Voraxaze

Drug overview for VORAXAZE (glucarpidase):

Generic name: GLUCARPIDASE
Drug class: Methotrexate Rescue Agents - Carboxypeptidase G2 Type
Therapeutic class: Antineoplastics

Glucarpidase (also known as carboxypeptidase G2 (CPDG2)) is a recombinant bacterial enzyme that is used as an antidote for methotrexate toxicity.

No enhanced Uses information available for this drug.

DRUG IMAGES

VORAXAZE 1,000 UNIT VIAL

The following indications for VORAXAZE (glucarpidase) have been approved by the FDA:

Indications:
Methotrexate toxicity

Professional Synonyms:
MTX toxicity

The following drug interaction information is available for VORAXAZE (glucarpidase):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 0 severe interactions.

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Levoleucovorin; Leucovorin/Glucarpidase 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)	CALCIUM FOLINATE, KHAPZORY, LEUCOVORIN CALCIUM, LEVOLEUCOVORIN CALCIUM

Drug Interaction

Drug Names

Levoleucovorin; Leucovorin/Glucarpidase

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)

CALCIUM FOLINATE, KHAPZORY, LEUCOVORIN CALCIUM, LEVOLEUCOVORIN CALCIUM

Moderate List
No disease contraindications

The following adverse reaction information is available for VORAXAZE (glucarpidase):

Overview
Severe
Less Severe

Adverse reaction overview.

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

There are 2 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Anaphylaxis Throat constriction

There are 11 less severe adverse reactions.

More Frequent	Less Frequent
None.	Flushing Headache disorder Hypotension Nausea Paresthesia Vomiting

Rare/Very Rare
Blurred vision Diarrhea Hypertension Skin rash Tremor

The following precautions are available for VORAXAZE (glucarpidase):

Pediatric
Pregnant
Lactation
Geriatric

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.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

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.