Voraxaze (glucarpidase)

Dosage of glucarpidase is expressed in terms of units; a unit of glucarpidase activity is defined as the quantity of enzyme needed to catalyze the hydrolysis of 0.454 mcg/mL (1 mcmol/L) of methotrexate per minute at 37degreesC.

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No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Glucarpidase/Levoleucovorin; Leucovorin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Glucarpidase hydrolyzes the carboxyl-terminal glutamate residue from folates such as leucovorin, rendering them inactive.(1)

CLINICAL EFFECTS: A leucovorin dose given near the time of glucarpidase administration may not be effective.

PREDISPOSING FACTORS: Leucovorin dose given within two hours of glucarpidase administration.

PATIENT MANAGEMENT: The combination of glucarpidase and leucovorin are used to treat toxic concentrations of methotrexate. Patients with potentially life threatening methotrexate serum levels or toxicity must receive both drugs. However, in addition to inactivating methotrexate, glucarpidase also inactivates leucovorin. To help decrease leucovorin inactivation, stagger leucovorin administration so it is not given within two hours of glucarpidase dose. Continue leucovorin treatment based upon pre-glucarpidase methotrexate blood levels.(1) Note that depending upon the laboratory assay used, glucarpidase administration may cause erroneous methotrexate measurements for 48 hours post dose.(1)

DISCUSSION: In a study of cancer patients treated with a high dose methotrexate and leucovorin rescue regimen, glucarpidase given two hours before leucovorin reduced the area-under-curve (AUC) of the active leucovorin metabolite, 5-methyltetrahydrofolate, by 92 per cent.(1)

The manufacturer states there are no known contraindications to the use of glucarpidase.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• No disease contraindications

Adverse effects reported in 1% or more of patients receiving glucarpidase include paresthesia, flushing, nausea and/or vomiting, hypotension, and headache.

Rare or Very Rare

• Anaphylaxis
• Throat constriction

Less Frequent

• Flushing
• Headache disorder
• Hypotension
• Nausea
• Paresthesia
• Vomiting

Rare or Very Rare

• Blurred vision
• Diarrhea
• Hypertension
• Skin rash
• Tremor

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Efficacy of glucarpidase as adjunctive therapy for the treatment of toxic plasma methotrexate concentrations (exceeding 0.454 mcg/mL (1 mcmol/L)) in pediatric patients with delayed methotrexate clearance due to renal impairment has been established in one study that included 12 patients 5-16 years of age. In this study, 3 of the 6 pediatric patients with pre-glucarpidase plasma methotrexate concentrations of 0.454-22.7 mcg/mL (1-50 mcmol/L) achieved rapid and sustained clinically important reductions (RSCIR) in plasma methotrexate concentrations, while none of the remaining 6 patients with pre-glucarpidase plasma methotrexate concentrations exceeding 22.7 mcg/mL (50 mcmol/L) achieved RSCIR.

In an analysis of pooled clinical safety data in 147 patients 1 month to 17 years of age, no overall difference in safety was observed between pediatric and adult patients.

Category C. (See Users Guide.)

It is not known whether glucarpidase is distributed into human milk. Caution is advised when glucarpidase is administered in nursing women.

In clinical studies, 15% of patients were 65 years of age or older and 4% were 75 years of age or older. No overall differences in safety or efficacy were observed between geriatric patients and younger adults.