Fomepizole

Description

DESCRIPTION Fomepizole injection is a competitive inhibitor of alcohol dehydrogenase. The chemical name of fomepizole is 4-methylpyrazole. It has the molecular formula C4H6N2 and a molecular weight of 82.1. The structural formula is: It is a clear to yellow liquid at room temperature. Its melting point is 25° C (77° F) and it may present in a solid form at room temperature. Fomepizole is soluble in water and very soluble in ethanol, diethyl ether, and chloroform. Each vial contains 1.5 mL (1 g/mL) of fomepizole. Image from Drug Label Content

What Is Fomepizole Used For?

INDICATIONS AND USAGE Fomepizole injection 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 (see DOSAGE AND ADMINISTRATION ).

Dosage and Administration

DOSAGE AND ADMINISTRATION Do not use polycarbonate syringes or polycarbonate-containing needles (including polycarbonate filter needles) when diluting or administering fomepizole injection. Fomepizole can interact with polycarbonate, compromising the integrity of the syringe and/or needle component containing polycarbonate. 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 injection, 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 Injection : Begin fomepizole injection 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 injection 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 Injection Treatment : Treatment with fomepizole injection 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 Injection 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...

Side Effects (Adverse Reactions)

ADVERSE REACTIONS 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 Cardiovascular: Sinus bradycardia/bradycardia, phlebosclerosis, tachycardia, phlebitis, shock, hypotension Gastrointestinal: Vomiting, diarrhea, dyspepsia, heartburn, decreased appetite, transient transaminitis Hemic/Lymphatic: Eosinophilia/hypereosinophilia, lymphangitis, disseminated intravascular coagulation, anemia Nervous: Lightheadedness, seizure, agitation, feeling drunk, facial flush, vertigo, nystagmus, anxiety, “felt strange”, decreased environmental awareness Respiratory: Hiccups, pharyngitis Skin/Appendages: Application site reaction, rash Special Senses: Abnormal smell, speech/visual disturbances, transient blurred vision, roar in ear Urogenital: Anuria

Drug Interactions

Drug Interactions Drug Interactions Oral doses of fomepizole (10-20 mg/kg), via alcohol dehydrogenase inhibition, significantly reduced the rate of elimination of ethanol (by approximately 40%) given to healthy volunteers in moderate doses. Similarly, ethanol decreased the rate of elimination of fomepizole (by approximately 50%) by the same mechanism. Reciprocal interactions may occur with concomitant use of fomepizole and drugs that increase or inhibit the cytochrome P450 system (e.g., phenytoin, carbamazepine, cimetidine, ketoconazole), though this has not been studied.

Contraindications

CONTRAINDICATIONS Fomepizole injection should not be administered to patients with a documented serious hypersensitivity reaction to fomepizole injection or other pyrazoles.

Pregnancy and Breastfeeding

Pregnancy Pregnancy Category C: 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.

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.

Overdosage

OVERDOSAGE Nausea, dizziness, and vertigo were noted in healthy volunteers receiving 50 and 100 mg/kg doses of fomepizole (at plasma concentrations of 290-520 µmol/L, 23.8-42.6 mg/L). These doses are 3-6 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.

How Supplied

HOW SUPPLIED Fomepizole is supplied as a sterile, preservative-free solution for intravenous use as: Supplied in single vial cartons. Each vial contains 1.5 mL (1 g/mL) of fomepizole. NDC 0517-0710-01 Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. AMERICAN REGENT, INC. SHIRLEY, NY 11967 RQ1076-A Revised: November 2020