FOMEPIZOLE, 4-METHYLPYRAZOLE
Chemistry - A synthetic alcohol dehydrogenase inhibitor, fomepizole is commonly called 4-methylpyrazole (4-MP).
Contraindications/Precaution/Reproductive Safety- There are no labeled contraindications tofomepizole's use. Fomepizole does not appear to be effective for treating ethylene glycol toxicity incats.
Fomepizole's safe use during pregnancy, lactation or in breeding animals has not been established. However, because of the morbidity and mortality associated with ethylene glycol toxicity, the benefits of fomepizole should generally outweigh its risks.
One dog during clinical trials was reported to develop anaphylaxis.
Use of fomepizole alone without adequate monitoring and adjunctive supportive care (e.g., correction of acid/base, fluid, electrolyte imbalances) may lead to therapeutic failure. If animal presents within 1-2 hours post ingestion, consider inducing vomiting and/or gastric lavage with activated charcoal to prevent further absorption.
Overdosage - Overdosage may cause significant CNS depression. No specific treatment is recommended.
Storage, Stability, Compatibility
Commercially available solutions should be stored at roomtemperature. The concentrate for injection may solidify at temperatures less than 25°C. Should thisoccur, resolubolize by running warm water over the vial. Solidification or resolubolization does notaffect drug potency or stability. Store reconstituted vial at room temperature and discard after 72hours. Reconstituted solutions may be further diluted in D5W or normal saline for IV infusion.Pharmacology - FOMEPIZOLE, 4-METHYLPYRAZOLE
Ethylene glycol itself is only mildly toxic in dogs, but when it is metabolized toglycoaldehyde, glycolate, glyoxalic acid and oxalic acids the resultant metabolic acidosis and renaltubular necrosis can be fatal. Fomepizole is a competitive inhibitor of alcohol dehydrogenase, theprimary enzyme that converts ethylene glycol into glycoaldehyde and other toxic metabolites. Thisallows ethylene glycol to be excreted primarily unchanged in the urine decreasing the morbidity andmortality associated with ethylene glycol ingestion.Uses, Indications
Fomepizole is used for the treatment of known or suspected ethylene glycoltoxicity in dogs (and humans).Pharmacokinetics - FOMEPIZOLE, 4-METHYLPYRAZOLE
Fomepizole is excreted primarily by the kidneys and apparently exhibits adose-dependent accumulation of the drug over time. Therefore, a reduction in subsequent doses cansafely occur.Contraindications/Precaution/Reproductive Safety- There are no labeled contraindications tofomepizole's use. Fomepizole does not appear to be effective for treating ethylene glycol toxicity incats.
Fomepizole's safe use during pregnancy, lactation or in breeding animals has not been established. However, because of the morbidity and mortality associated with ethylene glycol toxicity, the benefits of fomepizole should generally outweigh its risks.
Adverse Effects, Warnings
Giving concentrated drug rapidly intravenously may cause vein irritation and phlebosclerosis. Dilute as directed in the commercially available kit.One dog during clinical trials was reported to develop anaphylaxis.
Use of fomepizole alone without adequate monitoring and adjunctive supportive care (e.g., correction of acid/base, fluid, electrolyte imbalances) may lead to therapeutic failure. If animal presents within 1-2 hours post ingestion, consider inducing vomiting and/or gastric lavage with activated charcoal to prevent further absorption.
Overdosage - Overdosage may cause significant CNS depression. No specific treatment is recommended.