Fomepizole

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Fomepizole or 4-methylpyrazole is indicated for use as an antidote in confirmed or suspected methanol or ethylene glycol poisoning. It may be used alone or in combination with hemodialysis. {03}

Contents 1 Uses 2 Dosage 3 Transformation and elimination 4 See also 5 External links

Uses

Fomepizole is a competitive inhibitor of alcohol dehydrogenase, the enzyme that catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites. Ethylene glycol is first metabolized to glycolaldehyde which then undergoes further oxidation to glycolate, glyoxylate, and oxalate. It is glycolate and oxalate that are primarily responsible for the metabolic acidosis and renal damage that are seen in ethylene glycol poisoning. Methanol is first metabolized to formaldehyde and then undergoes subsequent oxidation via formaldehyde dehydrogenase to become formic acid. It is formic acid that is primarily responsible for the metabolic acidosis and visual disturbances that are associated with methanol poisoning.

Dosage

Fomepizole distributes rapidly into total body water. The volume of distribution is between 0.6 and 1.02 L/kg. The therapeutic concentration is from 8.2 to 24.6 mg (100 to 300 micromoles) per liter. Peak concentration following single oral doses of 7 to 50 mg/kg of body weight occurred in 1 to 2 hours. The half-life varies with dose and therefore has not been calculated.

Transformation and elimination

Hepatic; the primary metabolite is 4-carboxypyrazole (approximately 80 to 85% of an administered dose). Other metabolites include the pyrazoles 4-hydroxymethylpyrazole and the N -glucuronide conjugates of 4-carboxypyrazole and 4-hydroxymethylpyrazole.

Following multiple doses, fomepizole rapidly induces its own metabolism via the cytochrome P450 mixed-function oxidase system.

In healthy volunteers, 1 to 3.5% of an administered dose was excreted unchanged in the urine. The metabolites also are excreted unchanged in the urine.

Fomepizole is dialyzable.

See also

• Ethylene glycol
• Methanol

External links

• Advanced Consumer Drug Information
• Pediatrics Journal Vol. 107 No. 1 January 2001, pp. 170 - Fomepizole in the Treatment of Poisoning

v • d • e Antidotes (V03AB)
Methanol / Ethylene glycol	Ethanol - Fomepizole
Paracetamol (Acetaminophen)	Acetylcysteine - Glutathione - Methionine
Arsenic	Dimercaprol - Succimer
Cyanide	4-Dimethylaminophenol - Amyl nitrite - Hydroxocobalamin - Sodium nitrite - Sodium thiosulfate
Heparin	Protamine
Nerve agent / Organophosphate pesticide	Atropine - Biperiden - Diazepam - Oximes (Pralidoxime, Obidoxime) - see also Cholinesterase
Opioid	Diprenorphine - Nalorphine - Naloxone - Naltrexone - Nalmefene
Benzodiazepine	Flumazenil
Toxic metals (Cadmium, Mercury, Lead etc)	Edetates - Dimercaprol
Other	Ipecacuanha - Prednisolone/promethazine - Methylthioninium chloride - Potassium permanganate - Physostigmine - Copper sulfate - Potassium iodide - Digoxin Immune Fab - Prussian blue