Fomepizole (Antizol) is used as an antidote for ethanol, ethylene glycol, and methanol overdose.

Fomepizole Uses:

• Ethylene glycol or methanol poisoning

• Treatment of methanol or ethylene glycol poisoning alone or in combination with hemodialysis

Note:

• Fomepizole is the favored antidote for confirming or alleged ethylene glycol poisoning or methanol poisoning.
• If fomepizole is unavailable or if the patient is intolerant to fomepizole, ethanol therapy may be considered.
• Ethanol as an antidote is efficient in managing methanol and ethylene glycol poisoning; however, ethanol is related to a higher incidence of adverse events and medication errors.

Fomepizole (Antizol) Dose in Adults

Note: Fomepizole treatment should commence instantly upon suspicion of ethylene glycol or methanol consumption.

Fomepizole (Antizol) Dose in the treatment of Ethylene glycol and methanol toxicity:

• IV: Loading dose of 15 mg/kg should be given, followed by doses of 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours thereafter until ethylene glycol or methanol concentrations have decreased to <20 mg/dL and patient is symptomless with normal pH.

Note: For severe toxicity needing concomitant hemodialysis, see dosage modifications in renal damage

Fomepizole (Antizol) Dose in Childrens

Note: Fomepizole treatment should start instantly upon doubt of ethylene glycol or methanol consumption.

Fomepizole (Antizol) Dose in the treatment of Ethylene glycol or methanol toxicity; patient not requiring hemodialysis:

consider a consultation with a clinical toxicology or poison control center

• Infants, Children, and Adolescents:

  • IV: Initial: 15 mg/kg loading dose; followed by 10 mg/kg every 12 hours for 4 doses; then 15 mg/kg every 12 hours until ethylene glycol or methanol concentrations have been reduced to <20 mg/dL and the patient is asymptomatic with normal pH.

Note: For severe toxicity needing concomitant hemodialysis, see Dosage modification in kidney damage.

Pregnancy Risk Factor C

• There have never been any animal reproductive studies.
• Antidotes used in general should be considered the mother's health and prognosis.
• Pregnant women should receive antidotes if they have a clear indication and should not withhold them from fear of birth defects.

Use during breastfeeding:

• It is unknown if the drug is found in breast milk.
• Manufacturer suggests caution when giving fomepizole for breastfeeding women.

Dose in Kidney Disease:

Note:

• Haemodialysis should be deemed as an aide to fomepizole in patients with kidney failure, substantial or deteriorating metabolic acidosis, or ethylene glycol or methanol concentrations ≥50 mg/dL.
• The following dosing alterations should be used for any patient receiving hemodialysis irrespective of renal function.

• Prior to the start of hemodialysis:

  • To decide if the patient needs a dose of fomepizole at the beginning of hemodialysis, establish when the last dose was dispensed.
  • If the last dose of fomepizole was given less than 6 hours ago, do not give out another dose upon beginning hemodialysis.
  • If the last dose of fomepizole was given 6 or more hours ago, administer the next planned dose upon starting hemodialysis.

• During hemodialysis:

  • During hemodialysis, administer fomepizole every 4 hours. Alternatively, a loading dose of 10-20 mg/kg followed by 1-1.5 mg/kg/hour continuous infusion during hemodialysis has been described in case reports.

• Upon completion of hemodialysis:

  • To decide if the patient needs a dose of the drug at the time of completion of hemodialysis, verify when the last dose was administered.
  • If the last dose of the drug was given more than an hour ago, do not administer a dose at the end of hemodialysis.
  • If the last dose of the drug was given 1-3 hours ago, administer one-half of the next planned dose at the end of hemodialysis.
  • If the last dose of the drug was given >3 hours ago, administer the next scheduled dose at the end of hemodialysis.

• Maintenance dose when off hemodialysis:

  • Administer fomepizole every 12 hours (starting 12 hours from the last dose administered).

Dose in Liver disease:

• Fomepizole is metabolized in the liver.
• Specific dosage adjustments have not been determined in patients with hepatic damage.

