Antidote for Methanol Poisoning
Fomepizole is the preferred first-line antidote for methanol poisoning, with ethanol serving as an acceptable alternative only when fomepizole is unavailable. 1, 2
Primary Antidote: Fomepizole
Fomepizole (4-methylpyrazole) should be administered as the antidote of choice for methanol poisoning due to its superior safety profile, ease of use, and reduction in medication errors compared to ethanol. 1, 3
Mechanism of Action
- Fomepizole competitively inhibits alcohol dehydrogenase (ADH), the enzyme responsible for converting methanol to its toxic metabolites formaldehyde and formic acid 2
- By blocking ADH, fomepizole prevents the formation of formic acid, which causes the metabolic acidosis and visual disturbances (including blindness) characteristic of methanol poisoning 2, 4
Dosing Protocol
- Loading dose: 15 mg/kg IV infusion over 30-60 minutes 3, 5
- Maintenance: 10 mg/kg IV every 12 hours until methanol concentration is <30 mg/dL 3, 2, 5
- During hemodialysis: Increase to 1 mg/kg/hour continuous infusion to compensate for dialyzable removal 3, 6
- No blood level monitoring of fomepizole is required, simplifying administration 5
Advantages Over Ethanol
- Simpler dosing regimen without need for compounding 1
- More predictable pharmacokinetics 3
- Reduced medication errors 1, 3
- No risk of hypoglycemia or CNS depression 3
- Anticipated improved safety in children 1
- May reduce or eliminate need for hemodialysis when given early 7, 5, 6
Alternative Antidote: Ethanol
Ethanol may be used as an alternative ADH inhibitor only when fomepizole is unavailable. 1, 8, 9
Key Limitations
- Requires compounding of a 10% solution from 95% ethanol stock, as no commercially available 10% solution exists in the United States 1
- Necessitates blood level monitoring to maintain therapeutic concentrations 3
- Causes CNS depression and potential hypoglycemia 3
- Higher risk of medication errors during preparation and administration 1
Hemodialysis Considerations
Indications for Hemodialysis WITH Fomepizole
Even with fomepizole treatment, hemodialysis is indicated for:
- Severe metabolic acidosis with anion gap >27 mmol/L or pH <7.1 3, 9, 7
- Visual disturbances or neurological impairment 7, 6
- High methanol concentration >50 mmol/L (>310 mg/dL) 3
- Acute renal failure 9
- Hemodynamic instability 9
When Hemodialysis May Be Avoided
Fomepizole administered early, before onset of significant acidosis or organ injury, may eliminate the need for hemodialysis in stable patients. 7, 5, 6
Criteria for delayed or no hemodialysis:
- Stable patient with base deficit <15 mM 7
- No visual disturbances 7, 6
- Adequate buffer (bicarbonate) administration 7
- Close monitoring capability 7
Adjunctive Therapy
- Thiamine and pyridoxine should be administered as adjuvant therapy to support metabolic recovery 8, 9
- Sodium bicarbonate for correction of metabolic acidosis 4
- Folate may enhance formate metabolism (though not explicitly mentioned in guidelines, this is standard practice)
Critical Timing
Treatment should be initiated immediately based on clinical suspicion (history of ingestion, anion gap metabolic acidosis) without waiting for methanol level confirmation. 5
- The lethal dose of methanol is approximately 1-2 mL/kg 2
- A latent period of 12-24 hours exists before toxic symptoms develop due to delayed metabolism 4
- Early administration prevents irreversible visual and neurological damage 5, 6
Common Pitfalls
- Do not delay fomepizole while waiting for laboratory confirmation of methanol levels 5
- Do not underdose during hemodialysis—increase to 1 mg/kg/hour continuous infusion 3, 6
- Do not discontinue treatment prematurely—continue until methanol <30 mg/dL and anion gap normalizes, which may take 24-48 hours or longer 9, 2
- Monitor for alcohol withdrawal in patients with alcohol use disorder, especially during hemodialysis 8