Fomepizole (4-Methylpyrazole, 4-MP)
Pharmacology
Fomepizole (4-methylpyrazole) is a potent competitive inhibitor of alcohol dehydrogenase, the first enzyme in the metabolism of ethanol and other alcohols. Fomepizole can prevent the formation of toxic metabolites after methanol or ethylene glycol ingestion. Furthermore, early treatment with fomepizole for ethylene glycol or methanol poisoning (before the appearance of a significant acidosis) may obviate the need for dialysis. Since the introduction of fomepizole, most patients with ethylene glycol or methanol poisoning probably will be treated with this drug instead of ethanol, particularly in cases involving small children, patients taking disulfiram, patients with altered consciousness and ingestion of multiple substances, patients with pancreatitis or active liver disease, and hospitals lacking laboratory support to perform rapid ethanol levels (for monitoring treatment). Economic models have suggested that fomepizole may be more cost-effective than ethanol despite the high acquisition cost of fomepizole.
Fomepizole is eliminated mainly via zero-order kinetics, but cytochrome P-450 metabolism can undergo auto-induction within 2–3 days. The drug is dialyzable. It is well absorbed and has been used successfully with PO administration but is not approved for this route in the United States.
Indications are suspected or confirmed methanol (methyl alcohol [See Methanol]) or ethylene glycol (See Ethylene Glycol and Other Glycols) poisoning with one or more of the following:
A reliable history of ingestion of a toxic dose but no available blood concentration measurements (when used empirically, allows a 12-hour “window” after one dose to assess the patient);
Metabolic acidosis and an unexplained elevated osmolar gap (See Diagnosis of Poisoning); or
Serum methanol or ethylene glycol concentration of 20 mg/dL or higher.
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