The additive analgesic efficacy of acetaminophen, 1000 mg, and codeine, 60 mg, in dental pain. Double-blind comparison of meclofenamate sodium plus codeine, meclofenamate sodium, codeine, and placebo for relief of pain following surgical removal of third molars. Propiram and codeine in episiotomy pain. Double-blind comparison of the analgesic potency of ciramadol, codeine and placebo against postsurgical pain in ambulant patients. The relative analgesic efficacy of propiram fumarate, codeine, aspirin, and placebo in post-impaction dental pain. A double-blind study of diflunisal and codeine compared with codeine or diflunisal alone in postoperative pain. Analgesic efficacy of an ibuprofen-codeine combination. Double-blind parallel comparison of single oral doses of ketoprofen, codeine, and placebo in patients with moderate to severe dental pain. Narcotic receptor blockade and its effect on the analgesic response to placebo and ibuprofen after oral surgery. A double-blind trial of single-dose ciramadol for the treatment of post-episiotomy pain. Analgesic effect of naproxen sodium, codeine, a naproxen-codeine combination and aspirin on the postoperative pain of oral surgery. Analgesic effects of oral propiram fumarate, codeine sulfate and placebo in postoperative pain. Double-blind comparison of meclofenamate sodium with codeine and placebo for the pain of episiotomy. Comparison of zomepirac, APC with codeine, codeine and placebo in the treatment of moderate and severe postoperative pain. An appraisal of codeine as an analgesic: single-dose analysis. Analgesic efficacy of piroxicam in the treatment of postoperative pain. Analgesic efficacy of two ibuprofen-codeine combinations for the treatment of postepisiotomy and postoperative pain. Analgesic efficacy of meclofenamate sodium in episiotomy pain.
In a double-blind, randomized, single-dose trial the analgesic contribution of acetaminophen, 1000 mg, and codeine, 60 mg, was determined. The study was a 2 X 2 factorial experiment in which 120 patients suffering from pain as a result of oral surgery rated their pain intensity and pain relief for up to 5 hours after a single dose of one of: 1000 mg acetaminophen, 60 mg codeine, 1000 mg acetaminophen plus 60 mg codeine, or placebo. The factorial analysis showed that both 1000 mg acetaminophen and 60 mg codeine made a statistically significant (P less than 0.05) contribution to the analgesic effectiveness of the combination on all measures of efficacy (sum of pain intensity differences, largest pain intensity difference, total pain relief, largest pain relief, and time to remedication). The incidence of adverse effects did not appear to differ among the treatments, including placebo. A single-dose, randomized, double-blind, parallel-treatment study was performed in 200 outpatients with acute pain caused by the surgical removal of impacted third molars. Meclofenamate 100 mg plus codeine 60 mg, meclofenamate 50 mg plus codeine 30 mg, meclofenamate 100 mg, codeine 60 mg, and placebo treatment groups were compared for sum of pain intensity differences, peak pain intensity difference, sum of pain relief scores, peak pain relief, number of observations at which pain was half relieved, overall evaluation of effectiveness, and time to remedication with a backup analgesic. Meclofenamate 100 mg plus codeine 60 mg was significantly more effective (P less than .005) than codeine 60 mg for all variables except number of observations at which pain was half relieved. Both meclofenamate-codeine combinations and meclofenamate 100 mg alone were significantly more effective (P less than .005) than placebo for all variables. Eleven adverse experiences were reported in 7 patients (3.5%); the most common was somnolence in 1 patient receiving meclofenamate 100 mg plus codeine 60 mg, in 2 treated with meclofenamate 50 mg plus codeine 30 mg, and in 1 treated with codeine 60 mg. To evaluate relative efficacy, safety, and time course of analgesia, propiram fumarate (50 and 100 mg), a new narcotic agonist-antagonist, was compared with codeine sulfate (60 mg) and placebo in a clinical trial with a single peroral dose, parallel, stratified, randomized, and double-blind design involving 80 hospitalized postpartum women with medium or severe episiotomy pain. Using verbal subjective reports as index of response, patients rated pain intensity and side effects at periodic interviews for 6 h. Relative efficacy findings based on peak effects and summed pain-intensity differences suggested dose-dependent analgesia with propiram and also that 60 mg codeine lay between 50 mg propiram and placebo. Moreover, after 50 or 100 mg propiram, 8 of 20 patients reported greater than 50% reduction of initial pain compared with 7 of 20 after 60 mg codeine and 2 of 20 after placebo. After each of the propiram doses, distinct analgesia began within 1/2 h and reached peak effect between 1 h (p less than 0.02) and 2 h (p less than 0.05). After f60 mg codeine, onset was slower and peak later (4 h, p less than 0.05). All three active drugs continued to act until the 5th or 6th h. Drowsiness was the only statistically significant side effect reported after propiram. These results suggest that single 50 or 100 mg doses of propiram were effective in episiotomy pain, induced stronger analgesia than 60 mg codeine, and took effect more rapidly. The efficacy and safety