Drug Monograph
Full clinical overview, indications, dosage references & safety notes.
Drug class: Alcohol dehydrogenase inhibitor (antidote)
Main indication: Ethylene glycol (antifreeze) toxicosis
Available forms2 forms · 2 strengths documentedShow all ↓
Injection · concentrate
Concentrate 1 g/mL Antizol® and human-labelled generics
1.5 mL vials (1.5 g/vial).
No veterinary-labelled product is available; Antizol-Vet® was withdrawn from the US market in 2015.
Prepared dilution
50 mg/mL
Diluting one vial with 28.5 mL of 0.9% saline produces a 50 mg/mL preparation; this is a prepared concentration, not a marketed form.
Overview
Fomepizole (4-methylpyrazole; 4-MP) is a synthetic antidote used in dogs and cats for the treatment of ethylene glycol (antifreeze) toxicosis. It is most effective when administered early after ingestion and is considered a critical intervention in preventing severe renal damage and death. Its use is often combined with intensive supportive care, including fluid therapy and correction of metabolic abnormalities.
Mechanism of Action (MOA): Fomepizole acts as a competitive inhibitor of alcohol dehydrogenase, the enzyme responsible for metabolizing ethylene glycol into toxic metabolites such as glycolate and oxalate. By blocking this pathway, it allows ethylene glycol to be excreted unchanged in the urine, thereby reducing metabolic acidosis and preventing renal tubular injury.
Indications
Its effectiveness is highly time-sensitive and is greatest when administered early after ingestion. Ethylene glycol toxicosis in dogs is treated first with fomepizole, which inactivates alcohol dehydrogenase without the adverse effects of ethanol; in cats, high-dose fomepizole has been shown to be more effective than ethanol therapy.
- Ethylene glycol toxicosis (dogs): Indicated for known or suspected ingestion, with best efficacy when treatment is initiated within 8 hours. Early administration significantly reduces the risk of renal failure and improves survival: dogs treated within 8 hours of ingestion have a significantly better prognosis than those treated after 10 to 12 hours, and most dogs treated up to 8 hours after ingestion recover.
- Ethylene glycol toxicosis (cats): May be effective when given at high doses within 3 hours of ingestion. Treatment started later than this has not been effective.
Dosage (Reference)
Dog
In dogs, fomepizole is administered as a loading dose followed by progressively reduced doses due to its dose-dependent accumulation.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Ethylene glycol toxicosis (initial dose) | IV | 20 mg/kg | Once (initial loading dose) | Administer as the first (loading) dose, diluted and infused intravenously over 30 minutes. |
| Follow-up dose (12 hours) | IV | 15 mg/kg | 12 hours after the initial dose | Administer as a slow intravenous infusion over 15 to 30 minutes. |
| Follow-up dose (24 hours) | IV | 15 mg/kg | 24 hours after the initial dose | Administer as a slow intravenous infusion over 15 to 30 minutes. |
| Follow-up dose (36 hours) | IV | 5 mg/kg | 36 hours after the initial dose | This is the last dose of the fixed schedule; use the blood ethylene glycol result to decide whether further doses are needed. |
| Additional dosing (if needed) | IV | 5 mg/kg | Every 12 hours | Continue until the blood ethylene glycol concentration is negligible or undetectable, or the animal has recovered. |
Important dosing notes (dogs):
• Doses are stepped down over the course of treatment, and the drug’s accumulation makes that reduction safe.
• Use a non-polycarbonate syringe and needle to withdraw and give the drug: fomepizole interacts with polycarbonate and can compromise the integrity of the syringe or needle.
• Administration guidance extrapolated from the human product is to dilute the dose in at least 100 mL of 0.9% sodium chloride or 5% dextrose and infuse it over 30 minutes; do not give it undiluted or by bolus injection.
• The preservative-free human product should not be used beyond 24 hours after dilution. Some veterinary formularies describe a 72-hour discard limit for separately prepared 50 mg/mL or reconstituted solutions.
• Doses are stepped down over the course of treatment, and the drug’s accumulation makes that reduction safe.
• Use a non-polycarbonate syringe and needle to withdraw and give the drug: fomepizole interacts with polycarbonate and can compromise the integrity of the syringe or needle.
• Administration guidance extrapolated from the human product is to dilute the dose in at least 100 mL of 0.9% sodium chloride or 5% dextrose and infuse it over 30 minutes; do not give it undiluted or by bolus injection.
