Glucarpidase

What is Glucarpidase?

• Glucarpidase (Voraxaze) is a carboxypeptidase used to treat toxic levels of methotrexate (an anticancer drug) in the blood of patients with kidney problems.

Glutamate carboxypeptidase 1CG2

What are the uses of this medicine?

• This medicine is to reduce toxic plasma methotrexate concentration (greater than 1 micromole per liter) in adult and pediatric patients with delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered) due to impaired renal function.

How does this medicine work?

• Glucarpidase is a recombinant bacterial enzyme that hydrolyzes the carboxyl- terminal glutamate residue from folic acid and classical antifolates such as methotrexate.
• Glucarpidase converts methotrexate to its inactive metabolites 4-deoxy-4-amino-N10- methylpteroic acid (DAMPA) and glutamate.
• Voraxaze provides an alternate non-renal pathway for methotrexate elimination in patients with renal dysfunction during high-dose methotrexate treatment.

Who Should Not Use this medicine ?

Limitations of Use:

• Voraxaze is not recommended for use in patients who exhibit the expected clearance and expected plasma methotrexate concentration.
• Reducing plasma methotrexate concentration in these patients may result in subtherapeutic exposure to methotrexate.

What drug interactions can this medicine cause?

• Voraxaze can decrease leucovorin concentration, which may decrease the effect of leucovorin rescue unless leucovorin is dosed as recommended.
• Voraxaze may also reduce the concentrations other folate analogs.
• DAMPA (4-deoxy-4-amino-N10- methylpteroic acid), an inactive metabolite of methotrexate formed following Voraxaze administration, interferes with the measurement of methotrexate concentration using immunoassays. This interference results in an overestimation of the methotrexate concentration.

Is this medicine FDA approved?

• Initial U.S. Approval: 2012

How should this medicine be used?

Recommended dosage:

• The recommended dosage of Voraxaze is 50 Units per kilogram (kg) as a single intravenous injection administered over 5 minutes. Flush intravenous line before and after administration.

Concomitant Use with Leucovorin Rescue

• When administering Voraxaze concomitantly with leucovorin, administer leucovorin at least 2 hours before or 2 hours after the Voraxaze dose.
• For the first 48 hours after the dose of Voraxaze, administer the same leucovorin dose given prior to Voraxaze. Administer leucovorin at least 2 hours before or 2 hours after the dose of Voraxaze.
• Beyond 48 hours after the dose of Voraxaze, administer leucovorin based on the measured methotrexate concentration. Continue leucovorin until the methotrexate concentration has been maintained below the leucovorin treatment threshold for a minimum of 3 days.

Administration:

• Reconstitute the contents of the vial with 1 mL of 0.9% Sodium Chloride Injection, USP.
• Roll and tilt the vial gently to mix. Do not shake.
• Inspect the vial and discard Voraxaze if the solution is not clear, colorless, and free of particulate matter.
• Use reconstituted Voraxaze immediately or store under refrigeration at 36° to 46°F (2° to 8°C) for up to 4 hours if not used immediately. Voraxaze contains no preservative and is supplied as a single-dose vial. Discard any unused product.
• As a single intravenous injection administered over 5 minutes.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection: 1,000 Units as a lyophilized powder in a single-dose vial for reconstitution

This medicine is available in fallowing brand namesː

• Voraxaze

What side effects can this medication cause?

The most common side effects of this medicine include:

• paresthesia
• flushing
• nausea
• vomiting
• hypotension
• headache

What special precautions should I follow?

• Serious hypersensitivity reactions occurred.
• DAMPA (4-deoxy-4-amino-N10- methylpteroic acid), an inactive metabolite of methotrexate formed following Voraxaze administration, interferes with the measurement of methotrexate concentration using immunoassays. This interference results in an overestimation of the methotrexate concentration. Measure methotrexate concentrations within 48 hours following Voraxaze administration using a chromatographic method; immunoassays are unreliable for samples collected within 48 hours following Voraxaze administration.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• There are no available data on Voraxaze use in pregnant women or animal reproduction studies to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Can this medicine be used in children?

• The safety and effectiveness of Voraxaze have been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• GLUCARPIDASE

Inactive ingredients:

• LACTOSE MONOHYDRATE
• ZINC ACETATE
• TROMETHAMINE HYDROCHLORIDE

Who manufactures and distributes this medicine?

• Packager: BTG International Inc.

What should I know about storage and disposal of this medication?

• Store Voraxaze refrigerated at 36°F to 46°F (2°C to 8°C).
• Do not freeze.
• Do not use Voraxaze after the expiration date on the vial.

• Dailymed label info on Glucarpidase
• FDA Glucarpidase