Reactions 1480, p32 - 30 Nov 2013

O X SParacetamol/phenobarbital

Hepatotoxicity and various other toxicities: casereport

A 48-year-old man experienced an intentional overdose ofphenobarbital leading to unresponsiveness, bradycardia andhypotension; he subsequently developed hepatotoxicity whilereceiving paracetamol and phenobarbital concurrently.

The man, who had chronic hepatitis C infection, presentedto an emergency department after an intentional overdose ofphenobarbital [route, dosage and time to reaction onset notstated]. He had been receiving phenobarbital for many years totreat an underlying seizure disorder. At presentation, he wasunresponsive, with bradycardia and hypotension.

The man was intubated for airway protection and admittedto the ICU. A significantly elevated phenobarbitalconcentration was found on toxicology screen. He receivedsupportive care and was eventually extubated. However, hedeveloped right-sided abdominal pain after several days, andrequired a right hemicolectomy for severe colitis. He wassubsequently restarted on phenobarbital. Intravenousparacetamol 1000mg every 6 hours, as needed was given forpain. Jaundice was noted 3 days later. and his liver functiontests were elevated. Paracetamol was stopped, as it was feltlikely that paracetamol toxicity had caused these elevations.His transaminases subsequently normalised.

Author comment: "First, [paracetamol] is metabolized bythe cytochrome P450 system into its toxic metabolite, N-acetyl-p-benzoquinone imine. Second, potent inducers ofCYP2E1, such as phenobarbital, can significantly increase thelevels of the toxic metabolite causing increased risk for[paracetamol] hepatotoxicity."Umbel J, et al. Hepatotoxicty from combined use of acetaminophen andphenobarbital. American Journal of Gastroenterology 108 (Suppl. 1): S327-S328abstr. 1101, Oct 2013. Available from: URL: http://dx.doi.org/10.1038/ajg.2013.267 - USA 803096387

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Reactions 30 Nov 2013 No. 14800114-9954/13/1480-0001/$14.95 Adis © 2013 Springer International Publishing AG. All rights reserved