ANTIZOL Solution for injection Ref.[27786] Active ingredients: Fomepizole

Treatment Guidelines

Treatment of ethylene glycol and methanol poisonings consist of blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as Antizol (fomepizole) Injection, and correction of metabolic abnormalities. In patients with high ethylene glycol (≥50 mg/dL or ≥8.1 mmol/L) or methanol concentrations (≥50 mg/dL or ≥15.6 mmol/L), significant metabolic acidosis, or renal failure, hemodialysis should be considered in addition to treatment with Antizol to remove ethylene glycol or methanol and the respective toxic metabolites of these alcohols.

Treatment with Antizol

Begin Antizol treatment immediately upon suspicion of ethylene glycol or methanol ingestion based on patient disclosure or history and/or anion gap metabolic acidosis, increased osmolar gap, visual disturbances, or oxalate crystals in the urine, OR a documented serum ethylene glycol greater than 3.2 mmol/L (20 mg/dL) or methanol concentration greater than 6.2 mmol/L (20 mg/dL).

In addition to specific antidote treatment with Antizol, patients intoxicated with ethylene glycol or methanol should be managed as appropriate for metabolic acidosis, acute renal failure (ethylene glycol), adult respiratory distress syndrome, visual disturbances (methanol) and hypocalcemia. At frequent intervals throughout the treatment, patients poisoned with ethylene glycol should be monitored for ethylene glycol concentrations in serum and urine, and the presence of urinary oxalate crystals. Similarly, serum methanol concentrations should be monitored in patients poisoned with methanol. Hepatic enzymes and white blood cell counts should be monitored during treatment, as transient increases in serum transaminase concentrations and eosinophilia have been noted with repeated Antizol dosing.

Dosing of Antizol

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 (3.2 mmol/L for ethylene glycol and 6.2 mmol/L for methanol), and the patient is asymptomatic with normal pH. All doses should be administered as a slow intravenous infusion over 30 minutes (see Preparation for Intravenous Administration, below).

Dosage with Hemodialysis

Hemodialysis should be considered in addition to Antizol 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 (8.1 mmol/L for ethylene glycol and 15.6 mmol/L for methanol). Patients should be dialyzed to correct metabolic abnormalities and to lower the ethylene glycol concentrations below 50 mg/dL (8.1 mmol/L for ethylene glycol and 15.6 mmol/L for methanol).

The following guidelines for administering Antizol during hemodialysis should be used:

Before dialysis: Administer next scheduled dose if >6 hours since the last dose.

During dialysis: Administer doses every 4 hours.

Post-dialysis: If time since last dose is <1 hour, then give the next scheduled dose 12 hours from the last dose administered, and then follow the normal dosing schedule (see Dosing of Antizol). If time since last dose is ≥1 hour but <3 hours, then immediately administer 50% of the next scheduled dose, and then follow the normal dosing schedule.

If time since last dose is ≥3 hours, then immediately administer 100% of the next scheduled dose, and then follow the normal dosing schedule.

Discontinuation of Antizol Treatment

Treatment with Antizol may be discontinued when ethylene glycol or methanol concentrations are undetectable or have been reduced below 20 mg/dL (3.2 mmol/L for ethylene glycol and 6.2 mmol/L for methanol), and the patient is asymptomatic with normal pH.

Preparation for Intravenous Administration

When preparing Antizol solution avoid ocular, dermal, or inhalation exposures. In case of eye or skin exposure, flush immediately with copious amounts of water. Seek medical attention if irritation persists. Prepare solution in well-ventilated area. If accidental inhalation occurs, move to fresh air.

Antizol solidifies at temperatures less than 25°C (77°F). If the Antizol solution has become solid in the vial, the solution should be liquefied by placing the vial under warm running water or by holding in the hand. Solidification does not affect the efficacy, safety, or stability of Antizol. Using sterile technique, the appropriate dose of Antizol should be drawn from the vial with a syringe and injected into at least 100 mL of sterile 0.9% sodium chloride injection or dextrose 5% injection. Mix well. The entire contents of the resulting solution should be infused over 30 minutes. Antizol, like all parenteral products, should be inspected visually for particulate matter prior to administration.

Nausea, dizziness, and vertigo were noted in healthy volunteers receiving 50 and 100 mg/kg doses of Antizol (fomepizole) Injection (at plasma concentrations of 290-520 mcmol/L, 23.8-42.7 mg/L). These doses are 3-6 times the recommended dose. This dose-dependent CNS effect was short-lived in most subjects however in one subject it lasted up to 30 hours. Antizol is dialyzable, and hemodialysis may be useful in treating cases of overdosage.