Glucarpidase (Voraxaze) is a synthetic enzyme that inactivates methotrexate. It is used in patients with methotrexate overdose or toxicity. Methotrexate administered in high doses as in cancer patients may result in nephrotoxicity that can further impair the excretion of methotrexate. Life-threatening toxicity may occur that can be prevented by the intravenous administration of Glucarpidase.

Glucarpidase (Voraxaze) Uses:

• Methotrexate toxicity:

  • In patients with acute or chronic kidney disease where elimination of methotrexate is reduced and plasma concentration greater than 1 umol/L
  • Limitations of use: Not indicated when renal function is normal or mildly deranged when clearance is not impaired

• Off Label Use of Glucarpidase in Adults:

  • Intrathecal methotrexate overdose

Glucarpidase (Voraxaze) Dose in Adults

Note: Potential drug interaction with Leucovorin calcium as it competes for binding sites; Leucovorin not be administered within 2hr of Glucarpidase prior to or post-administration.

Glucarpidase (Voraxaze) Dose in the treatment of Methotrexate toxicity:

• IV: 50 units/kg as a single dose. A second dose may be required after 24 hours.

Glucarpidase (Voraxaze) Dose in the treatment of Intrathecal methotrexate overdose (off-label route/use):

• Intrathecal: 2,000 units as soon as possible after accidental methotrexate overdose.

Glucarpidase (Voraxaze) Dose in Childrens

Note: Potential drug interaction with Leucovorin calcium as it competes for binding sites; Leucovorin not be administered within 2hr of Glucarpidase prior to or post-administration.

Glucarpidase (Voraxaze) Dose in the treatment of Methotrexate toxicity:

• Infants, Children, and Adolescents:

  • IV: 50 units/kg as a single dose.

Glucarpidase (Voraxaze) Dose in the treatment of Intrathecal methotrexate overdose:

• Children ≥5 years and Adolescents:

  • Intrathecal: 2,000 units as soon as possible after accidental exposure.

Pregnancy Risk Factor C

• Animals are not considered for pregnancy.
• If given to a pregnant woman, the effects on the fetus remain unknown.
• The risk must be balanced against the maternal benefits of the antidote.

Use during breastfeeding:

• At the moment, it is not known if milk contains excretion.
• Take care when lactating with females

Dose in Kidney disease:

No dosage adjustment is necessary.

Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Side Effects of Glucarpidase (Voraxaze):

• Immunologic:

  • Antibody development

• Cardiovascular:

  • Flushing
  • Hypotension

• Central nervous system:

  • Headache

• Gastrointestinal:

  • Nausea/vomiting

• Neuromuscular & skeletal:

  • Paresthesia

Contraindications to Glucarpidase (Voraxaze):

The manufacturer's labeling does not list any contraindications.

Warnings and precautions

• Hypersensitivity

  • There have been cases of severe allergic reactions.

Glucarpidase: Drug Interaction

Monitoring parameters:

Monitor serum methotrexate levels:

• Use chromatographic method if less than 48 hours from the drug administration (DAMPA interferes with immunoassay results until >48 hours)
• Monitor CBC with differential counts, bilirubin, ALT, AST, and serum creatinine; evaluate for signs/symptoms of methotrexate toxicity.

How to administer Glucarpidase (Voraxaze)?

IV:

• Infuse over 5 minutes; flush IV line before and after its administration.
• Potential drug interaction with Leucovorin calcium as it competes for binding sites; Leucovorin should not be administered within 2hours (before or after) its administration.

Intrathecal (for intrathecal methotrexate overdose; off-label route/use):

• Glucarpidase was administered within 3 to 9 hours of accidental intrathecal methotrexate overdose in conjunction with lumbar drainage or ventriculolumbar perfusion.
• Administered over 5 minutes via lumbar route, ventriculostomy, Ommaya reservoir, or lumbar and ventriculostomy. In one case report, 1,000 units were administered through the ventricular catheter over 5 minutes and another 1,000 units were administered through the lumbar catheter.

Mechanism of action of Glucarpidase (Voraxaze):

• Methotrexate can be quickly reduced to inactive metabolites thanks to the enzyme-based function Glucarpidase. 
• This function doesn't involve the kidneys. This function is useful in the event of impaired renal clearance.

The beginning of action:

• Methotrexate toxicities: Lowers methotrexate concentrations within 15 minutes of IV administration

Time

• Methotrexate toxicities: Keeps a >95% decrease inmethotrexateConcentrations for up to 8 Days

Half-life elimination:

• Normal renal function
  • Serum enzyme activity: 5.6 hours
  • Total enzyme activity in serum: approximately 9 hours
  • A reduced renal function (CrCl 30 mg/minute): 8-10 hours

International Brand Names of Glucarpidase:

• Voraxaze

Glucarpidase Brand Names in Pakistan:

No Brands Available in Pakistan.