Fomepizole for the treatment of pediatric ethylene and diethylene glycol, butoxyethanol, and methanol poisonings.
BACKGROUND
The use and clinical efficacy of the alcohol dehydrogenase inhibitor fomepizole is well established for the treatment of ethylene glycol and methanol poisonings in adults.


METHODS
A computerized search of the U.S. National Academy of medicine and EMBase databases was undertaken to identify published cases of patients treated with fomepizole. This search strategy identified 14 published cases related to the topic of this review: 10 due to ethylene glycol poisoning, 1 due to diethylene glycol poisoning, 1 due to butoxyethanol ingestion, and 2 due to methanol poisoning. The median age of these cases was 5.5 years old. FOMEPIZOLE IN GLYCOL AND GLYCOL ETHER POISONING: For the 10 ethylene glycol poisoned patients, the median recorded values of their arterial pH was 7.27 (range 7.03-7.38), serum bicarbonate concentration was 13 mEq/L (range 2-25), and ethylene glycol concentration was 2,140 mg/L (range 130-3,840). Eight of these patients were not hemodialyzed. The eight patients who were not hemodialyzed had ethylene glycol concentrations as high as 3,500 mg/L and serum bicarbonate concentrations as low as 4 mEq/L. All 10 patients had resolution of their metabolic acidosis and recovered without sequelae. The half-times of ethylene glycol elimination ranged from 9 to 15 h during fomepizole therapy, which is faster than the 19.7 h reported in adults. The two patients who ingested diethylene glycol or butoxyethanol all recovered without sequelae. The patient who ingested the butoxyethanol had a serum bicarbonate concentration of 13 mEq/L and was not hemodialyzed. FOMEPIZOLE IN METHANOL POISONING: One of the two children who ingested methanol was hemodialyzed. Both cases had a similar degree of severity. DOES FOMEPIZOLE OBVIATE THE NEED FOR HEMODIALYSIS?: Based on the experience reviewed herein it appears that, as in adults, hemodialysis may not be necessary in most cases of pediatric ethylene glycol poisoning if treated with fomepizole. FOMEPIZOLE PHARMACOKINETICS: Plasma fomepizole concentrations were measured in three cases and were found to be therapeutic with apparent Michaelis-Menton kinetics, having a zero-order elimination rate of 0.6-1 mg/L/h at higher concentrations and a first-order elimination with an apparent elimination half-time of 3.9 h at lower concentrations. FOMEPIZOLE REGIMEN: Most cases used the current U.S.-approved regimen. ADVERSE EFFECTS OF FOMEPIZOLE: The one adverse effect reported during fomepizole therapy was transient nystagmus in a 6-year-old with a serum ethylene glycol concentration of 130 mg/L and a serum bicarbonate concentration of 2 mEq/L; it is likely that ethylene glycol itself was the cause. COMPARISON OF FOMEPIZOLE WITH ETHANOL THERAPY: Two cases were originally treated with ethanol but switched to fomepizole because of adverse effects. In both cases, the adverse reactions to ethanol resolved once fomepizole treatment was initiated.


CONCLUSIONS
The limited data available suggest that fomepizole, using the same dosage regimen as that used for adults, is efficacious and well tolerated in pediatric patients. In many cases of pediatric ethylene glycol poisoning treated with fomepizole, hemodialysis may not be necessary despite high concentrations and the presence of metabolic acidosis.
Brent
Jeffrey
J
Toxicology Associates, University of Colorado, School of Medicine, Denver, CO, USA. jeffrey.brent@UCDenver.edu
D000138:Acidosis / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000188:drug therapy; D000931:Antidotes / Q000008:administration & dosage* / Q000506:poisoning / Q000627:therapeutic use*; D001639:Bicarbonates / Q000627:therapeutic use; D002648:Child; D018450:Disease Progression; D000431:Ethanol / Q000506:poisoning / Q000627:therapeutic use; D019855:Ethylene Glycol / Q000097:blood / Q000506:poisoning*; D005026:Ethylene Glycols; D005030:Ethylenes; D000077604:Fomepizole; D006018:Glycols / Q000506:poisoning / Q000627:therapeutic use; D006801:Humans; D008297:Male; D000432:Methanol / Q000506:poisoning* / Q000627:therapeutic use; D010372:Pediatrics; D011720:Pyrazoles; D006435:Renal Dialysis / Q000009:adverse effects
D000931:Antidotes; D001639:Bicarbonates; D005026:Ethylene Glycols; D005030:Ethylenes; D006018:Glycols; D011720:Pyrazoles; D000431:Ethanol; C013484:diethylene glycol; D000077604:Fomepizole; C036216:ethylene; D019855:Ethylene Glycol; D000432:Methanol