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

General

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

Patients should be closely monitored for anaphylaxis symptoms (such as dyspnea, wheezing, flushing, etc.) as serious, life-threatening hypersensitivity reaction (anaphylaxis) has been reported following fomepizole administration. If such a reaction occurs, fomepizole therapy should be discontinued immediately and adequate medical treatment should be initiated (see CONTRAINDICATIONS and ADVERSE REACTIONS).

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

Pregnancy

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, nursing should be discontinued when Antizol is administered to nursing women.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Fomepizole is metabolized by the liver and excreted by the kidneys. The functions of both organs are generally lower in elderly patients; therefore, care should be taken when selecting the dose of fomepizole for elderly patients.

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 Antizol (fomepizole) Injection 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.

Post-Market Adverse Reactions

Serious, life-threatening hypersensitivity reaction (anaphylaxis) has been reported following fomepizole administration (see CONTRAINDICATIONS).

Oral doses of Antizol (10-20 mg/kg) significantly reduced the rate of elimination of ethanol (by approximately 40%), via alcohol dehydrogenase inhibition, when 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.