Role of Fomepizole in the Management of Ethylene Glycol Toxicity

Abstract

Objective. To systematically review English‐language articles on fomepizole administration in patients with ethylene glycol poisoning. Data Sources. MEDLINE, EMBASE, Current Contents, and PubMed. Search terms were fomepizole, 4‐methylpyrazole, and ethylene glycol. The search was supplemented with a bibliographic review of all relevant articles. Study Selection. All published reports of fomepizole administration in patients with ethylene glycol poisoning were reviewed, irrespective of study design. We identified one clinical trial and subsequent pharmacokinetic study, one case series, and 13 case reports. Results. Fomepizole has been investigated in 70 patients in open, unblinded studies. Most patients received an intravenous loading dose, with subsequent variable maintenance doses every 12 hours until plasma ethylene glycol levels became undetectable. Additional hemodialysis treatment generally was administered when patients had renal insufficiency or ethylene glycol levels above 50 mg/dl. Many patients had detectable ethanol levels either because of coadministration or as a result of adjunctive treatment at a referring center. Poorer patient outcomes, such as death and renal insufficiency, were associated with later clinical presentation time after ingestion. At therapeutic fomepizole levels (> 8.6 mg/ml), the half‐life of ethylene glycol was prolonged to over 19 hours. Fomepizole appeared to be well tolerated by most patients. Conclusion. Fomepizole is an effective alcohol dehydrogenase inhibitor that decreases production of ethylene glycol metabolites. Reduced mortality and morbidity are undetermined because of the small number of patients evaluated to date. Data on comparative efficacy of fomepizole versus ethanol and data on administration of fomepizole in children are limited.

Ethylene glycol poisoning

“…The metabolic acidosis should be treated with sodium bicarbonate infusion. An antidote (fomepizole) that blocks the conversion of EG is used to prevent the metabolism of EG to its toxic by-products [22][23][24]. Most of the EG is then excreted unchanged through the kidneys.…”

“…Intravenous calcium therapy should only be used if hypocalcaemia-induced seizures occur, despite administration of anticonvulsants, as calcium infusion may enhance the calcium oxalate precipitation. Therapy with thiamine, pyridoxine and magnesium-co-factors for the metabolism of EGmay enhance conversion of some toxic metabolites to nontoxic metabolites, but no human data supports this [14,22]. The administration of these co-factors may, however, be beneficial for alcoholics with vitamin deficiencies.…”

4-Hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one Induces Mitochondrial Dysfunction and Apoptosis upon Its Intracellular Oxidation

“…4-Acetoxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (6). A mixture of 5 (0.20 g, 0.62 mmol) and anhydrous AcONa (0.5 g) in acetic anhydride (10 mL) was refluxed for 1 h. The mixture was cautiously diluted with water (10 mL) and poured into cold water (100 mL).…”

“…This concept supports the therapeutic use of 4-methylpyrazole (4-MP), an ADH inhibitor, in ethylene glycol and methanol poisoning. 6,7 To test the possibility that the toxicity of a photoactive compound is exerted upon intracellular activation, we examined a furoquinolinone derivative, namely, 4-hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)one (HOFQ) (Figure 1), bearing a hydroxymethyl group at the 4 position. This compound has been reported to exert antiproliferative activity both in the presence and in the absence of light.…”

Ethylene glycol toxicity

“…Mortality and morbidity are undetermined because of the small number of patients evaluated to date. Data on comparative efficacy of fomepizole vs. ethanol and data on administration of fomepizole in children are limited (Druteika et al 2002). No evidence has yet been published concerning the use of fomepizole in horses.…”