Rasburicase

Class: Enzymes
ATC Class: V03AF07
VA Class: GA500
Chemical Name: urate (Aspergillus flavus clone 9C/9A reduced) oxidase
Molecular Formula: C1523H2383N417O462S7 (monomer)
CAS Number: 134774-45-1
Brands: Elitek

Warning(s)

  • Anaphylaxis
  • Risk of severe hypersensitivity reactions (e.g., anaphylaxis).a (See Hypersensitivity Reactions under Cautions.)

  • Immediately and permanently discontinue if clinical evidence of hypersensitivity reaction develops.a

  • Hemolysis
  • Risk of severe hemolysis in patients with a glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.a (See Hemolysis under Cautions.)

  • Immediately and permanently discontinue if hemolysis develops.a

  • Screen patients at higher risk (e.g., patients of African or Mediterranean ancestry) prior to starting therapy.a

  • Methemoglobinemia
  • Methemoglobinemia reported; immediately and permanently discontinue if methemoglobinemia develops.a (See Methemoglobinemia under Cautions.)

  • Interference with Uric Acid Measurements
  • Enzymatic degradation of uric acid occurs within blood samples left at room temperature, resulting in spuriously low uric acid levels.a

  • Collect blood in prechilled tubes containing heparin anticoagulant and immediately immerse and maintain in an ice-water bath; assay plasma samples within 4 hours of collection.a (See Specific Drugs and Laboratory Tests under Interactions.)

Introduction

Biosynthethic (recombinant DNA origin) form of urate oxidase prepared from a genetically modified strain of Saccharomyces cerevisiae.1 4 5 6

Uses for Rasburicase

Chemotherapy-induced Hyperuricemia

Initial management of plasma uric acid concentrations in pediatric patients with leukemia, lymphoma, or solid tumors who are receiving chemotherapy expected to result in tumor lysis and subsequent elevation of plasma uric acid concentrations.1 2 3 4 5 6

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Rasburicase Dosage and Administration

General

  • Initiate chemotherapy 4–24 hours after administering first dose of rasburicase.1

  • Administer concomitantly with IV hydration according to standard medical practice for management of plasma uric acid in patients at risk for tumor lysis syndrome.1

Administration

IV Administration

Administer by IV infusion.1

Do not administer as a rapid IV injection (e.g., IV push or bolus).1

Do not use filters during administration.1

Infuse through a different line than that used for other concomitant drugs; if not possible, flush the line with at least 15 mL of 0.9% sodium chloride injection prior to and after infusion of rasburicase solutions.1

Reconstitution

Reconstitute prior to administration.1

Determine number of vials needed to achieve the proper dosage based on the patient’s weight and the dose per kg.1

Reconstitute vial containing 1.5 mg of rasburicase lyophilized powder with 1 mL of provided diluent (sterile water for injection and poloxamer 188) to provide a solution containing 1.5 mg of rasburicase per mL.1

Mix by swirling very gently.1 Do not shake or form a vortex.1

Must be diluted further before IV administration.a

Dilution

Use strict aseptic technique since drug product contains no preservatives.1

Withdraw appropriate dose from reconstituted vials and add to the appropriate volume of 0.9% sodium chloride injection to achieve a final volume of 50 mL.1

Rate of Administration

Administer diluted solution by IV infusion over 30 minutes.1

Dosage

Pediatric Patients

Chemotherapy-induced Hyperuricemia
IV

Infants and children 1 month to 17 years of age: 0.15 or 0.2 mg/kg once daily for 5 days.1

Safety and efficacy established only for a single course of treatment.1 (See Sensitivity Reactions under Cautions.)

Prescribing Limits

Pediatric Patients

Chemotherapy-induced Hyperuricemia
IV

Infants and children 1 month to 17 years of age: Safety and efficacy of twice daily dosing, dosing for >5 days, or administration of >1 course of therapy not established.1

Special Populations

No special populations dosing recommendations at this time.1

Cautions for Rasburicase

Contraindications

  • G-6-PD deficiency.1 (See Hemolysis under Cautions.)

  • Known hemolytic reactions to rasburicase or any ingredient in the formulation.1 (See Hemolysis under Cautions.)

  • Known methemoglobinemia reactions to rasburicase or any ingredient in the formulation.1 (See Methemoglobinemia under Cautions.)

  • Known hypersensitivity to rasburicase or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Hemolysis

Potential for severe (e.g., grade 3 or 4) hemolytic reactions associated with G-6-PD deficiency; reported within 2–4 days of initiation of therapy.1

Immediately and permanently discontinue the drug if evidence of hemolysis appears; initiate appropriate patient monitoring and supportive measures (e.g., transfusion support).1

Contraindicated in patients with G-6-PD deficiency because hydrogen peroxide is a major product of the conversion of uric acid to allantoin.1

Prior to initiating therapy, screen patients at increased risk of G-6-PD deficiency (e.g., patients of African or Mediterranean descent).1

Methemoglobinemia

Risk of methemoglobinemia, resulting in serious hypoxemia requiring medical intervention.1

Immediately and permanently discontinue if methemoglobinemia develops and implement supportive measures (e.g., transfusion support, methylene blue administration).1

Unknown whether a deficiency of cytochrome b5 reductase (methemoglobin reductase) or of other antioxidant enzymes increases risk for methemoglobinemia or hemolytic anemia.1

