An appraisal of codeine as an analgesic: single-dose analysis. Additive analgesic effect of codeine and paracetamol can be detected in strong, but not moderate, pain after Caesarean section. Baseline pain-intensity is a determinant of assay-sensitivity in a postoperative analgesic trial. The additive analgesic efficacy of acetaminophen, 1000 mg, and codeine, 60 mg, in dental pain. No effect of preoperative paracetamol and codeine suppositories for pain after termination of pregnancies in general anaesthesia. Analysis of the analgesic efficacy of acetaminophen 1000 mg, codeine phosphate 60 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg in the relief of postoperative pain. A randomised, five-parallel-group, placebo-controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single-tablet combination of ibuprofen/paracetamol for postoperative dental pain. Analgesic efficacy of an ibuprofen-codeine combination. The analgesic efficacy of flurbiprofen compared to acetaminophen with codeine. Codeine 20 mg increases pain relief from ibuprofen 400 mg after third molar surgery. A repeat-dosing comparison of ibuprofen and an ibuprofen-codeine combination.
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. A randomized, double-blind, placebo-controlled single oral dose study was done in order to examine whether codeine has an additive analgesic effect to that of paracetamol for moderate and strong postoperative pain after abdominal surgery. The maximum recommended single dose of paracetamol 1000 mg (Paracet) was compared with a combination of a submaximal dose of paracetamol 800 mg plus codeine 60 mg (Paralgin forte) and placebo for pain relief after Caesarean section in 125 patients.
                Visual analogue pain intensity score (VAS 0-100 mm) and categorical pain relief score were recorded for 6 hours after the study drug intake. The main efficacy variables analyzed were: pain intensity difference and summed pain intensity differences during the first 3 and 6 h after study drug intake, total pain relief during the first 3 and 6 h, global evaluation score at the end of the observation period, and time to rescue analgesic.
                Because of protocol violations, 17 patients were excluded from the analysis of effects. Among the 108 patients included in the analysis of analgesic effect, 49 patients had moderate baseline pain (VAS between 40 and 60 mm on a 100 mm scale), and 59 patients had strong baseline pain (VAS more than 60 mm). In patients with strong baseline pain, statistically highly significant differences were documented in efficacy variables between the active drugs and placebo and between the two active drugs. However, in patients with moderate baseline pain, no differences were found between the study drugs in any of the analgesic efficacy variables.
                This study thus confirms that codeine has additive analgesic effect to paracetamol in pain after surgery. Our results show the importance of initial pain intensity in postoperative assessment of analgesic drugs. Assay-sensitivity and test power are increased by selecting patients with sufficiently high initial pain intensity and by comparing groups of patients with identical surgery and similar demographic variables. 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. Outpatient surgery demands rapid recovery and satisfied patients. The purpose of the study was to investigate whether rectal premedication with paracetamol and codeine would reduce the need of rescue analgesics, reduce the postoperative pain experience and result in faster eligibility for discharge. Ninety pregnant patients scheduled for day-case surgery with evacuation of the uterine cavity were randomly assigned into two groups. The paracetamol and codeine group was given a suppository with 60 mg of codeine and 800 mg of paracetamol together with standard premedication of intramuscular midazolam 0.08 mg/kg. The placebo group was given a placebo suppository and midazolam. All patients underwent the surgical procedure under general anaesthesia with alfentanil 15 microg/kg and propofol 1.5-2 mg/kg. There were no statistically significant differences between the groups in the postoperative pain experience as judged by Visual Analogue Scale (VAS-scale), verbal scale or the need for rescue analgesic medication with ketobemidone. Most of the patients experienced little postoperative pain with more than 70% scoring less than 20 mm on a VAS-scale from 0-100 mm at any time during the postoperative period. The paracetamol and codeine patients were significantly more sleepy at 30 min postoperatively. There were no differences between the groups in postoperative nausea or vomiting and no difference in discharge eligibility. The use of pre-operative suppository with paracetamol 800 mg and codeine 60 mg is unnecessary in this group of patients.
                Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain. Patients who experienced pain after surgery were administered a single dose of 1 of 3 treatments: acetaminophen 1000 mg, codeine phosphate 60 mg, or a combination of these. Patients rated their pain intensity on ordinal and visual analog scales just prior to medication and at intervals thereafter for up to 5 hours. They also rated pain relief, pain half gone, and any adverse effects. Sum of pain intensity difference and total pain relief scores were analyzed using Dunnett's procedure. The drug combination was statistically superior to codeine as measured by SPID, TOTPAR, pain half gone, and time to remedication. The combination achieved better mean scores than acetaminophen on all efficacy measures, but was (marginally) statistically superior only in pain half gone. No appreciable differences in adverse effects were noted among the treatments. The difficulty of showing the analgesic efficacy of codeine in a single dose trial is discussed. Combination analgesia is often recommended for the relief of severe pain. This was a double-blind, 5-arm, parallel-group, placebo-controlled, randomised, single-dose study designed to compare the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol with that of an ibuprofen/codeine combination, and a paracetamol/codeine combination, using the dental impaction pain model. Subjects with at least 3 impacted third molars and experiencing moderate to severe postoperative pain were randomised to receive: 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg; 2 tablets of ibuprofen 200 mg/codeine 12.8mg; 2 tablets of paracetamol 500mg/codeine 15mg; or placebo. Results for the primary endpoint, the sum of the mean scores of pain relief combined with pain intensity differences over 12hours, demonstrated that 1 and 2 tablets of the single-tablet combination of ibuprofen/paracetamol were statistically significantly more efficacious than 2 tablets of placebo (P<0.0001) and paracetamol/codeine (P⩽0.0001); furthermore, 2 tablets offered significantly superior pain relief to ibuprofen/codeine (P=0.0001), and 1 tablet was found noninferior to this combination. Adverse events were uncommon during this study and treatment emergent adverse events were statistically significantly less frequent in the groups taking the ibuprofen/paracetamol combination compared with codeine combinations. In conclusion, 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg provided highly effective analgesia that was comparable with, or superior to, other combination analgesics currently indicated for strong pain. A single-tablet combination of ibuprofen 200mg/paracetamol 500mg provides highly effective analgesia, comparable or superior to other combination analgesics indicated for strong pain.
                Copyright © 2011. Published by Elsevier B.V. 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. In a single-dose, parallel group, randomized block treatment allocation study, the relative analgesic efficacy of flurbiprofen, a nonsteroidal antiinflammatory drug, was compared to acetaminophen 650 mg with codeine 60 mg, zomepirac sodium 100 mg, and placebo. A total of 226 post-surgical dental patients (146 females and 80 males) participated in the study. Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination. The results of this study support previous work on flurbiprofen. A combination of 20 mg codeine base and ibuprofen 400 mg was compared with ibuprofen 400 mg in a randomised double-blind cross-over study of multiple doses in 25 patients after 2-stage bilateral third molar removal. The combination produced significantly greater pain relief and doubled the hours of minimum pain intensity and maximal relief on the day of surgery. The patients rated the combination significantly better than ibuprofen alone, and the combination was preferred by 16 of the 22 patients expressing a preference. There was no significant increase in side-effect incidence with the combination. The 30% increase in analgesic effect may be of clinical benefit, and this trial design, cross-over with multiple dosing in out-patients, may be a sensitive test for analgesics, potentially more predictive of side-effect problems than single-dose studies.
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.