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- Educational Only: Not for clinical decision-making.
- Verify Information: Always consult protocols and authoritative sources.
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Bedside Snapshot
- Primary Role: Antidote for methanol and ethylene glycol poisoning — prevents formation of toxic metabolites by inhibiting alcohol dehydrogenase (ADH)
- When to start: Start when strongly suspected or confirmed toxic alcohol ingestion with metabolic acidosis, elevated osm gap, or visual symptoms — don’t wait for levels
- Dosing pattern: Weight‑based IV loading (15 mg/kg over 30 min) followed by q12h maintenance; shorten interval to q4h during hemodialysis
- Role with dialysis: Fomepizole prevents further toxic metabolite formation while dialysis clears parent alcohol and metabolites — coordinate with nephrology/toxicology
- Adverse effects: Generally well-tolerated; common: headache, nausea, dizziness, mild LFT elevation, infusion reactions
- Critical concept: Fomepizole buys time — you still must correct acidosis, manage electrolytes, and arrange dialysis when indicated
Brand & Generic Names
- Generic Name: Fomepizole
- Brand Names: Antizol (U.S.); generic fomepizole injection in some regions
Medication Class
Alcohol dehydrogenase inhibitor — competitive ADH inhibitor used as an antidote in methanol and ethylene glycol poisoning to prevent formation of toxic metabolites (formic, glycolic/oxalic acids).
Pharmacology
Mechanism of Action:
- Competitive inhibition of alcohol dehydrogenase (ADH), preventing conversion of methanol and ethylene glycol into toxic metabolites (formic acid, glycolic/oxalic acids)
- Allows parent alcohols to be excreted unchanged or removed by dialysis while preventing additional metabolite‑driven toxicity
- Does not reverse existing organ damage; early use mitigates further injury
Pharmacokinetics:
- Route: IV only (dilute and infuse over ~30 minutes)
- Onset: Rapid inhibition of ADH following infusion; clinically effective within the dosing interval
- Distribution: Vd ≈0.6–1 L/kg; minimal protein binding
- Metabolism: Hepatic (CYP2E1) to inactive metabolites; auto‑induction may increase clearance over time
- Elimination: Renal excretion of metabolites; half‑life ~4–20 hrs depending on induction and dialysis; dialyzable — dosing interval shortened during hemodialysis
Indications
- Confirmed or strongly suspected ethylene glycol poisoning with anion gap metabolic acidosis and/or elevated osmolar gap
- Confirmed or suspected methanol poisoning with metabolic acidosis, visual symptoms, or high osm gap
- Adjunct to hemodialysis during severe poisoning to prevent further metabolite formation while dialysis clears parent alcohols and acids
- Occasional use in propylene glycol toxicity in consultation with toxicology (rare)
Dosing & Administration
Available Forms:
- IV solution for injection: commonly 1.5 g/1.5 mL vials (1000 mg/mL) — dilute prior to infusion (per product guidance)
Adult Dosing (Standard toxic alcohol protocol — follow local poison center/toxicology guidance):
| Phase | Dose | Route / Timing | Notes |
|---|---|---|---|
| Loading | 15 mg/kg | IV over 30 minutes | Weight‑based — dilute per local protocol |
| Maintenance (no HD) | 10 mg/kg | IV every 12 hours × 4 doses, then 15 mg/kg IV every 12 hours until levels safe and acidosis resolves | Typical sequence: 15 mg/kg → 10 mg/kg q12h ×4 → 15 mg/kg q12h thereafter until cleared |
| During Hemodialysis | Same mg/kg dose | IV every 4 hours (shortened interval because dialysis removes fomepizole) | Give a dose at the end of dialysis if one was missed, then resume normal schedule |
| Pediatrics | Use same mg/kg regimen; consult pediatric toxicology | IV | Always consult poison control |
Contraindications
Contraindications:
- Known hypersensitivity to fomepizole or any formulation components (rare)
Precautions:
- Hepatic impairment — metabolism may be reduced; monitor for accumulation
- Pregnancy — often used when maternal/fetal benefit outweighs theoretical risk; consult toxicology/OB
- Coordinate with toxicology/poison center and nephrology for timing of dialysis and dosing adjustments
Adverse Effects
Common:
- Headache, nausea, dizziness
- Metallic/unpleasant taste, mild infusion‑site reactions
- Transient mild LFT elevations
Serious (rare):
- Severe hypersensitivity/anaphylaxis (rare)
Special Populations
Pregnancy:
- Use when maternal life or fetal protection from toxic alcohol injury requires it — consult OB and toxicology
Pediatrics:
- Use weight‑based dosing; consult pediatric toxicology and poison control for dosing and monitoring nuances
Monitoring
- Serial basic metabolic panel: anion gap, bicarbonate, creatinine, potassium and other electrolytes
- Serum osmolality and osmolar gap trends; toxic alcohol levels when available (do not delay treatment)
- ABG and lactate for severe acidosis and hemodynamic compromise
- Clinical monitoring: neurologic status, visual symptoms (methanol), and urine output
- Hemodialysis parameters and timing — adjust dosing interval (q4h) during dialysis
Overdose Management
- Overdose of fomepizole is uncommon; management is supportive — monitor vitals and treat symptoms
- Hemodialysis removes fomepizole; dosing intervals must be shortened during dialysis to maintain inhibition
Drug–Drug Interactions (Selected)
- Fomepizole is metabolized by CYP2E1 and exhibits auto‑induction; interactions are generally limited, but monitor co‑administered medicines metabolized by CYP2E1.
- No routine interactions expected with ethanol per se, but ethanol is an alternative ADH inhibitor and managing co‑administration requires toxicology guidance.
Clinical Pearls
Start early: If clinical history and labs (anion gap, osm gap, acidosis) suggest toxic alcohols, start fomepizole immediately — do not wait for confirmatory levels.
Fomepizole + dialysis: Fomepizole prevents new metabolite formation, dialysis removes parent alcohol and existing toxic metabolites — coordinate both therapies.
Backup plan: If fomepizole is unavailable, ethanol (IV) can be used as an ADH inhibitor — requires toxicology guidance and more complex monitoring.
Documentation: Record indication, weight-based dosing, timing of doses, and dialysis details — critical for handoff to ICU/tox/nephrology.
References
- 1. Goldfrank’s Toxicologic Emergencies (latest edition) — Ethylene glycol and methanol chapters.
- 2. Antizol (fomepizole) prescribing information.
- 3. American Academy of Clinical Toxicology practice guidelines: Treatment of methanol and ethylene glycol poisoning.