University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• In children with an acute febrile illness, what is the efficacy of single-medication therapy with acetaminophen or ibuprofen compared with combination therapy combining the two medications in reducing fever while avoiding adverse effects?

Clinical Bottom Lines

1. Both acetaminophen and ibuprofen are effective antipyretics and are well-tolerated in short-term use in febrile children.
   
2. Ibuprofen is more effective at achieving temperature normalization than acetaminophen, though both effectively lower temperatures >1.5 C in most patients with standard dosing.
   
3. There is no data currently available comparing the efficacy and tolerability alternating regimens with ibuprofen and acetaminophen to single-drug regimens.¹
   

Summary of Key Evidence

1. 628 children aged 6 months to 6 years with initial temperature >38.5C were randomized to receive ibuprofen, acetaminophen, or dipyrone (banned in the US) in a 1:1:1 ratio. The study was double-blinded and multinational. There was no placebo arm.
   
2. 77% of patients receiving acetaminophen and 83% of patients receiving ibuprofen had a temperature decrease of = 1.5C. (no significant difference)
   
3. Temperature normalization (temperature decreased to = 37.5C) was achieved in 68% of patients receiving acetaminophen and 78% of patients receiving ibuprofen (P=0.004). This gives a number need to treat (NNT) of 10.
   
4. Adverse events attributed to the ibuprofen were diarrhea/vomiting (2.3%) and rash/exanthem (0.5%). Those for acetaminophen were vomiting (1.4%). These were not significantly different between the two groups..

Additional Comments

• Fever is a frequent occurrence in young children, and provokes significant anxiety in parents.² It is a leading reason for seeking medical care in both outpatient clinics and emergency rooms.³
  
• There is no consensus about when fever should be treated, or with what drug or combination of drugs. Individual physicians recommend a wide variety of treatment regimens to their patients.⁴
  
• The efficacy of combination antipyretic regimens alternating acetaminophen and ibuprofen has not been tested; however, they are frequently recommended by pediatricians.
  
• Parents frequently make errors in dosing antipyretics at home. In single-dose regimens, parents gave erroneous doses 50% of the time.⁵
  
• Both acetaminophen and ibuprofen have well-documented toxicities in overdose.
  
• Ibuprofen and acetaminophen dosing and timing are different, leading to additional confusion in regimens alternating the two drugs. Many regimens combining the two exceed the recommended total daily dose of acetaminophen even when followed correctly.⁴
  

Citation

1. Wong, Anthony et al. Antipyretic Effects of Dipyrone Versus Ibuprofen Versus Acetaminophen in Children: Results of a Multinational, Randomized, Modified Double-Blind Study. Clinical Pediatrics 2001;40:313-324.
   
2. Kramer MS, Naimatk L, Leduc DG, Parental Fever Phobia and its correlates. Pediatrics 1985;75:1110-1113.
   
3. McCarthy, P. Fever. Pediatrics in Review 1998; 19:401-407.
   
4. Mayoral CE, Marino RV, Rosenfeld W, Greensher J. Alternating Antipyretics: Is this an alternative? Pediatrics 2000; 105:1009-1012.
5. Li SF, Lacher B, Crain EF. Acetaminophen and ibuprofen dosing by parents. Pediatric Emergency Care 2000; 16(6):394-397.

CAT Author: Carolyn Lorenz, MD

CAT Appraisers: John Frohna, MD

Date appraised: April 7, 2004