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Rasburicase

Medically reviewed by Drugs.com. Last updated on Jun 16, 2020.

Pronunciation

(ras BYOOR i kayse)

Index Terms

  • Recombinant Urate Oxidase
  • Urate Oxidase

Dosage Forms

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

Solution Reconstituted, Intravenous [preservative free]:

Elitek: 1.5 mg (1 ea); 7.5 mg (1 ea)

Brand Names: U.S.

  • Elitek

Pharmacologic Category

  • Enzyme
  • Enzyme, Urate-Oxidase (Recombinant)

Pharmacology

Rasburicase is a recombinant urate-oxidase enzyme, which converts uric acid to allantoin (an inactive and soluble metabolite of uric acid); it does not inhibit the formation of uric acid.

Distribution

Pediatric patients: 110 to 127 mL/kg; Adults: 76 to 138 mL/kg

Onset of Action

Uric acid levels decrease within 4 hours of initial administration

Half-Life Elimination

~16 to 23 hours

Special Populations: Race

The geometric mean values of body weight-normalized clearance were approximately 40% lower in Japanese patients than in white patients.

Use: Labeled Indications

Hyperuricemia associated with malignancy: Initial management of plasma uric acid levels in pediatric and adult patients with leukemia, lymphoma, and solid tumor malignancies receiving chemotherapy expected to result in tumor lysis and elevation of plasma uric acid

Limitations of use: Indicated only for a single course of treatment

Contraindications

History of anaphylaxis or severe hypersensitivity to rasburicase or any component of the formulation; history of hemolytic reaction or methemoglobinemia associated with rasburicase; glucose-6-phosphatase dehydrogenase (G6PD) deficiency

Dosing: Adult

Hyperuricemia associated with malignancy: IV: 0.05 to 0.2 mg/kg once daily for 1 to 7 days (average of 2 to 3 days) with the duration of treatment dependent on plasma uric acid levels and clinical judgment (patients with significant tumor burden may require an increase to twice daily); the following dose levels are recommended based on risk of tumor lysis syndrome (TLS) (Coiffier 2008):

High risk: 0.2 mg/kg once daily (duration is based on plasma uric acid levels)

Intermediate risk: 0.15 mg/kg once daily (duration is based on plasma uric acid levels)

Low risk: 0.1 mg/kg once daily (duration is based on clinical judgment); a dose of 0.05 mg/kg was used effectively in one trial

Single-dose rasburicase (off-label dosing): 0.15 mg/kg (Campara 2009; Liu 2005) or 3 to 7.5 mg as a single dose (Hutcherson 2006; McBride 2013; McDonnell 2006; Reeves 2008; Trifilio 2006); repeat doses (1.5 to 6 mg) may be needed based on serum uric acid levels. A meta-analysis of 10 studies determined that the pooled response rate of single-dose rasburicase (doses ranging from 0.05 mg/kg to 0.2 mg/kg) was not inferior to daily rasburicase dosing while allowing for cost savings; monitor closely in case an additional dose may be needed (Feng 2013). Another meta-analysis of 15 studies determined that a single 6 mg dose was sufficient to lower and maintain uric acid and creatinine levels in adult patients with TLS; if the uric acid level is <12 mg/dL, single doses of 3 mg or 4.5 mg may be considered with close monitoring and if needed, repeat doses (Yu 2017).

Prevention in high-risk patients with hematologic malignancies (off-label dosing): IV: 3 mg as a single dose (Jones 2015)

Manufacturer’s labeling: IV: 0.2 mg/kg once daily for up to 5 days (use beyond 5 days or administration of more than 1 course is not recommended)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hyperuricemia associated with malignancy: Infants, Children, and Adolescents:

Multiple-dosing:

Manufacturer's labeling (Elitek): IV: 0.2 mg/kg/dose once daily for up to 5 days

Alternate dosing (Coiffier 2008): Limited data available: IV: 0.05 to 0.2 mg/kg/dose once daily for 1 to 7 days (average: 2 to 3 days) with the duration of treatment dependent on plasma uric acid levels and clinical judgment (patients with significant tumor burden may require an increase to twice daily); the following dose levels are recommended based on risk of tumor lysis syndrome (TLS):

