TY - JOUR

T1 - Acetaminophen treatment in children and adults with spinal muscular atrophy

T2 - a lower tolerance and higher risk of hepatotoxicity

AU - Naume, Marie Mostue

AU - Zhao, Qiaolin

AU - Haslund-Krog, Sissel Sundell

AU - Krag, Thomas

AU - Winter, Brenda C.M.de

AU - Revsbech, Karoline Lolk

AU - Vissing, John

AU - Holst, Helle

AU - Møller, Morten Hylander

AU - Hornsyld, Tessa Munkeboe

AU - Dunø, Morten

AU - Hoei-Hansen, Christina Engel

AU - Born, Alfred Peter

AU - Bo Jensen, Per

AU - Cathrine Ørngreen, Mette

N1 - Publisher Copyright: © 2023 The Authors

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Acetaminophen treatment

KW - Glutathione

KW - Hepatotoxicity

KW - Low skeletal muscle mass

KW - Spinal muscular atrophy

U2 - 10.1016/j.nmd.2023.11.005

DO - 10.1016/j.nmd.2023.11.005

M3 - Journal article

C2 - 38052667

AN - SCOPUS:85179110161

VL - 34

SP - 9

EP - 18

JO - Journal of Neuromuscular Diseases

JF - Journal of Neuromuscular Diseases

SN - 0960-8966

ER -