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

  1. Christopher J Derry,
  2. Sheena Derry,
  3. R Andrew Moore*

Editorial Group: Cochrane Pain, Palliative and Supportive Care Group

Published Online: 24 JUN 2013

Assessed as up-to-date: 21 MAY 2013

DOI: 10.1002/14651858.CD010210.pub2


How to Cite

Derry CJ, Derry S, Moore RA. Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010210. DOI: 10.1002/14651858.CD010210.pub2.

Author Information

  1. University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences, Oxford, Oxfordshire, UK

*R Andrew Moore, Pain Research and Nuffield Department of Clinical Neurosciences, University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, OX3 7LJ, UK. andrew.moore@ndcn.ox.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 24 JUN 2013

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Characteristics of included studies [ordered by study ID]
Daniels 2011

MethodsRandomised, double-blind, single-dose, 5 parallel groups.

Medication administered when baseline pain reached a moderate to severe intensity.

Pain assessed at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours.


ParticipantsSurgical removal of impacted third molar.

Mean age 20 years.

N = 678 (598 analysed).
M = 271, F = 407.


InterventionsIbuprofen 200 mg + paracetamol 500 mg, n = 173.
Ibuprofen 400 mg + paracetamol 1000 mg, n = 168.
Ibuprofen 400 mg + codeine 25.6 mg, n = 169.
Paracetamol 1000 mg + codeine 30 mg, n = 113.
Placebo, n = 55.


OutcomesPI: std 4-point scale.

PR: std 5-point scale.

Median time to use of rescue medication.

Number of participants reporting any adverse event and serious adverse events.

Number of participants withdrawing because of an adverse event.


NotesOxford Quality Score: R2, DB2, W1. Total = 5/5.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Patients were randomised, according to a computer-generated system".

Allocation concealment (selection bias)Unclear riskNot described.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskEach treatment consisted of 2 white tablets of a similar size and was administered as a single oral dose taken with approximately 300 mL of water.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskEach treatment consisted of 2 white tablets of a similar size and was administered as a single oral dose taken with approximately 300 mL of water.

SizeUnclear riskTreatment groups sizes 55 to 173.

Mehlisch 2010a

MethodsRandomised, double-blind, single-dose, 5 parallel groups.

Medication administered when baseline pain reached a moderate to severe intensity.

Pain assessed at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7 and 8 hours.


ParticipantsSurgical removal of impacted third molar.

Mean age 21 years.

N = 234.
M = 60, F = 174.


InterventionsIbuprofen 200 mg + paracetamol 500 mg, n = 33.
Ibuprofen 400 mg + paracetamol 1000 mg, n = 67.

Ibuprofen 400 mg, n = 69.
Paracetamol 1000 mg, n = 34.
Placebo, n = 31.


OutcomesPI: std 4-point scale.

PR: std 5-point scale.

Median time to use of rescue medication.

Number of participants using rescue medication.

Number of participants reporting any adverse event and serious adverse events.

Number of participants withdrawing because of an adverse event.


NotesOxford Quality Score: R2, DB2, W1. Total = 5/5.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomisation was done according to a computer-generated schedule".

Allocation concealment (selection bias)Low riskSubjects allocated a unique number in numerical sequence in a predefined order to allow stratification for sex and baseline pain.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskEach subject received a single oral dose containing 2 tablets (Advil and/or matching placebo) and 2 caplets (Tylenol ES and/or matching placebo) in a blinded fashion.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskEach subject received a single oral dose containing 2 tablets (Advil and/or matching placebo) and 2 caplets (Tylenol ES and/or matching placebo) in a blinded fashion.

SizeHigh riskTreatment group sizes 31 to 69.

Mehlisch 2010b

MethodsRandomised, double-blind, single dose and multi-dose stages (only single dose stage of trial used), 8 parallel groups.

Medication administered when baseline pain reached a moderate to severe intensity.

Pain assessed at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7 and 8 hours.


ParticipantsSurgical removal of impacted third molar.

Mean age 20 years.

N = 735.
M = 275, F = 460.


InterventionsIbuprofen 100 mg + paracetamol 250 mg, n = 71.
Ibuprofen 200 mg + paracetamol 500 mg, n = 143.
Ibuprofen 400 mg + paracetamol 1000 mg, n = 149.
Ibuprofen 200 mg, n = 75.
Ibuprofen 400 mg, n = 74.
Paracetamol 500 mg, n = 76.
Paracetamol 1000 mg, n = 74.
Placebo, n = 73.


OutcomesPI: std 4-point scale.

PR: std 5-point scale.

Median time to use of rescue medication.

Number of participants using rescue medication.

Number of participants reporting any adverse event and serious adverse events.

Number of participants withdrawing because of an adverse event.


