Fixed-Dose Rasburicase for Hyperuricemia Prevention in Cancer-Associated TLS

Tumor lysis syndrome (TLS) is an oncologic emergency caused by the rapid breakdown of malignant cells with release of intracellular contents. TLS can occur spontaneously or, more commonly, within 12 to 72 hours following chemoimmunotherapy.¹ TLS occurs most often in hematologic malignancies with a high cell burden, that rapidly proliferate and are chemosensitive (e.g., Burkitt lymphoma, acute lymphoblastic leukemia).²

Malignant cell lysis results in hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia, which can precipitate life-threatening arrhythmias, seizures, and cause acute kidney injury (AKI) due to intratubular deposition of uric acid and calcium phosphate.^2,3 The Cairo-Bishop criteria are commonly used to diagnose and grade TLS, distinguishing laboratory from clinical TLS based on specific metabolic thresholds and organ complications (Table 1).³

Table 1. Cairo-Bishop Diagnostic Criteria for TLS³

TLS is best managed when anticipated and prophylaxis is initiated prior to chemotherapy. The cornerstone of care includes aggressive hydration and management of hyperuricemia, and frequent electrolyte monitoring with prompt correction of abnormalities.²

In low TLS-risk patients, prophylaxis with a xanthine-oxidase inhibitor such as allopurinol or febuxostat should begin 2 to 3 days prior to chemotherapy and continue for 10 to 14 days to block new uric acid formation. Low-risk disease is characterized by a normal serum lactate dehydrogenase (LDH) and stage I disease, including a single extra-abdominal mass <10 cm or a completely resected abdominal lesion.²

In intermediate TLS-risk disease, allopurinol or febuxostat should be started prophylactically. Rasburicase may be used if the patient has renal dysfunction and uric acid, potassium, and/or phosphate above the ULN. Intermediate-risk disease is characterized by a serum LDH <2 times the upper limit of normal (ULN) and stage I or II disease.²

For high TLS-risk disease, rasburicase should be started prophylactically. High-risk disease is characterized by a serum LDH ≥2 times the ULN and either stage I disease with an abdominal mass or extra-abdominal mass >10 cm, or stage II to IV disease.²

Rasburicase (Elitek; Sanofi) is a recombinant urate oxidase that lowers uric acid by converting it to allantoin, an inactive, more soluble metabolite. It is FDA-approved for TLS prevention at a recommended dose of 0.2 mg/kg rounded up to the nearest vial size, administered as an intravenous infusion once daily for 1 to 7 days based on uric acid levels.⁴

Glucose-6-phosphate dehydrogenase (G6PD) testing is required prior to rasburicase use due to the risk of hemolysis and methemoglobinemia in patients with G6PD deficiency.⁴ In these patients, rasburicase should be substituted with allopurinol.²

The National Comprehensive Cancer Network (NCCN) guidelines and multiple studies suggest that fixed rasburicase doses of 3 mg or 6 mg can achieve comparable urate control to weight-based dosing while reducing costs (Table 2). A single dose is usually adequate. Redosing should be individualized and considered for patients who require urgent therapy with high cell burden, when adequate hydration is difficult or impossible, or in the setting of an AKI.²

Based on these findings, a pharmacist may:

1. Adjust a rasburicase order to a single 3 mg or 6 mg dose if a weight-based order was placed (per provider approval or institutional protocol)
2. Assess the patient profile for history or evidence of G6PD deficiency
3. Ensure adequatehydration is ordered

Implementing a fixed dose rasburicase protocol with pharmacist driven verification, emphasizing early prophylaxis, and standardized hydration can reduce cancer-associated TLS related morbidity and mortality. This approach maintains urate control comparable to weight-based regimens and supports cost conscious practice.

REFERENCES

1. Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol. 2008;26(16):2767-2778. doi:10.1200/JCO.2007.15.0177

2. NCCN. Clinical Practice Guidelines in Oncology. B-Cell Lymphomas, Version 3.2025. Accessed September 12, 2025. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf

3. Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol. 2004;127(1):3-11. doi:10.1111/j.1365-2141.2004.05094.x

4. Elitek [prescribing information]. Sanofi-aventis U.S.; May 2025. Accessed September 12, 2025. https://products.sanofi.us/elitek/Elitek.pdf

5. Bakhsh S, Khan MA, Alshamrani M, et al. Effectiveness of a Single Fixed Dose of 3 mg Rasburicase for the Prevention and Management of Hyperuricemia in Tumor Lysis Syndrome in Adults With Cancer. Cureus. 2024;16(9):e68664. doi:10.7759/cureus.68664

6. Trifilio S, Gordon L, Singhal S, et al. Reduced-dose rasburicase (recombinant xanthine oxidase) in adult cancer patients with hyperuricemia. Bone Marrow Transplant. 2006;37(11):997-1001. doi:10.1038/sj.bmt.1705379

7. Vines AN, Shanholtz CB, Thompson JL. Fixed-dose rasburicase 6 mg for hyperuricemia and tumor lysis syndrome in high-risk cancer patients. Ann Pharmacother. 2010;44(10):1529-1537. doi:10.1345/aph.1P296