What medication helps prevent tumor lysis syndrome in patients with leukemia or lymphoma undergoing chemotherapy?

Medications for Tumor Lysis Syndrome Prevention

The primary medications for preventing tumor lysis syndrome are rasburicase for high-risk patients and allopurinol for low-risk patients, combined with aggressive intravenous hydration in both cases. 1, 2

Risk Stratification Determines Medication Choice

High-risk patients should receive rasburicase as primary prophylaxis, not allopurinol. 2 High-risk features include:

• Pre-existing renal impairment, dehydration, or obstructive uropathy 2
• Bulky disease or high-grade lymphomas 2
• Rapidly increasing blast counts with hyperuricemia >8 mg/dL 1, 3
• Intensive polychemotherapy regimens 2

Low-risk patients should receive oral allopurinol combined with vigorous hydration (≥2 L/m²/day). 2

Rasburicase: The Superior Agent for High-Risk Patients

Rasburicase converts existing uric acid to allantoin, which is 5-10 times more soluble than uric acid, providing immediate reduction of pre-existing hyperuricemia. 2 This mechanism is fundamentally different from allopurinol, which only prevents new uric acid formation.

Dosing and Administration

Administer rasburicase at 0.20 mg/kg/day IV over 30 minutes for 3-5 days, with the first dose given at least 4 hours before starting chemotherapy. 2, 4

• The standard multi-day regimen remains guideline-recommended 2
• After completing rasburicase, transition to oral allopurinol 2
• Never administer rasburicase and allopurinol concurrently to avoid dangerous xanthine accumulation 2

Evidence of Superiority

In a randomized pediatric trial, rasburicase achieved significantly lower mean uric acid area under the curve (128±70 mg/dL/hour) compared to allopurinol (329±129 mg/dL/hour; p<0.001). 1 A retrospective study showed only 2.6% of patients receiving rasburicase required dialysis compared to 16% receiving allopurinol. 2

Critical Contraindications

Rasburicase is absolutely contraindicated in patients with G6PD deficiency, as it causes life-threatening hemolysis and methemoglobinemia. 2, 4 Additional contraindications include:

• History of anaphylaxis to rasburicase 2, 4
• Pregnancy and lactation 2, 4
• History of methemoglobinemia or hemolytic reactions 4

Mandatory G6PD screening must be performed before initiating rasburicase. 2

Allopurinol: First-Line for Low-Risk Patients

Allopurinol blocks xanthine oxidase enzyme activity, preventing conversion of xanthine and hypoxanthine to uric acid. 2 This prevents new uric acid formation but does not address pre-existing hyperuricemia.

Dosing Regimen

Administer allopurinol at 100 mg/m² every 8 hours orally (maximum 800 mg/day) or 200-400 mg/m²/day IV in divided doses (maximum 600 mg/day). 2

• Start 1-2 days before initiating chemotherapy 2
• Continue for 3-7 days after chemotherapy based on ongoing TLS risk 2

Critical Dosing Adjustment

Reduce allopurinol dose by 50% or more in patients with renal insufficiency, as the drug and its metabolites accumulate. 2 Failure to adjust dosing leads to drug accumulation and increased toxicity. 2

Important Limitation

Allopurinol increases xanthine and hypoxanthine levels, which have lower solubility and can cause xanthine crystal deposition in renal tubules. 2 This risk is particularly concerning in patients receiving aggressive hydration or those with pre-existing renal impairment. 2

Essential Supportive Measures

Aggressive IV hydration must be initiated, ideally 48 hours before chemotherapy, targeting urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg). 1, 3

• Loop diuretics (not thiazides) may be required to achieve target urine output 1, 3
• Avoid diuretics in patients with obstructive uropathy or hypovolemia 1

Critical Monitoring Requirements

When using rasburicase, blood samples must be immediately placed on ice to prevent continued ex vivo enzymatic degradation, which falsely lowers measured uric acid levels. 2, 4 Specific handling:

• Collect blood into prechilled tubes containing heparin 4
• Immediately immerse samples in ice water bath 4
• Centrifuge in precooled centrifuge (4°C) 4
• Analyze plasma within 4 hours of collection 4

Monitor uric acid, electrolytes (potassium, phosphate, calcium), creatinine, and BUN every 6 hours for the first 24 hours, then every 12 hours for 3 days. 3

Common Pitfalls to Avoid

Never use febuxostat (another xanthine oxidase inhibitor) concurrently with rasburicase, as this causes dangerous xanthine accumulation leading to xanthine crystal deposition and acute obstructive uropathy. 2 The sequential use is safe: rasburicase followed by allopurinol or febuxostat. 2

Premature resumption of chemotherapy before metabolic abnormalities correct can trigger recurrent TLS. 5 Ensure uric acid <8 mg/dL, creatinine <141 μmol/L, and pH ≥7.0 before restarting therapy. 5