Note: Fomepizole therapy should begin immediately upon suspicion of ethylene glycol or methanol ingestion. Consultation with a clinical toxicologist or poison control center is highly recommended to determine if fomepizole therapy is indicated.
Ethylene glycol or methanol toxicity; patient not requiring hemodialysis: Limited data available; consider consultation with a clinical toxicology or poison control center:
Infants, Children, and Adolescents: IV: Initial: 15 mg/kg loading dose; followed by 10 mg/kg every 12 hours for 4 doses; then 15 mg/kg every 12 hours until ethylene glycol or methanol concentrations have been reduced to <20 mg/dL and patient is asymptomatic with normal pH (Baum 2000; Benitez 2000; Boyer 2001; Brown 2001; De Brabander 2005; Detaille 2004; Fisher 1998). Note: For severe toxicity requiring concomitant hemodialysis, see "Dosing: Altered Kidney Function: Pediatric."
Infants, Children, and Adolescents (Limited data available [Brent 2010]): Note: Hemodialysis should be considered as an adjunct to fomepizole in patients with renal failure, significant or worsening metabolic acidosis, or ethylene glycol or methanol concentrations ≥50 mg/dL (Roberts 2015). The following dosage adjustments should be used for any patient receiving hemodialysis regardless of renal function.
Prior to the start of hemodialysis: To determine if the patient requires a dose of fomepizole at the start of hemodialysis, determine when the last dose was administered.
If <6 hours since last fomepizole dose: Do not administer dose upon beginning dialysis.
If ≥6 hours since last fomepizole dose: Administer next scheduled dose upon beginning dialysis.
During hemodialysis: Administer every 4 hours. Alternatively, a loading dose of 10 to 20 mg/kg followed by a continuous infusion 1 to 1.5 mg/kg/hour during hemodialysis has been described in case reports (Jobard 1996).
Upon completion of hemodialysis; dependent upon the time between the last dose and the end of hemodialysis: To determine if the patient requires a dose of fomepizole at the time of completion of hemodialysis, determine when the last dose was administered.
If <1 hour since last fomepizole dose: Do not administer a dose at the end of hemodialysis.
If 1 to 3 hours since last fomepizole dose: Administer 1/2 of the next scheduled dose at the end of hemodialysis.
If >3 hours since last fomepizole dose: Administer the next scheduled dose at the end of hemodialysis.
Maintenance dose off hemodialysis: Administer every 12 hours starting from the time last dose administered.
Fomepizole is metabolized in the liver. Specific dosage adjustments have not been determined in patients with hepatic impairment.
(For additional information see "Fomepizole: Drug information")
Note: Fomepizole therapy should begin immediately upon suspicion of ethylene glycol or methanol ingestion. Consultation with a clinical toxicologist or poison control center is highly recommended to determine if fomepizole therapy is indicated.
Ethylene glycol or methanol toxicity: IV: 15 mg/kg (loading dose), followed by doses of 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours until ethylene glycol or methanol concentrations have been reduced to <20 mg/dL and patient is asymptomatic with normal pH. Note: For severe toxicity requiring concomitant hemodialysis, see dosage adjustment in altered kidney function.
Note: Hemodialysis should be considered as an adjunct to fomepizole in patients with renal failure, significant or worsening metabolic acidosis, or ethylene glycol or methanol concentrations ≥50 mg/dL (Brent 1999; Roberts 2015). The following dosing adjustments should be used for any patient receiving hemodialysis regardless of renal function.
Prior to the start of hemodialysis:
To determine if the patient requires a dose of fomepizole at the start of hemodialysis, determine when the last dose was administered.
If the last dose of fomepizole was given <6 hours ago, do not administer another dose upon beginning hemodialysis.
If the last dose of fomepizole was given ≥6 hours ago, administer next scheduled dose upon beginning hemodialysis.
During hemodialysis: During hemodialysis, administer fomepizole every 4 hours. Alternatively, a loading dose of 10 to 20 mg/kg followed by 1 to 1.5 mg/kg/hour continuous infusion during hemodialysis has been described in case reports (Jobard 1996).
Upon completion of hemodialysis:
To determine if the patient requires a dose of fomepizole at the time of completion of hemodialysis, determine when the last dose was administered.
If the last dose of fomepizole was given <1 hour ago, do not administer a dose at the end of hemodialysis.
If the last dose of fomepizole was given 1 to 3 hours ago, administer one-half of the next scheduled dose at the end of hemodialysis.
If the last dose of fomepizole was given >3 hours ago, administer the next scheduled dose at the end of hemodialysis.
Maintenance dose when off hemodialysis: Administer fomepizole every 12 hours (starting 12 hours from last dose administered).
Fomepizole is metabolized in the liver. Specific dosage adjustments have not been determined in patients with hepatic impairment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous [preservative free]:
Generic: 1 g/mL (1.5 mL [DSC]); 1.5 g/1.5 mL (1.5 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Antizol: 1 g/mL (1.5 mL)
Generic: 1 g/mL (1.5 mL)
Parenteral: IV: Infuse as a diluted solution over 30 minutes; rapid infusion at a concentration of 25 mg/mL has been associated with vein irritation and phlebosclerosis. Avoid using polycarbonate syringes or polycarbonate-containing needles (including polycarbonate filter needles) during administration.
IV: All doses should be administered as a slow IV infusion (IVPB) over 30 minutes. Avoid using polycarbonate syringes or polycarbonate-containing needles (including polycarbonate filter needles) during administration.