of ciramadol (Cir) as an analgesic in relieving moderate to severe pain after oral surgery has been studied in 79 patients randomly assigned to receive single oral doses of Cir 15, 30 or 60 mg, codeine 60 mg or placebo. During the 6-hour observation period, the three ciramadol-treated groups indicated greater pain relief than the codeine 60 mg or placebo groups. In general, Cir 60 mg was significantly more effective than codeine 60 mg, and all doses of Cir were superior to placebo. The proportion of patients in each Cir group reporting adverse experiences was significantly higher than in either the placebo or codeine groups. The experimental system proved very effective in demonstrating analgesic potency of Cir. The very high incidence of side-effects in the three ciramadol-treated groups makes it unfit for further clinical use in ambulant patients. To evaluate the analgesic efficacy of orally administered 50 mg propiram fumarate, 650 mg aspirin, 60 mg codeine phosphate, and placebo in acute post-impaction dental pain, 159 patients with moderate or severe pain were randomly allocated to the four treatments in this single-dose double-blind, stratified, parallel-group study. A research nurse questioned the patients at 1/2 hour and hourly for 6 hours after medicating. A standard format was used to question subjects about their pain intensity and relief from the starting pain. Propiram, 50 mg, produced a level of analgesia approaching that of 650 mg aspirin in peak effect, total effect, and duration of action and was statistically superior to 60 mg codeine and placebo for every measure of analgesic efficacy. Several mild adverse effects were observed; however, they appeared to be evenly distributed among the active treatments. A double-blind, randomized, parallel-group study compared the analgesic efficacy of a single oral dose of 500 mg diflunisal, 60 mg codeine, 500 mg diflunisal plus 60 mg codeine given as separate agents, and placebo in 161 patients with moderate to severe postoperative pain. Standard subjective measures were used to evaluate analgesia. Eight-hour sum of pain intensity differences and total pain relief scores for all active treatments were significantly better than were those for placebo (p less than 0.05). Diflunisal plus codeine performed the best followed by diflunisal, codeine, and placebo. Diflunisal plus codeine was better than placebo from 1 1/2 to 8 hours (p less than 0.01), better than codeine from 1 1/2 to 6 hours (p less than 0.05), and better than diflunisal alone from 1/2 to 1 1/2 hours (p less than 0.05) for most measures of analgesia. Factorial analysis demonstrated a significant early codeine effect and a significant diflunisal effect throughout. No significant treatment group differences were observed regarding adverse effects. Our data demonstrate that diflunisal plus codeine is generally well tolerated and provides analgesia superior to that of diflunisal or codeine alone in the treatment of moderate to severe postoperative pain. Subjects who had undergone dental impaction surgery and who had moderate to severe postoperative pain were given, under double-blind, randomized conditions, a single dose of either codeine 60 mg, aspirin 650 mg, ibuprofen 400 mg, aspirin 650 mg + codeine 60 mg, ibuprofen 400 mg + codeine 60 mg, or placebo. A total of 249 subjects were included in the statistical analysis. On a report form, subjects recorded pain intensity, pain relief, and side effects hourly for four hours. They also gave an overall impression at the end of the observation period. Analysis of variance and pairwise contrasts were used to analyze the data. For the sum of pain intensity differences, the total of the hourly pain relief scores, and overall impression, there was a significant analgesic effect for codeine, aspirin, and ibuprofen and no significant interaction when they were used in combination. Ibuprofen alone was statistically superior to aspirin and also achieved higher mean scores than the aspirin-codeine combination. The ibuprofen-codeine combination was the most effective treatment for every analgesic parameter, but it was not statistically superior to ibuprofen alone. The possibility exists that the ibuprofen-codeine combination peaked out the sensitivity of the model. There was no notable difference in the frequency or intensity of side effects among the treatment groups, and no subject had to withdraw due to an adverse effect. This study again confirms the superiority of ibuprofen to aspirin and suggests that ibuprofen is at least as effective as an aspirin-codeine combination. Codeine added a small amount of additional analgesia when used in combination with ibuprofen. Ketoprofen, 25, 50, and 100 mg, was compared with 90 mg codeine and placebo for relief of pain due to removal of impacted third molar teeth. Treatment was self-administered as a single oral dose under double-blind conditions in five parallel groups established by a random code in healthy young adults. Based on 129 patient evaluations of pain experience and pain relief, ketoprofen was shown to have a more rapid onset and longer duration of action than codeine. In the derived variables of SPID (Sum of Pain Intensity Differences) and TOPAR (Total Pain Relief), all three doses of ketoprofen, with no dose-related differences among them, were found to provide statistically superior