Fatal liver failure after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy and atypical pharmacogenetic profile of drug-metabolizing enzymes
Lao, Yvonne Elisabeth; Molden, Espen; Kringen, Marianne K.; Annexstad, Ellen Johanne; Sæverud, Håvard Andreassen; Jacobsen, Dag; Hovda, Knut Erik
Journal article, Peer reviewed
Accepted version
Date
2020-01-24Metadata
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Lao Y, Molden, Kringen, Annexstad, Sæverud, Jacobsen, Hovda. Fatal liver failure after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy and atypical pharmacogenetic profile of drug-metabolizing enzymes. Basic & Clinical Pharmacology & Toxicology. 2020;127(1):47-51 https://doi.org/10.1111/bcpt.13389Abstract
Paracetamol has a good safety profile, but pharmacogenetic differences in drug-metabolizing enzymes
may have an impact on its risk of hepatotoxicity. We present a case of fatal acute liver failure (ALF) after
therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy, where
pharmacogenetic screening was conducted.
This 30-year-old man was electively admitted for a tracheostomy. A total of 14.5 g paracetamol was given
over four days. He developed a severe ALF and died 11 days after admission. Pharmacogenetic screening
showed absent CYP2D6 metabolism and increased CYP1A2 activity, which may have increased the
formation of toxic intermediate metabolite, N-acetyl-p-benzo-quinone imine (NAPQI). He also had
decreased function of UGT2B15, which increases the amount of paracetamol available for metabolism to
NAPQI. Having a reduced muscle mass and thus a reduced glutathione levels to detoxify produced NAPQI
may add to the risk of toxicity.
This case may indicate that pharmacogenetic variability is of potential relevance for the risk of
paracetamol-induced hepatotoxicity in patients with neuromuscular diseases. Further studies should
investigate if pharmacogenetic screening could be a tool to detect potentially increased risk of
hepatotoxicity in these patients at therapeutic doses of paracetamol, and hence provide information for
selection of analgesic treatment.