NotesOxford Quality Score: R2, DB2, W1. Total = 5/5.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Subjects were randomly assigned to a treatment according to a computer-produced randomisation schedule".

Allocation concealment (selection bias)Unclear riskSubjects were allocated a unique number in numerical sequence in a predefined order to allow stratification for sex and baseline pain.

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Placebo tablets for oral administration were identical to ibuprofen 200 mg, acetaminophen 500 mg and ibuprofen/acetaminophen combination doses".

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"Placebo tablets for oral administration were identical to ibuprofen 200 mg, acetaminophen 500 mg and ibuprofen/acetaminophen combination doses".

SizeUnclear riskTreatment group sizes 71 to 149.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Menhinick 2004Nonsurgical intervention.

Merry 2010One dose given preoperatively. No single dose data.

Mitchell 2008No suitable comparator (placebo or same dose ibuprofen). No single dose data.

Naidu 1994No suitable comparator (placebo or same dose ibuprofen).

 
Characteristics of ongoing studies [ordered by study ID]
NCT00921700

Trial name or titleAnalgesic effect of ibuprofen 400 mg/paracetamol 1000 mg, ibuprofen 400 mg/paracetamol 1000 mg/60 mg codeine and paracetamol 1000 mg/codeine 60 mg: a single dose, randomised, placebo-controlled and double-blind study.

MethodsRandomised, double-blind, single-dose, 4 parallel groups.

Medication administered when baseline pain reached a moderate to severe intensity.

Pain assessed at baseline and at intervals over 6 hours.

ParticipantsSurgical removal of impacted third molars.

M and F.

Age 18 to 30 years.

InterventionsIbuprofen 400 mg/paracetamol 1000 mg.

Ibuprofen 400 mg/ paracetamol 1000 mg/codeine 60 mg.

Paracetamol 1000 mg/codeine 60 mg.

Placebo.

All drugs administered in gelatin capsules.

OutcomesPI: std 4-point scale.

Adverse events.

Starting dateJune 2009.

Contact informationLasse A. Skoglund, DDS, DSci (lasses@odont.uio.no).

Per Skjelbred, DDS, MD, PhD (p.skjelbred@ulleval.no).

NotesEstimated enrolment 200, estimated completion date June 2011, estimated completion of analysis late 2012.

NCT01559259

Trial name or titleEvaluation of the efficacy of novel ibuprofen/acetaminophen combination formulations in the treatment of postsurgical dental pain.

MethodsRandomised, double-blind, single-dose, 5 parallel groups.

Medication administered when baseline pain reached a moderate to severe intensity.

Pain assessed at baseline and at intervals over 12 hours.

ParticipantsSurgical extraction of three or more third molar teeth.

M and F.

Age 16 to 40 years.

InterventionsIbuprofen 200 mg + acetaminophen 500 mg.

Ibuprofen 250 mg + acetaminophen 500 mg.

Ibuprofen 300 mg + acetaminophen 500 mg.

Ibuprofen 400 mg.

Placebo.

OutcomesPI: std 4-point scale.

PR: std 5-point scale.

Use of rescue medication.

Adverse events.

Starting dateApril 2012.

Contact informationPfizer CT.gov Call Center.

NotesEstimated enrolment 410, estimated completion date September 2012.

 
Comparison 1. ibuprofen 200 mg + paracetamol 500 mg versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Participants with ≥50% pain relief3508Risk Ratio (M-H, Fixed, 95% CI)10.29 [5.70, 18.58]

 2 Participants using rescue medication within 8 h2280Risk Ratio (M-H, Fixed, 95% CI)0.46 [0.37, 0.58]

 3 Participants with any adverse event3508Risk Ratio (M-H, Fixed, 95% CI)0.69 [0.55, 0.85]

 
Comparison 2. Ibuprofen 400 mg + paracetamol 1000 mg versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Participants with ≥50% pain relief3543Risk Ratio (M-H, Fixed, 95% CI)11.21 [6.18, 20.35]

 2 Participants using rescue medication within 8 h2320Risk Ratio (M-H, Fixed, 95% CI)0.31 [0.24, 0.40]

 3 Participants with any adverse event3543Risk Ratio (M-H, Fixed, 95% CI)0.62 [0.50, 0.77]

 
Comparison 3. Ibuprofen 400 mg + paracetamol 1000 mg versus ibuprofen 400 mg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Participants with ≥50% pain relief2359Risk Ratio (M-H, Fixed, 95% CI)1.30 [1.10, 1.55]

 2 Participants using rescue medication within 8 h2359Risk Ratio (M-H, Fixed, 95% CI)0.57 [0.42, 0.77]

 3 Participants with any adverse event2359Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.66, 0.99]