glucarpidase

(redirected from Voraxaze)

glucarpidase

(gloo-kar-pi-dase) ,

Voraxaze

(trade name)

Classification

Therapeutic: orphan drugs
Pharmacologic: enzymes
Pregnancy Category: C

Indications

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

Action

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.

Pharmacokinetics

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)

ROUTEONSETPEAKDURATION
IVwithin 15 minunknownup to 8 days

Contraindications/Precautions

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

Cardiovascular

  • hypotension

Gastrointestinal

  • nausea
  • vomiting

Dermatologic

  • flushing

Neurologic

  • paraesthesia

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)

Interactions

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.

Route/Dosage

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

Availability

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)

Implementation

  • 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 ?
The antidote, glucarpidase (Voraxaze), is used to treat toxic levels of methotrexate.
Glucarpidase (Voraxaze) rapidly breaks down methotrexate into a form that can then be eliminated from the body, according to the agency.
Specialist healthcare company BTG plc (LSE: BGC) today received from the US Food and Drug Administration (FDA) regulatory approval for its Biologics License Application (BLA) for Voraxaze (glucarpidase).
M2 PHARMA-January 18, 2012-FDA approves Voraxaze for reduction of methotrexate levels(C)2012 M2 COMMUNICATIONS
The European drugs regulator is seeking further manufacturing information on Voraxaze, effectively delaying approval of the treatment for patients suffering toxicity from methotrexate, a widely used anticancer agent.
Biotechnology group Protherics hopes to gain clearance for Voraxaze -a treatment for the side-effects of a specialist cancer drug -by the end of the year.
Biotechnology group Protherics hopes to gain clearance for Voraxaze - a treatment for the side-effects of a specialist cancer drug - by the end of the year.
7 December 2011 - British BTG plc (LSE:BGC) Wednesday said it had licensed to Japanese Ohara Pharmaceutical Co Ltd the rights to Voraxaze (glucarpidase), an experimental treatment for the rapid and sustained reduction of toxic methotrexate (MTX) levels caused by impaired renal function.
The news caused the share price to fall by around 25% Then a few days later the company admitted that US approval for its Voraxaze treatment could come a year later than expected.
Its shares fell on that announcement and at one point yesterday the stock fell 25%, before recovering slightly, after it admitted that US approval for its Voraxaze treatment could come a year later than expected.
Another product awaiting regulatory approval is Voraxaze, for the control of high dose methotrexate therapies in cancer.
"The CytoFab programme is progressing according to plan to meet future milestones, and we continue to prepare our Voraxaze filing for the FDA while progressing our other projects."