Indications for Rasburicase
Rasburicase is indicated for the initial management of plasma uric acid levels in pediatric and adult patients with leukemia, lymphoma, and solid tumor malignancies receiving anticancer therapy expected to result in tumor lysis syndrome (TLS) and subsequent elevation of plasma uric acid. 1
Primary Clinical Indications
Treatment of Clinical TLS
- All patients presenting with clinical TLS should receive rasburicase along with aggressive hydration through central venous access. 2
- Clinical TLS is defined by the presence of metabolic derangements (hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia) plus clinical manifestations such as acute kidney injury, cardiac arrhythmias, or seizures. 2
Treatment of Laboratory TLS
- Adults with laboratory TLS (at least 2 biochemical abnormalities including hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia) should receive rasburicase with hydration. 2, 3
- Laboratory TLS without clinical symptoms still warrants rasburicase treatment in adults to prevent progression to clinical TLS. 2
High-Risk Prophylaxis in Pediatric Patients
- Children at high risk of developing TLS or those with rapid worsening of biochemical TLS parameters should receive prophylactic rasburicase. 2, 3
- High-risk pediatric patients include those with newly diagnosed acute lymphoblastic leukemia (ALL) or stage III/IV non-Hodgkin lymphoma (NHL). 2
High-Risk Prophylaxis in Adult Patients
- Adults with aggressive NHL, high tumor burden, pre-existing hyperuricemia (>8 mg/dL), or baseline renal impairment should receive prophylactic rasburicase rather than allopurinol. 2, 4
- Prophylactic rasburicase in 100 adult patients with aggressive NHL normalized uric acid within 4 hours and maintained control throughout chemotherapy, with no patients requiring dialysis. 2
Specific High-Risk Populations
Hematologic Malignancies
- Patients with leukemia (particularly ALL and AML with excessive leukocytosis) and aggressive lymphomas are primary candidates for rasburicase. 2, 3, 5
- The drug is particularly important in AML patients with leukocytosis and signs of leukostasis. 5
- Bulky lymphoma disease carries high TLS risk due to rapid cell turnover and chemotherapy sensitivity. 4
Patients with Renal Compromise
- Rasburicase should be prioritized over allopurinol in patients with pre-existing renal impairment or obstructive uropathy. 4
- Unlike allopurinol, which only prevents new uric acid formation, rasburicase degrades existing uric acid to allantoin (5-10 times more soluble), allowing rapid reversal of renal insufficiency. 4, 6
Severe Hyperuricemia
- Patients with uric acid levels >8 mg/dL should receive rasburicase as primary therapy rather than allopurinol. 4, 7
- Rasburicase reduces plasma uric acid by 86% within 4 hours of the first dose, compared to only 12% with allopurinol. 2
Advantages Over Allopurinol
Mechanism and Speed of Action
- Rasburicase acts at the end of the purine catabolic pathway, enzymatically degrading uric acid to allantoin, allowing prompt continuation of chemotherapy. 2, 3, 6
- Allopurinol only prevents new uric acid formation but cannot degrade existing elevated levels, resulting in significant delays in resuming chemotherapy. 2
- The mean uric acid area under the curve was 2.6-fold lower with rasburicase (128 mg/dL/h) compared to allopurinol (329 mg/dL/h; P<0.0001). 2
Clinical Outcomes
- Rasburicase prevents dialysis requirement and reverses renal insufficiency more effectively than allopurinol. 2
- In pediatric trials, mean creatinine decreased from 1.44 to 1.02 times normal with rasburicase, while it increased from 1.32 to 1.47 times normal with allopurinol. 2
Absolute Contraindications
G6PD Deficiency
- Rasburicase is absolutely contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to risk of severe hemolysis. 1, 5
- Screen patients at higher risk for G6PD deficiency, particularly those of African American, Mediterranean, or Southeast Asian ancestry, before administration. 5, 1
Previous Severe Reactions
- Do not administer rasburicase to patients with history of anaphylaxis, severe hypersensitivity, hemolysis, or methemoglobinemia to rasburicase. 1, 3
Other Contraindications
- Pregnancy and lactation are contraindications. 4, 1
- Patients with pre-existing methemoglobinemia or metabolic disorders causing hemolytic anemia should not receive rasburicase. 3
Dosing Considerations
Standard Dosing
- The FDA-approved dose is 0.2 mg/kg/day administered intravenously over 30 minutes for up to 5 days. 1, 5
- Treatment should begin at least 4 hours before initiation of chemotherapy when used prophylactically. 2, 5
Alternative Fixed Dosing
- A single fixed dose of 6 mg rasburicase effectively normalizes uric acid in 95% of adult patients within 24-36 hours. 7, 8
- This approach is supported by institutional guidelines showing efficacy with reduced cost, though it is not the FDA-labeled dosing. 7, 8
- Patients with baseline uric acid >17 mg/dL may be more likely to require repeat dosing. 8
Duration of Treatment
Treatment Endpoint
- Continue rasburicase until plasma uric acid is extremely low or no longer detectable; treatment is not necessary once this endpoint is achieved. 3, 5
- Duration typically ranges from 1-7 days (average 3 days) based on clinical response. 5
Single Course Limitation
- Rasburicase is indicated only for a single course of treatment due to risk of antibody development. 1
- Rasburicase-specific antibodies developed in 17 of 131 patients in one study, though no severe adverse events occurred. 2
Important Clinical Pitfalls
Sample Handling
- Blood samples for uric acid measurement must be collected in pre-chilled tubes containing heparin and immediately placed in ice water bath, with assay within 4 hours. 1
- Rasburicase enzymatically degrades uric acid in blood samples left at room temperature, leading to falsely low measurements. 1