Glucarpidase

Pronunciation: gloo-KAR-pi-dayz
Class: Antidote

Trade Names

Voraxaze
- Injection, lyophilized powder for solution 1,000 units

Pharmacology

Recombinant carboxypeptidase that converts methotrexate to its inactive metabolites 4-deoxy-4-amino-N 10 —methylpteroic acid (DAMPA) and glutamate, providing an alternate nonrenal pathway for methotrexate elimination during high-dose methotrexate treatment.

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Pharmacokinetics

Absorption

Mean C max is 3.3 mcg/mL and AUC is 23.3 mcg•h/mL.

Distribution

Vd is 3.6 L, suggesting distribution is restricted to plasma volume.

Elimination

Mean half-life is 5.6 h; systemic Cl is 7.5 mL/min.

Special Populations

Renal Function Impairment

Half-life was prolonged (8.2 h) in patients with CrCl less than 30 mL/min.

Hepatic Function Impairment

No studies have been conducted.

Indications and Usage

For the treatment of toxic methotrexate plasma concentrations (more than 1 mcmol/L) in patients with delayed methotrexate Cl due to impaired renal function.

Contraindications

None well documented.

Dosage and Administration

Methotrexate Toxicity
Adults and Children

IV 50 units/kg as a single dose.

Concomitant Therapy

Do not administer leucovorin within 2 h before or after a dose of glucarpidase. For the first 48 h after glucarpidase, administer the leucovorin at the same dose as given prior to glucarpidase. After 48 h, administer leucovorin based on the measured methotrexate concentration. Do not discontinue leucovorin based on a single methotrexate concentration below the leucovorin treatment threshold; continue leucovorin until the methotrexate concentration has been maintained below the leucovorin treatment threshold for a minimum of 3 days.

General Advice

  • Administer as an IV bolus over 5 min. Flush the IV line before and after administration.
  • Reconstitute the vial with 1 mL of sodium chloride 0.9% for injection. Roll and tilt the vial gently to mix. Do not shake.
  • Continue hydration and alkalinization of the urine as indicated.

Storage/Stability

Store vials between 36° and 46°F. Do not freeze. Use reconstituted solution immediately or store between 36° and 46°F for up to 4 h. Discard unused solution.

Drug Interactions

Leucovorin

Leucovorin is a substrate for glucarpidase. Do not administer leucovorin within 2 h before or after a dose of glucarpidase. No dosage adjustment is recommended for the continuing leucovorin regimen because the leucovorin dose is based on the patient's preglucarpidase methotrexate concentration.

Other substrate interference

Other potential exogenous substrates of glucarpidase may include reduced folates and folate antimetabolites.

Adverse Reactions

Cardiovascular

Hypotension (1%).

CNS

Paresthesias (2%); headache (1%).

GI

Nausea/vomiting (2%).

Hypersensitivity

Serious allergic reactions, including anaphylaxis.

Miscellaneous

Flushing, including feeling hot and burning sensation (2%).

Precautions

Monitor

Monitor methotrexate blood concentrations and renal status at appropriate times. Monitor methotrexate concentrations with chromatographic method only in the 48 h following glucarpidase administration. DAMPA interferes with measurements of methotrexate concentrations using immunoassays.


Pregnancy

Category C.

Lactation

Undetermined.

Hypersensitivity

Serious allergic reactions occurred in less than 1% of patients.

Immunogenicity

Antiglucarpidase antibodies may occur.

Overdosage

Symptoms

No data available.

Patient Information

  • Advise patients that the medication will be prepared and administered by a health care provider.
  • Inform patients that allergic reactions, including potentially serious reactions, may occur during treatment.
  • Advise patients to immediately report any signs and symptoms of infusion reactions, such as fever, chills, flushing, feeling hot, rash, hives, itching, throat tightness or breathing problems, tingling, numbness, or headache.
  • Inform patients of the importance of continued monitoring of methotrexate blood concentrations and renal status at the appropriate times after discharge from the hospital.

Copyright © 2009 Wolters Kluwer Health.

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