Fomepizole is a medication used in the treatment of poisoning due to ingestion of certain toxic substances, specifically ethylene glycol (antifreeze) and methanol. These toxic substances can cause severe toxicity and organ damage if not promptly treated.

Fomepizole works by inhibiting the enzyme alcohol dehydrogenase, which is responsible for the metabolism of ethylene glycol and methanol into more toxic byproducts. By blocking this enzyme, fomepizole prevents the formation of these harmful metabolites, reducing the overall toxicity of the ingested substances.

Fomepizole (Antizol) is used as an antidote for ethanol, ethylene glycol, and methanol overdose.

Fomepizole Uses:

• Ethylene glycol or methanol poisoning

• Treatment of methanol or ethylene glycol poisoning alone or in combination with hemodialysis

Note:

• Fomepizole is the favored antidote for confirming or alleged 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 efficient in managing methanol and ethylene glycol poisoning; however, ethanol is related to a higher incidence of adverse events and medication errors.

Fomepizole (Antizol) Dose in Adults

Note: Fomepizole treatment should commence instantly upon suspicion of ethylene glycol or methanol consumption.

Fomepizole (Antizol) Dose in the treatment of Ethylene glycol and methanol toxicity:

• Loading Dose: At the beginning, a higher amount is given, specifically 15 milligrams for each kilogram of the person's weight.
• Follow-up Doses: After the first dose, smaller doses of 10 milligrams per kilogram are given every 12 hours. This is done for a total of 4 doses.
• Continuation Doses: After the initial 4 doses, the amount is increased again to 15 milligrams per kilogram, and it continues to be given every 12 hours.

The treatment continues until the levels of the harmful substances in the person's body (ethylene glycol or methanol) are reduced to less than 20 milligrams per deciliter, and the person feels better with a normal body pH.

Note: If the person's condition is very serious and they need hemodialysis (a medical procedure to clean the blood), the dosage might be adjusted based on their kidney function.

Fomepizole (Antizol) Dose in Childrens

Note: Fomepizole treatment should start instantly upon doubt of ethylene glycol or methanol consumption.

Fomepizole (Antizol) Dose in the treatment of Ethylene glycol or methanol toxicity; patient not requiring hemodialysis:

• Initial Dose: At the start, the child is given a higher amount of fomepizole, specifically 15 milligrams for each kilogram of their weight.
• Follow-up Doses: After the first dose, smaller doses of 10 milligrams per kilogram are given every 12 hours. This is done for a total of 4 doses.
• Continuation Doses: After the initial 4 doses, the amount is increased again to 15 milligrams per kilogram. This continues to be given every 12 hours.

The treatment goes on until the levels of the harmful substances in the child's body (ethylene glycol or methanol) are reduced to less than 20 milligrams per deciliter, and the child feels better with a normal body pH.

Important: If the child's condition is very serious and they need a special blood-cleaning procedure called hemodialysis, the dosage might be adjusted based on their kidney function.

Pregnancy Risk Factor C

• We don't have specific studies about how this medicine affects animals when they're having babies.
• However, when it comes to people, especially pregnant women, the decision to use antidotes, like this medicine, should be based on the mom's health and how she's expected to recover.
• If there's a clear need for the antidote, it should be given to pregnant women, and concerns about it causing birth defects shouldn't stop its use, according to Bailey in 2003.
• The main idea is that the health of the mom is the priority when deciding whether to use this medicine during pregnancy.

Use during breastfeeding:

• We're not sure if the medication fomepizole passes into breast milk.
• The people who make the medicine suggest being careful when giving it to breastfeeding moms.
• This means it's important to consider the potential risks and benefits, and it might be a good idea for nursing mothers to use it with caution.

Dose in Kidney Disease:

Note:

• If someone has kidney problems, a serious condition called renal failure, or if there's a significant or worsening issue with the balance of acids in their body, or if the levels of harmful substances (ethylene glycol or methanol) in their body are really high (≥50 mg/dL), it's recommended to think about using hemodialysis along with the medicine fomepizole.
• Hemodialysis is a special procedure to clean the blood.
• In these situations, the dosage of fomepizole may need to be adjusted, and this adjustment applies to anyone getting hemodialysis, no matter their kidney function.

Prior to the start of hemodialysis:

• Check Timing: Before starting hemodialysis, find out when the person last took fomepizole.
• If Within 6 Hours: If the last dose was taken less than 6 hours ago, don't give another dose when starting hemodialysis.
• If 6 Hours or More: If the last dose was taken 6 hours or more ago, go ahead and give the next scheduled dose when starting hemodialysis.

During hemodialysis:

• Every 4 Hours: While someone is undergoing hemodialysis, give them fomepizole every 4 hours.
• Alternate Method: In some cases, instead of giving it every 4 hours, a larger starting dose (10-20 mg for each kilogram of body weight) followed by a continuous smaller amount (1-1.5 mg for each kilogram per hour) through an infusion during hemodialysis has been used, as mentioned in a report from 1996 by Jobard.

