3 treatment groups. CONCLUSIONS: In this study of patients with acute gouty arthritis, rofecoxib 50 mg once daily provided more effective treatment than diclofenac sodium SR 150 mg and meloxicam 15 mg administered orally once daily for 7 days in > or = 1 efficacy assessment of overall analgesic effect on day 3 or day 8. Rofecoxib achieved a rapid onset of pain relief, demonstrating significant improvement 30 minutes after dosing. All of the regimens appeared well tolerated in the population studied.     

Valdecoxib versus rofecoxib in acute postsurgical pain: results of a randomized controlled trial

The analgesic efficacy of the cyclooxygenase-2 specific inhibitors, valdecoxib and rofecoxib, were evaluated in patients following oral surgery. In a randomized, double-blind, controlled trial, patients experiencing moderate or severe pain received single-dose valdecoxib 40 mg (n=99), rofecoxib 50 mg (n=101), or placebo (n=50) within 4 hours after multiple third molar extraction with bone removal. Onset of action was significantly faster with valdecoxib 40 mg (30 minutes) compared with rofecoxib 50 mg (45 minutes), as measured by pain intensity difference and pain relief scores (P 相似文献   

Analgesic efficacy of the cyclooxygenase-inhibiting nitric oxide donor AZD3582 in postoperative dental pain: Comparison with naproxen and rofecoxib in two randomized, double-blind, placebo-controlled studies

OBJECTIVE: This study assessed the analgesic efficacy of single doses of 4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate (AZD3582) in acute postoperative dental pain after the removal of an impacted mandibular third molar (ie, wisdom tooth). METHODS: Two randomized, placebo-controlled, double-blind studies were performed. In a dose-finding study, 242 patients were randomized to AZD3582 375, 750, 1500, or 2250 mg (n = 41, 37, 42, and 41, respectively); naproxen 500 mg (n = 39); or placebo (n = 42). In a comparator study, 282 patients were randomized to AZD3582 500 mg (n = 78) or 750 mg (n = 83), rofecoxib 50 mg (n = 80), or placebo (n = 41). Primary outcomes included time to rescue medication, time to pain relief, and mean pain intensity difference (MPID), as well as safety profile. Pain was rated on a visual analog scale. RESULTS: In the dose-finding study, 52% (126/242) were women; the mean (SD) age was 25.1 (4) years, mean weight was 69.0 kg, and the mean (SD) body mass index (BMI) was 23.7 (3) kg/m2. In the comparator study, 58% (164/282) were women; the mean (SD) age was 27 (6.4) years, mean weight was 71 kg, and mean (SD) BMI was 24.2 (3) kg/m2. In the dose-finding study, the AZD3582 750-, 1500-, and 2250-mg groups were superior to placebo in the primary variables "time to rescue medication (0-8 hours)" (hazard ratios [HRs] [95% CIs], 0.17 [0.07-0.42], P < 0.003; 0.23 [0.11-0.50], P < 0.001; and 0.15 [0.06-0.36], P < 0.001, respectively), "time to meaningful pain relief" (HRs [95% CIs], 3.42 [1.87-6.25], P < 0.003; 2.49 [1.37-4.50], P < 0.003; and 3.07 [1.70-5.55], P < 0.001, respectively), and MPID (analysis of covariance [ANCOVA] least squares mean [LSM] differences [95% CIs], 25.8 [17.3-34.4], P < 0.003; 20.4 [12.1-28.7], P < 0.003; and 29.3 [20.9-37.6], P < 0.001, respectively). AZD3582 and naproxen did not show any statistically significant differences for the 3 primary variables, except that naproxen was superior to the AZD3582 375-mg dose for the variables time to meaningful pain relief (HR difference, 0.48 [95% CI, 0.29-0.78], P < 0.004) and MPID (difference in ANCOVA LSM, -10.2, [95% CI, -18.2 to -2.2], P < 0.012). The median times to meaningful pain relief were 115 minutes for AZD3582 375 mg, 66 minutes for 750 mg, 85 minutes for 1500 mg, 81 minutes for 2250 mg, and 162 minutes for placebo (P = NS, P = 0.003, P < 0.003, and P < 0.001, respectively). The median time to first rescue medication was 144 minutes for placebo, and <50% of the subjects on any of the AZD3582 doses or naproxen took rescue medication within 8 hours after dosing. In the comparator study, AZD3582 750 mg was superior to placebo in "time to rescue medication (0-24 hours)" (HR [95% CI], 0.4 [0.3-0.6], P < 0.001), "time to confirmed perceptible pain relief" (2.1 [1.1-3.8], P = 0.02), and MPID (11.9 [4.2-19.5], P = 0.002). However, inferiority of AZD3582 to rofecoxib for MPID could not be excluded (tolerance limit of 10 mm; P = NS for noninferiority testing). The median times to confirmed perceptible pain relief were 45 minutes for AZD3582 500 mg, 40 minutes for 750 mg, and 37 minutes for rofecoxib. The median times to first rescue medication were 218 minutes for AZD3582 500 mg, 365 minutes for 750 mg, 635 minutes for rofecoxib, and 90 minutes for placebo. Overall, AZD3582 was well tolerated. However, an effect on orthostatic blood pressure could not be excluded because there seemed to be more subjects with dizziness and orthostatic blood pressure reduction who were administered AZD3582 > or =750 mg. The proportions of patients with vertigo and decreased orthostatic blood pressure each group were as follows: AZD3582 500 mg, 6%; AZD3582 750 mg, 12%; rofecoxib, 3%; and placebo, 5%. CONCLUSIONS: AZD3582 750 mg had similar analgesic efficacy as equimolar doses of naproxen, but noninferiority to rofecoxib was not demonstrated.     

