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Antizol (Fomepizole) - Warnings and Precautions

 
 



BOX WARNING

DOSING DURING HEMODIALYSIS

Dose every 4 hours

 

PRECAUTIONS

General

Antizol should not be given undiluted or by bolus injection. Venous irritation and phlebosclerosis were noted in two of six normal volunteers given bolus injections (over 5 minutes) of Antizol at a concentration of 25 mg/mL.

Minor allergic reactions (mild rash, eosinophilia) have been reported in a few patients receiving Antizol (see ADVERSE REACTIONS). Therefore, patients should be monitored for signs of allergic reactions.

Laboratory Tests

In addition to specific antidote treatment with Antizol, patients intoxicated with ethylene glycol or methanol must be managed for metabolic acidosis, acute renal failure (ethylene glycol), adult respiratory distress syndrome, visual disturbances (methanol), and hypocalcemia. Fluid therapy and sodium bicarbonate administration are potential supportive therapies. In addition, potassium and calcium supplementation and oxygen administration are usually necessary. Hemodialysis is necessary in the anuric patient, or in patients with severe metabolic acidosis or azotemia (see DOSAGE AND ADMINISTRATION). Treatment success should be assessed by frequent measurements of blood gases, pH, electrolytes, BUN, creatinine, and urinalysis, in addition to other laboratory tests as indicated by individual patient conditions. 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. Electrocardiography should be performed because acidosis and electrolyte imbalances can affect the cardiovascular system. In the comatose patient, electroencephalography may also be required. In addition, 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.

Drug Interactions

Oral doses of Antizol (10-20 mg/kg), via alcohol dehydrogenase inhibition, significantly reduced the rate of elimination of ethanol (by approximately 40%) given to healthy volunteers in moderate doses. Similarly, ethanol decreased the rate of elimination of Antizol (by approximately 50%) by the same mechanism.

Reciprocal interactions may occur with concomitant use of Antizol and drugs that increase or inhibit the cytochrome P450 system (e.g., phenytoin, carbamazepine, cimetidine, ketoconazole), though this has not been studied.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

There have been no long-term studies performed in animals to evaluate carcinogenic potential.

There was a positive Ames test result in the Escherichia coli tester strain WP2 uvr A and the Salmonella typhimurium tester strain TA102 in the absence of metabolic activation. There was no evidence of a clastogenic effect in the in vivo mouse micronucleus assay.

In rats, fomepizole (110 mg/kg) administered orally for 40 to 42 days resulted in decreased testicular mass (approximately 8% reduction). This dose is approximately 0.6 times the human maximum daily exposure based on surface area (mg/m2). This reduction was similar for rats treated with either ethanol or fomepizole alone. When fomepizole was given in combination with ethanol, the decrease in testicular mass was significantly greater (approximately 30% reduction) compared to those rats treated exclusively with fomepizole or ethanol.

Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with fomepizole. It is also not known whether Antizol can cause fetal harm when administered to pregnant women or can affect reproduction capacity. Antizol should be given to pregnant women only if clearly needed.

Nursing Mothers

It is not known whether fomepizole is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Antizol is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Safety and effectiveness in geriatric patients have not been established.

Page last updated: 2007-02-08

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