In high‐income countries, paracetamol toxicity is a common cause of acute liver injury. Paracetamol is commonly taken in overdose either deliberately or unintentionally. All rights reserved.Paracetamol (acetaminophen) is the most widely used non‐prescription analgesic in the world. The marginal clinical benefit of fomepizole adjunct therapy beyond NAC monotherapy remains to be clearly defined, and routine use for APAP overdose is premature based on current evidence.Ĥ-Methylpyrazole Acetaminophen CYP2E1 Fomepizole Hepatotoxicity NAC.Ĭopyright © 2021 Elsevier B.V. NAC remains the standard of care antidote, but given that fomepizole is approved and generally safe, it may be considered for APAP toxicity as off-label use by experienced clinicians, in rare circumstances associated with increased risk of hepatotoxicity despite standard NAC dosing. Fomepizole has been linked to few adverse effects.īased on in vitro and animal studies, and bolstered by case reports, fomepizole likely offers benefit as an adjunct antidote for APAP toxicity, however this remains to be shown in a human trial. Studies have shown a reduction in oxidative metabolites likely by shunting metabolism away from CYP2E1 and a resultant decrease in liver injury in animals, independent of CYP2E1 interactions. Fomepizole's action is mediated by inhibition of CYP2E1 to prevent oxidant stress generation, and inhibition of c-Jun N-terminal kinase (JNK) to decrease amplification of oxidant stress signaling to mitochondria. Eleven preclinical studies (in vitro and animal), fourteen case reports/series, and one human volunteer study were included. Reports on fomepizole as a therapeutic adjunct for APAP toxicity span heterogeneous types of evidence. The objective is to comprehensively review the literature on fomepizole as a potential adjunct antidote for acetaminophen toxicity.Ī scoping review was performed using standardized search terms from inception through July 2021. While N-acetylcysteine (NAC) is an effective antidote, it has therapeutic limitations in massive overdose or delayed presentation. Acetaminophen (paracetamol, APAP) poisoning is a prominent global cause of drug-induced liver injury.

Antidote for tylenol