fomepizole

Action and Spectrum

Mechanism of action 

fomepizole is a medication explicitly targeting the metabolism of toxic alcohols such as ethylene glycol and methanol. It does this by inhibiting the enzyme alcohol dehydrogenase (ADH), which is responsible for catalyzing the metabolism of these compounds. By inhibiting ADH, fomepizole blocks the formation of toxic intermediates, preventing their accumulation in the body and reducing the potential for harm. 

Spectrum 

The spectrum of fomepizole refers to the range of toxic alcohols that the medication is effective against. It is used explicitly for the treatment of ethylene glycol and methanol toxicity. It works by inhibiting the enzyme alcohol dehydrogenase (ADH), which is responsible for catalyzing the metabolism of these compounds. By inhibiting ADH, fomepizole blocks the formation of toxic intermediates, preventing their accumulation in the body and reducing the potential for harm. 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

Nausea 

headache 

1-10% 

Dizziness 

Venous irritation 

Backache 

Fever 

Metallic taste 

Drowsiness 

Increase in LFT 

Nystagmus 

Abdominal pain 

<1% 

Eosinophilia 

Rash 

Black Box Warning

Contraindication / Caution

Contraindications 

The most notable contraindication for fomepizole is a known hypersensitivity or allergy to the drug. People who have had an allergic reaction to fomepizole should not take the medication. 

Another contraindication for fomepizole is if the patient has consumed a significant amount of ethanol before starting treatment. The patient’s blood alcohol level must be known as fomepizole will not work if it is high and would potentially cause accumulation of toxic intermediates. 

Pregnancy and breastfeeding are also considered contraindications for fomepizole use. Fomepizole has been classified as a pregnancy category C drug. It may harm a developing fetus and should only be used during pregnancy if the benefits outweigh the potential risks. 

Patients with a history of significant hepatic or renal dysfunction are also contraindicated. 

Caution 

Fomepizole is a safe and effective treatment for methanol and ethylene glycol poisoning. Still, as with any medication, it does have some potential side effects and precautions that should be considered. 

Some potential side effects of fomepizole include: 

• Nausea 
• Vomiting 
• Headache 
• Dizziness 
• Injection site reactions (if fomepizole is given by injection) 

Fomepizole can also interact with other medications, such as metronidazole or disulfiram, which can also be metabolized by alcohol dehydrogenase enzyme, so it’s essential to inform your healthcare provider about all medications you are currently taking. 

Fomepizole can also be dangerous when given to people who have not been diagnosed with methanol or ethylene glycol poisoning, as it can cause an accumulation of these toxic alcohols in the body. Therefore, it should only be used under the care of a healthcare provider and in the context of a confirmed or suspected poisoning. 

Pregnancy / Lactation

Pregnancy consideration: It may harm a developing fetus and should only be used during pregnancy if the benefits outweigh the potential risks. 

Pregnancy category: C 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology 

fomepizole is a competitive inhibitor of the enzyme alcohol dehydrogenase (ADH), which is responsible for the metabolism of methanol and ethylene glycol. When these toxic alcohols are ingested, they are metabolized by ADH into formaldehyde and formic acid. These toxic byproducts can cause damage to the nervous system, the retina, and other organs. By inhibiting ADH, fomepizole blocks the metabolism of methanol and ethylene glycol, preventing the formation of these toxic byproducts and reducing the severity of poisoning. 

Pharmacodynamics 

• Inhibition of ADH 
• Decreased formation of toxic byproducts 
• Reduced severity of poisoning symptoms 
• Preservation of NAD+ (a cofactor needed for the metabolism of glucose and fatty acids) 
• Reduced oxidative stress 

It’s important to note that fomepizole does not act as an antagonist or a substitute for methanol or ethylene glycol, it is a specific inhibitor of the ADH enzyme, so it doesn’t have any direct effects on the toxic alcohols themselves. It’s also important to note that fomepizole can only effectively treat methanol and ethylene glycol poisoning and no other toxic alcohols, such as isopropanol or propylene glycol, as those have different metabolism pathways. 

Pharmacokinetics 

Absorption 

The onset of action of fomepizole is around 1.5-2 hours 

Distribution 

The volume of distribution of fomepizole is also around 0.6-1.02 L/kg. It means that fomepizole distributes readily into most body tissues, but its binding to plasma protein is relatively low. 

Metabolism 

The liver metabolizes to a small extent, and the remaining unmetabolized drug is excreted through urine. 

Elimination/excretion 

It is excreted primarily in urine, with about 75-90% of the drug being eliminated in this way. The elimination half-life of fomepizole is around 4 hours. But it can be prolonged in patients with renal impairment. 

Adminstartion

Administration 

Intravenous preparation 

Before administration, fomepizole should be diluted in at least 100 mL of normal saline (NS) or dextrose 5% in water (D5W). This helps to prevent irritation and damage to the veins, as well as to ensure that the medication is distributed evenly throughout the solution. The recommended dosage of fomepizole is 15 mg/kg every 12 hours for adults and 15 mg/kg every 8 hours for children. 

Storage 

fomepizole injection concentrate can solidify if it’s kept at temperatures below 25°C. This is due to the properties of the active ingredient in the medication. 

The Diluted solution is stable for at least 24 hr when stored at 20-25°C or refrigerated at 2-8°C. The stability of the diluted solution may be affected by temperature, and it should be stored at a temperature between 2-8°C (refrigeration) to ensure optimal stability. It is also recommended to check for any visible particulate or cloudiness in the solution before administering it. It’s important to note that the diluted solution should be used within 24 hours of preparation, as the potency and stability of the medication may decrease over time. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: fomepizole 

Pronounced: [ foe-MEP-i-zole ] 

Why do we use fomepizole? 

The primary use of fomepizole is to treat methanol and ethylene glycol poisoning. It works by inhibiting the enzyme alcohol dehydrogenase (ADH), which is responsible for breaking down methanol and ethylene glycol into toxic byproducts that can cause damage to the nervous system and other organs.