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Overview
Fomepizole is a {{{drugClass}}} that is FDA approved for the treatment of ethylene glycol or methanol poisoning. Common adverse reactions include headache, nausea, dizziness, drowsiness, and metallic taste.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
Fomepizole is indicated as an antidote for ethylene glycol (such as antifreeze) or methanol poisoning, or for use in suspected ethylene glycol or methanol ingestion, either alone or in combination with hemodialysis
Treatment Guidelines : If ethylene glycol or methanol poisoning is left untreated, the natural progression of the poisoning leads to accumulation of toxic metabolites, including glycolic and oxalic acids (ethylene glycol intoxication) and formic acid (methanol intoxication). These metabolites can induce metabolic acidosis, nausea/vomiting, seizures, stupor, coma, calcium oxaluria, acute tubular necrosis, blindness, and death. The diagnosis of these poisonings may be difficult because ethylene glycol and methanol concentrations diminish in the blood as they are metabolized to their respective metabolites. Hence, both ethylene glycol and methanol concentrations and acid base balance, as determined by serum electrolyte (anion gap) and/or arterial blood gas analysis, should be frequently monitored and used to guide treatment.
Treatment consists of blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as fomepizole, and correction of metabolic abnormalities. In patients with high ethylene glycol or methanol concentrations (≥ 50 mg/dL), significant metabolic acidosis, or renal failure, hemodialysis should be considered to remove ethylene glycol or methanol and the respective toxic metabolites of these alcohols.
Treatment with fomepizole :Begin fomepizole treatment immediately upon suspicion of ethylene glycol or methanol ingestion based on patient history and/or anion gap metabolic acidosis, increased osmolar gap, visual disturbances, or oxalate crystals in the urine, OR a documented serum ethylene glycol or methanol concentration greater than 20 mg/dL.
Hemodialysis :Hemodialysis should be considered in addition to fomepizole in the case of renal failure, significant or worsening metabolic acidosis, or a measured ethylene glycol or methanol concentration of greater than or equal to 50 mg/dL. Patients should be dialyzed to correct metabolic abnormalities and to lower the ethylene glycol concentrations below 50 mg/dL.
Discontinuation of fomepizole Treatment :Treatment with fomepizole may be discontinued when ethylene glycol or methanol concentrations are undetectable or have been reduced below 20 mg/dL, and the patient is asymptomatic with normal pH.
Dosing of fomepizole :A loading dose of 15 mg/kg should be administered, followed by doses of 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours thereafter until ethylene glycol or methanol concentrations are undetectable or have been reduced below 20 mg/dL, and the patient is asymptomatic with normal pH. All doses should be administered as a slow intravenous infusion over 30 minutes (see Administration).
Dosage with Renal Dialysis : Fomepizole Injection is dialyzable and the frequency of dosing should be increased to every 4 hours during hemodialysis.
Fomepizole Dosing in Patients Requiring Hemodialysis
There is limited information regarding Off-Label Guideline-Supported Use of Fomepizole in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Fomepizole in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Fomepizole in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Fomepizole in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Fomepizole in pediatric patients.
Contraindications
Fomepizole should not be administered to patients with a documented serious hypersensitivity reaction to fomepizole or other pyrazoles.
Warnings
Precautions
General
Fomepizole should not be given undiluted or by bolus injection. Venous irritation and phlebosclerosis were noted in two of six normal volunteers given bolus injections (over 5 minutes) of fomepizole at a concentration of 25 mg/mL.
Minor allergic reactions (mild rash, eosinophilia) have been reported in a few patients receiving fomepizole (see ADVERSE REACTIONS). Therefore, patients should be monitored for signs of allergic reactions.
Laboratory Tests
In addition to specific antidote treatment with fomepizole, patients intoxicated with ethylene glycol or methanol must be managed for metabolic acidosis, acute renal failure (ethylene glycol), adult respiratory distress syndrome, visual disturbances (methanol), and hypocalcemia. Fluid therapy and sodium bicarbonate administration are potential supportive therapies. In addition, potassium and calcium supplementation and oxygen administration are usually necessary. Hemodialysis is necessary in the anuric patient, or in patients with severe metabolic acidosis or azotemia (see DOSAGE AND ADMINISTRATION). Treatment success should be assessed by frequent measurements of blood gases, pH, electrolytes, BUN, creatinine, and urinalysis, in addition to other laboratory tests as indicated by individual patient conditions. At frequent intervals throughout the treatment, patients poisoned with ethylene glycol should be monitored for ethylene glycol concentrations in serum and urine, and the presence of urinary oxalate crystals. Similarly, serum methanol concentrations should be monitored in patients poisoned with methanol.
Electrocardiography should be performed because acidosis and electrolyte imbalances can affect the cardiovascular system. In the comatose patient, electroencephalography may also be required. In addition, hepatic enzymes and white blood cell counts should be monitored during treatment, as transient increases in serum transaminase concentrations and eosinophilia have been noted with repeated fomepizole dosing.
Adverse Reactions
Clinical Trials Experience
The most frequent adverse events reported as drug-related or unknown relationship to study drug in the 78 patients and 63 normal volunteers who received fomepizole injection were headache (14%), nausea (11%), and dizziness, increased drowsiness, and bad taste/metallic taste (6% each). All other adverse events in this population were reported in approximately 3% or fewer of those receiving fomepizole and were as follows:
Body as a Whole : Abdominal pain, fever, multiorgan system failure, pain during fomepizole injection, inflammation at injection site, lumbalgia/backache, hangover.
Skin/Appendages : Application site reaction, rash.
