Rasburicase (Monograph)

Brand name: Elitek
Drug 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

Medically reviewed by Drugs.com on Feb 20, 2024. Written by ASHP.

Introduction

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

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.

Rasburicase Dosage and Administration

General

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

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

Administration

IV Administration

Administer by IV infusion.

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

Do not use filters during administration.

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.

Reconstitution

Reconstitute prior to administration.

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

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.

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

Must be diluted further before IV administration.

Dilution

Use strict aseptic technique since drug product contains no preservatives.

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.

Rate of Administration

Administer diluted solution by IV infusion over 30 minutes.

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.

Safety and efficacy established only for a single course of treatment. (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.

Special Populations

No special populations dosing recommendations at this time.

Cautions for Rasburicase

Contraindications

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

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

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

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

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.

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

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

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

Methemoglobinemia

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

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

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

Sensitivity Reactions

Hypersensitivity Reactions

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

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.

Safety in patients with atopic allergy or asthma is unknown.

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. Alkalinization of the urine is not needed.

Immunogenicity

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

Specific Populations

Pregnancy

Category C.

Lactation

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

Pediatric Use

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

Geriatric Use

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

Adult Use

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

Common Adverse Effects

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

Drug Interactions

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

Specific Drugs and Laboratory Tests

Rasburicase Pharmacokinetics

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

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.

Duration

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

Distribution

Extent

Not known whether rasburicase is distributed into milk.

Elimination

Half-life

18 hours.

Stability

Storage

Parenteral

Powder for Injection and Diluent

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

Actions

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

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

Advice to Patients

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

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

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

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

• 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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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