Rasburicase is a urate oxidase enzyme prepared by recombinant technology, which converts uric acid to allantoin (an inactive and soluble metabolite of uric acid).

• It is used in the initial management of plasma uric acid levels in pediatric and adult patients with:

  • leukemia,
  • lymphoma, and
  • solid tumor malignancies getting chemotherapy expected to result in tumor lysis and elevation of plasma uric acid

• It is indicated only for a single course of treatment

Read: Asymptomatic Hyperuricemia Guidelines

Rasburicase Dose in Adults

Rasburicase Dosage in the treatment of Hyperuricemia associated with malignancy:

• • 0.05 to 0.2 mg/kg once daily for 1 to 7 days is given (average of 2 to 3 days) with the duration of treatment dependent on plasma uric acid levels and clinical judgment.
  • Patients with a high tumor burden may require twice daily or an increase in the dose

• The following dose levels are recommended according to risk of tumor lysis syndrome (TLS):

  • High risk:

    • 2 mg/kg once daily is given (duration is based on plasma uric acid levels)

  • Intermediate risk:

    • 1.5 mg/kg once daily is given (duration is based on plasma uric acid levels)

  • Low risk:

    • 1 mg/kg once daily is given(duration is based on clinical judgment).
    • Doses as low as 0.05 mg/kg have been used effectively in studies.

• Off label Single-dose rasburicase :

  • 15 mg/kg  or 3 to 7.5 mg as a single dose is given
  • repeat doses (1.5 to 6 mg) might be needed based on serum uric acid levels.
  • if the uric acid level is less than 12 mg/dL, then single doses of 3 mg or 4.5 mg may be considered with close monitoring and if needed, repeat doses.

• Prevention of hyperuricemia in high-risk patients with hematologic malignancies (off-label dosing):

  • 3 mg intravenous as a single dose is given

• Manufacturer’s labeling:

  • 0.2 mg/kg once a day for up to 5 days.
  • Use beyond 5 days or administration of more than 1 course is not recommended.

Rasburicase Dose in Childrens

Rasburicase Dosage in the treatment of Hyperuricemia associated with malignancy:

• Infants, Children, and Adolescents:
  • Multiple-dosing:

    • Manufacturer's labeling (Elitek):

      • 0.2 mg/kg/dose intravenous once daily is given for up to 5 days

    • Alternate dosing

      • 0.05 to 0.2 mg/kg/dose intravenous once daily is given for 1 to 7 days (average: 2 to 3 days) with the duration of treatment according to plasma uric acid levels and clinical judgment.
      • Patients with a high tumor burden may require twice daily or an increase in the dose.

  • The following dose levels are adjusted based on risk of tumor lysis syndrome (TLS):

    • High risk and baseline uric acid level of greater than 7.5 mg/dL:

      • 2 mg/kg/dose once daily is given(duration is based on plasma uric acid levels)

    • Intermediate risk and baseline uric acid level of less than 7.5 mg/dL:

      • 1.5 mg/kg/dose once daily is given (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:

      • 1 mg/kg/dose once daily is given (duration is based on clinical judgment)

• Single-dose:

  • 0.15 mg/kg/dose intravenous is given; additional doses may be needed based on serum uric acid levels

• Prevention in high-risk patients with hematologic malignancies:

  • 0.2 mg/kg/dose IV as a single dose is given

Pregnancy Risk Factor C

• Animal reproduction studies showed adverse effects.
• Only use during pregnancy if the benefits to the mother exceed the risks to the fetus.

Rasburicase use during breastfeeding:

• It is unknown if breast milk contains rasburicase.
• The potential for serious adverse reactions in breastfed infants should be considered.

Dose in kidney disease:

• There are no dosage adjustments given in the manufacturer's labeling.

Dose in Liver disease:

• There are no dosage adjustments given in the manufacturer's labeling.

Common Side Effects of Rasburicase Include:

• Cardiovascular:

  • Peripheral Edema

• Central Nervous System:

  • Headache
  • Anxiety

• Dermatologic:

  • Rash

• Endocrine & Metabolic:

  • Hypophosphatemia
  • Hypervolemia

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Abdominal Pain
  • Constipation
  • Diarrhea
  • Mucositis

• Hepatic:

  • Hyperbilirubinemia
  • Increased Serum ALT

• Immunologic:

  • Antibody Development
  • Development Of Igg Antibodies

• Infection:

  • Sepsis

• Respiratory:

  • Pharyngolaryngeal Pain

• Miscellaneous:

  • Fever

Less Common Side Effects Of Rasburicase Include:

• Cardiovascular:

  • Ischemic Heart Disease
  • Supraventricular Arrhythmia

• Endocrine & Metabolic:

  • Hyperphosphatemia

• Gastrointestinal:

  • Gastrointestinal Infection

• Hematologic & Oncologic:

  • Pulmonary Hemorrhage

• Hypersensitivity:

  • Hypersensitivity

• Infection:

  • Infection

• Respiratory:

  • Respiratory Failure

Contraindications to Rasburicase Include:

• History of anaphylaxis, severe hypersensitivity to the formulation or any component thereof;
• History of hemolytic reaction or methemoglobinemia caused by rasburicase
• glucose-6phosphatase dehydrogenase (G6PD) deficiency

Warnings and precaution

• Hemolysis: [US Boxed Warning]

  • Patients with G6PD deficiency are advised to avoid rasburicase due to the potential for hemolysis (1%).
  • If hemolysis is developing, stop immediately and continue to treat the patient.
  • Before starting therapy, it is important to screen patients at greater risk of G6PD deficiency (eg, those with Mediterranean or African descent).
  • Within 2 to 4 days after rasburicase is initiated, severe hemolytic reactions may occur.

• Hypersensitivity [US Boxed Warning]

  • There have been cases of fatal and serious hypersensitivity reactions, including anaphylaxis.
  • Patients with severe hypersensitivity reactions must stop immediately and permanently.
  • Any time treatment is initiated, reactions can occur.
  • Signs and symptoms include bronchospasm or chest tightness, dyspnea/hypotension, hypoxia, shock, and urticaria.
  • We haven't been able to determine if more than one course is safe and effective.

• Methemoglobinemia: [US Boxed Warning]:

  • Methemoglobinemia (1%) has been observed.
  • Stop immediately and permanently if a patient develops methemoglobinemia.
  • start appropriate treatment (eg, transfusion, methylene blue) if methemoglobinemia occurs.

Monitor:

• Plasma uric acid levels are done (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)
• Also, monitor for hypersensitivity reactions

How to administer Rasburicase?

• The intravenous infusion is given over 30 minutes
• do not give as a bolus.
• Do not filter during infusion.
• If not possible to GIVE 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 given in the manufacturer's labeling.
• rasburicase generally can be administered irrespective of chemotherapy timing.

Mechanism of action of Rasburicase:

• Rasburicase, a recombinant enzyme for urate oxidation, converts uric acids to allantoin (an inactive metabolite and soluble form of uric Acid).
• It doesn't inhibit the formation uric acid.

Onset: Uric acid levels decrease within 4 hours after administration

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

Half-life elimination: almost 16 to 23 hours

International Brands of Rasburicase:

• Elitek
• Fasturtec
• Rasuritek

Rasburicase brand names in Pakistan:

Rasburicase is not available in Pakistan.