Acetaminophen treatment in children and adults with spinal muscular atrophy: a lower tolerance and higher risk of hepatotoxicity

Marie Mostue Naume*, Qiaolin Zhao, Sissel Sundell Haslund-Krog, Thomas Krag, Brenda C M de Winter, Karoline Lolk Revsbech, John Vissing, Helle Holst, Morten Hylander Møller, Tessa Munkeboe Hornsyld, Morten Dunø, Christina Engel Hoei-Hansen, Alfred Peter Born, Per Bo Jensen, Mette Cathrine Ørngreen

*Corresponding author for this work

Abstract

Acute liver failure has been reported sporadically in patients with spinal muscular atrophy (SMA) and other neuromuscular disorders with low skeletal muscle mass receiving recommended dosages of acetaminophen. It is suggested that low skeletal muscle mass may add to the risk of toxicity. We aimed to describe the pharmacokinetics and safety of acetaminophen in patients with SMA. We analyzed acetaminophen metabolites and liver biomarkers in plasma from SMA patients and healthy controls (HC) every hour for six or eight hours on day 1 and day 3 of treatment with therapeutic doses of acetaminophen. Twelve patients with SMA (six adults and six children) and 11 HC participated in the study. Adult patients with SMA had significantly lower clearance of acetaminophen compared to HC (14.1 L/h vs. 21.5 L/h). Formation clearance of acetaminophen metabolites, glucuronide, sulfate, and oxidative metabolites were two-fold lower in the patients compared to HC. The liver transaminases and microRNAs increased nine-fold in one adult SMA patient after two days of treatment. The other patients and HC did not develop abnormal liver biomarkers. In this study, patients with SMA had lower clearance and slower metabolism of acetaminophen, and one patient developed liver involvement. We recommend giving 15 mg/kg/dose to SMA adults (with a maximum of 4000 mg/day) and monitoring standard liver biomarkers 48 h after first-time treatment of acetaminophen.

Original languageEnglish
JournalNeuromuscular disorders : NMD
Volume34
Pages (from-to)9-18
Number of pages10
ISSN0960-8966
DOIs
Publication statusPublished - 2024

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