Treatment Guidelines : If ethylene glycol or methanol poisoning is left untreated, the natural progression of the poisoning leads to accumulation of toxic metabolites, including glycolic and oxalic acids (ethylene glycol intoxication) and formic acid (methanol intoxication). These metabolites can induce metabolic acidosis, nausea/vomiting, seizures, stupor, coma, calcium oxaluria, acute tubular necrosis, blindness, and death. The diagnosis of these poisonings may be difficult because ethylene glycol and methanol concentrations diminish in the blood as they are metabolized to their respective metabolites. Hence, both ethylene glycol and methanol concentrations and acid base balance, as determined by serum electrolyte (anion gap) and/or arterial blood gas analysis, should be frequently monitored and used to guide treatment.
Treatment consists of blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as fomepizole, and correction of metabolic abnormalities. In patients with high ethylene glycol or methanol concentrations (≥ 50 mg/dL), significant metabolic acidosis, or renal failure, hemodialysis should be considered to remove ethylene glycol or methanol and the respective toxic metabolites of these alcohols.
Treatment with fomepizole : Begin fomepizole treatment immediately upon suspicion of ethylene glycol or methanol ingestion based on patient history and/or anion gap metabolic acidosis, increased osmolar gap, visual disturbances, or oxalate crystals in the urine, OR a documented serum ethylene glycol or methanol concentration greater than 20 mg/dL.
Hemodialysis : Hemodialysis should be considered in addition to fomepizole in the case of renal failure, significant or worsening metabolic acidosis, or a measured ethylene glycol or methanol concentration of greater than or equal to 50 mg/dL. Patients should be dialyzed to correct metabolic abnormalities and to lower the ethylene glycol concentrations below 50 mg/dL.
Discontinuation of fomepizole Treatment : Treatment with fomepizole may be discontinued when ethylene glycol or methanol concentrations are undetectable or have been reduced below 20 mg/dL, and the patient is asymptomatic with normal pH.
Dosing of fomepizole : A loading dose of 15 mg/kg should be administered, followed by doses of 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours thereafter until ethylene glycol or methanol concentrations are undetectable or have been reduced below 20 mg/dL, and the patient is asymptomatic with normal pH. All doses should be administered as a slow intravenous infusion over 30 minutes (see Administration).
Dosage with Renal Dialysis : Fomepizole Injection is dialyzable and the frequency of dosing should be increased to every 4 hours during hemodialysis.
Fomepizole Dosing in Patients Requiring Hemodialysis
DOSE AT THE BEGINNING OF HEMODIALYSIS
If <6 hours since last fomepizole dose
If ≥ 6 hours since last fomepizole dose
Do not administer dose
Administer next scheduled dose
DOSING DURING HEMODIALYSIS
Dose every 4 hours
DOSING AT THE TIME HEMODIALYSIS IS COMPLETED
Time between last dose and the end of
hemodialysis
<1 hour
Do not administer dose at the end of
hemodialysis
1-3 hours
Administer 1/2 of next scheduled dose
>3 hours
Administer next scheduled dose
MAINTENANCE DOSING OFF HEMODIALYSIS
Give next scheduled dose 12 hours from last dose administered
Administration : Fomepizole solidifies at temperatures less than 25°C (77°F). If the fomepizole solution has become solid in the vial, the solution should be liquefied by running the vial under warm water or by holding in the hand. Solidification does not affect the efficacy, safety, or stability of fomepizole. Using sterile technique, the appropriate dose of fomepizole should be drawn from the vial with a syringe and injected into at least 100 mL of sterile 0.9% sodium chloride injection or dextrose 5% injection. Mix well. The entire contents of the resulting solution should be infused over 30 minutes. Fomepizole, like all parenteral products, should be inspected visually for particulate matter prior to administration.
Stability : Fomepizole diluted in 0.9% sodium chloride injection or dextrose 5% injection remains stable and sterile for at least 24 hours when stored refrigerated or at room temperature. Fomepizole does not contain preservatives. Therefore, maintain sterile conditions, and after dilution do not use beyond 24 hours.
Solutions showing haziness, particulate matter, precipitate, discoloration, or leakage should not be used.
