Repeated supratherapeutic doses of paracetamol in children-a literature review and suggested clinical approach

• Published in: Acta Paediatrica Vol. 95; no. 10; pp. 1165 - 1171
• Main Authors: Kozer, Eran, Greenberg, Revital, Zimmerman, Deena R., Berkovitch, Matitiahu
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2006; Blackwell
• Subjects: Acetaminophen - administration & dosage; Acetaminophen - adverse effects; Acetaminophen - therapeutic use; Algorithms; Analgesics, Non-Narcotic - administration & dosage; Analgesics, Non-Narcotic - adverse effects; Analgesics, Non-Narcotic - therapeutic use; Biological and medical sciences; Child; Drug Overdose; General aspects; Humans; Liver - drug effects; Liver - injuries; Medical sciences; Paracetamol; pediatrics supratherapeutic doses; Risk Factors; Wounds and Injuries - chemically induced; Human; Pediatrics; Antimigrainous agent; Review; pediatrics supratherapeutic doses; Posology; Paracetamol; Analgesic; Treatment; Antipyretic; Dose; Child; Bibliographic review
• ISSN: 0803-5253; 1651-2227
• DOI: 10.1080/08035250600580503

The safety of paracetamol when given in the recommended dosage is well documented. However, in recent years there have been many reports of liver failure associated with repeated exposure to supratherapeutic doses of paracetamol. This paper reviews the literature on chronic supratherapeutic paracetamol exposure in children and the different dosing guidelines. Based on which, we suggest the following approach: liver injury secondary to repeated dosing of paracetamol should be considered when a child has received more than 75 mg/kg/d for at least 2 d, or if risk factors for paracetamol toxicity have been identified. Liver transaminases, coagulation factors, and paracetamol serum concentrations should be measured in these children and in symptomatic children with vomiting, right upper quadrant abdominal pain, and jaundice who have taken paracetamol. Treatment with N‐acetyl cysteine should be started regardless of paracetamol concentrations if transaminases or INR are elevated. Conclusion: Liver injury secondary to repeated dosing of paracetamol is rare but may result in severe morbidity and mortality. The cumulative dose of paracetamol should not exceed 75 mg/kg/d. Children treated with higher doses for more than 2 d should be evaluated for possible liver injury and treated with N‐acetyl cysteine if evidence of liver injury is found.