Common Side Effects of Fomepizole (Antizol):

• Central nervous system:

  • Headache

• Gastrointestinal:

  • Nausea

Less Common Side Effects of Fomepizole (Antizol):

• Cardiovascular:

  • Bradycardia
  • Facial Flushing
  • Hypotension
  • Phlebitis
  • Shock
  • Tachycardia

• Central Nervous System:

  • Dizziness
  • Drowsiness
  • Metallic Taste
  • Agitation
  • Altered Sense Of Smell
  • Anxiety
  • Seizure
  • Speech Disturbance
  • Vertigo

• Dermatologic:

  • Skin Rash

• Gastrointestinal:

  • Unpleasant Taste
  • Abdominal Pain
  • Decreased Appetite
  • Diarrhea
  • Heartburn
  • Hiccups
  • Vomiting

• Genitourinary:

  • Anuria

• Hematologic & Oncologic:

  • Anemia
  • Disseminated Intravascular Coagulation (DIC)
  • Eosinophilia
  • Lymphangitis

• Hepatic:

  • Increased Liver Enzymes

• Local:

  • Application Site Reaction
  • Inflammation At Injection Site
  • Pain At Injection Site

• Neuromuscular & Skeletal:

  • Back Pain

• Ophthalmic:

  • Nystagmus
  • Transient Blurred Vision
  • Visual Disturbance

• Respiratory:

  • Pharyngitis

• Miscellaneous:

  • Fever
  • Multi-Organ Failure

Contraindication to Fomepizole (Antizol):

Sensitivity of fomepizole, other Pyrazoles or any element in the formulation

Warnings and precautions

• Hepatic impairment

  • Patients with hepatic impairment should not use this medication. It is metabolized in their liver.

• Renal impairment

  • Patients with kidney damage should not use this product. The urine contains fomepizole (and its metabolites) and should be used with caution
  • Patients with severe renal disease, significant acidosis (pH >7.25-7.3), worsening metabolism acidosis or ethylene glycol and methanol concentrations greater than 50 mg/dL should consider hemoodialysis as an adjunct to fomepizole.

Monitoring parameters:

Preferably, fomepizole plasma concentrations should be monitored; however, fomepizole concentrations are generally not available.

Use these parameters to check the response to fomepizole:

• Plasma (preferred)/urinary ethylene glycol or methanol concentrations,
• urinary oxalate (ethylene glycol),
• plasma (preferred)/urinary osmolality,
• renal/hepatic function,
• serum electrolytes,
• arterial blood gases;
• anion and osmolar gaps,
• resolution of clinical signs and symptoms of ethylene glycol or methanol intoxication

How to administer Fomepizole (Antizol)?

All doses should be administered as a slow intravenous infusion (IVPB) over 30 minutes.

Mechanism of action of Fomepizole (Antizol):

• It inhibits alcohol-dehydrogenase competitively, which is an enzyme that catalyzes methanol and ethylene glycol metabolism to toxic metabolites.
• Ethylene glycol can be metabolized into glycolaldehyde and then oxidized to glyoxylate, glycolate, and oxalate.
• Metabolic acidosis is caused by renal damage and oxalate. 
• Methanol is first metabolized into formaldehyde and then oxidized to formic acid. 
• Metabolic acidosis is caused by visual disturbances and formic acid.

The beginning of effect:

• Maximum Peak Effect: 1.5-2 Hours

Absorption when administered orally:

• Readily absorbed.

Protein binding:

• Negligible

Metabolism:

• It is metabolized in the liver to 4-carboxypyrazole (80% to 85% of dose), 4-hydroxymethylpyrazole, and their N-glucuronide conjugates; following multiple doses, induces its own metabolism via CYP oxidases after 30-40 hours

Half-life elimination:

• Has not been calculated; varies with dose

Excretion:

• Urine (1% to 3.5% as unchanged drug and metabolites)

International Brand Names of Fomepizole:

• Antizol
• FomepizoleAP-HP

Fomepizole Brand Names in Pakistan:

No Brands Available in Pakistan.