Name: FOMEPIZOLE (AntizolR)
Classification:

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 bevridges) 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 unexplanable 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.
Dose:

Loading dose:

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

Subsequent doses:

  • 10 mg/kg q12h X 4 doses
  • then, 15 mg/kg q 12 h
  • continue until ethylene glycol < 0.4 mmol/L or serum methanol levels <0.06 mmol/L

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 followin):

  • 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
Administration:

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.

Caution:
  • Use with caution in hepatic failure, eliminated extensively by liver. Dose adjustment may be required
Drug Interactions:
  • 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.
Adverse Effects:
  • headache
  • nausea
  • dizziness
  • increased drowsiness
  • bad taste/metallic taste
  • increase in hepatic enzymes
Monitoring Therapy:
  • ethylene glycol or methanol levels
  • blood gases
Adult Critical Care Protocol:
  • May be administered by IV infusion by a nurse in Adult Critical Care


Lynne Kelly, Pharmacist, CCTC
Brenda Morgan, Clinical Nurse Specialist, CCTC
Last Update: September 19, 2018

LHSCHealth Professionals

Last Updated September 20, 2018 | © 2007, LHSC, London Ontario Canada