II. Indications
- Toxic Alcohol ingestion
- Other indications to consider (off label)
- Large Acetaminophen ingestion (>30 to 40 g) with Late presentations
- Adjunct to primary management with N-Acetylcysteine (NAC)
- Indications for Fomepizole (discuss with Poison Control)
- Massive Acetaminophen ingestion (>=30 g) or markedly elevated serum concentration
- Early mitochondrial dysfunction findings (Lactic Acid elevation, Metabolic Acidosis with Anion Gap)
- Evolving hepatotoxicity with a late presentation
- Rapid hepatic transaminase level rise
- Concern for Acute Hepatic Failure
- Large Acetaminophen ingestion (>30 to 40 g) with Late presentations
III. Mechanism
-
Toxic Alcohol ingestion
- Fomepizole is a specific competitive inhibitor of Alcohol dehydrogenase
- Fomepizole is the preferred agent in Toxic Alcohol ingestion
- In eythylene glycol Poisoning, inhibits formation of the toxic metabolites glycolate and oxalate
- In Methanol Poisoning, inhibits formation of the toxic metabolite formic acid
-
Acetaminophen Overdose
- Fomepizole is a CYP2E1 Inhibitor, preventing oxidative metabolite formation (NAPQI)
- Acetaminophen is primarily metabolized in the the liver by Glucuronidation and sulfation
- However, 10% of Acetaminophen is oxidized to NAPQI by CYP2E1
- Fomepizole also blocks JNK activation, preventing further peroxynitrite formation
- Excess NAPQI binds mitochondrial Proteins, causing oxidative stress and mitochondrial dysfunction
- Activation of c-Jun N-Terminal Kinase (JNK) is one mechansim for hepatocellular injury
- Fomepizole is a CYP2E1 Inhibitor, preventing oxidative metabolite formation (NAPQI)
IV. Dosing: Ethylene Glycol Poisoning
- Fomepizole Prolongs Alcohol's natural Half-Life from 3 to 20 hours
- Load: 15 mg/kg
- Next: 10 mg/kg q12 hours for 4 doses
- Maintenance: 15 mg/kg every 12 hours
- End point: Ethylene Glycol level <20 mg/dl
V. Dosing: Methanol Poisoning
- Start Fomepizole immediately (at same dosing as for Ethylene Glycol) if Methanol toxicity is suspected
- Indications to continue Fomepizole
- Methanol level >20 mg/dl
- Osmolal Gap >10 mOsm/L
- Serum bicarbonate <20 mmol/L
VI. Dosing: Large Acetaminophen Overdose with late presentation (off-label)
- Start: 15 mg/kg load
- Next: 10 mg/kg every 12 hours until no longer recommended by expert Consultation
VII. References
- LoVecchio (2026) Crit Dec Emerg Med 40(6): 36
- Akakpo (2022) Arch Toxicol 96(2):453-65 +PMID: 34978586 [PubMed]