glucarpidase (Rx)

Brand and Other Names:Voraxaze
  • Print

Dosing & Uses

AdultPediatric

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

Next:

Interactions

Interaction Checker

and glucarpidase

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            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)

                  Previous
                  Next:

                  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

                  Previous
                  Next:

                  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
                  Previous
                  Next:

                  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.

                  Previous
                  Next:

                  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

                  Previous
                  Next:

                  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

                  Previous
                  Next:

                  Images

                  BRAND FORM. UNIT PRICE PILL IMAGE
                  Voraxaze intravenous
                  -
                  1,000 unit vial

                  Copyright © 2010 First DataBank, Inc.

                  Previous
                  Next:

                  Patient Handout

                  Patient Education
                  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) 2021 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.

                  Previous
                  Next:

                  Formulary

                  FormularyPatient Discounts

                  Adding plans allows you to compare formulary status to other drugs in the same class.

                  To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

                  Adding plans allows you to:

                  • View the formulary and any restrictions for each plan.
                  • Manage and view all your plans together – even plans in different states.
                  • Compare formulary status to other drugs in the same class.
                  • Access your plan list on any device – mobile or desktop.

                  The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                  Tier Description
                  1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                  2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                  3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                  4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  NC NOT COVERED – Drugs that are not covered by the plan.
                  Code Definition
                  PA Prior Authorization
                  Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                  QL Quantity Limits
                  Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                  ST Step Therapy
                  Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                  OR Other Restrictions
                  Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
                  Additional Offers
                  Email to Patient

                  From:

                  To:

                  The recipient will receive more details and instructions to access this offer.

                  By clicking send, you acknowledge that you have permission to email the recipient with this information.

                  Email Forms to Patient

                  From:

                  To:

                  The recipient will receive more details and instructions to access this offer.

                  By clicking send, you acknowledge that you have permission to email the recipient with this information.

                  Previous
                  Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.