Fomepizole — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	IV	Loading dose: 20 mg/kg	Then 15 mg/kg at 12 and 24 hours, then 5 mg/kg at 36 hours	Duration: Continue until ethylene glycol levels are undetectable or clinical signs resolve (typically 48-72 hours) Notes: Administer slowly over 15-30 minutes. Start as soon as possible after ethylene glycol ingestion. If ethylene glycol levels are not available, treat empirically if ingestion is suspected and within 8-12 hours.
Cat	IV	Loading dose: 20 mg/kg	Then 15 mg/kg at 12, 24, and 36 hours	Duration: Continue for 48 hours or until clinical improvement Notes: Off-label use. Efficacy is less established in cats; ethanol may be preferred in some cases. Monitor for adverse effects.
Horse	IV	20 mg/kg	Repeat every 12 hours as needed	Duration: Until clinical signs resolve Notes: Off-label use. Limited data; use with caution.

Clinical Indications & Species Uses

General Indications

Antidote for ethylene glycol poisoning
Antidote for methanol poisoning

Dog (Canine)

Antidote for ethylene glycol (antifreeze) poisoning
Antidote for methanol poisoning (rarely reported)

Cat (Feline)

Antidote for ethylene glycol poisoning (off-label; limited efficacy data)

Horse (Equine)

Antidote for ethylene glycol poisoning (off-label; anecdotal use)

Pharmacology & Mechanism of Action

Drug Class: Antidote | Pharmacological Group: Alcohol Dehydrogenase Inhibitor

Mechanism of Action: Fomepizole is a competitive inhibitor of alcohol dehydrogenase (ADH), the enzyme responsible for the metabolism of ethylene glycol (EG) and methanol to their toxic metabolites. In ethylene glycol poisoning, ADH converts EG to glycolaldehyde, which is further metabolized to glycolic acid, glyoxylic acid, and oxalic acid, leading to severe metabolic acidosis and acute kidney injury. By inhibiting ADH, fomepizole prevents the formation of these toxic metabolites, allowing EG to be excreted unchanged in the urine. Fomepizole has a higher affinity for ADH than ethanol and does not cause central nervous system depression, making it a safer alternative to ethanol as an antidote.

Pharmacodynamics: Fomepizole rapidly and effectively inhibits ADH activity. In dogs, a single intravenous dose of 20 mg/kg produces complete inhibition of ADH for approximately 8-12 hours. The drug is most effective when administered early in the course of ethylene glycol poisoning, before significant accumulation of toxic metabolites occurs. It does not reverse existing metabolic acidosis or renal damage but prevents further progression. Fomepizole also inhibits alcohol dehydrogenase in other species, but its efficacy and safety have been most extensively studied in dogs.

⚡ Pharmacokinetics Summary

Absorption: Fomepizole is administered intravenously; oral absorption is rapid but not commonly used due to vomiting and the need for rapid onset. In dogs, oral bioavailability is approximately 80%, but the IV route is preferred in emergency situations.

Distribution: Fomepizole distributes widely into total body water. The volume of distribution in dogs is approximately 0.6-0.7 L/kg. It crosses the blood-brain barrier to a limited extent. Protein binding is minimal (less than 10%).

Metabolism: Fomepizole is primarily metabolized in the liver by alcohol dehydrogenase to 4-carboxypyrazole and 4-hydroxymethylpyrazole, which are inactive. Metabolism is saturable, and the drug exhibits dose-dependent kinetics.

Excretion: Fomepizole and its metabolites are excreted primarily in the urine. In dogs, approximately 80-90% of the dose is excreted in the urine as metabolites, with about 10% excreted unchanged. The elimination half-life in dogs is dose-dependent, ranging from 5 to 10 hours at therapeutic doses.

Half-Life: Dogs: 5-10 hours (dose-dependent); Cats: approximately 10-12 hours (limited data); Humans: 5-10 hours.

Bioavailability: Oral bioavailability in dogs is approximately 80%, but IV administration is preferred for rapid effect.

