Intravenous Poisoning by methanol or ethylene glycol
Adult: Loading dose: 15 mg/kg followed by 10 mg/kg 12 hourly for 4 doses, then increase dose to 15 mg/kg 12 hourly until ethylene glycol or methanol serum concentrations are <20 mg/100 mL. Doses are given via slow infusion over 30 minutes.
In patients with renal failure, significant worsening metabolic acidosis or ≥50 mg/dL ethylene glycol or methanol serum concentrations requiring haemodialysis: Increase frequency to 4 hourly during haemodialysis. Doses to be given prior to or after haemodialysis are determined based on time of last administered dose or time of haemodialysis (refer to detailed product guideline).
Withdraw appropriate dose from a vial and dilute with at least 100 mL of NaCl 0.9% inj or dextrose 5% inj.
Renal and hepatic impairment. Pregnancy and Lactation.
Blood and lymphatic system disorders: Anaemia. Gastrointestinal disorders: Abdominal pain, vomiting. General disorders and admin site conditions: Fever. Nervous system disorders: Headache, agitation. Vascular disorders: Hypotension.
Monitor for serum plasma or urinary concentrations of ethylene glycol or methanol, plasma/urinary osmolality; urinary oxalate crystals; arterial blood gas, anion and osmolar gaps, electrolytes, urinalysis, renal and LFT, CBC, ECG; EEG (in comatose).
Symptoms: Nausea, dizziness and vertigo. Management: May perform haemodialysis.
May decrease the rate of elimination of ethanol and similarly, ethanol may decrease the rate of elimination of fomepizole. May produce reciprocal interactions with CYP450 inducers (e.g. carbamazepine, phenytoin) or CYP450 inhibitors (e.g. cimetidine, ketoconazole).
Description: Fomepizole is a competitive inhibitor of alcohol dehydrogenase, an enzyme that catalyses the oxidation of ethanol to acetaldehyde and the metabolism of ethylene glycol and methanol to their toxic metabolites. Onset: Peak effect: Approx 1.5-2 hours. Pharmacokinetics: Absorption: Readily absorbed from the gastrointestinal tract but usually given via IV. Distribution: Rapidly distributed into total body water. Volume of distribution: 0.6-1.02 L/kg. Negligible protein binding. Metabolism: Metabolised in the liver to primary metabolite 4-carboxypyrazole, and other metabolites, 4-hydroxymethylpyrazole and N-glucuronide conjugate; rapidly induces its own metabolism by CYP450 enzymes after multiple doses, resulting to increased rate of elimination. Excretion: Via urine (1-3.5% as unchanged drug and metabolites). Elimination half-life: Varies with dose.
Store below 25°C. Protect from light. Diluted solution: Store between 2-8°C for not more than 24 hours.
V03AB34 - fomepizole ; Belongs to the class of antidotes. Used in the management of ethylene glycol or methanol poisoning.
AFT Pharmaceuticals Ltd. Antizol 1 g/mL Concentrate for Injection data sheet February 2019. Medsafe. http://www.medsafe.govt.nz/. Accessed 29/10/2020.Anon. Fomepizole. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 29/10/2020.Anon. Fomepizole. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 29/10/2020.Antizol Injection (Paladin Laboratories USA Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 29/10/2020.Buckingham R (ed). Fomepizole. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 29/10/2020.