Fomepizole
Related FACEM curriculum (2022) learning objectives:
- ME 3.8.1.6(e) Principles of management of toxicological presentations including: Indications for antidotes
- ME 3.8.2.4 Identify the appropriate antidote or antivenom.
Presentations
- Fomepizole 1.5 g/1.5 mL ampoules.
- Fomepizole sulfate 160 mg/20 mL ampoules (100 mg of fomepizole per 20 mL ampoule).
Toxicological Indications
- Methanol poisoning (confirmed or suspected).
- Ethylene glycol poisoning (confirmed or suspected).
- Can be used alone or with haemodialysis.
Contraindications
- Known hypersensitivity (not yet reported).
Mechanism of Action
- Potent competitive inhibitor of alcohol dehydrogenase.
- Blocks metabolism of methanol and ethylene glycol into toxic metabolites.
- Toxic alcohols are excreted unchanged in urine.
Pharmacokinetics
- Volume of distribution: 0.7 L/kg.
- Undergoes hepatic metabolism to inactive 4-carboxypyrazole.
- Metabolism is saturable at therapeutic doses.
- Induces its own metabolism after 48 hours.
- Dialysable.
Administration
Dosing
- Loading dose: 15 mg/kg in 100 mL normal saline or 5% dextrose IV over 30 minutes.
- Maintenance dose: 10 mg/kg in 100 mL normal saline or 5% dextrose IV over 30 minutes every 12 hours for 48 hours.
- If administration exceeds 48 hours: increase dose to 15 mg/kg every 12 hours.
- During Haemodialysis: Administer every 4 hours or use continuous infusion at 1 mg/kg/hour.
Monitoring
- Fomepizole concentration monitoring is unnecessary.
Therapeutic Endpoints
- Continue until methanol or ethylene glycol levels are <30 mg/dL.
Adverse Drug Reactions
- Most common: infusion site discomfort.
- Minor effects: headache, nausea, dizziness.
Specific Considerations
- Pregnancy: Safety not established; consider ethanol as an alternative.
- Paediatric: No restrictions.
Controversies
- Threshold concentration for starting alcohol dehydrogenase inhibitors (current recommendation: 20 mg/dL, likely conservative).
- Superiority of fomepizole over ethanol:
- Advantages: predictable pharmacokinetics, fewer adverse effects, easier monitoring, reduced haemodialysis requirement.
- Disadvantages: limited availability, higher cost.
- Use of fomepizole alone to potentially eliminate need for haemodialysis in methanol poisoning.