• The preservative-free human product should not be used beyond 24 hours after dilution. Some veterinary formularies describe a 72-hour discard limit for separately prepared 50 mg/mL or reconstituted solutions.
Cat
In cats, significantly higher doses are required compared to dogs, and treatment must be initiated very early to be effective.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Ethylene glycol toxicosis (initial dose) | Slow IV | 125 mg/kg | Once (initial loading dose) | Administer as the initial high dose; cats must be treated within 3 hours of ingestion. |
| Follow-up doses | IV | 31.25 mg/kg | Every 12 hours | After the 36-hour dose, continue at the same dose and interval if ethylene glycol remains detectable. Stop when it is undetectable, or continue through 60 hours if testing is unavailable. |
Important dosing notes (cats):
• Requires doses approximately 6× higher than those used in dogs.
• Cats in which treatment began 4 hours after ethylene glycol ingestion had 100% mortality with either fomepizole or ethanol therapy.
• Monitor body temperature throughout treatment and provide external heat: cats may become hypothermic while receiving fomepizole.
• Prepare and give the feline doses the same way as the canine ones: a non-polycarbonate syringe and needle, and – extrapolating from the human product – dilution in at least 100 mL of 0.9% sodium chloride or 5% dextrose, infused over 30 minutes rather than given undiluted or as a bolus.
• Requires doses approximately 6× higher than those used in dogs.
• Cats in which treatment began 4 hours after ethylene glycol ingestion had 100% mortality with either fomepizole or ethanol therapy.
• Monitor body temperature throughout treatment and provide external heat: cats may become hypothermic while receiving fomepizole.
• Prepare and give the feline doses the same way as the canine ones: a non-polycarbonate syringe and needle, and – extrapolating from the human product – dilution in at least 100 mL of 0.9% sodium chloride or 5% dextrose, infused over 30 minutes rather than given undiluted or as a bolus.
Warnings & Precautions
Fomepizole is generally well tolerated in dogs and cats, but its effectiveness is highly dependent on early administration and appropriate supportive care. Careful monitoring and timely intervention are essential to optimize outcomes.
- Advanced toxicity: If azotemia is already present, prognosis is poor and response to treatment is reduced. In dogs, most of the ethylene glycol has already been metabolised by that stage, so there is little benefit from inhibiting alcohol dehydrogenase, and management shifts to correcting fluid, electrolyte and acid-base disorders, establishing diuresis and considering dialysis – although treatment up to 36 hours after ingestion may still prevent further renal damage.
- Metabolic acidosis management: May increase serum bicarbonate levels; correction of severe acidosis should prioritize fluid therapy and fomepizole before considering bicarbonate administration.
- Early decontamination: Decontamination has a very narrow window and its value is disputed: emesis or gastric lavage has been suggested within 1 to 2 hours of ingestion, but ethylene glycol is absorbed so rapidly that it is not recommended beyond the first 30 minutes, activated charcoal is not likely to reduce absorption, and vomiting must not be induced in an animal already showing neurological signs.
- CNS effects: Does not prevent CNS depression caused by unmetabolized ethylene glycol and may prolong it.
- Cats (dose considerations): Require significantly higher doses compared to dogs, increasing the need for careful monitoring during treatment.
- Administration precautions: Giving the concentrated solution by rapid intravenous injection may cause phlebitis and phlebosclerosis, so it should not be given undiluted or as a bolus injection – venous irritation and phlebosclerosis were seen in two of six human volunteers given a 25 mg/mL bolus over five minutes.
- Hypersensitivity: The current human-labelled product is contraindicated after a documented serious hypersensitivity reaction to fomepizole or another pyrazole; veterinary references list no labelled contraindications.
- Pyrazole substitution: Other pyrazoles must not be substituted for fomepizole: they may be toxic to the bone marrow and the liver.
- Drugs causing CNS depression: Avoid drugs that cause central nervous system depression, including ethanol. Competitive alcohol substrates can add to CNS depression, so monitor respiration; fomepizole contributes slightly to CNS depression in cats but not in dogs.
- Pregnancy and lactation: Safe use during pregnancy, lactation or in breeding animals has not been established and it is not known whether the drug passes into milk; because ethylene glycol toxicosis carries high morbidity and mortality, the benefit of treating generally outweighs the risk.
- Look-alike, sound-alike names: Take care not to confuse fomepizole with omeprazole or esomeprazole: the names look and sound alike.
Drug Interactions
Clinically relevant drug interactions with fomepizole in dogs and cats are primarily related to its inhibition of alcohol dehydrogenase, which can significantly alter the metabolism of ethanol.
- Ethanol: Concurrent use is generally not recommended. Fomepizole inhibits ethanol metabolism, which can lead to accumulation of ethanol and increased risk of toxicity (e.g., CNS depression, coma, or death). If both are used, close monitoring of blood ethanol concentrations is essential.
- Effect of ethanol on fomepizole: The interaction runs in both directions: in people, fomepizole reduced the rate of ethanol elimination by about 40% and ethanol reduced the rate of fomepizole elimination by about 50%.
- Other drugs sharing the alcohol pathway: Fomepizole also inhibits the metabolism of other drugs and compounds that share the alcohol pathway, so use it cautiously with any other drug given at the same time.
- Cytochrome P450 inducers and inhibitors: In human prescribing information, unstudied reciprocal interactions may occur with cytochrome P450 inducers or inhibitors, including phenytoin, carbamazepine, cimetidine and ketoconazole.
Side Effects & Overdose
Side Effects
Fomepizole is generally well tolerated in dogs and cats, although veterinary reports are inconsistent: mild sedation, ataxia and hypothermia have been reported in cats and one anaphylactic reaction in a dog. Reported adverse effects are usually mild and may vary between species, particularly when higher doses are used in cats.
- Mild sedation: Reported in cats receiving high doses.
- Ataxia and hypothermia (cats): May occur during treatment.
- Injection-related reactions: Rapid IV administration of concentrated solutions may cause phlebitis or phlebosclerosis; proper dilution is recommended.
- Anaphylaxis (rare): Reported in one dog during clinical use.
- Characteristic odor: Breath and urine may carry the distinctive smell of the drug for up to a week after dosing.
- Laboratory monitoring: In people, repeated dosing has been associated with transient increases in serum transaminases and eosinophilia; monitor hepatic enzymes and white blood cell counts during treatment. Minor allergic reactions, including mild rash and eosinophilia, have also been reported in people.
- Reported effects in people: In people the most frequent adverse effects are headache (14%), nausea (11%), and dizziness, increased drowsiness and a metallic taste (about 6% each).
Overdose
Overdose of fomepizole may result in significant central nervous system depression. The effect is dose-dependent.
- What an overdose looks like: In people, doses three to six times the recommended dose caused nausea, dizziness and vertigo, short-lived in most subjects and lasting up to 30 hours in one.
- Dialysis: Fomepizole is dialyzable and may be removed in severe cases.
- Poison control: For a known or suspected overdose, consultation with a 24-hour poison control centre providing veterinary-specific information is recommended.
Key Notes
Practical clinical points that help optimize the use of fomepizole in dogs and cats in emergency toxicology settings:
- Diagnostic confirmation: Measurement of blood ethylene glycol concentrations guides treatment duration: obtain a baseline concentration to document the diagnosis, then repeat testing during treatment to decide whether therapy can stop after 36 hours. In dogs the result decides whether dosing continues; for cats, guidance differs on whether dosing continues past 36 hours at all.
- Dialysis support: Fomepizole is dialysable. Human prescribing information increases dosing frequency to every 4 hours during haemodialysis; a canine or feline dialysis-adjusted regimen is not established in the veterinary references.
- Critical care setting: Cats are usually managed as inpatients. A dog treated with fomepizole within 5 hours of ingestion may be managed as an outpatient, while a dog presenting later usually requires inpatient care for intravenous fluids; fomepizole also requires less intensive care than ethanol therapy.
- Cost consideration: Treatment can be expensive, especially in large dogs, which may influence clinical decision-making.
- Test-kit interference: Fomepizole may cause false readings on ethylene glycol screening tests, so check the instructions for the test kit in use before acting on a result taken during treatment.
- Storage and handling: Store tightly sealed, protected from light and at room temperature. The concentrate may solidify below 25°C (77°F); liquefy it with warm water or by holding the vial in the hand, and solidification does not affect potency or stability.
- Ethanol as the fallback: If fomepizole cannot be obtained, ethanol is the alternative, but it requires hospitalisation, a constant intravenous infusion, and continuous monitoring of respiratory and acid-base status.
