Etoricoxib in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled dose-ranging study. Evaluation of the dose range of etoricoxib in an acute pain setting using the postoperative dental pain model. Etoricoxib provides analgesic efficacy to patients after knee or hip replacement surgery: a randomized, double-blind, placebo-controlled study. 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. The efficacy of etodolac for patients with pain following oral surgery. Analgesic efficacy of pre-operative etoricoxib for termination of pregnancy in an ambulatory centre. Comparison of etodolac, zomepirac, and placebo for relief of pain after oral surgery. Conventional and extended-release etodolac for postsurgical dental pain. Analgesic efficacy of etoricoxib in primary dysmenorrhea: results of a randomized, controlled trial.
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.
                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.
                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.
                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. This study was conducted to evaluate the dose range of etoricoxib in acute pain using the postoperative dental pain model further.
                This double-blind, randomized controlled study evaluated etoricoxib (90 and 120 mg), ibuprofen (600 mg), and acetaminophen (600 mg/codeine) (60 mg, (A/C)) in patients aged ≥ 18 years with moderate or severe pain after surgical extraction of ≥ 2 third molars (≥ 1 impacted). The patients reported pain intensity and pain relief over 24 hours. The primary efficacy endpoint was total pain relief over 6 hours (TOPAR6). Adverse events were evaluated throughout the study.
                There were 588 patients randomized to placebo (n=46),etoricoxib (90 mg (n=191)), etoricoxib (120 mg (n=97)), ibuprofen(2400 mg (n=192)), and A/C (n=62). The overall analgesic effect (TOPAR6) of etoricoxib (90, 120 mg) was significantly greater than that of placebo (P ≤ 0.001), and not inferior to that of ibuprofen; no discernible difference was observed between etoricoxib 90 and 120 mg. Both etoricoxib doses were superior to A/C (P ≤ 0.001). Etoricoxib (90 and 120 mg) and ibuprofen(2400 mg) were generally well tolerated and had a similar incidence of adverse events (AEs). A/C was associated with significantly more AEs that led to discontinuation (ie, nausea and vomiting).
                Etoricoxib (90 and 120 mg) showed similar efficacy in the postoperative dental pain model, which was noninferior to ibuprofen and superior to A/C. A higher number of tooth extractions or a higher mean impaction score may have led to a greater separation in efficacy between the 2 etoricoxib doses. In this randomized, double-blind, placebo-controlled, multicenter study we assessed the analgesic effect of etoricoxib (a new cyclooxygenase-2 inhibitor) in patients having had knee or hip replacement surgery. A total of 228 patients with moderate or severe pain were randomly allocated within 72 h after surgery to receive etoricoxib 120 mg, controlled-release naproxen sodium 1100 mg, or placebo (1:1:1) on day 1 followed by etoricoxib and placebo (1:2) on days 2 to 7. Patients reported pain scores, rescue (opioid-combination) medication use, and the response to study drug. On day 1, etoricoxib provided an analgesic effect superior to placebo and similar to controlled-release naproxen sodium as demonstrated by the total pain relief score over 8 h, the primary end-point; least-squares mean scores were 11.0, 11.5, and 5.6, respectively (P < 0.001 versus placebo). Similarly, a larger percentage of patients receiving etoricoxib and naproxen sodium than those receiving placebo reported good to excellent responses to study drug: 53%, 60%, and 26% respectively. On days 2-7, etoricoxib demonstrated a significant reduction of rescue medication use, 35% (P < 0.001 versus placebo). The clinical relevance of the decrease was confirmed by Patient's Global Evaluation (P < 0.05 versus placebo). Patients receiving etoricoxib also experienced significantly less "worst" and "average" pain than did those on placebo. Etoricoxib was generally well tolerated in this study; the incidence of adverse experiences was infrequent and similar across treatment groups. In summary, etoricoxib provided analgesia that was similar to controlled-release naproxen sodium on day 1 and superior to placebo with reduced supplemental opioid use over 7 days.
                In a postsurgery setting (knee and hip replacements), etoricoxib 120 mg provided analgesia superior to placebo and similar to controlled-release naproxen sodium 1100 mg. Patients receiving etoricoxib suffered less pain and took less opioid rescue medication compared with patients on placebo. 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.
                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.
                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.
                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. The analgesic efficacy of etodolac for 161 patients reporting moderate to severe pain after oral surgery was evaluated. The patients were given single oral doses of one of the following test drugs--aspirin, 650 mg; etodolac, 50 mg; or etodolac, 200 mg--or placebo. There were at least 39 patients in each drug group. After medication, patients recorded pain intensity and pain relief at half-hour intervals for the first hour and then hourly for up to eight hours. Pain intensity differences, total pain relief, onset of analgesia, and each patient's overall opinion of the drug were analyzed. Time--effect curves were derived from the pain relief and pain intensity difference scores. Analgesic effects produced by both doses of etodolac were comparable with those of 650 mg of aspirin. All active drugs were significantly more effective than placebo, and the 200-mg dose of etodolac provided an earlier onset and longer duration of analgesia than the other test drugs. Etoricoxib is a second generation cyclooxygenase-2 inhibitor with a rapid-onset time and a long duration of action. It is ideal for providing pre-emptive analgesia for ambulatory surgeries. We hypothesised that pre-operative etoricoxib can decrease the use of fentanyl post-operatively, when compared with placebo in patients undergoing termination of pregnancy. We also compared their pain scores, time to discharge, side effects and satisfaction with analgesia post-operatively.
