Fomepizole (fomepizole)

Fomepizole therapy should be initiated immediately upon suspected 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 if the serum ethylene glycol or methanol concentration exceeds 20 mg/dL.

For the treatment of ethylene glycol or methanol toxicity, the recommended initial dose of fomepizole in adults is 15 mg/kg, followed by doses of 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours thereafter until serum ethylene glycol or methanol concentrations have decreased to less than 20 mg/dL and the patient is asymptomatic and has a normal arterial blood pH value. All fomepizole doses should be administered by slow IV infusion over 30 minutes. (See Dosage and Administration: Administration.)

While comparative efficacy of various dosages of fomepizole in the treatment of ethylene glycol or methanol intoxication have not been established in children, dosages used in a limited number of case reports involving infants and children 8 months to 13 years of age were the same as those recommended for adults.

In addition to specific antidote treatment with fomepizole, management of ethylene glycol or methanol intoxication may require treatment of metabolic acidosis, acute renal failure, adult respiratory distress syndrome, visual disturbances (methanol intoxication), and hypocalcemia. Hemodialysis should be considered in addition to fomepizole therapy in patients with acute renal failure, substantial or deteriorating metabolic acidosis, or a serum ethylene glycol or methanol concentration exceeding 50 mg/dL. Since fomepizole is dialyzable, the frequency of dosing should be increased to every 4 hours in patients undergoing hemodialysis. Information regarding the scheduling of fomepizole doses in relation to the initiation and termination of hemodialysis is shown in the table.

Table 1. Fomepizole Dosing in Patients Requiring Hemodialysis

Dose at the Beginning of Hemodialysis If <6 hours since last fomepizole If >=6 hours since last fomepizole dose dose Do not administer dose Administer next scheduled dose Dose during Hemodialysis Dose every 4 hours Dose at the Time Hemodialysis Is Completed Time between last dose and the end of hemodialysis <1 hour Do not administer dose at the end of hemodialysis 1-3 hours Administer half of next scheduled dose >3 hours Administer next scheduled dose Maintenance Dosing off Hemodialysis Give next scheduled dose 12 hours from last dose administered

The manufacturer states that the pharmacokinetics of fomepizole have not been evaluated adequately in patients with renal or hepatic impairment, nor have they been studied sufficiently in geriatric patients to determine whether the pharmacokinetics differ from those in younger individuals. Because fomepizole is extensively eliminated by the kidneys, the risk of toxic reactions to the drug may be greater in patients with renal dysfunction. In addition, since geriatric individuals are more likely to have decreased renal function, care should be taken in dosage selection for such patients.

Fomepizole is administered by IV infusion.

Commercially available fomepizole for injection concentrate must be diluted prior to IV administration; the drug must not be given undiluted or by rapid IV injection. For IV infusion, the manufacturer recommends diluting the drug in at least 100 mL of 0.9% sodium chloride injection or 5% dextrose injection. The diluted solution of fomepizole should be infused over a period of 30 minutes; more rapid infusion of a 25-mg/mL solution of fomepizole has resulted in vein irritation and phlebosclerosis.

Solutions of fomepizole prepared in 5% dextrose injection or 0.9% sodium chloride injection are stable for at least 24 hours when stored at a controlled room temperature of 20-25degreesC or when refrigerated at 2-8degreesC. Because of the risk of microbial contamination in products without preservatives, the manufacturer recommends that the solutions be used within 24 hours after preparation.

Fomepizole for injection concentrate solidifies at temperatures less than 25degreesC. If the fomepizole solution has solidified in the vial, the solution should be liquefied by passing the vial under warm water or by holding the vial in the hand. Solidification does not affect the efficacy, safety, or stability of fomepizole.

As with all parenteral products, diluted solutions of fomepizole should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Fomepizole solutions should be discarded if they are hazy, discolored, or contain a precipitate or if they exhibit leakage.

Fomepizole is contraindicated in patients with a documented history of serious hypersensitivity to the drug or other pyrazoles. Patients receiving fomepizole should be monitored for manifestations of an allergic reaction; if a severe hypersensitivity reaction occurs, fomepizole should be discontinued immediately.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Fomepizole/Ethyl Alcohol

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Fomepizole inhibits the activity of alcohol dehydrogenase, an enzyme needed to help eliminate alcohol. Additionally, alcohol can decrease the rate of elimination of fomepizole by the same mechanism.

CLINICAL EFFECTS: This interaction may cause an increase in the adverse events associated with both increased alcohol levels as well as increased fomepizole levels. Increase fomepizole levels may result in headache, nausea, dizziness, and drowsiness. Increased alcohol levels may cause sedation, decreased motor skills, and loss of consciousness.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should be advised of this potential hazard and should be encouraged not to ingest alcohol containing products during the course of therapy with fomepizole. Patients should be informed about unsuspected sources of alcohol, such as medications. Alcohol is used to improve docetaxel and paclitaxel solubility. - The quantity of alcohol in paclitaxel injection formulations (0.385-0.396 grams/mL) is similar across manufacturers. A paclitaxel 200 mg dose contains approximately 13 grams of alcohol. - The quantity of alcohol in docetaxel formulations varies approximately 3-fold depending upon the manufacturer. FDA data on alcohol content (2): Product Manufacturer Alcohol/200 mg dose Docetaxel Inj. Pfizer 6.4 grams Docetaxel Inj. Sandoz 5.5 grams Docetaxel Inj. Accord 4.0 grams Taxotere-one vial Sanofi 4.0 grams formulation Docetaxel Inj. Hospira 3.7 grams Docefrez Sun Pharma 2.9 grams Taxotere-two vial Sanofi 2.0 grams formulation

DISCUSSION: Fomepizole (10-20 mg/kg) significantly reduced the rate of elimination of ethanol by approximately 40%, given in moderate doses to healthy volunteers. This occurred because of inhibition of alcohol dehydrogenase. Similarly, ethanol decreased the rate of elimination of fomepizole by approximately 50%, by the same mechanism.(1)

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

• Disease of liver
• Kidney disease with reduction in glomerular filtration rate (GFr)

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

Rare or Very Rare

• Bradycardia
• Hypotension
• Injection site sequelae
• Nystagmus
• Phlebosclerosis
• Seizure disorder
• Skin rash
• Tachycardia

More Frequent

• Dizziness
• Headache disorder
• Nausea

Rare or Very Rare

• Abdominal pain with cramps
• Altered consciousness
• Anorexia
• Blurred vision
• Diarrhea
• Drowsy
• Dysgeusia
• Fever
• Heartburn
• Hiccups
• Parosmia
• Pharyngitis
• Slurred speech
• Vertigo
• Vomiting

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.