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.

Author(s)

Sheena Derry, Samuel M Karlin, R Andrew Moore

Abstract

Plain language summary

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

Acute pain is often felt soon after injury. Most people who have surgery have moderate or severe pain afterwards. Painkillers are tested in people with pain, often following the removal of wisdom teeth. This pain is usually treated with painkillers taken by mouth. Results can be applied to other forms of acute pain.

A series of Cochrane reviews looks at how good painkillers are. We know that in some circumstances combining different analgesics in the same tablet gives good pain relief to more people than either analgesic alone. This is particularly true using a combination of two painkillers that work by different mechanisms. This review looked at how good the combination of ibuprofen and codeine was in relieving moderate or severe pain after surgery, and is an update of an earlier review conducted in 2013.

For the original review, we found six studies with 1342 participants. For this update we searched up to December 2014, but found no additional studies. Ibuprofen 400 mg plus high doses of codeine (25.6 mg to 60 mg) provided effective pain relief for over 6 in 10 (64%) of participants, compared with just under 2 in 10 (18%) of participants with placebo (high quality evidence).

Adverse events occurred at similar rates with the ibuprofen/codeine combination and placebo in these single dose studies (moderate quality evidence). No serious adverse events or withdrawals due to adverse events occurred with the combination. It is important not to exceed the recommended dose for this combination painkiller.

Author(s)

Sheena Derry, Samuel M Karlin, R Andrew Moore

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

Since the last version of this review was published in 2013 we identified no new studies.

Combinations of ibuprofen plus codeine are good analgesics and are probably better than either drug alone. The particular combination of ibuprofen 400 mg plus codeine 25.6 mg to 60 mg demonstrates good efficacy. Use of combination analgesics that contain codeine has been a source of some concern because of misuse from over‐the‐counter preparations.

Implications for research 

It is not clear what the implications are for research. Studies offer no new methodological insights, and, while additional data are always welcome, there are potential ethical issues from including participants in studies that do not add to existing knowledge in a meaningful way.

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