Allopurinol Dosing for Tumor Lysis Syndrome Prophylaxis
For tumor lysis syndrome prophylaxis, allopurinol should be administered orally at a dose of 100 mg/m² three times daily (maximum 800 mg/day), starting at least 48 hours before chemotherapy when possible. 1
Risk Stratification for TLS Prophylaxis
Proper patient risk stratification is essential for determining the appropriate prophylactic approach:
High-Risk Patients
Patients with any of these factors:
- Host factors: Dehydration, hyponatremia, pre-existing renal impairment, obstructive uropathy, hyperuricemia (>10 mg/dL in adults)
- Disease factors: Bulky disease, high-grade lymphomas (especially Burkitt's), metastatic germ cell tumors, acute lymphoblastic leukemia, elevated LDH (>2× upper limit)
- Treatment factors: Intensive polychemotherapy with cisplatin, cytarabine, etoposide, or methotrexate
Prophylaxis Algorithm
High-risk patients:
- First-line: Rasburicase (0.20 mg/kg/day IV) + hydration
- After rasburicase course: Switch to oral allopurinol
Low-risk patients:
- Oral allopurinol (100 mg/m² three times daily, maximum 800 mg/day)
- Hydration (≥2 L/m²/day)
- Urine alkalinization
Allopurinol Administration Details
- Timing: Begin at least 48 hours before tumor-specific therapy when possible 1
- Duration: Continue throughout chemotherapy and until uric acid levels normalize
- Dose adjustment for renal impairment 2:
- Creatinine clearance 10-20 mL/min: 200 mg/day
- Creatinine clearance <10 mL/min: ≤100 mg/day
- Extreme renal impairment (clearance <3 mL/min): Extend dosing interval
Hydration Requirements
- Maintain hydration of at least 2 L/m²/day 1
- Target urine output: ≥100 mL/hour in adults 1
- Consider loop diuretics to maintain urine output if needed (except in patients with obstructive uropathy or hypovolemia)
Monitoring During TLS Prophylaxis
For high-risk patients, monitor:
- Uric acid, electrolytes (Na, K, Ca, P), creatinine, BUN: Every 12 hours for first 3 days, then daily 1
- Vital signs and fluid status
Special Considerations
- Patients with G6PD deficiency or other metabolic disorders that can cause hemolytic anemia should receive allopurinol rather than rasburicase 1
- For prevention of uric acid nephropathy during intensive chemotherapy of neoplastic disease, higher doses (600-800 mg daily for 2-3 days) may be used 2
- Taking allopurinol after meals generally improves tolerability 2
Comparative Efficacy
While allopurinol prevents formation of new uric acid, it does not reduce existing uric acid levels. Rasburicase acts more rapidly by converting existing uric acid to soluble allantoin 3. In hyperuricemic patients, time to plasma uric acid control is approximately 4 hours with rasburicase versus 27 hours with allopurinol 4.
A randomized trial showed that patients receiving rasburicase had 2.6-fold less exposure to uric acid compared to those receiving allopurinol, with an 86% versus 12% reduction in plasma uric acid levels 4 hours after the first dose 5.