pharmacopeia
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Mechanism of action

Sourced from openFDA

Glucarpidase is a recombinant bacterial enzyme that hydrolyzes the carboxyl- terminal glutamate residue from folic acid and classical antifolates such as methotrexate. Glucarpidase converts methotrexate to its inactive metabolites 4-deoxy-4-amino-N 10 - methylpteroic acid (DAMPA) and glutamate.

Indications

Sourced from openFDA
  • 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.

Contraindications

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  • None. None.contraindicated

Dosage & administration

Sourced from openFDA

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. Flush intravenous line before and after administration. 2.2 Concomitant Use with Leucovorin Rescue When administering VORAXAZE concomitantly with leucovorin, administer leucovorin at least 2 hours before or 2 hours after the VORAXAZE dose [see Drug Interactions ( 7.1 )] . For the first 48 hours after a dose of VORAXAZE: Administer the same leucovorin dosage given prior to the VORAXAZE dose. Beyond 48 hours after a dose of VORAXAZE : Determine the leucovorin dosage based on the measured methotrexate concentration. Do not discontinue leucovorin based on the determination of a single methotrexate concentration below the leucovorin rescue threshold. Continue leucovorin until the methotrexate concentration has been maintained below the leucovorin rescue threshold for a minimum of 3 days.

Warnings & precautions

Sourced from openFDA

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 ) ]. 5.2 Interference with Immunoassay Measurements of Methotrexate DAMPA (4-deoxy-4-amino-N 10 - 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. Based on the half-life of DAMPA (about 9 hours), VORAXAZE may interfere with the measurement of methotrexate concentration for up to 48 hours following a VORAXAZE dose [see Clinical Pharmacology ( 12.1 ) ]. When measuring methotrexate concentration following a VORAXAZE dose, a chromatographic method is preferred over an immunoassay.

Adverse reactions

Sourced from openFDA

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. The evaluation of adverse reactions in patients who received VORAXAZE was confounded, because patients had toxic plasma methotrexate concentration due to prolonged methotrexate clearance, which is associated with myelosuppression, mucositis, acute hepatitis, and renal dysfunction and failure. The safety of VORAXAZE is based on data from 290 patients who were enrolled in Study 1 or Study 2, two single-arm, open-label, multicenter studies conducted in patients who had markedly delayed methotrexate clearance due to impaired renal function.

Use in specific populations

Sourced from openFDA

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. 8.2 Lactation Risk Summary There are no data on the presence of glucarpidase in human milk or its effects on the breastfed infant or on milk production. VORAXAZE is administered in combination with methotrexate. Refer to methotrexate prescribing information for additional information. 8.4 Pediatric Use The safety and effectiveness of VORAXAZE have been established in pediatric patients. Use of VORAXAZE for this indication is supported by evidence from a single-arm, open-label study in adult and pediatric patients 5 years of age and older with additional safety data in pediatric patients 1 to 17 years of age as described below. Of the 22 patients in the efficacy dataset in Study 1, 12 were pediatric patients with ages ranging from 5 years to 16 years.

Pharmacokinetics

Sourced from openFDA
Metabolism
The pharmacokinetics of glucarpidase in the absence of methotrexate were studied in 8 healthy subjects following VORAXAZE 50 Units/kg administered as an intravenous injection over 5 minutes. Serum glucarpidase activity levels were measured by an enzymatic assay and serum total glucarpidase concentrations were measured by ELISA.

Approval history

Sourced from openFDA
  • Jan 17, 2012BLABLA125327Btg International Inc

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
349 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Off Label Use8625%
  2. 2Underdose6218%
  3. 3Laboratory Test Interference5716%
  4. 4Acute Kidney Injury3510%
  5. 5Blood Creatinine Increased339.5%
  6. 6Drug Effect Incomplete339.5%
  7. 7Toxicity To Various Agents339.5%
  8. 8Rebound Effect318.9%
  9. 9Drug Ineffective298.3%
  10. 10Death257.2%
  11. 11Renal Failure257.2%
  12. 12Mucosal Inflammation226.3%
  13. 13Drug Level Increased164.6%
  14. 14Alanine Aminotransferase Increased154.3%
  15. 15False Positive Investigation Result154.3%

Literature

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Recent PubMed references pinned to Glucarpidase as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 35 ClinicalTrials.gov registrations naming Glucarpidase as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Glucarpidase work?
Glucarpidase is a recombinant bacterial enzyme that hydrolyzes the carboxyl- terminal glutamate residue from folic acid and classical antifolates such as methotrexate. Glucarpidase converts methotrexate to its inactive metabolites 4-deoxy-4-amino-N 10 - methylpteroic acid (DAMPA) and glutamate.
What is Glucarpidase used for?
According to FDA labeling, Glucarpidase carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Glucarpidase?
Glucarpidase is classified as Detoxifying agents for antineoplastic treatment, Carboxypeptidase, Enzyme Interactions.
What are the brand names for Glucarpidase?
Glucarpidase is marketed under brand names including Voraxaze.
What are the contraindications for Glucarpidase?
Glucarpidase labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.
Note. Data for glucarpidase is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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