Fomepizole

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

It is not known whether fomepizole is excreted in human milk. Because many drugs are excreted in human milk, nursing should be discontinued when fomepizole is administered to nursing women.

Carcinogenesis

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

Mutagenesis

There was a positive Ames test result in the Escherichia coli tester strain WP2uvrA and the Salmonella typhimurium tester strain TA102 in the absence of metabolic activation using fomepizole concentrations of 100, 333, 1000, 3330, and 5000 μg/plate.

In addition, the mutagenicity of fomepizole was tested in the in vivo mouse micronucleus assay. In the 35 animals tested, dosed at 75, 150, and 300 mg/kg, the bone marrow showed that fomepizole did not induce a significant increase in the frequency of micronucleated polychromatic erythrocytes; thus, this test did not indicate bone marrow cytotoxicity. The mutagenicity of fomepizole is considered to be negative in this assay.

Impairment of fertility

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.

The most frequent adverse events reported as drug-related or unknown relationship to study drug in the 78 patients and 63 normal volunteers who received fomepizole were headache (14%), nausea (11%), and dizziness, increased drowsiness, and bad taste/metallic taste (6% each). All other adverse events in this population were reported in approximately 3% or fewer of those receiving Antizol and were as follows:

Body as a Whole: Abdominal pain, fever, pain during Antizol injection, inflammation at injection site, lumbalgia/backache, hangover.

Cardiovascular: Phlebosclerosis, phlebitis, hypotension.

Gastrointestinal: Vomiting, diarrhea, dyspepsia, heartburn, decreased appetite, transient increase in liver function tests.

Hemic/Lymphatic: Eosinophilia/hypereosinophilia, lymphangitis, anemia.

Central Nervous System (CNS): Lightheadedness, agitation, feeling drunk, facial flush, vertigo, nystagmus, anxiety, “felt strange”, decreased environmental awareness.

Respiratory: Hiccups, pharyngitis.

Skin/Appendages: Application site reaction, rash.

Special Senses: Abnormal smell, speech/visual disturbances, transient blurred vision, roar in ear.