Acetaminophen and Ibuprofen Overdosage

Jennifer Argentieri; Kerry Morrone; Yehudit Pollack

doi:10.1542/pir.33-4-188

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Jennifer Argentieri, MD
Kerry Morrone, MD
Yehudit Pollack, MD

Children's Hospital at Montefiore
Bronx, NY

Suggested Reading

An Update of N-acetylcysteine Treatment for Acute Acetaminophen Toxicity in Children. Marzullo L. Curr Opin Pediatr. 2005;17(2):239–245
OpenUrl CrossRef PubMed
Acetaminophen Toxicity in Children. American Academy of Pediatrics. Committee on Drugs. Pediatrics. 2001;108(4):1020–1024
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Clinical Report—Fever and Antipyretic Use in Children. Section on Clinical Pharmacology and Therapeutics; Committee on Drugs, Sullivan JE, Farrar HC . Pediatrics. 2011;127(3):580–587
Efficacy and Safety of Ibuprofen and Acetaminophen in Children and Adults: A Meta-Analysis and Qualitative Review. Pierce CA, Voss B. Ann Pharmacother. 2010;44(3):489–506
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Nonsteroidal Antiinflammatory Drugs. Holubek W. In: Nelson LS, Lewin NA, Howland MA, et al, eds. Goldfrank's Toxicologic Emergencies. 9th ed. New York, NY: McGraw-Hill Companies; 2011:528–536.
Acetylcysteine for Acetaminophen Poisoning. Heard KJ. N Engl J Med. 2008;359(3):285–292
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Author Disclosure
Drs Argentieri, Morrone, and Pollack have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

Fever is one of the most common symptoms managed by pediatricians. Many parents fear that fever is harmful to their children, leading to an estimated 30% of illness visits. Acetaminophen and ibuprofen remain the most common antipyretic medications, with numerous over-the-counter and prescription preparations available in the United States. Studies have reported that as many as one-half of parents administer the incorrect dose of acetaminophen and ibuprofen.

Acetaminophen is metabolized mainly in the liver by conjugation with sulfate and glucuronide. When an excessive amount of acetaminophen is present, it overwhelms the normal conjugation pathway, and metabolism is channeled to the cytochrome P-450 pathway, which produces the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). NAPQI is detoxified by glutathione; however, when gluthathione becomes depleted, NAPQI binds directly to hepatocytes, causing cellular necrosis.

A therapeutic dosage of acetaminophen is 75 mg/kg per 24-hour period, not to exceed 4 g in 24 hours. Single dosages of 10 to 15 mg/kg given every 4 to 6 hours orally generally are regarded as safe and effective. Liver toxicity in children has been reported after one dose of 120 to 150 mg/kg, with a higher risk of toxicity associated with fasting, liver disease, a history of excessive alcohol use, or the coadministration of medications that induce the cytochrome P-450 pathway.

Clinical manifestations of acetaminophen overdose can be gradual and nonspecific. Four clinical …