What is Rasburicase
Rasburicase is a recombinant urate oxidase enzyme that rapidly converts existing uric acid into allantoin—a highly soluble metabolite that is 5-10 times more easily excreted by the kidneys—making it the most effective treatment for hyperuricemia associated with tumor lysis syndrome. 1
Biochemical Structure and Origin
- Rasburicase is produced by genetically modifying Saccharomyces cerevisiae (baker's yeast) to express the urate oxidase gene cloned from Aspergillus flavus 2
- The enzyme is a tetrameric protein with four identical subunits, each consisting of a 301 amino acid polypeptide chain with a molecular mass of approximately 34 kDa 2
- It is supplied as a sterile, white to off-white lyophilized powder for intravenous administration after reconstitution 2
Mechanism of Action
- Rasburicase catalyzes the enzymatic oxidation of poorly soluble uric acid into allantoin, an inactive and significantly more soluble metabolite 1, 2
- This is fundamentally different from allopurinol, which only prevents new uric acid formation by inhibiting xanthine oxidase but cannot degrade existing uric acid 1
- The conversion to allantoin allows for rapid renal excretion, addressing pre-existing hyperuricemia immediately 1
Clinical Indications
- Primary indication: Initial management of plasma uric acid levels in patients with leukemia, lymphoma, and solid tumor malignancies receiving anticancer therapy expected to result in tumor lysis syndrome 1, 2
- Particularly valuable in high-risk patients with bulky disease, high-grade lymphomas, acute lymphoblastic leukemia, and elevated LDH 1
- Approved for use in pediatric patients aged 1 month to 17 years and adults 2
Pharmacodynamics and Efficacy
- Rasburicase produces dramatic reductions in plasma uric acid within 4 hours—achieving 86% reduction compared to only 12% with allopurinol 1
- Following administration, plasma uric acid levels decrease within 4 hours and are maintained below 7.5 mg/dL in 98% of adult and 90% of pediatric patients for at least 7 days 2
- Treatment is associated with significant decreases in serum creatinine and improvements in renal function 1
- Chemotherapy can typically be started 4 hours after rasburicase initiation 1
Dosing and Administration
- FDA-approved dose: 0.2 mg/kg/day intravenously, infused over 30 minutes, for up to 5 days 3, 2
- The terminal half-life ranges from 15.7 to 22.5 hours in both pediatric and adult patients 2
- Minimal drug accumulation (<1.3-fold) occurs between days 1 and 5 of dosing 2
Critical Safety Warnings
- Contraindicated in patients with G6PD deficiency due to risk of severe hemolysis and methemoglobinemia 1
- Common adverse reactions include hypersensitivity reactions, hemolysis, and methemoglobinemia 1
- Rasburicase-specific antibodies may develop in some patients 1
- Use with caution in patients with history of allergic reactions 1
Important Drug Interactions and Considerations
- Never administer allopurinol concurrently with rasburicase—this causes xanthine accumulation and eliminates the substrate needed for rasburicase to work 1, 3
- Do not alkalinize urine in patients receiving rasburicase—this increases calcium phosphate precipitation risk without providing benefit 1, 4, 3
- Rasburicase causes enzymatic degradation of uric acid in blood samples at room temperature, potentially causing spuriously low readings; blood must be collected in prechilled heparin tubes, immediately placed in ice water bath, centrifuged in precooled centrifuge (4°C), and analyzed within 4 hours 2
Special Populations
- In children <2 years of age, mean uric acid AUC was higher (150 mg·hr/dL) compared to ages 2-17 years (108 mg·hr/dL), with lower rates of achieving normal uric acid by 48 hours (83% vs 93%) 2
- No overall differences in pharmacokinetics, safety, or effectiveness were observed between elderly (≥65 years) and younger adult patients 2
- Japanese patients showed approximately 40% lower body-weight normalized clearance compared to Caucasians 2