fomepizole

Current recommendations for treatment of severe toxic alcohol poisonings.

Mégarbane B, Borron SW, Baud FJ.

Source

Réanimation Médicale et Toxicologique, Hôpital Lariboisière, 2 rue Ambroise Paré, 5010 Paris, France. bruno-megarbane@wanadoo.fr

Abstract

BACKGROUND: Ethylene glycol (EG) and methanol are responsible for accidental, suicidal, and epidemic poisonings, resulting in death or permanent sequelae. Toxicity is due to the metabolic products of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. Conventional management of these intoxications consists of ethanol and hemodialysis. Fomepizole, a potent ADH inhibitor, has largely replaced antidotal ethanol use in France and two recent prospective U.S. trials definitively established its efficacy. Fomepizole appears safer than ethanol and while no comparative study of efficacy exists, fomepizole is recommended as the first-line antidote. FOCUS: Fomepizole, administered early in EG intoxication, prevents renal injury. In the absence of renal failure, EG clearance is rapid, avoiding the need for prolonged fomepizole administration. The long elimination half-life of methanol poisonings, with absent hemodialysis, necessitates prolonged administration of fomepizole. In the U.S. trials, patients were dialyzed when plasma EG or methanol concentrations were >/=0.5 g/l. However, EG-poisoned patients treated with fomepizole prior to the onset of significant acidosis may not require hemodialysis. Indeed, fomepizole may also obviate the need for hemodialysis in selected methanol-poisoned patients, in the absence of neurological and ocular impairment or severe acidosis. When dialysis is indicated, 1 mg.kg.h continuous infusion of fomepizole should be provided to compensate for its elimination. CONCLUSIONS: Fomepizole is an effective and safe first-line recommended antidote for EG and methanol intoxication. In selected patients, fomepizole may obviate the need for hemodialysis.