analgesia to codeine and placebo. All five treatments were associated with some adverse reactions. The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo, codeine, and ibuprofen after oral surgery. Eighty-one patients undergoing complicated dental extractions were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg, 30 minutes before surgery. After surgery, patients self administered one of three possible postsurgical medications, which included placebo, codeine 60 mg, and ibuprofen 400 mg, when their pain reached a moderate or severe intensity. The study was double-blind with the three postsurgical treatments being randomly allocated within each presurgical treatment block. Pain intensity, pain relief, pain half gone, and overall evaluations were assessed for up to 6 hours. Ibuprofen was significantly more efficacious (p < .05) than codeine or placebo for most analgesic measures. The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine. Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen, but surprisingly prolonged (p < .05) the duration of its action. The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response, but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism. A randomized double-blind trial was carried out in 54 women to evaluate the effectiveness of ciramadol in a single (60 or 30 mg) oral dose regimen, compared with 60 mg codeine and placebo, in the treatment of post-episiotomy pain. Ciramadol gave a significantly better analgesic effect, at both 2 and 6 hours, and produced negligible side-effects. Codeine did less well than placebo in this study. In a double-blind study, 198 outpatients with pain after oral surgery were randomly assigned to treatment with a single oral dose of naproxen sodium 550 mg, codeine sulfate 60 mg, a combination of naproxen sodium 550 mg with codeine sulfate 60 mg, aspirin 650 mg or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medication. Orthogonal contrasts for the four treatments making up the factorial component showed that the naproxen effect was significant for every measurement of total and peak analgesia; the codeine effect was significant for total and peak pain relief and patients' overall evaluation. The naproxen-codeine interaction was not statistically significant for any measure, which suggests that the analgesic effect of the combination represents the additive effect of its constituents. Based on pairwise comparisons, aspirin was significantly superior to placebo for most measures of effect, naproxen was significantly superior to both aspirin and codeine for all measures and the combination was significantly superior to naproxen for patients' overall evaluation. No more patients experienced adverse effects with aspirin or naproxen than with placebo, but significantly more patients receiving the codeine-containing treatments experienced adverse effects than those receiving aspirin and naproxen. Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of propiram fumarate 50 mg, codeine sulfate 60 mg and placebo in the relief of moderate to severe postoperative pain. One hundred and twenty patients completed a randomized, double-blind, single-dose, stratified, parallel-groups trial and were observed for either 4 or 6 hours. Based upon each of the summary efficacy measures--SPID, % SPID and TOTAL--propiram and codeine were approximately equally effective and both were statistically superior to placebo. Propiram was significantly more effective than codeine at hour 5 for Pain Intensity Difference. Two adverse effects were attributed to propiram. Propiram fumarate 50 mg is an effective oral analgesic similar to codeine sulfate 60 mg, with the possibility of a longer duration of action. Meclofenamate sodium, a nonsteroidal anti-inflammatory agent, was compared at two dose levels (100 mg and 200 mg) with codeine (60 mg) and placebo in a double-blind, randomized study of 218 women after normal vaginal delivery. The purpose was to determine the analgesic efficacy and safety of meclofenamate sodium for the short-term treatment of acute episiotomy pain. Meclofenamate sodium was significantly better than placebo in most measures of pain relief and reduction of pain intensity. The 100-mg dose of meclofenamate sodium was significantly better than codeine in relieving pain. Adverse experiences with the study medications were minimal (6.4%). Patients receiving codeine reported more side effects than did those receiving either dose of meclofenamate sodium. Meclofenamate sodium is a safe, effective analgesic for acute episiotomy pain. nan Codeine, a relatively weak oral narcotic agent, is the most frequently prescribed oral opiate drug. It is also frequently utilized as a control drug in comparative analgesic efficacy studies. These studies are often single dose analysis of pain relief following surgery or childbirth. We conducted a single dose, post-operative analysis of 116 patients who were randomly assigned to receive codeine 60 mg, acetaminophen 600 mg, the combination of codeine and acetaminophen at these doses, or a placebo. Only the combination agent was uniformly superior to placebo. Codeine 60 mg was not consistently superior to placebo in this post-operative single dose analysis. A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic, in acceptable oral doses, in the single dose setting. Previous reports, however, suggest that the multiple doses of codeine may afford adequate analgesia. Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult. Two randomized, double-blind, single-dose studies were conducted to assess the analgesic efficacy and safety of piroxicam for the treatment of moderate or severe postoperative pain. Study 1 evaluated the analgesic efficacy of piroxicam 20 mg compared with that of codeine sulfate 60 mg and placebo. A final patient population of 149 subjects rated pain intensity and pain relief at one half hour and one hour following treatment and then hourly for six hours, with a global assessment made at the completion of 24 hours. Piroxicam 20 mg was significantly more efficacious than placebo for all analgesic variables, including the sum of the pain intensity differences (SPID), total pain relief (TOTAL), percent SPID, duration of effect, and time to remedication. Codeine 60 mg was significantly superior to placebo for percent SPID and some hourly measures. Piroxicam 20 mg was significantly more effective than codeine 60 mg for percent SPID and a few hourly measures including time to remedication. Study 2 assessed the efficacy of piroxicam 20 mg or 40 mg compared with aspirin 648 mg and placebo. Sixty patients rated their pain intensity and relief hourly for 12 hours and at 24 hours after administration of study medication. Both doses of piroxicam were significantly more effective than placebo from Hours 2 to 12 for pain intensity difference (PID) and relief scores, as well as for SPID and TOTAL. Aspirin was significantly more effective than placebo from Hours 2 to 8 for relief and Hours 2 to 10 for PID as well as SPID and TOTAL. Piroxicam 40 mg was significantly more effective than aspirin 648 mg for SPID, TOTAL, and hourly measures beginning with Hour 6 through Hour 12. Piroxicam 20 mg was significantly better than aspirin for a few hourly measures: Hours 7 to 9 for relief and Hour 7 for PID. In addition, effects of piroxicam 20 mg had a significantly longer duration than aspirin. Similarly, piroxicam 20 mg had a significantly longer time to remedication compared with aspirin and placebo. The results of these studies provide evidence in support of the longer duration of analgesic efficacy of piroxicam compared with codeine or aspirin in patients with postoperative pain. Our purpose was to compare the analgesic efficacy and safety of single oral doses of the combination of ibuprofen 400 mg plus codeine 60 mg and the combination of ibuprofen 200 mg plus codeine 30 mg with ibuprofen 400 mg alone, codeine sulfate 60 mg alone, and placebo. One hundred ninety-five patients with severe pain resulting from episiotomy, cesarean section, or gynecologic surgery completed a randomized, double-blind, stratified, parallel-group study. Patients were observed during a 4-hour period after medication. Based on the sum of the pain intensity differences (SPID), total pain relief (TOTPAR), and most of the hourly direct measures of pain and relief, both doses of the combination and ibuprofen 400 mg alone were statistically superior to placebo. Codeine 60 mg was statistically superior to placebo based on TOTPAR, the global ratings, and a few hourly measures. The mean effect of the combination of ibuprofen 400 mg plus codeine 60 mg was significantly superior to the mean effect of ibuprofen 400 mg alone 1/2, 1, and 2 hours after medication and to the mean effect of ibuprofen 400 mg alone and codeine 60 mg alone for SPID, TOTPAR, and other measures as well. The low-dose combination was significantly more effective than codeine 60 mg for a few hourly measures but was not significantly superior to ibuprofen 400 mg. Based on these findings it appears that the combination of ibuprofen 400 mg plus codeine 60 mg, particularly in the first few hours after medication, is more efficacious than its constituents. Meclofenamate sodium was compared, double-blind, with codeine and placebo for the treatment of acute episiotomy pain. One hundred sixty-eight women with moderate or severe episiotomy pain after normal delivery were assigned randomly to one of four treatment groups: one received meclofenamate sodium 200 mg at dose 1 and 100 mg at doses 2 and 3; one received meclofenamate sodium 100 mg at dose 1 and 50 mg at doses 2 and 3; one received codeine 60 mg at all three doses; and one received placebo at all three doses. Efficacy measurements were evaluated periodically for 6 hours after medication. After the first administration, both doses of meclofenamate sodium were significantly superior to placebo and to codeine from 2-6 hours in pain intensity difference and pain relief. For second and third doses, data were available for too few patients to allow valid analysis and interpretation. Adverse effects occurred in 4 patients in each meclofenamate sodium group, and in 8 in the codeine group and in 6 in the placebo group. The study indicates that single 100- and 200-mg doses of meclofenamate sodium are as safe as, and significantly more effective than, codeine 60 mg or placebo for episiotomy pain.
Single dose codeine 60 mg provides good analgesia to few individuals, and does not compare favourably with commonly used alternatives such as paracetamol, NSAIDs and their combinations with codeine, especially after dental surgery; the large difference between dental and other surgery was unexpected. Higher doses were not evaluated.