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

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. Fixed-dose combinations of ibuprofen and oxycodone are available, and the drugs may be separately used in combination in some acute pain situations.

Objectives: To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus oxycodone for moderate to severe postoperative pain.

Search methods: We searched the Cochrane Central Register of Controlled Trials, (CENTRAL), on The Cochrane Library, (Issue 4 of 12, 2013), MEDLINE (1950 to 21st May 2013), EMBASE (1974 to 21st May 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 oxycodone 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 the area under the pain relief versus time curve to derive the proportion of participants prescribed ibuprofen plus oxycodone, ibuprofen alone, oxycodone alone, or placebo with at least 50% pain relief over six hours, using validated equations. We calculated relative risk (RR) and number needed to treat to benefit (NNT). 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 1202 participants. All examined the same dose combination. Included studies provided data from 603 participants for the comparison of ibuprofen 400 mg + oxycodone 5 mg with placebo, 717 participants for the comparison of ibuprofen 400 mg + oxycodone 5 mg with ibuprofen 400 mg alone, and 471 participants for the comparison of ibuprofen 400 mg + oxycodone 5 mg with oxycodone 5 mg alone.The proportion of participants achieving at least 50% pain relief over 6 hours was 60% with ibuprofen 400 mg + oxycodone 5 mg and 17% with placebo, giving an NNT of 2.3 (2.0 to 2.8). For ibuprofen 400 mg alone the proportion was 50%, producing no significant difference between ibuprofen 400 mg + oxycodone 5 mg and ibuprofen 400 mg alone. For oxycodone 5 mg alone the proportion was 23%, giving an NNT for ibuprofen 400 mg + oxycodone 5 mg compared with oxycodone alone of 2.9 (2.3 to 4.0).Ibuprofen + oxycodone resulted in longer times to remedication than with placebo. The median time to use of rescue medication was more than 5 hours for ibuprofen 400 mg + oxycodone 5 mg, and 2.3 hours or less with placebo. Fewer participants needed rescue medication with ibuprofen + oxycodone combination than with placebo or ibuprofen alone. The proportion was 40% with ibuprofen 400 mg + oxycodone 5 mg, 83% with placebo, 53% with ibuprofen alone, and 83% with oxycodone alone, giving NNT to prevent one patient needing rescue medication of 2.4 (2.0 to 2.9), 11 (6.1 to 56), and 2.6 (2.1 to 3.4) for comparisons of ibuprofen 400 mg + oxycodone 5 mg with placebo, ibuprofen alone, and oxycodone alone, respectively.The proportion of participants experiencing one or more adverse events was 25% with ibuprofen 400 mg + oxycodone 5 mg, 25% with placebo, 26% with ibuprofen alone, and 35% with oxycodone alone; they were not significantly different. Serious adverse events were reported only after abdominal surgery 6/169 with the combination, 1/175 with ibuprofen alone, 3/52 with oxycodone alone, and 1/60 with placebo. Withdrawals for reasons other than lack of efficacy were fewer than 5% and balanced across treatment arms.

Authors' conclusions: The combination of ibuprofen 400mg + oxycodone 5mg provided analgesia for longer than oxycodone alone, but not ibuprofen alone (at the same dose). There was also a smaller chance of needing additional analgesia over about eight hours, and with no greater chance of experiencing an adverse event.

1

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

3

Forest plot of comparison: 1 Ibuprofen 400 mg + oxycodone 5 mg versus placebo, outcome: 1.1 Participants with ≥ 50% pain relief at 6 hours.

4

L'Abbé plot showing ≥ 50% pain relief over 4 to 6 hours with ibuprofen 400 mg + oxycodone 5 mg and placebo in individual studies. Size of circle is proportional to size of study (inset scale). Pink circle = abdominal and pelvic surgery; cream circles = dental surgery.

1.1. Analysis

Comparison 1 Ibuprofen 400 mg + oxycodone 5 mg versus placebo, Outcome 1 Participants with ≥50% pain relief at 6 hours.

1.2. Analysis

Comparison 1 Ibuprofen 400 mg + oxycodone 5 mg versus placebo, Outcome 2 Participants using rescue medication within 6 hours.

1.3. Analysis

Comparison 1 Ibuprofen 400 mg + oxycodone 5 mg versus placebo, Outcome 3 Participants with any adverse event over 6 hours.

2.1. Analysis

Comparison 2 Ibuprofen 400 mg + oxycodone 5 mg versus ibuprofen 400 mg, Outcome 1 Participants with ≥50% pain relief at 6 hours.

2.2. Analysis

Comparison 2 Ibuprofen 400 mg + oxycodone 5 mg versus ibuprofen 400 mg, Outcome 2 Participants using rescue medication within 6 hours.

2.3. Analysis

Comparison 2 Ibuprofen 400 mg + oxycodone 5 mg versus ibuprofen 400 mg, Outcome 3 Participants with any adverse event over 6 hours.

3.1. Analysis

Comparison 3 Ibuprofen 400 mg + oxycodone 5 mg versus oxycodone 5 mg, Outcome 1 Participants with ≥50% pain relief at 6 hours.

3.2. Analysis

Comparison 3 Ibuprofen 400 mg + oxycodone 5 mg versus oxycodone 5 mg, Outcome 2 Participants using rescue medication within 6 hours.

3.3. Analysis

Comparison 3 Ibuprofen 400 mg + oxycodone 5 mg versus oxycodone 5 mg, Outcome 3 Participants with any adverse event over 6 hours.