paracetamol/phenobarbital

Reactions 1480, p32 - 30 Nov 2013 O X S Paracetamol/phenobarbital Hepatotoxicity and various other toxicities: case report A 48-year-old man experienced an intentional overdose of phenobarbital leading to unresponsiveness, bradycardia and hypotension; he subsequently developed hepatotoxicity while receiving paracetamol and phenobarbital concurrently. The man, who had chronic hepatitis C infection, presented to an emergency department after an intentional overdose of phenobarbital [route, dosage and time to reaction onset not stated]. He had been receiving phenobarbital for many years to treat an underlying seizure disorder. At presentation, he was unresponsive, with bradycardia and hypotension. The man was intubated for airway protection and admitted to the ICU. A significantly elevated phenobarbital concentration was found on toxicology screen. He received supportive care and was eventually extubated. However, he developed right-sided abdominal pain after several days, and required a right hemicolectomy for severe colitis. He was subsequently restarted on phenobarbital. Intravenous paracetamol 1000mg every 6 hours, as needed was given for pain. Jaundice was noted 3 days later. and his liver function tests were elevated. Paracetamol was stopped, as it was felt likely that paracetamol toxicity had caused these elevations. His transaminases subsequently normalised. Author comment: "First, [paracetamol] is metabolized by the cytochrome P450 system into its toxic metabolite, N- acetyl-p-benzoquinone imine. Second, potent inducers of CYP2E1, such as phenobarbital, can significantly increase the levels of the toxic metabolite causing increased risk for [paracetamol] hepatotoxicity." Umbel J, et al. Hepatotoxicty from combined use of acetaminophen and phenobarbital. American Journal of Gastroenterology 108 (Suppl. 1): S327-S328 abstr. 1101, Oct 2013. Available from: URL: http://dx.doi.org/10.1038/ ajg.2013.267 - USA 803096387 1 Reactions 30 Nov 2013 No. 1480 0114-9954/13/1480-0001/$14.95 Adis © 2013 Springer International Publishing AG. All rights reserved

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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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