Store at controlled room temperature, 20°C to 25°C (68°F to 77°F); fomepizole solidifies at temperatures <25°C (77°F). If solution becomes solid in the vial, it should be carefully warmed by running the vial under warm water or by holding in the hand. Solidification does not affect the efficacy, safety, or stability of the drug. Diluted solution should be used within 24 hours and may be stored at room temperature or under refrigeration.
Pharmacy supply of emergency antidotes: Guidelines suggest that at least 1.5 to 4.5 g of fomepizole be stocked. Suggested amount is stated to be a sufficient quantity to treat 1 patient weighing 100 kg for an initial 8- to 24-hour period (Dart 2018); actual amount to be stocked should take into account site-specific and population-specific needs.
Treatment of known or suspected methanol or ethylene glycol (antifreeze) poisoning alone or in combination with hemodialysis (FDA approved in adults).
Note: Fomepizole is the preferred antidote for known or suspected ethylene glycol poisoning or methanol poisoning. If fomepizole is unavailable or if the patient is intolerant to fomepizole, ethanol therapy may be considered. Ethanol as an antidote is effective in the management of methanol and ethylene glycol poisoning (Thanacoody 2016; Zakharov 2015); however, ethanol is associated with a higher incidence of adverse events and medication errors (Bestic 2009; Lepik 2009; Lepik 2011).
Fomepizole may be confused with omeprazole
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Headache (14%)
Gastrointestinal: Nausea (11%)
1% to 10% (≤3% unless otherwise noted):
Cardiovascular: Bradycardia, facial flushing, hypotension, phlebitis, shock, tachycardia
Central nervous system: Dizziness (6%), drowsiness (6%), metallic taste (≤6%), agitation, altered sense of smell, anxiety, seizure, speech disturbance, vertigo
Dermatologic: Skin rash
Gastrointestinal: Unpleasant taste (≤6%), abdominal pain, decreased appetite, diarrhea, heartburn, hiccups, vomiting
Genitourinary: Anuria
Hematologic & oncologic: Anemia, disseminated intravascular coagulation (DIC), eosinophilia, lymphangitis
Hepatic: Increased liver enzymes
Local: Application site reaction, inflammation at injection site, pain at injection site
Neuromuscular & skeletal: Back pain
Ophthalmic: Nystagmus, transient blurred vision, visual disturbance
Respiratory: Pharyngitis
Miscellaneous: Fever, multi-organ failure
<1%, postmarketing and/or case reports: Hypersensitivity reaction (mild; mild rash, eosinophilia)
Hypersensitivity to fomepizole, other pyrazoles, or any component of the formulation
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; metabolized in the liver.
• Renal impairment: Use with caution in patients with renal impairment; fomepizole and its metabolites are excreted in the urine. Hemodialysis should be considered as an adjunct to fomepizole in patients with renal failure, significant acidosis (pH <7.25 to 7.3), worsening metabolic acidosis, or ethylene glycol or methanol concentrations ≥50 mg/dL.
• Isopropanol (isopropyl alcohol) poisoning: Fomepizole should not be administered in known isopropanol ingestions as the toxicity of isopropanol is predominantly due to the parent alcohol; inhibiting the metabolism of isopropanol may result in prolonged CNS depression, hypotension, or respiratory depression (Bekka 2001; Kraut 2018).
Other warnings/precautions:
• Administration: Should not be given undiluted or by bolus injection. Avoid using polycarbonate syringes or polycarbonate-containing needles (including polycarbonate filter needles) during dilution or administration; fomepizole may interfere with the integrity of polycarbonate products.
None known.
There are no known significant interactions.
Animal reproduction studies have not been conducted. In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey, 2003).
Vital signs, arterial blood gases, acid-base status, renal function (BUN, creatinine, and urinalysis), liver function, WBC counts, anion and osmolar gaps, clinical signs and symptoms of toxicity (arrhythmias, seizures, coma); urinary oxalate, serum and urinary ethylene glycol or serum methanol level depending upon the agent ingested; formic acid level (methanol ingestion).
Ethylene glycol or methanol serum concentration: Goal: <20 mg/dL; therapeutic plasma fomepizole level: 0.8 mcg/mL.
Fomepizole competitively inhibits alcohol dehydrogenase, an enzyme which catalyzes the metabolism of ethanol, ethylene glycol, and methanol to their toxic metabolites. Ethylene glycol is metabolized to glycoaldehyde, then oxidized to glycolate, glyoxylate, and oxalate. Glycolate and oxalate are responsible for metabolic acidosis and renal damage. Methanol is metabolized to formaldehyde, then oxidized to formic acid. Formic acid is responsible for metabolic acidosis and visual disturbances.
Onset of effect: Peak effect: Maximum: 1.5 to 2 hours.
Absorption: Oral: Readily absorbed.
Distribution: Vd: 0.6 to 1.02 L/kg; rapidly into total body water.
Protein binding: Negligible.
Metabolism: Hepatic to 4-carboxypyrazole (80% to 85% of dose), 4-hydroxymethylpyrazole, and their N-glucuronide conjugates; following multiple doses, induces its own metabolism via CYP oxidases after 30 to 40 hours.
Half-life elimination: Varies with dose and duration. After 96 hours of administration, the self-induction of fomepizole metabolism results in a shortened half-life of 1.5 to 2 hours (McMartin 2012).
Excretion: Urine (1% to 3.5% as unchanged drug and metabolites).
Solution (Antizol Intravenous)
1 g/mL (per mL): $1,233.20
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
