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Meta-Analysis
. 2013 Jun 24;2013(6):CD010210.
doi: 10.1002/14651858.CD010210.pub2.

Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain

Christopher J Derry  1 , Sheena Derry, R Andrew Moore
Affiliations
Meta-Analysis

Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain

Christopher J Derry et al. Cochrane Database Syst Rev. .

Abstract

Background: Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations.

Objectives: To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute 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) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles.

Selection criteria: Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults.

Data collection and analysis: Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on 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 events.

Main results: Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543 participants for the comparison of ibuprofen 400 mg + paracetamol 1000 mg with placebo, and 359 participants for the comparison of ibuprofen 400 mg + paracetamol 1000 mg with ibuprofen 400 mg alone.The proportion of participants achieving at least 50% maximum pain relief over 6 hours was 69% with ibuprofen 200 mg + paracetamol 500 mg, 73% with ibuprofen 400 mg + paracetamol 1000 mg, and 7% with placebo, giving NNTs of 1.6 (1.5 to 1.8) and 1.5 (1.4 to 1.7) for the lower and higher doses respectively compared with placebo. For ibuprofen 400 mg alone the proportion was 52%, giving an NNT for ibuprofen 400 mg + paracetamol 1000 mg compared with ibuprofen alone of 5.4 (3.5 to 12).Ibuprofen + paracetamol at the 200/500 mg and 400/1000 mg doses resulted in longer times to remedication than placebo. The median time to use of rescue medication was 7.6 hours for ibuprofen 200 mg + paracetamol 500 mg, 8.3 hours with ibuprofen 400 mg + paracetamol 1000 mg, and 1.7 hours with placebo. Fewer participants needed rescue medication with ibuprofen + paracetamol combination than with placebo or ibuprofen alone. The proportion was 34% with ibuprofen 200 mg + paracetamol 500 mg, 25% with ibuprofen 400 mg + paracetamol 1000 mg, and 79% with placebo, giving NNTs to prevent use of rescue medication of 2.2 (1.8 to 2.9) and 1.8 (1.6 to 2.2) respectively compared with placebo. The proportion of participants using rescue medication with ibuprofen 400 mg was 48%, giving an NNT to prevent use for ibuprofen 400 mg + paracetamol 1000 mg compared with ibuprofen alone of 4.3 (3.0 to 7.7).The proportion of participants experiencing one or more adverse events was 30% with ibuprofen 200 mg + paracetamol 500 mg, 29% with ibuprofen 400 mg + paracetamol 1000 mg, and 48% with placebo, giving NNT values in favour of the combination treatment of 5.4 (3.6 to 10.5) and 5.1 (3.5 to 9.5) for the lower and higher doses respectively. No serious adverse events were reported in any of the included studies. Withdrawals for reasons other than lack of efficacy were fewer than 5% and balanced across treatment arms.

Authors' conclusions: Ibuprofen plus paracetamol combinations provided better analgesia than either drug alone (at the same dose), with a smaller chance of needing additional analgesia over about eight hours, and with a smaller chance of experiencing an adverse event.

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Conflict of interest statement

RAM and SD have received research support from charities, government and industry sources at various times. RAM has consulted for various pharmaceutical companies and has received lecture fees from pharmaceutical companies related to analgesics and other healthcare interventions. CD 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 200 mg + paracetamol 500 mg versus placebo, outcome: 1.1 Participants with ≥50% pain relief.
4
4
Studies comparing ibuprofen 200 mg + paracetamol 500 mg with placebo, with the outcome of at least 50% maximum pain relief over 4 to 6 hours.
5
5
Forest plot of comparison: Ibuprofen 400 mg + paracetamol 1000 mg versus placebo, outcome: 2.1 Participants with ≥ 50% pain relief.
6
6
Studies comparing ibuprofen 400 mg plus paracetamol 1000 mg with placebo, with the outcome of at least 50% maximum pain relief over 4‐6 hours
1.1
1.1. Analysis
Comparison 1 ibuprofen 200 mg + paracetamol 500 mg versus placebo, Outcome 1 Participants with ≥50% pain relief.
1.2
1.2. Analysis
Comparison 1 ibuprofen 200 mg + paracetamol 500 mg versus placebo, Outcome 2 Participants using rescue medication within 8 h.
1.3
1.3. Analysis
Comparison 1 ibuprofen 200 mg + paracetamol 500 mg versus placebo, Outcome 3 Participants with any adverse event.
2.1
2.1. Analysis
Comparison 2 Ibuprofen 400 mg + paracetamol 1000 mg versus placebo, Outcome 1 Participants with ≥50% pain relief.
2.2
2.2. Analysis
Comparison 2 Ibuprofen 400 mg + paracetamol 1000 mg versus placebo, Outcome 2 Participants using rescue medication within 8 h.
2.3
2.3. Analysis
Comparison 2 Ibuprofen 400 mg + paracetamol 1000 mg versus placebo, Outcome 3 Participants with any adverse event.
3.1
3.1. Analysis
Comparison 3 Ibuprofen 400 mg + paracetamol 1000 mg versus ibuprofen 400 mg, Outcome 1 Participants with ≥50% pain relief.
3.2
3.2. Analysis
Comparison 3 Ibuprofen 400 mg + paracetamol 1000 mg versus ibuprofen 400 mg, Outcome 2 Participants using rescue medication within 8 h.
3.3
3.3. Analysis
Comparison 3 Ibuprofen 400 mg + paracetamol 1000 mg versus ibuprofen 400 mg, Outcome 3 Participants with any adverse event.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD010210

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