(gloo-kar-pi-dase) ,


(trade name)


Therapeutic: orphan drugs
Pharmacologic: enzymes
Pregnancy Category: C


Lowering of toxic methotrexate levels (>1 micromole/L) associated with renal failure.


A carboxypeptidase enzyme that breaks methotrexate down into inactive metabolites that can be readily eliminated by non-renal pathways.

Therapeutic effects

Prevention of damage associated with high levels of methotrexate including kidney and liver damage, mucusitis and bone marrow depression.


Absorption: IV administration results in complete bioavailability.
Distribution: Restricted to plasma volume.
Metabolism and Excretion: Unknown.
Half-life: 5.6 hr.

Time/action profile (reduction of methotrexate levels)

IVwithin 15 minunknownup to 8 days


Contraindicated in: Patients with expected clearance of methotrexate (methotrexate levels within 2 standard deviations of the mean methotrexate excretion curve specific for the dose given) or those with normal or mildly impaired renal function.
Use Cautiously in: Lactation: Use cautiously; Obstetric: Use only if clearly needed.

Adverse Reactions/Side Effects

Central nervous system

  • headache


  • hypotension


  • nausea
  • vomiting


  • flushing


  • paraesthesia


  • allergic reactions including anaphylaxis (life-threatening)


Drug-Drug interaction

↓ effectiveness of leucovorin (should not be given within 2 hr before or after), similar effects may occur with other substrates of the enzyme including reduced folates and folate antimetabolites.


Intravenous (Adults and Children >1 mo) 50 Units/kg as a single dose.


Lyophilized powder for injection (requires reconstitution): 1,000 units/vial

Nursing implications

Nursing assessment

  • Assess for signs and symptoms of allergic reactions (fever, chills, flushing, feeling hot, rash, hives, itching, throat tightness or breathing problems, tingling, numbness, or headache) periodically following injection. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.

Potential Nursing Diagnoses

Deficient knowledge, related to medication regimen (Patient/Family Teaching)


  • Continue to administer leucovorin after glucarpidase. Do not administer leucovorin within 2 hrs before or after dose of glucarpidase. For the first 48 hrs administer same leucovorin dose as given prior to glucarpidase. Beyond 48 hrs after glucarpidase administer leucovorin dose based on methotrexate concentration. Do not discontinue leucovorin based on a single methotrexate concentration below leucovorin treatment threshold. Continue leucovorin until methotrexate concentration has been maintained below leucovorin treatment threshold for at least 3 days.
  • Continue hydration and alkalinization of urine as needed.
  • Intravenous Administration
  • Reconstitute vial with 1 mL sterile saline for injection. Roll and tilt vial to mix; do not shake. Solution should be clear and colorless; do not administer if solution is discolored, cloudy or contains particulate matter. May be refrigerated for up to 4 hr if not used immediately. Discard unused product.
  • Rate: Administer as a bolus over 5 min. Flush IV line before and after injection.

Patient/Family Teaching

  • Advise patient to notify health care professional if signs and symptoms of allergic reactions occur.
  • Emphasize the importance of continued monitoring of methotrexate blood levels and renal status following hospital discharge.
  • Advise female patient to notify health care professional if pregnancy is known or suspected.

Evaluation/Desired Outcomes

  • Maintenance of methotrexate level below the leucovorin treatment threshold for more than 3 days.
References in periodicals archive ?
Glucarpidase is indicated for the treatment of toxic plasma methotrexate levels.
Two of the projects are being undertaken by Dr Syed Goda, senior research scientist with the following topics: Protein engineering of Glucarpidase to improve cancer therapy strategies; New synthesis of novel bioactive class of natural products; Mast cell proteases as key clinical markers in allergic disease.
Glucarpidase, an intravenously delivered recombinant enzyme, was approved for the treatment of patients with toxic levels of methotrexate in their blood due to kidney failure, according to the FDA.
Glucarpidase (Voraxaze) rapidly breaks down methotrexate into a form that can then be eliminated from the body, according to the agency.
In 2008, Protherics, which previously owned the rights to glucarpidase, was warned by the FDA against promoting the drug before it was approved.
These measures did not reduce MTXbelowthe toxic concentration, however, and the decision was made to give the patient glucarpidase [carboxypeptidase [G.
2] every 6 h) should also be continued for 48 h after glucarpidase administration because the enzyme hydrolyzes leucovorin and its active circulating metabolite, 5-methyltetrahydrofolate, to inactive forms.
Glucarpidase rapidly and efficiently lowers the serum methotrexate concentration by providing an alternative route of elimination and, when administered as soon as possible after the recognition of nephrotoxicity, can effectively prevent methotrexate toxicity.
The antidote, glucarpidase (Voraxaze), is used to treat toxic levels of methotrexate.
With use of these criteria for the drugs discussed above, there are only 10 that are probably compatible with breastfeeding: glucarpidase, ingenol mebutate, sodium picosulfate, tal-iglucerase alfa, crofelemer, linaclotide, peginesatide, aclidinium bromide, tafluprost, and ocriplasmin.
Methotrexate concentrations within 48 hours following glucarpidase administration can only be reliably measured by a chromatographic method due to interference from metabolites[4-deoxy-4-amino-N10-methylpteroic acid (DAMPA)].
Leucovorin should not be administered within 2 hours before or after a glucarpidase dose because leucovorin is a substrate for glucarpidase.