Dosing & Uses
Dosage Forms & Strengths
injection, as lyophilized powder for reconstitution
- 1,000 units/vial
Methotrexate Toxicity
Indicated for treatment of toxic plasma methotrexate concentrations (>1 micromole/L) in patients with delayed methotrexate clearance due to impaired renal function
50 units/kg as a single IV injection over 5 minutes
Renal & Hepatic Impairment
Renal impairment: No dose adjustment is recommended
Hepatic impairment: No specific studies have been conducted
Dosage Forms & Strengths
injection, as lyophilized powder for reconstitution
- 1,000 units/vial
Methotrexate Toxicity
Indicated for treatment of toxic plasma methotrexate concentrations (>1 micromole/L) in patients with delaye methotrexate clearance due to impaired renal function
50 units/kg as a single IV injection over 5 minutes
Clinical trials in children
- Effectiveness in pediatric patients was established in 22 patients in the efficacy dataset; 12 were pediatric patients with ages ranging from 5-16 years
- The pooled clinical safety database included data for 147 patients from 1 month up to 17 years; no overall differences in safety were observed between pediatrics and adult patients
Renal & Hepatic Impairment
Renal impairment: No dose adjustment is recommended
Hepatic impairment: No specific studies have been conducted
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (8)
- folic acid
glucarpidase will decrease the level or effect of folic acid by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)
- L-methylfolate
glucarpidase will decrease the level or effect of L-methylfolate by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)
- leucovorin
glucarpidase will decrease the level or effect of leucovorin by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)
- pemetrexed
glucarpidase will decrease the level or effect of pemetrexed by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)
- pentamidine
glucarpidase will decrease the level or effect of pentamidine by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)
- pralatrexate
glucarpidase will decrease the level or effect of pralatrexate by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)
- sulfamethoxazole
glucarpidase will decrease the level or effect of sulfamethoxazole by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)
- trimethoprim
glucarpidase will decrease the level or effect of trimethoprim by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)
Minor (0)
Adverse Effects
1-10%
Paresthesias (2%)
Flushing (2%)
Nausea/vomiting (2%)
Headache (1%)
Hypotension (1%)
<1%
Blurred vision
Diarrhea
Hypersensitivity
Hypertension
Rash
Throat irritation/throat tightness
Tremor
Frequency Not Defined
Antibody formation
Postmarketing Reports
Serious hypersensitivity reactions
Warnings
Contraindications
None
Cautions
Serious allergic reactions (occurred in <1% of patients)
Leucovorin is a substrate for glucarpidase; other potential substrates of glucarpidase include reduced folates and folate antimetabolites (eg, folic acid, L-methylfolate, pemetrexed, pralatrexate, trimethoprim, pentamidine)
Immunogenicity: 17% (n=16) of patients developed anti-glucarpidase antibodies; 12 of the 16 patients had received 1 dose and the other 4 patients had received 2 doses
Hypersensitivity reactions reported
When measuring methotrexate concentration following a glucarpidase dose, a chromatographic method is preferred over an immunoassay
Monitoring methotrexate serum concentrations
- Methotrexate concentrations within 48 hours following administration of glucarpidase can only be reliably measured by a chromatographic method
- DAMPA (4-deoxy-4-amino-N10-methylpteroic acid) is an inactive metabolite of methotrexate resulting from treatment with glucarpidase that interferes with the measurement of methotrexate concentration using immunoassays (ie, immunoassays overestimates the methotrexate concentration)
- Due to the long half-life of DAMPA (~9 hours), measurement of methotrexate using immunoassays is unreliable for samples collected within 48 hours following glucarpidase administration
Continuation and timing of leucovorin rescue
- Leucovorin is a substrate for glucarpidase
- Do not administer leucovorin within 2 hr before or after glucarpidase
- No dose adjustment is recommended for the continuing leucovorin regimen because the leucovorin dose is based on the patient’s pre-glucarpidase methotrexate concentration
- For the first 48 hours after glucarpidase, administer the same leucovorin dose as given prior to glucarpidase
- Beyond 48 hours after glucarpidase, administer leucovorin based on the measured methotrexate concentration
- Do not discontinue therapy with leucovorin based on the determination of a single methotrexate concentration below the leucovorin treatment threshold
- Therapy with leucovorin should be continued until the methotrexate concentration has been maintained below the leucovorin treatment threshold for a minimum of 3 days
- Continue hydration and alkalinization of the urine as indicated
Pregnancy & Lactation
Pregnancy
There are no available data on 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
Therapy is administered in combination with methotrexate, which can cause embryo-fetal harm; refer to methotrexate prescribing information for additional information
Lactation
There are no data on presence of glucarpidase in human milk or effects on breastfed infant or on milk production
Therapy administered in combination with methotrexate; refer to methotrexate prescribing information for additional information
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Recombinant bacterial enzyme that hydrolyzes the carboxyl-terminal glutamate residue from folic acid and classical antifolates such as methotrexate
Converts methotrexate to its inactive metabolites 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) and glutamate
Provides an alternate nonrenal pathway for methotrexate elimination in patients with renal dysfunction during high-dose methotrexate treatment
Absorption
Peak Plasma Concentration: 3.3 mcg/mL
AUC: 23.3 mcg•hr/mL
Distribution
Vd: 3.6 L
Elimination
Half-life (based on serum activity levels): 5.6 hr; 8.2 hr (renal impairment)
Half-life (based on serum total concentrations): 9 hr
Systemic clearance: 7.5 mL/min
Administration
IV Preparation
Reconstitute the lyophilized powder in the vial with 1 mL of sterile saline for injection, USP
Do not shake
Roll and tilt the vial gently to mix
Inspect the vial and discard if the solution is not clear, colorless, and free of particulate matter
Use reconstituted solution immediately or store under refrigeration at 36-46°F (2-8°C) for up to 4 hr if not used immediately
Contains no preservative and is supplied as a single-use vial
Discard any unused product
IV Administration
Administer IV as a bolus over 5 minutes
Flush IV line before and after administration
Storage
Unopened vials are stable until date indicated on package when stored at refrigerated 36-46°F (2-8°C)
Reconstituted solution: May store under refrigeration at 36-46°F (2-8°C) for up to 4 hr if not used immediately
Do not freeze
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Voraxaze intravenous - | 1,000 unit vial |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
glucarpidase intravenous
NO MONOGRAPH AVAILABLE AT THIS TIME
USES: Consult your pharmacist.
HOW TO USE: Consult your pharmacist.
SIDE EFFECTS: Consult your pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Consult your pharmacist.
DRUG INTERACTIONS: Consult your pharmacist.Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: No monograph available at this time.
MISSED DOSE: Consult your pharmacist.
STORAGE: Consult your pharmacist.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.
Information last revised July 2016. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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