Special Senses : Abnormal smell, speech/visual disturbances, transient blurred vision, roar in ear.
Urogenital : Anuria
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Fomepizole in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Drug Interactions
General
Fomepizole should not be given undiluted or by bolus injection. Venous irritation and phlebosclerosis were noted in two of six normal volunteers given bolus injections (over 5 minutes) of fomepizole at a concentration of 25 mg/mL.
Minor allergic reactions (mild rash, eosinophilia) have been reported in a few patients receiving fomepizole (see ADVERSE REACTIONS). Therefore, patients should be monitored for signs of allergic reactions.
Laboratory Tests
In addition to specific antidote treatment with fomepizole, patients intoxicated with ethylene glycol or methanol must be managed for metabolic acidosis, acute renal failure (ethylene glycol), adult respiratory distress syndrome, visual disturbances (methanol), and hypocalcemia. Fluid therapy and sodium bicarbonate administration are potential supportive therapies. In addition, potassium and calcium supplementation and oxygen administration are usually necessary. Hemodialysis is necessary in the anuric patient, or in patients with severe metabolic acidosis or azotemia (see DOSAGE AND ADMINISTRATION). Treatment success should be assessed by frequent measurements of blood gases, pH, electrolytes, BUN, creatinine, and urinalysis, in addition to other laboratory tests as indicated by individual patient conditions. At frequent intervals throughout the treatment, patients poisoned with ethylene glycol should be monitored for ethylene glycol concentrations in serum and urine, and the presence of urinary oxalate crystals. Similarly, serum methanol concentrations should be monitored in patients poisoned with methanol.
Electrocardiography should be performed because acidosis and electrolyte imbalances can affect the cardiovascular system. In the comatose patient, electroencephalography may also be required. In addition, hepatic enzymes and white blood cell counts should be monitored during treatment, as transient increases in serum transaminase concentrations and eosinophilia have been noted with repeated fomepizole dosing.
Animal reproduction studies have not been conducted with fomepizole. It is also not known whether fomepizole can cause fetal harm when administered to pregnant women or can affect reproduction capacity. Fomepizole should be given to pregnant women only if clearly needed.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Fomepizole in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Fomepizole during labor and delivery.
Nursing Mothers
It is not known whether fomepizole is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when fomepizole is administered to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatic Use
Safety and effectiveness in geriatric patients have not been established.
Gender
There is no FDA guidance on the use of Fomepizole with respect to specific gender populations.
Race
There is no FDA guidance on the use of Fomepizole with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Fomepizole in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Fomepizole in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Fomepizole in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Fomepizole in patients who are immunocompromised.
Administration and Monitoring
Administration
Intravenous
Fomepizole solidifies at temperatures less than 25°C (77°F). If the fomepizole solution has become solid in the vial, the solution should be liquefied by running the vial under warm water or by holding in the hand. Solidification does not affect the efficacy, safety, or stability of fomepizole. Using sterile technique, the appropriate dose of fomepizole should be drawn from the vial with a syringe and injected into at least 100 mL of sterile 0.9% sodium chloride injection or dextrose 5% injection. Mix well. The entire contents of the resulting solution should be infused over 30 minutes. Fomepizole, like all parenteral products, should be inspected visually for particulate matter prior to administration.
Stability : Fomepizole diluted in 0.9% sodium chloride injection or dextrose 5% injection remains stable and sterile for at least 24 hours when stored refrigerated or at room temperature. Fomepizole does not contain preservatives. Therefore, maintain sterile conditions, and after dilution do not use beyond 24 hours.
Solutions showing haziness, particulate matter, precipitate, discoloration, or leakage should not be used.
Monitoring
There is limited information regarding Monitoring of Fomepizole in the drug label.
Description
IV Compatibility
There is limited information regarding IV Compatibility of Fomepizole in the drug label.
Overdosage
Nausea, dizziness, and vertigo were noted in healthy volunteers receiving 50 and 100 mg/kg doses of fomepizole (at plasma concentrations of 290 to 520 µmol/L, 23.8 to 42.6 mg/L). These doses are 3 to 6 times the recommended dose. This dose-dependent CNS effect was short-lived in most subjects and lasted up to 30 hours in one subject.
Fomepizole is dialyzable, and hemodialysis may be useful in treating cases of overdosage.
Pharmacology
There is limited information regarding Fomepizole Pharmacology in the drug label.
There is limited information regarding Pharmacodynamics of Fomepizole in the drug label.
Pharmacokinetics
There is limited information regarding Pharmacokinetics of Fomepizole in the drug label.
Nonclinical Toxicology
Carcinogenesis & Mutagenesis & Impairment Of Fertility
There have been no long-term studies performed in animals to evaluate carcinogenic potential.
There was a positive Ames test result in the Escherichia coli tester strain WP2uvrA and the Salmonella typhimurium tester strain TA102 in the absence of metabolic activation. There was no evidence of a clastogenic effect in the in vivo mouse micronucleus assay.
In rats, fomepizole (110 mg/kg) administered orally for 40 to 42 days resulted in decreased testicular mass (approximately 8% reduction). This dose is approximately 0.6 times the human maximum daily exposure based on surface area (mg/m2). This reduction was similar for rats treated with either ethanol or fomepizole alone. When fomepizole was given in combination with ethanol, the decrease in testicular mass was significantly greater (approximately 30% reduction) compared to those rats treated exclusively with fomepizole or ethanol.
Clinical Studies
There is limited information regarding Clinical Studies of Fomepizole in the drug label.
How Supplied
Storage
There is limited information regarding Fomepizole Storage in the drug label.
Images
Drug Images
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