Intervention Review

You have free access to this content

Combined and alternating paracetamol and ibuprofen therapy for febrile children

  1. Tiffany Wong1,2,*,
  2. Antonia S Stang3,
  3. Heather Ganshorn4,
  4. Lisa Hartling5,
  5. Ian K Maconochie6,
  6. Anna M Thomsen2,
  7. David W Johnson7

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 30 OCT 2013

Assessed as up-to-date: 6 SEP 2013

DOI: 10.1002/14651858.CD009572.pub2

How to Cite

Wong T, Stang AS, Ganshorn H, Hartling L, Maconochie IK, Thomsen AM, Johnson DW. Combined and alternating paracetamol and ibuprofen therapy for febrile children. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD009572. DOI: 10.1002/14651858.CD009572.pub2.

Author Information

  1. 1

    University of British Columbia, BC Children's Hospital, Department of Pediatrics, Vancouver, Canada

  2. 2

    Alberta Children's Hospital, Calgary, Canada

  3. 3

    Community Health Services, Department of Pediatrics, Calgary, AB, Canada

  4. 4

    University of Calgary, Libraries and Cultural Resources, Calgary, Alberta, Canada

  5. 5

    University of Alberta, Department of Pediatrics, Edmonton, Alberta, Canada

  6. 6

    St Mary's Hospital, Department of Paediatrics A&E, London, UK

  7. 7

    Faculty of Medicine, University of Calgary, Alberta Children's Hospital, Department of Pediatrics, Calgary, Alberta, Canada

*Tiffany Wong, Department of Pediatrics, University of British Columbia, BC Children's Hospital, Vancouver, Canada.

