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  1. Pharmacology

    1. 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.

    2. 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.

  2. 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:

    1. 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);

    2. Metabolic acidosis and an unexplained elevated osmolar gap (See Diagnosis of Poisoning); or

    3. Serum methanol or ethylene glycol concentration of 20 mg/dL or higher.

    4. Other substances that are metabolized by alcohol dehydrogenase to toxic metabolites include propylene glycol, diethylene glycol, triethylene glycol, glycol ethers (eg, ethylene glycol ethyl ether, ethylene glycol butyl ether), and 1,4-butanediol. The criteria for fomepizole therapy and evidence for improved outcomes are lacking for all these substances. However, case reports of poisonings from some of these other glycols (eg, propylene glycol, diethylene glycol) have suggested benefit when fomepizole therapy is coupled with dialysis to remove the potentially toxic parent compound and concomitantly prevent the formation of toxic metabolites.

    5. Disulfiram reaction (or risk for): to halt progression or the production of acetaldehyde, assuming that ethanol is still present (based on case reports).

  3. Contraindications. History of allergy to the drug or to other pyrazoles.

  4. Adverse effects

    1. Venous irritation and phlebosclerosis after intravenous injection of the undiluted product.

    2. Headache, nausea, and dizziness are the most commonly reported side effects. Less common effects are vomiting, tachycardia, hypotension, feeling of inebriation, rash, fever, and eosinophilia.

    3. Transient non–dose-dependent elevation of hepatic transaminases has been reported after multiple doses.

    4. Although safety and effectiveness in children have not been established by the manufacturer, fomepizole has been used successfully and reported for pediatric poisonings (in children as young as 8 months).

    5. Use in pregnancy. FDA Category C (indeterminate). Has been used in pregnant patients without immediate adverse effects on the mother or fetus (See Introduction in Section III).

  5. Drug ...

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