Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute
postoperative pain.
Author(s): Derry CJ(1), Derry S, Moore RA.
Affiliation(s): Author information:
(1)Pain Research and Nuffield Department of Clinical Neurosciences, University of
Oxford, Oxford, UK.
Publication date & source: 2013, Cochrane Database Syst Rev. , 6:CD010210
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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