Glucarpidase
Generic Name: glucarpidase
Brand Names:
Voraxaze
11 DESCRIPTION Glucarpidase is a carboxypeptidase produced by recombinant DNA technology in genetically modified Escherichia coli. Glucarpidase is a 390-amino acid homodimer protein with a molecular weight of 83 kDa. Each potency Unit corresponds to the enzymatic cleavage of 1 µmol/L of methotrexate per minute at 37°C. VORAXAZE (glucarpidase) for injection, for intravenous use is supplied as a sterile, preservative-free, white lyophilized powder in single-dose vials.
Overview
11 DESCRIPTION Glucarpidase is a carboxypeptidase produced by recombinant DNA technology in genetically modified Escherichia coli. Glucarpidase is a 390-amino acid homodimer protein with a molecular weight of 83 kDa. Each potency Unit corresponds to the enzymatic cleavage of 1 µmol/L of methotrexate per minute at 37°C. VORAXAZE (glucarpidase) for injection, for intravenous use is supplied as a sterile, preservative-free, white lyophilized powder in single-dose vials.
Uses
1 INDICATIONS AND USAGE VORAXAZE is indicated to reduce toxic plasma methotrexate concentration (greater than 1 micromole per liter) in adult and pediatric patients with delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered) due to impaired renal function. Limitations of Use: VORAXAZE is not recommended for use in patients who exhibit the expected clearance and expected plasma methotrexate concentration. Reducing plasma methotrexate concentration in these patients may result in subtherapeutic exposure to methotrexate [see Clinical Studies ( 14 )] .
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of VORAXAZE is 50 Units per kilogram as a single intravenous injection over 5 minutes. ( 2.1 ). For the first 48 hours after the dose of VORAXAZE, administer the same leucovorin dose given prior to VORAXAZE. Administer leucovorin at least 2 hours before or 2 hours after the dose of VORAXAZE. ( 2.2 ) Beyond 48 hours after the dose of VORAXAZE, administer leucovorin based on the measured methotrexate concentration. Continue leucovorin until the methotrexate concentration has been maintained below the leucovorin treatment threshold for a minimum of 3 days. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of VORAXAZE is 50 Units per kilogram (kg) as a single intravenous injection administered over 5 minutes.
Side Effects
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Hypersensitivity Reactions [Warnings and Precautions ( 5.1 )]. The most common related adverse events (>1%) were paresthesia, flushing, nausea and/or vomiting, hypotension and headache. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact BTG at 877-377-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under controlled but widely varying conditions, adverse reaction rates observed in clinical trials of VORAXAZE cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.
Interactions
7 DRUG INTERACTIONS 7.1 Effects of VORAXAZE on Leucovorin VORAXAZE can decrease leucovorin concentration, which may decrease the effect of leucovorin rescue unless leucovorin is dosed as recommended [see Dosage and Administration ( 2.2 ), Clinical Pharmacology ( 12.3 )] . VORAXAZE may also reduce the concentrations other folate analogs or folate analog metabolic inhibitors. 7.2 Effect of VORAXAZE on Measurement of Methotrexate Concentration DAMPA (4-deoxy-4-amino-N10- methylpteroic acid), an inactive metabolite of methotrexate formed following VORAXAZE administration, interferes with the measurement of methotrexate concentration using immunoassays. This interference results in an overestimation of the methotrexate concentration.
Warnings
5 WARNINGS AND PRECAUTIONS Serious Hypersensitivity Reactions: Serious hypersensitivity reactions occurred. ( 5.1 ) Monitoring Methotrexate Concentration: Measure methotrexate concentrations within 48 hours following VORAXAZE administration using a chromatographic method; immunoassays are unreliable for samples collected within 48 hours following VORAXAZE administration. ( 5.2 ) 5.1 Serious Hypersensitivity Reactions Serious hypersensitivity reactions occurred in less than 1% of patients [ see Adverse Reactions ( 6.1 ) ]. 4 CONTRAINDICATIONS None. None.
Pregnancy
8.1 Pregnancy Risk Summary There are no available data on VORAXAZE 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. VORAXAZE is administered in combination with methotrexate, which can cause embryo-fetal harm. Refer to methotrexate prescribing information for additional information. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Storage
16 HOW SUPPLIED/STORAGE AND HANDLING VORAXAZE (glucarpidase) for injection is supplied as a sterile, preservative-free white lyophilized powder in an individually packaged glass single-dose vial closed with a bromo butyl elastomeric stopper and blue flip-off seal. 1,000 Units of glucarpidase per vial (1 vial per carton) NDC 50633-210-11 Store VORAXAZE refrigerated at 36°F to 46°F (2°C to 8°C).
Frequently Asked Questions
What is Glucarpidase used for?▼
1 INDICATIONS AND USAGE VORAXAZE is indicated to reduce toxic plasma methotrexate concentration (greater than 1 micromole per liter) in adult and pediatric patients with delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered) due to impaired renal function. Limitations of Use: VORAXAZE is not recommended for use in patients who exhibit the expected clearance and expected plasma methotrexate concentration. Reducing plasma methotrexate concentration in these patients may result in subtherapeutic exposure to methotrexate [see Clinical Studies ( 14 )] .
What are the side effects of Glucarpidase?▼
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Hypersensitivity Reactions [Warnings and Precautions ( 5.1 )]. The most common related adverse events (>1%) were paresthesia, flushing, nausea and/or vomiting, hypotension and headache. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact BTG at 877-377-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under controlled but widely varying conditions, adverse reaction rates observed in clinical trials of VORAXAZE cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.
Can I take Glucarpidase during pregnancy?▼
8.1 Pregnancy Risk Summary There are no available data on VORAXAZE 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. VORAXAZE is administered in combination with methotrexate, which can cause embryo-fetal harm. Refer to methotrexate prescribing information for additional information. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
What are the important warnings for Glucarpidase?▼
5 WARNINGS AND PRECAUTIONS Serious Hypersensitivity Reactions: Serious hypersensitivity reactions occurred. ( 5.1 ) Monitoring Methotrexate Concentration: Measure methotrexate concentrations within 48 hours following VORAXAZE administration using a chromatographic method; immunoassays are unreliable for samples collected within 48 hours following VORAXAZE administration. ( 5.2 ) 5.1 Serious Hypersensitivity Reactions Serious hypersensitivity reactions occurred in less than 1% of patients [ see Adverse Reactions ( 6.1 ) ]. 4 CONTRAINDICATIONS None. None.
Related Medications
Buprenorphine Base
buprenorphine base
Dosage form: POWDER. Active ingredients: BUPRENORPHINE (1 kg/kg). Category: BULK INGREDIENT.
Children Acetaminophen Cherry
children acetaminophen cherry
Uses temporarily: reduces fever relieves minor aches and pains due to: the common cold flu headache sore throat toothache
Paliperidone Palmitate (sterile)
paliperidone palmitate (sterile)
Dosage form: SOLUTION. Active ingredients: PALIPERIDONE PALMITATE (1 mg/mg). Category: BULK INGREDIENT.
Medical Disclaimer
This drug information is for educational purposes only and should not replace professional medical advice. Drug information is sourced from the FDA National Drug Code Directory and Structured Product Labeling. Always consult with a healthcare provider before starting, stopping, or changing any medication.