Childhood hepatotoxicity with paracetamol doses less than 150 mg/kg per day

• Published in: Medical journal of Australia Vol. 171; no. 9; p. 497
• Main Authors: Hynson, Jenny L, South, Mike
• Format: Journal Article
• Language: English
• Published: Australia 01-11-1999
• Subjects: acetaminophen; Acetaminophen - adverse effects; Acetaminophen - therapeutic use; Alanine Transaminase - blood; Analgesics, Non-Narcotic - adverse effects; Analgesics, Non-Narcotic - therapeutic use; antipyretic agents; Aspartate Aminotransferases - blood; Chemical and Drug Induced Liver Injury - diagnosis; Chemical and Drug Induced Liver Injury - etiology; Child; Child, Preschool; Female; Humans; Liver Function Tests; Male
• DOI: 10.5694/j.1326-5377.1999.tb123758.x
• EISSN: 1326-5377
• ISSN: 0025-729X

Paracetamol is widely used as an antipyretic and analgesic. Adverse effects are regarded as unlikely at doses below 150 mg/kg per day. However, lower doses have resulted in hepatotoxicity, and there is growing evidence of the potential for hepatotoxicity in children given multiple therapeutic or supratherapeutic doses of paracetamol. The nomogram devised by Rumack and Matthews was based on data obtained from previously well adult patients who had taken a single large dose of paracetamol. The relevance of this to children given multiple doses in the context of a febrile illness is unknown, particularly as the metabolism in this population appears to be quite different. It has been suggested that the therapeutic index for paracetamol may be as low as 1.7, and that sick children under the age of two years given in excess of 90 mg/kg per day for more than one day should be regarded as being at higher risk. The product information recommends a maximum daily dose of 60 mg/kg, but it is not uncommon for children to receive doses in excess of 90 mg/kg per day in the hospital setting. Although the number of reported cases of hepatotoxicity induced by therapeutic doses of paracetamol is small, it is possible that cases have gone unrecognised. It is important to administer the drug with caution and according to current dosage guidelines.