title: Therapeutic acetaminophen is not associated with liver injury in children: a systematic review.
abstract: BACKGROUND
  Concern exists about the potential for liver injury with therapeutic dosing of acetaminophen in children.
  
  
  OBJECTIVE
  We systematically reviewed the medical literature to determine the rate at which liver injury has been reported for children prescribed therapeutic doses of acetaminophen (≤75 mg/kg per day orally or intravenously or ≤100 mg/kg per day rectally).
  
  
  METHODS
  We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials to locate all studies in which acetaminophen was administered to a defined pediatric population for ≥24 hours and for all case reports of liver injury after therapeutic acetaminophen dosing. Trained reviewers extracted data from each report. Major and minor hepatic adverse events (AEs) were defined prospectively. Causality was assessed by using the Naranjo algorithm.
  
  
  RESULTS
  A total of 62 studies that enrolled 32,414 children were included. No child (0% [95% confidence interval: 0.000-0.009]) was reported to have exhibited signs or symptoms of liver disease, to have received an antidote or transplantation, or to have died. Major or minor hepatic AEs were reported for 10 children (0.031% [95% confidence interval: 0.015-0.057]). The highest transaminase value reported was 600 IU/L. Naranjo scores (2-3) suggested "possible" causation. Twenty-two case reports were identified. In 9 cases, the Naranjo score suggested "probable" causation (5-6).
  
  
  CONCLUSIONS
  Hepatoxicity after therapeutic dosing of acetaminophen in children is rarely reported in defined-population studies. Case reports suggest that this phenomenon may occur, but few reports contain sufficient data to support a probable causal relationship.
authors.affiliation: Rocky Mountain Poison & Drug Center, 777 Bannock St, MC 0180, Denver, CO 80204, USA. eric.lavonas@rmpdc.org
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lavonas
authors.forename: Kate M
authors.initials: KM
authors.lastname: Reynolds
authors.forename: Richard C
authors.initials: RC
authors.lastname: Dart
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D002648:Child; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008099:Liver / Q000187:drug effects*; D017093:Liver Failure / Q000175:diagnosis / Q000209:etiology*; D008111:Liver Function Tests
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen