Fomepizole
**Fomepizole** (also known as 4-methylpyrazole or 4-MP) is a synthetic antidote primarily used in veterinary medicine to treat **ethylene glycol (antifreeze) poisoning** in dogs and cats. Key clinical points: * **Time-Critical Efficacy**: It is highly effective in dogs if administered within 8 hours of ingestion. In cats, it requires significantly higher doses and must be given within 3 hours of ingestion to prevent fatal renal damage. * **Mechanism**: It prevents the formation of toxic metabolites rather than clearing the parent compound. * **Clinical Pearl**: Once azotemia (elevated kidney values) develops, the prognosis drops precipitously, though fomepizole may still be administered up to 36 hours post-ingestion to halt further damage while supportive care (like hemodialysis) is instituted. * **Cost & Availability**: Treatment can be cost-prohibitive, especially for large breed dogs, and rapid availability of the drug is often a limiting factor in emergency settings.
Mechanism: Fomepizole acts as a potent, competitive inhibitor of **alcohol dehydrogenase (ADH)**, the primary enzyme responsible for the initial metabolism of ethylene glycol. **The Toxic Pathway:** Ethylene Glycol → (via **ADH**) → Glycoaldehyde → Glycolate → Glyoxalic Acid → Oxalic Acid. *Note: Oxalic acid binds with systemic calcium to form calcium oxalate crystals, which precipitate in the renal tubules causing acute tubular necrosis and severe metabolic acidosis.* **Fomepizole's Action:** By competitively binding to **ADH** with an affinity roughly 8,000 times greater than that of ethylene glycol, fomepizole effectively blocks the first step of this cascade. * Ethylene glycol remains unmetabolized in the bloodstream. * The parent compound (which is only mildly CNS-depressant) is then safely and slowly excreted unchanged in the urine. * This prevents the life-threatening metabolic acidosis and acute kidney injury associated with the toxic metabolites.
Dosing by species
- For treatment of ethylene glycol toxicity · Initially, 125 mg/kg slow IV ; at 12, 24, 36 hours give 31.25 mg/kg IV . · IV · Specific intervals (0, 12, 24, 36 hours) · 36 hours · Cats must be treated within 3 hours of ingestion. Treat supportively with supplemental fluids. Cats whose treatment began 4 hours post ethylene glycol had 100% mortality.
- For treatment of ethylene glycol toxicity · Initially load at 20 mg/kg IV ; at 12 hours post initial dose give 15 mg/kg IV ; at 24 hours post initial dose give another 15 mg/kg IV and at 36 hours after initial dose give 5 mg/kg; may give additional 5 mg/kg doses as necessary · IV · Specific intervals (0, 12, 24, 36 hours) · 36+ hours · May give additional 5 mg/kg doses as necessary if animal has not recovered or has additional ethylene glycol in blood.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- No labeled contraindications, but use with caution if the patient is already receiving ethanol therapy.
Adverse effects
- Vein irritation and phlebosclerosis (if given rapidly or undiluted)
- Anaphylaxis (rare)
- Mild sedation (particularly in cats)
Drug interactions
- Ethanol · Fomepizole inhibits alcohol dehydrogenase; ethanol metabolism is reduced significantly and alcohol poisoning (CNS depression, coma, death) can occur. Concurrent use is generally not recommended. If used together, mandatory monitoring of ethanol blood levels is required.
Monitoring
- Ethylene glycol blood levels (to document diagnosis and determine if therapy can be discontinued after 36 hours)
- Blood gases (acid-base status)
- Serum electrolytes
- Hydration status
- Renal function tests (Urine output, urinalysis, BUN, serum creatinine)
- Body temperature (especially in cats)
Overdose
Overdosage may cause significant **CNS depression**. There is no specific antidote or treatment recommended for fomepizole overdose; provide supportive care as needed.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.