Publication History

  1. Publication Status: New
  2. Published Online: 30 OCT 2013



References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Erlewyn-Lajeunesse 2006 {published data only}
  • Erlewyn-Lajeunesse MD, Coppens K, Hunt LP, Chinnick PJ, Davies P, Higginson I M, et al. Randomised controlled trial of combined paracetamol and ibuprofen for fever. Archives of Disease in Childhood 2006;91(5):414-6.
Hay 2008 {published data only}
  • Hay AD, Costelloe C, Redmond NR, Montgomery AA, Fletcher M, Hollinghurst S, et al. Paracetamol and ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial. British Medical Journal 2008;337:a1302.
Kramer 2008 {published data only}
  • Kramer LC, Richards PA, Thompson AM, Harper DP, Fairchok MP. Alternating antipyretics: antipyretic efficacy of acetaminophen versus acetaminophen alternated with ibuprofen in children. Clinical Pediatrics 2008;47(9):907-11.
Nabulsi 2006 {published data only}
  • Nabulsi M, Tamim H, Mahfoud Z, Itani M, Sabra R, Chamseddine F, et al. Alternating ibuprofen and acetaminophen in the treatment of febrile children: a pilot study. BMC Medicine 2006;4(4):b3540.
Paul 2010 {published data only}
  • Paul IM, Sturgis SA, Yang C, Engle L, Watts H, Berlin CM Jr. Efficacy of standard doses of ibuprofen alone, alternating, and combined with acetaminophen for the treatment of febrile children. Clinical Therapeutics 2010;32(14):2433-40.
Sarrell 2006 {published data only}
  • Sarrell EM, Wielunsky E, Cohen HA. Antipyretic treatment in young children with fever: acetaminophen, ibuprofen, or both alternating in a randomized, double-blind study. Archives of Pediatrics & Adolescent Medicine 2006;160(2):197-202.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Del Vecchio 2001 {published data only}
Diez Domingo 2001 {published data only}
  • Diez Domingo J, Burgos Ramirez A, Garrido Garcia J, Ballester Sanz A, Moreno Carretero E. Use of alternating antipyretics in the treatment of fever in Spain [Utilizacion de la alternancia de antipireticos en el tratamiento de la fiebre en Espana]. Anales Espanoles de Pediatria December 2001;55(6):503-10.
Drucker 2009 {published data only}
  • Drucker R. Comparison of acetaminophen, ibuprofen, and both agents for treatment of fever in children acetaminophen plus ibuprofen and ibuprofen alone are equally effective in reducing fever. Archives of Disease in Childhood 2009;94(1):30.
Lal 2000 {published data only (unpublished sought but not used)}
  • Lal A, Gomber S, Talukdar B. Antipyretic effects of nimesulide, paracetamol and ibuprofen-paracetamol. Indian Journal of Pediatrics 2000;67(12):865-70.
Malik 2007 {published data only}
  • Malik K, Goldman RD. PRETx update: Alternating antipyretics in febrile children. International Pediatrics 2007;22(2):95-7.
Mayoral 2000 {published data only}
Miller 2007 {published data only}
Nabulsi 2010 {published data only}
  • Nabulsi M. Is combining or alternating antipyretic therapy more beneficial than monotherapy for febrile children?. British Medical Journal 2010;340(7737):92-3.
Pashapour 2009 {published data only (unpublished sought but not used)}
  • Pashapour N, Macooei AA, Golmohammadlou S. Alternating ibuprofen and acetaminophen in the treatment of febrile hospitalized children aged 9-24 months. Iranian Journal of Pediatrics June 2009;19(2):164-8.
Pereira 2012 {published data only}
  • Pereira GL, Dagostini JMC, da Silva Dal Pizzol T. Alternating antipyretics in the treatment of fever in children: a systematic review of randomized clinical trials [Uso alternado de antipiréticos para tratamento da febre em crianças: revisão sistemática de ensaios clínicos randomizados]. Jornal de Pediatria 2012;88(4):289-96.
Purssell 2011 {published data only}
Ruiz Lazaro 2009 {published data only}
  • Ruiz Lazaro PJ. Ibuprofen, alone or combined with paracetamol, is more effective than paracetamol alone in home treatment of fever in children from 6 months to 6 years of age [Administrar ibuprofeno, solo o combinado con paracetamol, es mas efectivo que utilizar solo paracetamol en el tratamiento domiciliario de la fiebre en ninos de 6 meses a 6 anos de edad]. FMC Formacion Medica Continuada En Atencion Primaria 2009;16(5):311.
Uhl 2008 {published data only}
  • Uhl D. Ibuprofen and/or paracetamol for the treatment of fever in children? [Ibuprofen und paracetamol im wechsel geben?]. Deutsche Apotheker Zeitung 2008;148(44):52-5.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Beasley 2008
  • Beasley R, Clayton T, Crane J, von Mutius E, Lai CKW, Montefort S, et al. Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from Phase Three of the ISAAC programme. Lancet 2008;372:1039-48.
Brewer 1968
Brown 1992
Canadian Pediatric Society 1998
  • Position Paper DT98-01 of the Drug Therapy and Hazardous Substances Committee. Paediatric Child Health 1998; Vol. 3, issue 4:273-4.
Chiappini 2009
  • Chiappini E, Principi N, Longhi R, Tovo PA, Beccheruci P, et al. Management of fever in children: summary of the Italian Pediatric Society guidelines. Clinical Therapeutics 2009;8:1826-43.
Cohet 2004
  • Cohet C, Cheng S, MacDonald C, Baker M, Foliaki S, Huntington N, et al. Infections, medication use, and the prevalence of symptoms of asthma, rhinitis, and eczema in childhood. Journal of Epidemiology and Community Health 2004;58:852-7.
Crocetti 2001
Del-Rio-Navarro 2008
  • Del-Rio-Navarro BE, Ito-Tsuchiya FM, Berber A, Zepeda-Ortega B, Sienra-Monge JJ, Garcia-Almaraz R, et al. Study of the relationship between acetaminophen and asthma in Mexican children aged 6 to 7 years in 3 Mexican cities using ISAAC methodology. Journal of Investigational Allergology and Clinical Immunology 2008;18(3):194.
Drwal-Klein 1992
  • Drwal-Klein LA, Phelps SJ. Antipyretic therapy in the febrile child. Clinical Pharmacology 1992;11:1005-21.
Etminan 2009
  • Etminan M, Sadatsafavi M, Jafari S, Doyle-Waters M, Aminzadeh K, Fitzgerald JM. Acetaminophen use and the risk of asthma in children and adults: A systematic review and metaanalysis. Chest November 2009;136(5):1316-23.
Feldberg 1973
GRADEpro 2008 [Computer program]
  • Brozek J, Oxman A, Schünemann H. GRADEpro. Version 3.2 for Windows .. 2008.
Guyatt 2008
  • Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. British Medical Journal 2008;336:924-6.
Heubi 1998
Higgins 2002
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. Available from The Cochrane Collaboration 2011.
Kanabar 2007
Kauffman 1992
Kelley 1992
  • Kelley MT, Walson PD, Edge JH, Cox S, Mortensen ME. Pharmacokinetics and pharmacodynamics of ibuprofen isomers and acetaminophen in febrile children. Clinical Pharmacology & Therapeutics 1992;52:181-9.
Kluger 1995
Kwiatkowski 1995
Lesko 1999
Lesko 2002
Li 2000
Lowe 2010
L’Italien 2001
  • L'Italien C, Jacqz-Aigrain E. Risks and benefits of nonsteroidal anti-inflammatory drugs in children: a comparison with paracetamol. Paediatric Drugs 2001;3:817-58.
Mackowiak 1998
McIntyre 1996
Nabulsi 2009
Newson 2000
NICE Clinical Guidelines
  • Feverish illness in children: Assessment and initial management in children younger than 5 years. National Institue for Health and Clinical Excellence May 2013.
Perrott 2004
  • Perrott DA, Piira T, Goodenough B, Champion GD. Efficacy and safety of acetaminophen vs ibuprofen for treating children's pain or fever. A meta-analysis. Archives of Pediatrics & Adolescent Medicine 2004;158:521-6.
Renn 2000
  • Renn E. The antipyretic use of acetaminophen versus ibuprofen in a pediatric care setting. Physical Therapy 2000;25:395-7.
Review Manager [Computer program]
  • The Cochrane Collaboration. Review Manager (RevMan). Version 5.0. Copenhagen: The Cochrane Collaboration, 2008.
Schmitt 1980
Schnaiderman 1993
  • Schnaiderman D, Lahat E, Sheefer T, Aladjem M. Antipyretic effectiveness of acetaminophen in febrile seizures: Ongoing prophylaxis versus sporadic usage. European Journal of Paediatrics 1993;152:747-9.
Sullivan 2011
van Stuijvenberg 1998
  • van Stuijvenberg M, Derksen-Lubsen G, Steyerberg EW, Habbema JDF, Moll HA. Randomized controlled trial of ibuprofen syrup administered during febrile illness to prevent febrile seizure recurrences. Pediatrics 1998;102:1-7.
Walson 1989
Widal 1922
  • Widal MF, Abrami P, Lenmoyez J. Anaphylaxis and Idiosyncrasy [Anaphylaxie et idiosyncrasie]. La Presse Medicale 1922;30:189-92.
Wilson 1991
  • Wilson JT, Brown D, Kearns GL, Eichler VF, Johnson VA, Bertrand KM, et al. Single-dose, placebo-controlled comparative study of ibuprofen and acetaminophen antipyresis in children. Journal of Pediatrics 1991;119:803-11.