Upon completion of hemodialysis:

• Check Timing: After hemodialysis, figure out when the person last had fomepizole.
• If Within 1 Hour: If the last dose was taken less than 1 hour ago, don't give another dose at the end of hemodialysis.
• If 1-3 Hours: If the last dose was taken between 1 and 3 hours ago, give half of the next scheduled dose at the end of hemodialysis.
• If More Than 3 Hours: If the last dose was taken more than 3 hours ago, give the full next scheduled dose at the end of hemodialysis.

Maintenance dose when off hemodialysis:

• Maintenance Dose: If the person is not undergoing hemodialysis, give fomepizole every 12 hours.
• Start Timing: Begin this 12-hour cycle from the time when the last dose was given.

Dose in Liver disease:

• Liver Processing: Fomepizole is broken down by the liver.
• No Specific Changes: There aren't specific changes in the dosage for people with liver problems.

Common Side Effects of Fomepizole (Antizol):

• Central nervous system:
  • Headache
• Gastrointestinal:
  • Nausea

Less Common Side Effects of Fomepizole (Antizol):

• Cardiovascular:
  • Bradycardia
  • Facial Flushing
  • Hypotension
  • Phlebitis
  • Shock
  • Tachycardia
• Central Nervous System:
  • Dizziness
  • Drowsiness
  • Metallic Taste
  • Agitation
  • Altered Sense Of Smell
  • Anxiety
  • Seizure
  • Speech Disturbance
  • Vertigo
• Dermatologic:
  • Skin Rash
• Gastrointestinal:
  • Unpleasant Taste
  • 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

Contraindication to Fomepizole (Antizol):

Allergy Warning: Don't use fomepizole if you are allergic to it, other medications like it (pyrazoles), or any part of the medicine.

Warnings and precautions

Hepatic impairment

• Be careful using this medicine if you have liver problems because it gets processed in the liver.

Renal impairment

• If you have kidney issues, be cautious when using this medicine because it and its byproducts are removed through urine.
• If there's severe kidney failure, worsening imbalance in body acids, or high levels of harmful substances in the body, think about using hemodialysis along with the medicine.

Monitoring parameters:

• Fomepizole Levels: Ideally, we would check how much fomepizole is in the blood, but usually, we can't do that.
• Use These Measures:
  • Substance Levels: Check levels of harmful substances in the blood or urine, like ethylene glycol or methanol.
  • Urinary Oxalate: For ethylene glycol, check the amount of oxalate in the urine.
  • Osmolality: Measure the concentration of substances in the blood or urine.
  • Organ Function: Keep an eye on how well the kidneys and liver are working.
  • Electrolytes: Check the balance of salts in the blood.
  • Blood Gases: Examine the gases in the blood.
  • Anion and Osmolar Gaps: Assess certain values in the blood.
  • Symptom Resolution: See if the person's signs and symptoms of ethylene glycol or methanol poisoning are getting better.

How to administer Fomepizole (Antizol)?

• Put all the doses into the body through a slow drip in a vein (intravenous infusion), and this should take about 30 minutes each time.

Mechanism of action of Fomepizole (Antizol):

• How It Works: Fomepizole blocks an enzyme called alcohol dehydrogenase. This enzyme usually turns harmful substances like ethanol, ethylene glycol, and methanol into toxic forms.
• For Ethylene Glycol: Ethylene glycol changes into glycoaldehyde, then to glycolate, glyoxylate, and oxalate. Glycolate and oxalate cause problems like metabolic acidosis and harm the kidneys.
• For Methanol: Methanol transforms into formaldehyde, then to formic acid. Formic acid leads to issues like metabolic acidosis and problems with vision.

Onset and Peak Effect:

• The medicine starts working in about 1.5-2 hours after taking it, and it reaches its strongest point during that time.

How It Gets into the Body:

• When taken by mouth, the body easily absorbs it.

Distribution:

• It spreads quickly throughout the body, with a volume similar to 0.6-1.02 liters for every kilogram of body weight.

Protein Binding:

• The medicine doesn't attach much to proteins in the body.

Metabolism:

• The liver changes it into 4-carboxypyrazole (about 80-85% of the dose), 4-hydroxymethylpyrazole, and their N-glucuronide conjugates.
• After several doses, the medicine starts making the liver process it faster.

How Long It Lasts:

• We're not sure exactly how long it stays in the body because it varies with the dose.

Leaving the Body:

• A small amount (1-3.5%) comes out unchanged in the urine, along with its byproducts.

International Brand Names of Fomepizole:

• Antizol
• FomepizoleAP-HP

Fomepizole Brand Names in Pakistan:

Not Available.