Pharm

Fomepizole

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Fomepizole, 4-methylpyrazole, Antizol

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