High risk and baseline uric acid level >7.5 mg/dL: 0.2 mg/kg/dose once daily (duration is based on plasma uric acid levels)

Intermediate risk and baseline uric acid level <7.5 mg/dL: 0.15 mg/kg/dose once daily (duration is based on plasma uric acid levels); may consider managing initially with a single dose

Low risk and baseline uric acid level <7.5 mg/dL: 0.1 mg/kg/dose once daily (duration is based on clinical judgment); a dose of 0.05 mg/kg was used (with good results) in one trial

Single-dose: Limited data available: IV: 0.15 mg/kg/dose; additional doses may be needed based on serum uric acid levels (Liu 2005)

Prevention in high-risk patients with hematologic malignancies: IV: 0.2 mg/kg/dose as a single dose (Jones 2015)

Reconstitution

Reconstitute with provided diluent (use 1 mL diluent for the 1.5 mg vial and 5 mL diluent for the 7.5 mg vial). Mix by gently swirling; do not shake or vortex. Discard if discolored or containing particulate matter. Total dose should be further diluted in NS to a final volume of 50 mL. Because the provided diluent is in a glass ampule, the diluent should be filtered prior to adding to the rasburicase vial for reconstitution (ISMP [Smetzer 2017]).

Administration

IV: IV infusion over 30 minutes; do not administer as a bolus. Do not filter during infusion. If not possible to administer through a separate line, IV line should be flushed with at least 15 mL saline prior to and following rasburicase infusion.

The optimal timing of rasburicase administration (with respect to chemotherapy administration) is not specified in the manufacturer's labeling. In some studies, chemotherapy was administered 4 to 24 hours after the first rasburicase dose (Cortes 2010; Kikuchi 2009; Vadhan-Raj 2012); however, rasburicase generally may be administered irrespective of chemotherapy timing.

Storage

The lyophilized drug product and the diluent for reconstitution should be stored at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Reconstituted solution and solution diluted for infusion may be stored for up to 24 hours at 2°C to 8°C (36°F to 46°F). Discard unused product.

Drug Interactions

Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy

Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Monitor therapy

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Monitor therapy

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Monitor therapy

Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Monitor therapy

Test Interactions

Specific handling procedures must be followed to prevent the degradation of uric acid in plasma samples. Blood must be collected in prechilled tubes containing heparin anticoagulant. Samples must then be immediately immersed and maintained in an ice water bath. Prepare samples by centrifugation in a precooled centrifuge (4°C). Samples must be analyzed within 4 hours of collection.

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (50%)

Central nervous system: Headache (26%), anxiety (24%)

Dermatologic: Rash (13%; serious: <1%)

Endocrine & metabolic: Hypophosphatemia (17%), hypervolemia (12%)

Gastrointestinal: Nausea (27% to 58%), vomiting (38% to 50%), abdominal pain (20% to 22%), constipation (20%), diarrhea (20%), mucositis (15%)

Hepatic: Hyperbilirubinemia (16%), increased serum ALT (11%)

Immunologic: Antibody development (children: 11%; IgE: 6%), development of IgG antibodies (18%; neutralizing 8%)

Infection: Sepsis (12%; serious: 5%)

Respiratory: Pharyngolaryngeal pain (14%)

Miscellaneous: Fever (46%)

1% to 10%:

Cardiovascular: Ischemic heart disease (≥2%), supraventricular arrhythmia (≥2%)

Endocrine & metabolic: Hyperphosphatemia (10%)

Gastrointestinal: Gastrointestinal infection (≥2%)

Hematologic & oncologic: Pulmonary hemorrhage (≥2%)

Hypersensitivity: Hypersensitivity (4%)

Infection: Infection (abdominal, ≥2%)

Respiratory: Respiratory failure (≥2%)

<1%, postmarketing, and/or case reports: Anaphylaxis, hemolysis, methemoglobinemia, muscle spasm, seizure

ALERT: U.S. Boxed Warning

Hypersensitivity reactions:

Rasburicase may cause serious and fatal hypersensitivity reactions, including anaphylaxis. Immediately and permanently discontinue rasburicase in patients who experience a serious hypersensitivity reaction.