                After approval by the hospital research ethics committee and receipt of informed written consent, we recruited 40 American Society of Anesthesiologists Physical Status Classification I and II patients scheduled for elective first trimester termination of pregnancy. Patients were randomly allocated to receive either oral etoricoxib 120 mg (Group E, n=20) or placebo tablet (Group P, n=20) pre-operatively. A blinded observer evaluated the post-operative pain scores, need for supplementary analgesia, side effects and satisfaction scores. Sample size was calculated (power of 0.8 and alpha=0.05) to detect a 20 percent difference in fentanyl usage. Amount of fentanyl used, pain scores and satisfaction scores were analysed using non-parametric tests. The incidence of side effects was analysed using chi-squared test.
                Etoricoxib 120 mg significantly decreased the amount of fentanyl required after termination of pregnancy compared to placebo (0 microg/patient, interquartile range [IQR] 0-25 versus 50 microg/patient, IQR 0-50, p-value is less than 0.05). Patients who received etoricoxib 120 mg also had significantly lower pain scores than the placebo group at time of discharge (8 +/- 11 versus 1 +/- 3, p-value is less than 0.05) and at six hours post operation (8 +/- 12 versus 0 +/- 0, p-value is less than 0.01). There was no difference in their side effects, and time to discharge and overall satisfaction were similar in both groups.
                Pre-operative administration of oral etoricoxib 120 mg decreased the use of fentanyl and pain scores after minor gynaecological surgery without significant side effects. A double-blind, randomized study of 137 patients compared the effectiveness of single doses of etodolac, 200 and 400 mg, zomepirac, 100 mg, and placebo in relieving moderate to severe pain following third molar extractions. Throughout the 12-hour evaluation period, doses of both etodolac and zomepirac were significantly superior to placebo for total analgesic effect, as measured by the sum of pain intensity difference (SPID) and sum of pain relief (TOTPAR) scores. However, there were no significant differences among the active drugs. It was concluded that etodolac, 200 and 400 mg, provides analgesic efficacy comparable to that of zomepirac, 100 mg, and superior to that of placebo. This double-masked, parallel-group, randomized study compared the analgesic efficacy and tolerability of a single investigational 1200-mg dose of extended-release etodolac with those of a single 400-mg dose of extended-release etodolac and twice-daily doses of conventional etodolac 200 and 400 mg and placebo given 8 hours apart in 237 patients with moderate or severe postoperative pain following surgical removal of > or = 2 impacted third molars. Both doses of conventional etodolac and the 1200-mg dose of extended-release etodolac were significantly more effective on all summary analgesic measures than placebo (P < 0.05). Conventional etodolac had an onset of analgesic activity within 45 (400 mg) to 60 (200 mg) minutes and an analgesic duration of 5 to 6 hours. Extended-release etodolac 1200 mg had an onset of action within 60 minutes and an analgesic duration of 12 to 24 hours. At hours 2 and 3, conventional etodolac 400 mg was significantly more effective than the other treatments; from hours 6 through 12, extended-release etodolac 1200 mg was significantly more effective than the other treatments (both, P < 0.05). No serious adverse events were observed in this study, with an incidence of side effects in the active etodolac groups no different than that with placebo. Extended-release etodolac 1200 mg has a prolonged analgesic duration and an acceptable side-effect profile in the oral surgery pain model. To determine the efficacy of etoricoxib in the treatment of primary dysmenorrhea.
                Seventy-three women were randomly assigned to receive single oral doses of etoricoxib 120 mg, placebo, or naproxen sodium 550 mg at the onset of moderate to severe pain associated with menses. During 3 consecutive menstrual cycles in this double-blind, 3-period, crossover study, pain intensity and pain relief were assessed over the 24-hour period following dosing, and global ratings of therapy were made at 8 and 24 h after dosing. Tolerability was assessed by spontaneous reports of adverse experiences.
                Etoricoxib 120 mg provided analgesic efficacy superior to placebo for the primary endpoint, total pain relief over 8 h (TOPAR8, p<0.001), and for all secondary endpoints (p<0.050). The analgesic effect of etoricoxib 120 mg over the first 8 h was similar to that of naproxen sodium 550 mg. All treatments were well tolerated.
                Etoricoxib 120 mg provided rapid and sustained analgesia that was superior to placebo and similar to that of naproxen sodium 550 mg.
                Copyright 2003 S. Karger AG, Basel
The additional study did not change the results from the first review published in 2009, but does make the result more robust. Single dose oral etoricoxib produces high levels of good quality pain relief after surgery and adverse events did not differ from placebo. The 120 mg dose is as effective as, or better than, other commonly used analgesics.