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Practice Uncertainties Page

Is combining or alternating antipyretic therapy more beneficial than monotherapy for febrile children?

BMJ 2009; 339 doi: (Published 01 October 2009) Cite this as: BMJ 2009;339:b3540
  1. Mona Nabulsi, associate professor of paediatrics; head of division of general paediatrics
  1. 1Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, American University of Beirut, PO Box 113-6044/C8, Beirut, Lebanon
  1. Correspondence to: M Nabulsi mn04{at}
  • Accepted 6 July 2009

Although fever is a beneficial host response, it is an important cause of anxiety for parents and doctors. The quest for effective treatment has led to new combination regimens of antipyretic drugs for febrile children. These are popular among caregivers and healthcare providers,1 2 3 4 but they have been tested in clinical trials only recently.4 5 6 7 8 The new regimens consist of combinations of ibuprofen and paracetamol (acetaminophen) given at variable time schedules. The main concern about these treatments is safety, because they may increase the risk of renal toxicity, as a result of reduced glutathione in the kidney and tubular necrosis,9 10 or the risk of infection with invasive group A streptococci.11 We therefore need to know whether these combinations are more effective than, and as safe as, monotherapy in children with fever.

What is the evidence of the uncertainty?

A systematic search of PubMed, Medline, CINAHL, Cochrane, and Embase databases for systematic reviews and randomised clinical trials, published in any language, using the MeSH terms or keywords “fever” and “ibuprofen” and …

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