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Fomepizole for Acetaminophen Overdose - #PHARMFAX

Updated: Aug 23, 2023

Fomepizole has shown promise as an adjunctive therapy in acetaminophen overdoses.

 


Fomepizole has shown promise as an adjunctive therapy in acetaminophen overdoses. Let's review how the acetamophen is metabolized. Roughly 90% acetaminophen is conjugated into non-toxic metabolites, while 10% goes through the cytochrome pathway, specifically CYP2E1 and CYP1A2. The latter results in a toxic by-product called N-acetyl P-benzoquinine imine or NAPQI.


Glutathione turns the toxic metabolite into non-toxic compounds. In the setting of acetaminophen overdoses, glutathione stores are depleted and allows toxic NAPQI to damage to the liver. N-acetylcysteine, or NAC, is the mainstay of thereapy for treatment since it serves as a glutathione precursor.


Fomepizole is a potent alcohol dehydrogenase inhibitor used in toxic alcohol poisonings. Another property of fomepizole is that it inhibits CYP2E1 metabolism. This would prevent additional formation of NAPQI and subsequent hepatotoxicity. Limited to retrospective and case series, fomepizole has been considered in massive ingestions, late-presentations, and those requiring prolonged NAC infusions. NAC remains the primary therapy and higher quality studies are needed to better understand fomepizole's role for acetaminophen poisonings.


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  1. Shah K, Beuhler M. Fomepizole as an Adjunctive Treatment in Severe Acetaminophen Toxicity. Am J Emerg Med. 2020 Feb;38(2):410.e5-410.e6.

  2. Filip et al. Fomepizole as an adjunctive therapy for acetaminophen poisoning: cases reported to the toxicology investigators consortium (ToxIC) database 2015-2020. Clin Toxicol (Phila). 2022 Sep;60(9):1006-1011.

  3. Pourbagher-Shahri et al. Use of fomepizole (4-methylpyrazole) for acetaminophen poisoning: A scoping review. Toxicol Lett. 2022 Feb 1;355:47-61.





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