Single dose oral oxycodone and oxycodone plus paracetamol (acetaminophen) for acute postoperative pain in adults: Cochrane systematic review

Abstract

Background

Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review that concluded, based on limited data, that all doses of oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in postoperative pain, but with increased incidence of adverse events compared with placebo. Additional new studies provide more reliable estimates of efficacy and harm.

Objectives

To assess efficacy, duration of action, and associated adverse events of single dose oral oxycodone, with or without paracetamol, in acute postoperative pain in adults.

Search methods

Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched in May 2009.

Selection criteria

Randomised, double blind, placebo-controlled trials of single dose orally administered oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain.

Data collection and analysis

Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants remedicating over specified time periods, and time-to-use of rescue medication, were sought as additional measures of efficacy. Adverse events and withdrawals information was collected.

Main results

This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal.

Authors' conclusions

Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non-steroidal anti-inflammatory drugs, with the benefit of longer duration of action.

Author(s)

Gaskell Helen, Derry Sheena, Moore R Andrew, McQuay Henry J

Summary

Single dose oxycodone and oxycodone plus paracetamol (also known as acetaminophen) for analgesia in adults with acute postoperative pain

This review update assessed evidence from 2641 participants in 20 randomised, double blind, placebo-controlled clinical trials of oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Oral oxycodone 10 mg plus paracetamol 650 mg provided effective analgesia. About half of those treated experienced at least half pain relief over 4 to 6 hours, and the effects lasting up to 10 hours. Higher doses gave more effect. Associated adverse events (predominantly nausea, vomiting, dizziness and somnolence) were more frequent with oxycodone or oxycodone plus paracetamol than with placebo, but studies of this type are of limited use for studying adverse effects. Limited information about oxycodone on its own suggests that it provided analgesia at doses greater than 5 mg, and that addition of paracetamol made it more effective.

Reviewer's Conclusions

Implications for practice

The earlier review had insufficient data to guide clinical practice. In this updated review the most robust evidence is for oxycodone plus paracetamol, with a clear dose response for both the proportion of patients achieving at least 50% pain relief and time to remedication. Of several combinations of oxycodone and paracetamol, most data are available for oxycodone 10 mg plus paracetamol 650 mg, with over 1000 participants. For this combination, the NNT was below three (indicating good effect) and median time to remedication was about 10 hours. This is at least comparable to typically used doses of NSAIDs, with probably longer duration. Since oxycodone 10 mg is two to three times stronger than codeine 60 mg, it is not surprising that oxycodone 10 mg plus paracetamol 650 mg is more effective than codeine 60 mg plus paracetamol 650 mg, which has an NNT of about four and a shorter time median time to remedication.

For oxycodone alone, and for other combinations of oxycodone plus paracetamol, the limited data available makes not only results, but also comparison with other data on other analgesics used in similar clinical situations, much less robust. Limited information on adverse events suggests they are more frequent with oxycodone plus paracetamol than placebo, and while they were reported as mild to moderate in severity, they may become problematic with repeated dosing.

Implications for research

Randomised, double blind, placebo-controlled trials in moderate to severe postoperative pain are required to better evaluate the effects of oxycodone, with or without paracetamol, and to better establish dose-response relationships. Because the efficacy of oxycodone plus paracetamol is now established, it may be more appropriate for resources to be put towards clinical effectiveness trials to establish which postoperative analgesic protocol leads to the best results for the most patients.

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