Protein Binding: Minimal (<10%)

Available Formulations & Strengths

Injectable Solution 1 g/mL (5 mL vial) (IV)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to fomepizole or other pyrazoles
Severe hepatic impairment (use with caution)
Do not use as a general antidote for other poisonings

Warnings & Clinical Precautions:

For intravenous use only; avoid extravasation as it may cause tissue irritation.
Use with caution in patients with pre-existing hepatic or renal disease.
Fomepizole may cause false-positive results in some urine ketone tests.
In cats, use with caution due to limited safety data; monitor for adverse effects.
Not approved for use in food animals; extra-label use requires veterinary oversight and extended withdrawal times.
Fomepizole is less effective if administered more than 12 hours after ethylene glycol ingestion; aggressive supportive care (e.g., fluid therapy, sodium bicarbonate for acidosis) is essential.
Do not confuse with other pyrazole compounds.

Adverse Effects & Reactions

Common:

Mild injection site reactions
Transient increase in liver enzymes (ALT, AST)
Nausea or vomiting (rare in animals)

Serious / Severe:

Hepatotoxicity (rare, with high doses or prolonged use)
Allergic reactions (anaphylaxis, rare)
Metabolic acidosis (if used late in poisoning, due to existing metabolites)

Rare:

Seizures (reported in humans, not well-documented in animals)
Bone marrow suppression (theoretical)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Ethanol	Additive ADH inhibition; may be used together in severe cases, but fomepizole alone is preferred to avoid CNS depression.	Moderate
Other hepatotoxic drugs (e.g., acetaminophen, phenobarbital)	Increased risk of hepatotoxicity.	Moderate
Drugs metabolized by alcohol dehydrogenase (e.g., chloral hydrate)	May increase their toxicity due to reduced metabolism.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Nausea
Vomiting
Dizziness
Hepatotoxicity (elevated liver enzymes, jaundice)
Metabolic acidosis (rare)

Emergency Treatment Protocol: There is no specific antidote for fomepizole overdose. Treatment is symptomatic and supportive. Monitor liver function and provide intravenous fluids. In severe cases, consider hemodialysis to enhance elimination.

Food Animal Withdrawal Times

Fomepizole is not approved for use in food animals. If used extra-label, a prolonged withdrawal period (e.g., 30 days for meat and 7 days for milk) is recommended, but specific data are lacking. Consult FARAD (Food Animal Residue Avoidance Databank) for current recommendations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25°C, excursions permitted to 15-30°C).

Handling & Special Conditions: Protect from freezing. Keep vial tightly closed. Use only if solution is clear and colorless.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: FDA-approved for human use (Antizol); not approved for veterinary use, but widely used in veterinary medicine as an antidote.

Extra-Label (Off-Label) Use: In the US, fomepizole is not FDA-approved for veterinary use, but it is a prescription drug for human use. Its use in animals is considered extra-label and is permitted under AMDUCA (Animal Medicinal Drug Use Clarification Act) provided a valid veterinarian-client-patient relationship exists and appropriate withdrawal times are observed for food animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Fomepizole is the preferred antidote for ethylene glycol poisoning in dogs due to its safety profile and ease of administration compared to ethanol. It is most effective when administered within 8-12 hours of ingestion, before the development of severe metabolic acidosis and acute kidney injury. Treatment should be initiated immediately if ethylene glycol ingestion is suspected, even before laboratory confirmation. Concurrent supportive care is critical: aggressive intravenous fluid therapy to maintain diuresis, correction of metabolic acidosis with sodium bicarbonate, and monitoring of renal function and electrolytes. In cats, fomepizole is less effective and ethanol may be considered, but fomepizole is still used off-label with careful monitoring. Prognosis is good if treatment is initiated early; however, if anuria or severe renal failure has developed, the prognosis is guarded. Fomepizole is also used for methanol poisoning, though this is rare in veterinary medicine. Always confirm the diagnosis with ethylene glycol levels if available, but do not delay treatment. Monitor liver enzymes during therapy, especially with prolonged use.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)