Fomepizole Treatment Protocol for Methanol and Ethylene Glycol Poisoning
Immediate Administration
Begin fomepizole immediately upon suspicion of toxic alcohol ingestion—do not wait for laboratory confirmation. 1 Administer a loading dose of 15 mg/kg IV over 30 minutes, followed by 10 mg/kg every 12 hours for four doses, then increase to 15 mg/kg every 12 hours until the patient is asymptomatic with normal pH and ethylene glycol/methanol levels are undetectable or below 20 mg/dL. 1
Triggers for Immediate Treatment
Start fomepizole based on any of the following: 1
- Clinical suspicion from patient history of ingestion
- Anion gap metabolic acidosis (unexplained)
- Increased osmolal gap
- Visual disturbances (methanol)
- Oxalate crystals in urine (ethylene glycol)
- Documented serum level >20 mg/dL of either toxic alcohol
Critical Technical Considerations
Never use polycarbonate syringes or needles when preparing or administering fomepizole, as the drug degrades polycarbonate and compromises syringe/needle integrity. 1 Dilute in at least 100 mL of normal saline or D5W and infuse over 30 minutes. 1 If the solution has solidified at temperatures below 25°C, liquefy by running under warm water—this does not affect efficacy or safety. 1
Hemodialysis Decision-Making
Strong Indications for Hemodialysis (Initiate Immediately)
Add hemodialysis to fomepizole when any of the following criteria are met: 2, 1
- Anion gap >27 mmol/L 3, 2
- Glycolate concentration >12 mmol/L (ethylene glycol metabolite) 3, 2
- Ethylene glycol or methanol concentration ≥50 mg/dL 3, 2, 1
- Coma or seizures 3, 2
- Acute kidney injury (KDIGO stage 2 or 3) 3, 2
- Significant or worsening metabolic acidosis despite treatment 2, 1
Conditional Indications (Consider Hemodialysis)
Consider hemodialysis for: 3, 2
- Anion gap 23-27 mmol/L 3
- Glycolate concentration 8-12 mmol/L 3
- Chronic kidney disease with eGFR <45 mL/min/1.73m² 2
- Osmolal gap >50 (when using fomepizole) 3
When Fomepizole Alone May Suffice
Patients treated early with fomepizole before significant acidosis develops may not require hemodialysis if: 4, 5
- No metabolic acidosis present
- Normal renal function (serum creatinine normal)
- Glycolate concentration ≤76.8 mg/dL (10.1 mmol/L) for ethylene glycol 5
- No neurological or visual impairment (methanol) 4
This approach is supported by evidence showing that fomepizole administered early prevents renal injury by blocking toxic metabolite formation. 5
Dosing During Hemodialysis
Fomepizole is dialyzable—increase dosing frequency to every 4 hours during hemodialysis. 1 Follow this algorithm: 1
At hemodialysis initiation:
- If <6 hours since last dose: Do not give additional dose
- If ≥6 hours since last dose: Give next scheduled dose
During hemodialysis: Dose every 4 hours 1
At hemodialysis completion:
- If <1 hour since last dose: Skip dose
- If 1-3 hours since last dose: Give half the scheduled dose
- If >3 hours since last dose: Give full scheduled dose
After hemodialysis: Resume 12-hour dosing interval 1
Treatment Endpoints and Discontinuation
Stop fomepizole when ALL of the following are achieved: 1, 3
- Ethylene glycol/methanol concentration <20 mg/dL (ideally <4 mmol/L or 25 mg/dL) 1, 3
- Patient is asymptomatic 1
- Normal pH (acid-base homeostasis restored) 1, 3
- Anion gap normalized to <18 mmol/L 3, 2
For hemodialysis cessation: 3
- Ethylene glycol concentration <4 mmol/L (25 mg/dL) 3
- All acid-base abnormalities corrected 3
- Sustained normalization of glycolate concentration and anion gap 3
Safety Profile and Adverse Effects
Fomepizole demonstrates excellent safety with minimal adverse effects. 6 In a 16-year French post-marketing study of 536 patients, only 7% experienced mild, transient adverse reactions including: 6
- Injection site pain/burning (most common)
- Nausea/vomiting
- Vessel puncture site inflammation
- Drowsiness/confusion
- Transient aminotransferase elevation
No adverse effects required discontinuation of fomepizole, and no deaths were attributed to the drug. 6 A 7-year Japanese surveillance study confirmed no serious adverse drug reactions. 7
Critical Pitfalls to Avoid
Do not rely solely on reported ingestion dose to guide treatment decisions—the amount ingested correlates poorly with toxicity. 2 Both parent compound levels and acid-base status must guide therapy. 2, 1
Do not wait for a positive osmolal gap to initiate treatment—the osmolal gap may be normal or even negative if the toxic alcohol has already been metabolized to acidic metabolites. 3, 8 A normal osmolal gap does not rule out poisoning in the presence of high anion gap metabolic acidosis. 8
Monitor for alcohol withdrawal syndrome, especially during hemodialysis in patients with alcohol use disorder, as both fomepizole and ethanol are removed by dialysis. 3
Recognize that ethylene glycol and methanol concentrations diminish as they metabolize—falling parent compound levels with worsening acidosis indicate ongoing toxic metabolite accumulation. 1 Serial monitoring of both parent compounds and acid-base status is essential. 1
Comparative Advantage Over Ethanol
Fomepizole is superior to ethanol as first-line antidote due to: 4
- More predictable alcohol dehydrogenase inhibition 3
- No CNS depression or intoxication 4
- No requirement for ICU-level monitoring of therapeutic levels 2
- Simpler dosing regimen 4
- Fewer treatment failures 3
When ethanol is used instead of fomepizole, hemodialysis thresholds are lower (ethylene glycol >20 mg/dL rather than >50 mg/dL) because ethanol therapy is less reliable and carries greater risks with prolonged administration. 3
Clinical Outcomes
Early fomepizole administration prevents renal injury—patients treated before significant glycolate accumulation (≤76.8 mg/dL) and with normal baseline creatinine had no renal injury. 5 Mean arterial pH normalizes to 7.4 within 4 hours of treatment initiation and remains stable. 7 Overall mortality for ethylene glycol poisoning is 18.7%, with chronic kidney disease developing in 16.8% of survivors. 2