Hemolysis:

Do not administer rasburicase to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Immediately and permanently discontinue rasburicase in patients developing hemolysis. Screen patients at higher risk for G6PD deficiency (eg, patients of African or Mediterranean ancestry) prior to starting rasburicase.

Methemoglobinemia:

Rasburicase can result in methemoglobinemia in some patients. Immediately and permanently discontinue rasburicase in patients developing methemoglobinemia.

Interference with uric acid measurements:

Rasburicase enzymatically degrades uric acid in blood samples left at room temperature. Collect blood samples in prechilled tubes containing heparin and immediately immerse and maintain sample in an ice water bath. Assay plasma samples within 4 hours of collection.

Warnings/Precautions

Concerns related to adverse effects:

• Hemolysis: [US Boxed Warning]: Due to the risk for hemolysis (<1%), rasburicase is contraindicated in patients with G6PD deficiency. Discontinue immediately and permanently in any patient developing hemolysis. Patients at higher risk for G6PD deficiency (eg, African or Mediterranean descent) should be screened prior to therapy. Severe hemolytic reactions occurred within 2 to 4 days of rasburicase initiation.

• Hypersensitivity: [US Boxed Warning]: Serious and fatal hypersensitivity reactions (including anaphylaxis) have been reported; immediately and permanently discontinue in patients developing a serious hypersensitivity reaction. Reactions may occur at any time during treatment (including the initial dose); signs and symptoms may include bronchospasm, chest pain/tightness, dyspnea, hypotension, hypoxia, shock, or urticaria. The safety and efficacy of more than one course of administration has not been established.

• Methemoglobinemia: [US Boxed Warning]: Methemoglobinemia has been reported (<1%). Discontinue immediately and permanently in any patient developing methemoglobinemia. Initiate appropriate treatment (eg, transfusion, methylene blue) if methemoglobinemia occurs.

Other warnings/precautions:

• Hydration: Patients at risk for tumor lysis syndrome should receive appropriate IV hydration as part of uric acid management; however, alkalinization (with sodium bicarbonate) concurrently with rasburicase is not recommended (Coiffier 2008).

• Multiple courses: Rasburicase is immunogenic and can elicit an antibody response; efficacy may be reduced with subsequent courses of therapy.

• Uric acid degradation: [US Boxed Warning]: Enzymatic degradation of uric acid in blood samples will occur if left at room temperature, which may interfere with serum uric acid measurements; specific guidelines for the collection of plasma uric acid samples must be followed, including collection in prechilled tubes with heparin anticoagulant, immediate ice water bath immersion and assay within 4 hours (sample should remain on ice until analyzed).

Monitoring Parameters

Plasma uric acid levels (4 hours after rasburicase administration, then every 6 to 8 hours until TLS resolution), CBC, G6PD deficiency screening (in patients at high risk for deficiency); monitor for hypersensitivity reactions

Pregnancy Considerations

Based on data from animal reproduction studies, in utero exposure to rasburicase may cause fetal harm. Information related to the use of rasburicase in pregnancy is limited (Middeke 2014).

Patient Education

What is this drug used for?

• It is used to treat or prevent high uric acid levels during chemo.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Nausea

• Vomiting

• Stomach pain

• Diarrhea

• Anxiety

• Constipation

• Mouth irritation

• Mouth sores

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Methemoglobinemia like blue or gray color of the lips, nails, or skin; abnormal heartbeat; seizures; severe dizziness or passing out; severe headache; fatigue; loss of strength and energy; or shortness of breath

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting

• Infusion reaction

• Yellow skin or eyes

• Dark urine

• Pale skin

• Severe loss of strength and energy

• Swelling of arms or legs

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.