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(gloo KAR pid ase)

Index Terms

  • Carboxypeptidase-G2
  • CPDG2
  • CPG2
  • Voraxaze

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Voraxaze: 1000 units (1 ea)

Brand Names: U.S.

  • Voraxaze

Pharmacologic Category

  • Antidote
  • Enzyme


Recombinant enzyme which rapidly hydrolyzes the carboxyl-terminal glutamate residue from extracellular methotrexate into inactive metabolites (DAMPA and glutamate), resulting in a rapid reduction of methotrexate concentrations independent of renal function


Vd: IV: 3.6 L; distribution restricted to plasma volume

Onset of Action

Methotrexate toxicity: Reduces methotrexate concentrations by ≥97% within 15 minutes of IV administration

Duration of Action

Methotrexate toxicity: Maintains a >95% reduction of methotrexate concentrations for up to 8 days

Half-Life Elimination

IV: Normal renal function: 6-9 hours; impaired renal function (CrCl <30 mL/minute): 8-10 hours (Phillips, 2008)

Special Populations: Renal Function Impairment

Half-life is prolonged in patients with CrCl less than 30 mL/min.

Use: Labeled Indications

Methotrexate toxicity: Treatment of toxic methotrexate plasma concentrations (>1 micromole/L) in patients with delayed clearance due to renal impairment.

Note: Due to the risk of subtherapeutic methotrexate exposure, glucarpidase is NOT indicated when methotrexate clearance is within the expected range (plasma methotrexate concentration ≤2 standard deviations of mean methotrexate excretion curve specific for dose administered) or with normal renal function or mild renal impairment.

Off Label Uses

Intrathecal methotrexate overdose

Data from a limited number of patients studied suggest that glucarpidase may be beneficial for the treatment of accidental intrathecal methotrexate overdose [O’Marcaigh 1996], [Widemann 2004]. Additional data may be necessary to further define the role of glucarpidase in this condition.


There are no contraindications listed in the manufacturer’s labeling.

Dosing: Adult

Methotrexate toxicity: IV: 50 units/kg (Buchen 2005; Widemann 1997; Widemann 2010); may require a second dose 24 hours later (Schwartz 2007; Widemann 1997)

Intrathecal methotrexate overdose (off-label route/use): Intrathecal: 2,000 units as soon as possible after accidental methotrexate overdose (Widemann 2004)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Methotrexate toxicity: IV: Refer to adult dosing.

Intrathecal methotrexate overdose (off-label route/use): Intrathecal: Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

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


IV: Reconstitute each vial (1000 units/vial) with 1 mL normal saline. Mix gently by rolling or tilting vial; do not shake. Upon reconstitution, solution should be clear, colorless and free of particulate matter.

Intrathecal (off-label route/use): Reconstitute 2000 units with 12 mL preservative-free normal saline (Widemann, 2004)


IV: Infuse over 5 minutes; flush IV line before and after glucarpidase 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 (Widemann 2004). Administered over 5 minutes via lumbar route, ventriculostomy, Ommaya reservoir, or lumbar and ventriculostomy (O'Marcaigh 1996; Widemann 2004). 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 (O'Marcaigh 1996).


Store intact vials refrigerated at 2°C to 8°C (36°F to 46°F); do not freeze. Reconstituted solutions should be used immediately or may be stored for up to 4 hours under refrigeration.

Drug Interactions

Leucovorin Calcium-Levoleucovorin: Glucarpidase may decrease serum concentrations of the active metabolite(s) of Leucovorin Calcium-Levoleucovorin. Specifically, 6S-5-methyltetrahydrofolateconcentrations may be reduced. Glucarpidase may decrease the serum concentration of Leucovorin Calcium-Levoleucovorin. Management: Avoid leucovorin administration within 2 hours of glucarpidase dosing. Continue to administer the pre-glucarpidase leucovorin dose for at least the first 48 hours after glucarpidase administration, and dose based on methotrexate concentration thereafter. Consider therapy modification

Test Interactions

Methotrexate levels: During the first 48 hours following glucarpidase administration, the only reliable method of measuring methotrexate concentrations is the chromatographic method. DAMPA, an inactive methotrexate metabolite with a half-life of 9 hours, may interfere with immunoassay and result in the overestimation of the methotrexate concentration (when collected within 48 hours of glucarpidase administration).

Adverse Reactions

>10%: Immunologic: Antibody development (21%)

1% to 10%:

Cardiovascular: Flushing (2%), hypotension (1%)

Central nervous system: Headache (1%)

Gastrointestinal: Nausea/vomiting (2%)

Neuromuscular & skeletal: Paresthesia (2%)

<1%, postmarketing, and/or case reports: Blurred vision, diarrhea, hypersensitivity reaction, hypertension, localized warm feeling, skin rash, throat irritation, tremor


Concerns related to adverse effects:

• Allergic reaction: Serious allergic reactions have been reported.

Concurrent drug therapy issues:

• Leucovorin calcium: Leucovorin calcium administration should be continued after glucarpidase; the same dose as was given prior to glucarpidase should be continued for the first 48 hours after glucarpidase; after 48 hours, leucovorin doses should be based on methotrexate concentrations. A single methotrexate concentration should not determine when leucovorin should be discontinued; continue leucovorin until the methotrexate concentration remains below the threshold for leucovorin treatment for ≥3 days. Leucovorin calcium is a substrate for glucarpidase and may compete with methotrexate for binding sites; do not administer leucovorin calcium within 2 hours before or after glucarpidase.

Other warnings/precautions:

• Appropriate use: In addition to leucovorin, glucarpidase use should be accompanied with adequate hydration and urinary alkalinization.

• Intrathecal methotrexate overdose: Glucarpidase for intrathecal methotrexate overdose (off-label route/use) should be used in conjunction with immediate lumbar drainage; concurrent dexamethasone (4 mg IV every 6 hours for 4 doses) may minimize methotrexate-induced chemical arachnoiditis; leucovorin calcium (100 mg IV every 6 hours for 4 doses) may prevent systemic methotrexate toxicity (Widemann, 2004).

• Monitoring methotrexate: During the first 48 hours after glucarpidase administration, the only reliable method of measuring methotrexate concentrations is the chromatographic method. DAMPA, an inactive methotrexate metabolite with a half-life of 9 hours, may interfere with immunoassay and result in the overestimation of the methotrexate concentration (when collected within 48 hours of glucarpidase administration).

Monitoring Parameters

Serum methotrexate levels: Use chromatographic method if <48 hours from glucarpidase administration (DAMPA interferes with immunoassay results until >48 hours)

CBC with differential, bilirubin, ALT, AST, serum creatinine; evaluate for signs/symptoms of methotrexate toxicity

Pregnancy Risk Factor


Pregnancy Considerations

Animal reproduction studies have not been conducted. If administered to a pregnant woman, the risk to the fetus is unknown; use only if clearly needed. In general, medications used as antidotes should take into consideration the health and prognosis of the mother.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea or vomiting. Have patient report immediately to prescriber severe dizziness, passing out, flushing, chills, headache, sensation of warmth, or burning or numbness feeling (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.