What is one proposed mechanism for fomepizole adjunct therapy in acetaminophen toxicity?
Fomepizole is primarily recognized for its inhibition of alcohol dehydrogenase; however, its inhibition of CYP2E1 makes it a promising adjunct agent in the treatment of acetaminophen toxicity cases with high likelihood of developing hepatotoxicity despite N-acetylcysteine therapy. Normally, acetaminophen is primarily metabolized to non-toxic metabolites through glucronidation. In the setting of acetaminophen overdose, the glucuronidation pathway becomes saturated which shifts more acetaminophen to be metabolized through CYP2E1. Through CYP2E1, acetaminophen is converted to its toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Fomepizole’s inhibition of CYP2E1 can reduce the production of NAPQI and thus decrease the severity of the hepatotoxicity.
- Shah KR, Beuhler MC. Fomepizole as an adjunctive treatment in severe acetaminophen toxicity. The American Journal of Emergency Medicine. 2020;38(2):410.e5-410.e6.
- Rampon G, Wartman H, Osmon S, Scalzo A. Use of fomepizole as an adjunct in the treatment of acetaminophen overdose: a case series. Toxicology Communications. 2020;4(1):1-4.
Contributed by: Cedric White, PharmD (Cedric.White@bmc.org) with oversight from Natalija Farrell, PharmD, BCPS, DABAT (Natalija.Farrell@bmc.org)