FOMEPIZOLE (Antizol)

Alcohol dehydrogenase inhibitor

Antidote for known or suspected ethylene glycol or methanol ingestion.

• Competitively inhibits the enzyme alcohol dehydrogenase. Alcohol dehydrogenase is needed to oxidize ethanol alcohol (found in alcoholic beverages) to acetaldehyde and to carry out the initial steps in the metabolism of ethylene glycol (found in antifreeze) and methanol (found in windshield washer fluid).
• It is the metabolites of methanol and ethylene glycol that are toxic. By preventing the metabolism of methanol or alcohol, toxicity can be prevented.
• Consider fomepizole treatment immediately upon suspicion of ethylene glycol or methanol ingestion based on patient history and/or unexplainable anion gap metabolic acidosis, osmolar gap, visual disturbances, or oxalate crystals in the urine.
• Serum ethylene glycol >3.2 mmol/l or methanol concentration >6.2 mmol/L should be treated.
• Off-label use in acetaminophen toxicity.

CONTACT: Ontario Poison Control for treatment guidance (800-268-9017).

Loading dose:

• 15 mg/kg (mix in minibag and administer over 30 minute infusion)

Subsequent doses:

• 10 mg/kg q12h x 48 hours
• then, 15 mg/kg q 12 h until ethylene glycol concentration is undetectable or below 3.2 mmol/L and asymptomatic, or methanol concentration is reduced below 6.2 mmol/L and patient is asymptomatic with normal pH

Dosing during hemodialysis:

Before dialysis: 

• Give the next scheduled dose of fomepizole if more than 6 hours since the last dose

During dialysis:

• Administer doses every 4 hours

Post dialysis:

• If less than one hour since the last dose, give the next scheduled dose 12 hours after the last
• If 1 to less than 3 hours since the last dose, give 50% of the next scheduled dose immediately after dialysis completion, then resume normal scheduling
• If 3 hours since last dose, give 100% of the next dose immediately after dialysis completion, then resume normal scheduling.

May require increased dosing frequency after 30-40 hours of treatment due to fomepizole inducing its own hepatic metabolism

Criteria for stopping fomepizole (one of the following):

• Concentration of methanol or ethylene glycol is undetectable
• Concentration of methanol is below 3.2 mmol/L or ethylene glycol is below 6.2 mmol/L AND the patient is asymptomatic with a normal pH

Intermittent IV Administration
Mix dose in a minibag with a minimum volume of 100 ml dextrose 5 or sodium chloride 0.9% and administer over at least 30 minutes.

Fomepizole solidifies at temperatures below 25C. Efficacy, safety and stability is not affected. Warm the solidified drug by running the vial under warm water or by holding in the hand.

HEMODIALYSIS

Hemodialysis should be considered as an adjust to fomepizole in patients with renal failure, significant or worsening metabolic acidosis or ethylene glycol concentrations 8.1 mmol/L or greater, or methanol concentrations 15.6 mmol/L or greater

Caution:

Use with caution in hepatic failure, eliminated extensively by liver. Dose adjustment may be required.

Do not concurrently administer fomepizole and ethanol to treat ethylene glycol or methanol toxicity (they have competing mechanisms as antidotes).  

• Fomepizole reduces the metabolism of ethanol
• Ethanol administration reduces the metabolism of fomepizole by preferential metabolism of ethanol. While ethanol infusion can be used instead of fomepizole to treat methanol or ethylene glycol overdose, these two treatments should not be used together.

• Bradycardia, tachycardia
• Hypotension, shock
• Facial flushing
• Headache, dizziness, agitation, drowsiness, vertigo
• Seizures, speech disturbances
• Vertigo, nystagmus
• Nausea/vomiting, decreased appetite, diarrhea, heartburn, hiccoughs
• Anemia, DIC, esosinophilia, lymphangitis
• Pharyngitis
• Rash
• Fever
• Back pain
• Bad taste/metallic taste or altered sense of smell
• Increase in hepatic enzymes
• Pain at injection site

• Ethylene glycol or methanol levels
• Blood gases
• Neurological status
• Vision (methanol)
• Hourly urine output

• May be administered by IV infusion by a nurse in Adult Critical Care