Contraindications of Fomepizole Use
The only absolute contraindication for fomepizole is a documented serious hypersensitivity reaction to fomepizole or other pyrazoles. 1
Understanding Fomepizole
Fomepizole (4-methylpyrazole) is a competitive inhibitor of alcohol dehydrogenase used primarily as an antidote for toxic alcohol poisoning, particularly ethylene glycol and methanol poisoning. It is preferred over ethanol due to:
- More predictable pharmacokinetics and no need for blood level monitoring 2
- Reduction in medication errors compared to ethanol therapy 3
- No risk of causing hypoglycemia or central nervous system depression 2
- Anticipated safety in children 3
Safety Profile
Fomepizole has a robust safety profile with minimal contraindications:
- A 16-year post-marketing study in France found adverse reactions in only 7% of patients, all of which were mild and transient 4
- Most common adverse effects include:
Special Populations
Pediatric Use
- Limited data suggests fomepizole is efficacious and well-tolerated in pediatric patients using the same dosage regimen as adults 5
- In many cases of pediatric ethylene glycol poisoning, hemodialysis may not be necessary despite high concentrations and metabolic acidosis when fomepizole is used 5
Pregnancy and Nursing
- No specific contraindications are noted for pregnancy or nursing mothers
- Standard precautions for medication use during pregnancy should be observed
Clinical Considerations
While not contraindications, clinicians should be aware of these important considerations:
- Dosage adjustment is required during hemodialysis as fomepizole is dialyzable 2
- Standard dosing is 15 mg/kg loading dose followed by 10 mg/kg every 12 hours until alcohol concentrations are <30 mg/dL 2
- Fomepizole should be continued until toxic alcohol is eliminated from the body and acidosis is normalized 6
Hemodialysis Considerations with Fomepizole
Hemodialysis should still be considered in patients with:
- Severe metabolic acidosis (anion gap >27 mmol/L) despite fomepizole treatment 2
- High ethylene glycol concentration (>50 mmol/L or >310 mg/dL) despite fomepizole treatment 2
- Visual disturbances, altered mental status, acute renal failure, or hemodynamic instability 6
Monitoring During Treatment
- Monitor anion gap to evaluate treatment effectiveness 6
- Cessation of extracorporeal treatment is recommended once anion gap is <18 mmol/L 2
- Monitor acid-base status, as normalization typically occurs within hours after initiation of fomepizole 7
In summary, fomepizole has very few contraindications, with documented serious hypersensitivity reaction being the only absolute contraindication. Its favorable safety profile makes it the preferred treatment for toxic alcohol poisoning in most clinical scenarios.