Sensitivity Reactions

Hypersensitivity Reactions

Risk of severe hypersensitivity reactions (e.g., anaphylaxis); may occur any time during treatment, even during the first dose.1

If a serious hypersensitivity reaction occurs(e.g., bronchospasm, chest pain and tightness, dyspnea, hypoxia, hypotension, shock, and/or urticaria), immediately and permanently discontinue drug and initiate appropriate therapy.1

Safety in patients with atopic allergy or asthma is unknown.2 3 6

General Precautions

Hydration

Maintain adequate hydration according to standard medical practice for the management of plasma uric acid in patients at risk for tumor lysis syndrome.1 Alkalinization of the urine is not needed.6 9

Immunogenicity

Antibodies to rasburicase may develop; may be associated with inhibition of rasburicase activity.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether rasburicase is distributed into milk; discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in infants <1 month of age.a

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than pediatric patients.a

Adult Use

Insufficient experience in adults to determine whether they respond differently than pediatric patients.a

Common Adverse Effects

Vomiting, fever, nausea, headache, abdominal pain, constipation, diarrhea, mucositis, rash.1

Interactions for Rasburicase

Does not substantially induce or inhibit CYP isoenzymes including 1A, 2A, 2B, 2C, 2E, or 3A in vivo; clinically relevant pharmacokinetic interactions unlikely.1

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Allopurinol

Pharmacokinetic interactions unlikely1

Antineoplastic agents (cyclophosphamide, cytarabine, daunorubicin, etoposide, mercaptopurine, methotrexate, thioguanine, vincristine)

Pharmacokinetic interactions unlikely1

Methylprednisolone

Pharmacokinetic interactions unlikely1

Test for uric acid

Interference with uric acid measurements due to enzymatic degradation of uric acid in blood/plasma/serum samples left at room temperature, resulting in spuriously low uric acid concentrations1

Collect blood samples in prechilled test tubes containing heparin and immediately immerse in an ice water bath1

Analyze uric acid concentrations in plasma; prepare plasma samples from whole blood by centrifugation in a precooled centrifuge (4°C) and assay within 4 hours of sample collection1

Rasburicase Pharmacokinetics

Pharmacokinetics evaluated in pediatric patients; insufficient data available to evaluate pharmacokinetics in adults.1

Absorption

Onset

Age-adjusted target plasma uric acid concentrations (i.e., ≤6.5 mg/dL in children <13 years of age or ≤7.5 mg/dL in those ≥13 years of age) achieved within 48 hours following initiation of rasburicase therapy.1 3

Duration

Target plasma uric acid concentrations maintained for 24 hours after the last administered rasburicase dose.1 3

Distribution

Extent

Not known whether rasburicase is distributed into milk.a

Elimination

Half-life

18 hours.a

Stability

Storage

Parenteral

Powder for Injection and Diluent

2–8°C.1 Do not freeze; protect from light.a

Actions

  • Catalyzes oxidation of uric acid into an inactive and soluble metabolite (allantoin).1

  • Active only at the end of the purine catabolic pathway that produces uric acid.1

Advice to Patients

  • Risk of hypersensitivity reactions (e.g., anaphylaxis).1 Importance of immediately seeking medical attention if symptoms of severe sensitivity (e.g., chest pain, dyspnea, hypotension, urticaria) occur.1

  • Risk of adverse hematologic effects (e.g., hemolysis, methemoglobinemia).1

  • Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.a

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Rasburicase

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For IV infusion

1.5 mg

Elitek

Sanofi-Aventis

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Sanofi-Aventis Inc. Elitek (rasburicase) injection for intravenous use prescribing information. New York, NY; 2002 Jul 22.

2. Goldman SC, Holcenberg JS, Finklestein JZ et al. A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis. Blood. 2001; 97:2998-3003. [IDIS 463743] [PubMed 11342423]

3. Pui CH, Mahmoud HH, Wiley JM et al. Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients with leukemia or lymphoma. J Clin Oncol. 2001; 19:697-704. [IDIS 460147] [PubMed 11157020]

4. Easton J, Noble S, Jarvis B. Rasburicase. Pediatr Drugs. 2001; 3:433-9

5. Anon. Rasburicase (Elitek) for hyperuricemia. Med Letter Drug Ther. 2002; 44:96-7.

6. Lohr LK. Rasburicase, a new, recombinate form of urate oxidase, treats hyperuricemia in tumor lysis syndrome. Hem/Onc Today. October 2002. From the Hem/Onc Today website. Accessed 2003 Jan 23.

7. Smalley RV, Guaspari A, Haase-Statz S et al. Allopurinol: intravenous use for prevention and treatment of hyperuricemia. J Clin Oncol. 2000; 18:1758-63. [IDIS 447152] [PubMed 10764437]

8. Nabi Biopharmaceuticals. Aloprim (allopurinol sodium) for injection, for intravenous infusion prescribing information (dated 1999 Jun). In: Physicians’ desk reference. From the PDR electronic library website. Accessed 2003 Jan 27.

9. Sanofi-Aventis Inc., New York, NY: Personal communication.

a. Sanofi-Aventis Inc. Elitek (rasburicase) injection for intravenous use prescribing information. New York, NY; 2005 Mar.

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