Single dose oral codeine, as a single agent, for acute postoperative pain in adults

Abstract

Background Codeine is an opioid metabolised to active analgesic compounds, including morphine. It is widely available by prescription, and combination drugs including low doses of codeine are commonly available without prescription. Objectives To assess the efficacy, the time to onset of analgesia, the time to use of rescue medication and any associated adverse events of single dose oral codeine in acute postoperative pain. Search methods We searched CENTRAL, MEDLINE, EMBASE and PubMed to November 2009. Selection criteria Single oral dose, randomised, double-blind, placebo-controlled trials of codeine for relief of established moderate to severe postoperative pain in adults. Data collection and analysis Studies were assessed for methodological quality and data independently extracted by two review authors. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours were used to calculate the number of participants achieving at least 50% pain relief, which were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Data on adverse events and withdrawals were collected. Main results Thirty-five studies were included (1223 participants received codeine 60 mg, 27 codeine 90 mg, and 1252 placebo). Combining all types of surgery (33 studies, 2411 participants), codeine 60 mg had an NNT of at least 50% pain relief over 4 to 6 hours of 12 (8.4 to 18) compared with placebo. At least 50% pain relief was achieved by 26% on codeine 60 mg and 17% on placebo. Following dental surgery the NNT was 21 (12 to 96) (15 studies, 1146 participants), and following other types of surgery the NNT was 6.8 (4.6 to 13) (18 studies, 1265 participants). The NNT to prevent use of rescue medication within 4 to 6 hours was 11 (6.3 1 Single dose oral codeine, as a single agent, for acute postoperative pain in adults (Review)

Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery

“…However, this analgesia was not sufficient when a comparison was made between codeine alone and its use in combination with paracetamol and NSAIDs. 20 Similarly, our study showed more effective postoperative analgesia and lower meperidine consumption with the naproxen sodium-codeine phosphate combination. In previous studies, codeine and other drugs were administered as different pills to patients, whereas our study used single pills that included both naproxen sodium and codeine.…”

“…In both meta-analyses, opioid-related side effects such as drowsiness and somnolence were more frequent in the groups receiving codeine, although this was not statistically significant. 19,20 Forbes et al compared naproxen sodium, codeine sulfate, naproxen sodium and codeine sulfate for postoperative pain after oral surgery. 21 In this paper codeine dose was 60 mg in groups receiving codeine which was twice the dose of our study.…”

Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery

“…However, this analgesia was not sufficient when a comparison was made between codeine alone and its use in combination with paracetamol and NSAIDs. 20 Similarly, our study showed more effective postoperative analgesia and lower meperidine consumption with the naproxen sodium-codeine phosphate combination. In previous studies, codeine and other drugs were administered as different pills to patients, whereas our study used single pills that included both naproxen sodium and codeine.…”

“…In both meta-analyses, opioid-related side effects such as drowsiness and somnolence were more frequent in the groups receiving codeine, although this was not statistically significant. 19,20 Forbes et al compared naproxen sodium, codeine sulfate, naproxen sodium and codeine sulfate for postoperative pain after oral surgery. 21 In this paper codeine dose was 60 mg in groups receiving codeine which was twice the dose of our study.…”

A conservative method of testing whether combination analgesics produce additive or synergistic effects using evidence from acute pain and migraine

“…Data obtained from the following sources: paracetamol (Toms et al., ), codeine (Derry et al., ), oxycodone (Gaskell et al., ), tramadol (Moore and McQuay, ), and dextropropoxyphene (Moore et al., ).…”

Acetaminophen, ibuprofen, and tramadol analgesic interactions after adenotonsillectomy

“…Any effect due to M1 metabolite or variability in M1 metabolite concentration attributable to single nuclear polymorphisms of the P450 enzyme CYP2D6 is encompassed by the C 50,TRAN variability (PPV 2.5). Codeine is also metabolized by CYP2D6 and large variability has also been reported with codeine 60 mg after dental surgery in adults where the number needed to treat was 21 (95%CI 12 to 96) for one participant to experience at least 50% pain relief over 4 to 6 hours …”

Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery

“…However, this analgesia was not sufficient when a comparison was made between codeine alone and its use in combination with paracetamol and NSAIDs. 20 Similarly, our study showed more effective postoperative analgesia and lower meperidine consumption with the naproxen sodium-codeine phosphate combination. In previous studies, codeine and other drugs were administered as different pills to patients, whereas our study used single pills that included both naproxen sodium and codeine.…”

“…In both meta-analyses, opioid-related side effects such as drowsiness and somnolence were more frequent in the groups receiving codeine, although this was not statistically significant. 19,20 Forbes et al compared naproxen sodium, codeine sulfate, naproxen sodium and codeine sulfate for postoperative pain after oral surgery. 21 In this paper codeine dose was 60 mg in groups receiving codeine which was twice the dose of our study.…”

A conservative method of testing whether combination analgesics produce additive or synergistic effects using evidence from acute pain and migraine

“…Data obtained from the following sources: paracetamol (Toms et al., ), codeine (Derry et al., ), oxycodone (Gaskell et al., ), tramadol (Moore and McQuay, ), and dextropropoxyphene (Moore et al., ).…”

Acetaminophen, ibuprofen, and tramadol analgesic interactions after adenotonsillectomy

“…Any effect due to M1 metabolite or variability in M1 metabolite concentration attributable to single nuclear polymorphisms of the P450 enzyme CYP2D6 is encompassed by the C 50,TRAN variability (PPV 2.5). Codeine is also metabolized by CYP2D6 and large variability has also been reported with codeine 60 mg after dental surgery in adults where the number needed to treat was 21 (95%CI 12 to 96) for one participant to experience at least 50% pain relief over 4 to 6 hours …”

Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery

“…However, this analgesia was not sufficient when a comparison was made between codeine alone and its use in combination with paracetamol and NSAIDs. 20 Similarly, our study showed more effective postoperative analgesia and lower meperidine consumption with the naproxen sodium-codeine phosphate combination. In previous studies, codeine and other drugs were administered as different pills to patients, whereas our study used single pills that included both naproxen sodium and codeine.…”

“…In both meta-analyses, opioid-related side effects such as drowsiness and somnolence were more frequent in the groups receiving codeine, although this was not statistically significant. 19,20 Forbes et al compared naproxen sodium, codeine sulfate, naproxen sodium and codeine sulfate for postoperative pain after oral surgery. 21 In this paper codeine dose was 60 mg in groups receiving codeine which was twice the dose of our study.…”

A conservative method of testing whether combination analgesics produce additive or synergistic effects using evidence from acute pain and migraine

“…Data obtained from the following sources: paracetamol (Toms et al., ), codeine (Derry et al., ), oxycodone (Gaskell et al., ), tramadol (Moore and McQuay, ), and dextropropoxyphene (Moore et al., ).…”

Acetaminophen, ibuprofen, and tramadol analgesic interactions after adenotonsillectomy

“…Any effect due to M1 metabolite or variability in M1 metabolite concentration attributable to single nuclear polymorphisms of the P450 enzyme CYP2D6 is encompassed by the C 50,TRAN variability (PPV 2.5). Codeine is also metabolized by CYP2D6 and large variability has also been reported with codeine 60 mg after dental surgery in adults where the number needed to treat was 21 (95%CI 12 to 96) for one participant to experience at least 50% pain relief over 4 to 6 hours …”