What is rasburicase?

Rasburicase: A Recombinant Urate Oxidase Enzyme for Tumor Lysis Syndrome

Rasburicase is a recombinant urate oxidase enzyme that rapidly converts existing uric acid to allantoin, which is 5-10 times more soluble in urine than uric acid, making it a highly effective treatment for hyperuricemia associated with tumor lysis syndrome. 1, 2

Biochemical Properties and Mechanism of Action

• Rasburicase (brand name Elitek) is a tetrameric protein with identical subunits, each made up of a single 301 amino acid polypeptide chain with a molecular mass of about 34 kDa 3
• The gene encoding urate oxidase was cloned from Aspergillus flavus and expressed in a modified strain of Saccharomyces cerevisiae, allowing production and purification of the recombinant enzyme 1, 3
• Rasburicase catalyzes the enzymatic oxidation of poorly soluble uric acid into an inactive and more soluble metabolite (allantoin), which is readily excreted by the kidneys 3, 1
• The half-life for elimination of rasburicase is approximately 16-21 hours, with no apparent accumulation when administered over multiple days 1

Clinical Applications

• Rasburicase is primarily indicated for the initial management of plasma uric acid levels in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis syndrome 3, 1
• It is particularly valuable in high-risk patients, including those with bulky disease, high-grade lymphomas, acute lymphoblastic leukemia, and elevated LDH 2, 4
• Rasburicase should be administered to adult cancer patients who carry a high risk of tumor lysis syndrome and are candidates for tumor-specific therapy 1
• It is also indicated for patients who have already developed clinical tumor lysis syndrome or laboratory tumor lysis syndrome 1

Dosing and Administration

• The FDA-approved dose is 0.2 mg/kg/day administered intravenously over 30 minutes for up to 5 days 3, 5
• Studies have shown efficacy with single fixed-dose regimens ranging from 1.5 mg to 7.5 mg, with 4.5-6 mg being commonly used in clinical practice 6, 5, 7
• The drug is supplied as a sterile, white to off-white, lyophilized powder intended for intravenous administration following reconstitution with a diluent 3
• Chemotherapy can typically be started 4 hours after initiation of rasburicase treatment 1

Efficacy

• Rasburicase rapidly decreases plasma uric acid levels, with reductions of 86% observed within 4 hours of the first dose compared to only 12% with allopurinol 1
• In hyperuricemic patients, median plasma uric acid levels typically decrease from >9 mg/dL to approximately 1.0 mg/dL after treatment 1, 8
• Single fixed-dose rasburicase (4.5 mg) has been shown to normalize uric acid in 68% of patients within 24 hours 6
• Rasburicase treatment is associated with significant decreases in serum creatinine levels and improvements in renal function 1, 9

Safety and Adverse Effects

• Common adverse reactions include hypersensitivity reactions, hemolysis in patients with G6PD deficiency, and methemoglobinemia 1
• Rasburicase-specific antibodies may develop in some patients (reported in 17 patients in one study) 1
• The drug is contraindicated in patients with G6PD deficiency due to the risk of severe hemolysis 1, 3
• Special handling procedures are required for blood samples from patients receiving rasburicase, as it causes enzymatic degradation of uric acid in blood/plasma/serum samples at room temperature, potentially resulting in falsely low uric acid readings 3

Advantages Over Allopurinol

• Rasburicase degrades existing uric acid, while allopurinol only prevents new formation by inhibiting xanthine oxidase 1, 2
• Rasburicase acts more rapidly than allopurinol, with significant reductions in uric acid levels within hours rather than days 1
• Rasburicase allows for earlier administration of chemotherapy due to rapid degradation of uric acid 2
• In comparative studies, rasburicase demonstrated a 2.6-fold decrease in uric acid exposure compared to allopurinol 1

Clinical Considerations

• Allopurinol should not be administered concurrently with rasburicase to avoid xanthine accumulation and lack of substrate for rasburicase 2
• Urine alkalinization is not recommended in patients receiving rasburicase therapy 2
• Rasburicase should be used with caution in patients with a history of allergic reactions 1
• Cost considerations have led many institutions to adopt fixed-dose protocols rather than weight-based dosing, with similar efficacy outcomes 7