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Meta-Analysis
. 2015 Feb 5;2015(2):CD010107.
doi: 10.1002/14651858.CD010107.pub3.

Single dose oral ibuprofen plus codeine for acute postoperative pain in adults

Sheena Derry  1 , Samuel M Karlin, R Andrew Moore
Affiliations
Meta-Analysis

Single dose oral ibuprofen plus codeine for acute postoperative pain in adults

Sheena Derry et al. Cochrane Database Syst Rev. .

Abstract

Background: This is an update of the original Cochrane review published in Issue 3, 2013. There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone, and that the drug-specific effects are essentially additive. This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations and when tested in the same and different trials. Some combinations of ibuprofen and codeine are available without prescription (but usually only from a pharmacy) where the dose of codeine is lower, and with a prescription when the dose of codeine is higher.Use of combination analgesics that contain codeine has been a source of some concern because of misuse from over-the-counter preparations.

Objectives: To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus codeine for acute moderate-to-severe postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, ClinicalTrials.gov, and the reference lists of articles. The date of the most recent search was 1 December 2014.

Selection criteria: Randomised, double-blind, placebo- or active-controlled clinical trials of single dose oral ibuprofen plus codeine for acute postoperative pain in adults.

Data collection and analysis: Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants prescribed ibuprofen plus codeine, placebo, or the same dose of ibuprofen alone with at least 50% pain relief over six hours, using validated equations. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects. Analyses were planned for different doses of ibuprofen and codeine, but especially for codeine where we set criteria for low (< 10 mg), medium (10 to 20 mg), and high (> 20 mg) doses.

Main results: Since the last version of this review no new studies were found. Information was available from six studies with 1342 participants, using a variety of doses of ibuprofen and codeine. In four studies (443 participants) using ibuprofen 400 mg plus codeine 25.6 mg to 60 mg (high dose codeine) 64% of participants had at least 50% maximum pain relief with the combination compared to 18% with placebo. The NNT was 2.2 (95% confidence interval 1.8 to 2.6) (high quality evidence). In three studies (204 participants) ibuprofen plus codeine (any dose) was better than the same dose of ibuprofen (69% versus 55%) but the result was barely significant with a relative benefit of 1.3 (1.01 to 1.6) (moderate quality evidence). In two studies (159 participants) ibuprofen plus codeine appeared to be better than the same dose of codeine alone (69% versus 33%), but no analysis was done. There was no difference between the combination and placebo in the reporting of adverse events in these acute studies (moderate quality evidence).

Authors' conclusions: The combination of ibuprofen 400 mg plus codeine 25.6 mg to 60 mg demonstrates good analgesic efficacy. Very limited data suggest that the combination is better than the same dose of either drug alone, and that similar numbers of people experience adverse events with the combination as with placebo.

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Conflict of interest statement

RAM and SD have received research support from charities, government and industry sources at various times, but none related to this review. RAM has consulted for various pharmaceutical companies and has received lecture fees from pharmaceutical companies related to analgesics and other healthcare interventions. SK has no interests to declare.

Figures

1
1
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: ibuprofen 400 mg + high dose codeine (ibu/cod) versus placebo, outcome: 2.1 Participants with at least 50% pain relief.
4
4
Studies comparing ibuprofen plus codeine with placebo, with the outcome of at least 50% maximum pain relief over 4 to 6 hours. Colour code: white ‐ ibuprofen 200 mg + codeine 15 mg; yellow ‐ ibuprofen 200 mg + codeine 30 mg; light pink ‐ ibuprofen 400 mg + codeine 25.6 mg; medium pink ‐ ibuprofen 400 mg + codeine 30 mg; red ‐ ibuprofen 400 mg + codeine 60 mg; blue ‐ ibuprofen 800 mg + codeine 60 mg.
5
5
Studies comparing ibuprofen plus codeine with same dose of ibuprofen, with the outcome of at least 50% maximum pain relief over 4 to 6 hours. Colour code: darker yellow ‐ ibuprofen 200 mg + codeine 20 mg versus ibuprofen 200 mg; lighter yellow ‐ ibuprofen 400 mg + codeine 60 mg versus ibuprofen 400 mg.
6
6
Forest plot of comparison: ibuprofen + codeine (all doses; ibu/cod) versus same dose of ibuprofen alone (ibu), outcome: 3.1 Participants with at least 50% pain relief.
1.1
1.1. Analysis
Comparison 1 Ibuprofen 400 mg + high dose codeine versus placebo, Outcome 1 Participants with ≥ 50% pain relief.
1.2
1.2. Analysis
Comparison 1 Ibuprofen 400 mg + high dose codeine versus placebo, Outcome 2 Participants with any adverse event.
2.1
2.1. Analysis
Comparison 2 Ibuprofen + codeine (all doses) versus same dose of ibuprofen alone, Outcome 1 Participants with ≥ 50% pain relief.
See this image and copyright information in PMC

Update of

References

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References to other published versions of this review

Derry 2013
    1. Derry S, Karlin SM, Moore RA. Single dose oral ibuprofen plus codeine for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2013, Issue 3. [DOI: 10.1002/14651858.CD010107.pub2] - DOI - PubMed

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