The efficacy of preoperative versus postoperative rofecoxib for preventing acute postoperative dental pain: a prospective randomized crossover study using bilateral symmetrical oral surgery

BACKGROUND: Previous data have demonstrated that rofecoxib has good analgesic efficacy for acute postoperative dental pain. However, up to half of these patients require rescue analgesics within the first 24 hours. As the timing of analgesic interventions may be an important factor in pain control, the present study tested the hypothesis that rofecoxib administered preoperatively would improve the analgesic efficacy and reduce rescue analgesic requirements within the first 24 hours compared with postoperative administration. METHODS: This was a double-blind, randomized, crossover study where 45 patients had each of their identical impacted mandibular third molars removed under local anesthesia on 2 separate occasions. Patients acted as their own control; one side was pretreated with rofecoxib 50 mg, 2 hours before surgery, followed by placebo 15 minutes after surgery, and the contralateral side was pretreated with placebo 2 hours before surgery and posttreated with rofecoxib 50 mg 15 minutes after surgery. The difference in postoperative pain between 2 sides was assessed by 4 primary end-points: pain intensity as measured by a 100-mm visual analogue scale hourly for 12 hours, time to rescue analgesic, postoperative analgesic consumption, and patient's global assessment. RESULTS: Patients reported significantly lower pain scores (P = 0.04), longer time to rescue analgesic (P = 0.02), lesser postoperative analgesic consumption (P = 0.008), and better global assessment (P = 0.01) in the pretreated compared with the posttreated sides. There were significantly more patients in the pretreated group who did not required rescue analgesic within the first 24 hours (80% vs. 58%, P = 0.01), and the pain scores were extremely low in both groups during the 12 hours postoperative period (9.8 +/- 5.0 mm vs. 14.3 +/- 7.4 mm). CONCLUSION: Rofecoxib is an excellent analgesic for preventing postoperative dental pain and when given 2 hours preoperatively rendered most patients relatively pain free, requiring no rescue analgesics on the first postoperative day.     

The effect of three cyclo-oxygenase inhibitors on intensity of primary dysmenorrheic pain

OBJECTIVE: To determine the effect of 3 different cyclo-oxygenase (COX) inhibitors on primary dysmenorrheic pain. METHOD: Eleven female patients self-medicated with either placebo (sugar), 25 mg of the COX-2 specific inhibitor rofecoxib, 50 mg of the nonselective COX inhibitor diclofenac potassium, or 7.5 mg of the COX-2 selective inhibitor meloxicam, over 4 menstrual cycles. Pain was assessed using the McGill Pain Questionnaire and a visual analog scale. RESULTS: The pain response index, present pain index, and visual analog scale were highly correlated as measures of intensity of pain (r=0.81 to 0.96, P<0.0001). Rofecoxib and diclofenac potassium both decreased the duration of dysmenorrheic pain compared with placebo (P<0.001) and with meloxicam (P<0.01), and were equally effective in improving pain, compared with placebo, after each capsule (P<0.001). When compared with placebo, both drugs also provided 50% or more pain relief, after each capsule (P<0.0048). Meloxicam, although superior to placebo, was not as effective as rofecoxib and diclofenac potassium in reducing pain, and when compared with placebo, was associated with providing 50% or more of pain relief only after the third and fourth capsules (P=0.016). CONCLUSIONS: Rofecoxib and diclofenac potassium, when taken in recommended doses, were equally effective in alleviating pain associated with primary dysmenorrhea.