Glucarpidase

Glucarpidase is used for the treatment of toxic plasma methotrexate concentrations (greater than 1 micromole/L) in patients with delayed methotrexate clearance due to impaired renal function.

Glucarpidase is available under the following different brand names: Voraxaze.

Dosages of Glucarpidase:

Dosage Forms and Strengths

Injection, as Lyophilized Powder for Reconstitution

• 1,000 units/vial

Dosage Considerations – Should be Given as Follows:

Methotrexate Toxicity

• Indicated for the treatment of toxic plasma methotrexate concentrations (greater than 1 micromole/L) in patients with delayed methotrexate clearance due to impaired renal function
• 50 units/kg as a single intravenous (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 and Hepatic Impairment

• Renal impairment: No dose adjustment is recommended
• Hepatic impairment: No specific studies have been conducted

Common side effects of benzhydrocodone/acetaminophen include:

• Numbness and tingling
• Flushing
• Nausea
• Vomiting
• Headache
• Low blood pressure (hypotension)

Less common side effects of glucarpidase include:

• Blurred vision
• Diarrhea
• Hypersensitivity
• High blood pressure (hypertension)
• Rash
• Throat irritation/throat tightness
• Tremor

Other side effects of glucarpidase include:

• Antibody formation

Postmarketing side effects of glucarpidase reported include:

• Serious hypersensitivity reactions

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Glucarpidase has no listed severe interactions with other drugs.
• Glucarpidase has no listed serious interactions with other drugs.

Moderate interactions of glucarpidase include:

• folic acid
• L-methylfolate
• leucovorin
• pemetrexed
• pentamidine
• pralatrexate
• sulfamethoxazole
• trimethoprim

Glucarpidase has no listed mild interactions with other drugs.

Warnings

This medication contains glucarpidase. Do not take Voraxaze if you are allergic to glucarpidase or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• None

Effects of Drug Abuse

• No information is available

Short-Term Effects

• See "What Are Side Effects Associated with Using Glucarpidase?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Glucarpidase?"

Cautions

• Serious allergic reactions (occurred in less than 1% of patients)
• Leucovorin is a substrate for glucarpidase; other potential substrates of glucarpidase include reduced folates and folate antimetabolites (e.g., 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 (i.e., immunoassays overestimate the methotrexate concentration)
• Due to the long half-life of DAMPA (approximately 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 hours 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 before 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 and Lactation

There are no available data on the use of glucarpidase 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. Glucarpidase therapy is administered in combination with methotrexate, which can cause embryo-fetal harm; refer to methotrexate prescribing information for additional information. Consult your doctor if you are pregnant or plan to become pregnant.

There are no data on the presence of glucarpidase in human milk or its effects on breastfed infants or milk production. Glucarpidase therapy is administered in combination with methotrexate; refer to methotrexate prescribing information for additional information. Consult your doctor before breastfeeding.