Fomepizole

What is fomepizole used for?

Fomepizole is a prescription medicine that is used to treat methanol or ethylene glycol poisoning.

Description

Antizol® (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 as solid 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.

Mechanism of Action

Antizol® (fomepizole) is a competitive inhibitor of alcohol dehydrogenase. Alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde. Alcohol dehydrogenase also catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites.

Ethylene glycol, the main component of most antifreezes and coolants, is metabolized to glycoaldehyde, which undergoes subsequent sequential oxidations to yield glycolate, glyoxylate, and oxalate. Glycolate and oxalate are the metabolic byproducts primarily responsible for the metabolic acidosis and renal damage seen in ethylene glycol toxicosis. The lethal dose of ethylene glycol in humans is approximately 1.4 mL/kg.

Methanol, the main component of windshield wiper fluid, is slowly metabolized via alcohol dehydrogenase to formaldehyde with subsequent oxidation via formaldehyde dehydrogenase to yield formic acid. Formic acid is primarily responsible for the metabolic acidosis and visual disturbances (e.g., decreased visual acuity and potential blindness) associated with methanol poisoning. A lethal dose of methanol in humans is approximately 1-2 mL/kg.

Fomepizole has been shown in vitro to block alcohol dehydrogenase enzyme activity in dog, monkey, and human liver. The concentration of fomepizole at which alcohol dehydrogenase is inhibited by 50% in vitro is approximately 0.1 μmol/L.

In a study of dogs given a lethal dose of ethylene glycol, three animals each were administered fomepizole, ethanol, or left untreated (control group). The three animals in the untreated group became progressively obtunded, moribund, and died. At necropsy, all three dogs had severe renal tubular damage. Fomepizole or ethanol, given 3 hours after ethylene glycol ingestion, attenuated the metabolic acidosis and prevented the renal tubular damage associated with ethylene glycol intoxication.

Several studies have demonstrated that Antizol® plasma concentrations of approximately 10μmol/L (0.82 mg/L) in monkeys are sufficient to inhibit methanol metabolism to formate, which is also mediated by alcohol dehydrogenase. Based on these results, concentrations of Antizol® in humans in the range of 100 to 300 μmol/L (8.6-24.6 mg/L) have been targeted to assure adequate plasma concentrations for the effective inhibition of alcohol dehydrogenase.

In healthy volunteers, oral doses of Antizol® (10-20 mg/kg) significantly reduced the rate of elimination of moderate doses of ethanol, which is also metabolized through the action of alcohol dehydrogenase

Before taking fomepizole, tell your doctor:

• If you are allergic to fomepizole; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take fomepizole with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take fomepizole?

• Tell all of your health care providers that you take fomepizole. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• You will need to have your heart checked before starting fomepizole and while taking it. This includes an ECG. Talk with your doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using fomepizole while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

How is fomepizole best taken?

Use fomepizole as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

What are the side effects of fomepizole that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

What are some other side effects of fomepizole?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Upset stomach.
• Dizziness.
• Feeling sleepy.
• Bad taste in your mouth.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out fomepizole?

• If you need to store fomepizole at home, talk with your doctor, nurse, or pharmacist about how to store it.

Label

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL- 1.5 ML (4 VIALS)

• NDC 46129-200-02
  Rx only
  ANTIZOL® (fomepizole) Injection
  Four 1.5 mL (1 g/mL)
  single use vials
  Caution: Must be diluted before use
  

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL- 1.5 ML (1 VIAL)

• NDC 46129-200-01
  Rx only
  ANTIZOL® (fomepizole) Injection
  1.5 mL (1 g/mL)
  one single use vial
  Caution: Must be diluted before use