What is the recommended dose of allopurinol (xanthine oxidase inhibitor) for tumor lysis syndrome prophylaxis in a patient at risk?

Allopurinol Dosing for Tumor Lysis Syndrome Prophylaxis

For tumor lysis syndrome prophylaxis, administer allopurinol at 100 mg/m² orally every 8 hours (or 10 mg/kg/day divided every 8 hours) with a maximum of 800 mg/day, or 200-400 mg/m²/day IV in 1-3 divided doses with a maximum of 600 mg/day. 1

Standard Dosing Regimen

Oral dosing:

• 100 mg/m² every 8 hours (equivalent to 10 mg/kg/day divided every 8 hours) 1
• Maximum daily dose: 800 mg/day 1

Intravenous dosing:

• 200-400 mg/m²/day in 1-3 divided doses 1
• Maximum daily dose: 600 mg/day 1

Timing and Duration

• Start 1-2 days before initiating chemotherapy 1
• Continue for 3-7 days after chemotherapy, based on ongoing TLS risk 1
• This timing allows adequate xanthine oxidase inhibition before tumor cell lysis begins 2

Critical Dose Adjustments

Renal impairment:

• Reduce dose by 50% or more in patients with renal insufficiency, as allopurinol is renally excreted and accumulates with its metabolites 1, 2

Concurrent medications:

• Reduce 6-mercaptopurine and azathioprine doses by 65-75% when given with allopurinol, as allopurinol inhibits their degradation 1
• Adjust doses of dicumarol, thiazide diuretics, chlorpropamide, and cyclosporine when used concomitantly 1

Important Limitations and When to Use Rasburicase Instead

Allopurinol only prevents new uric acid formation—it does not reduce pre-existing hyperuricemia. 1

Use rasburicase instead of allopurinol for:

• Patients with pre-existing hyperuricemia (≥7.5 mg/dL or 450 μmol/L) 1
• High-risk patients (bulky disease, high-grade lymphomas, pre-existing renal impairment, dehydration, obstructive uropathy) 2, 3
• Intermediate-risk patients who develop hyperuricemia despite allopurinol prophylaxis 1

The evidence strongly favors rasburicase in high-risk scenarios: only 2.6% of patients receiving rasburicase required dialysis compared to 16% receiving allopurinol in pediatric studies 2

Critical Safety Considerations

Xanthine crystallization risk:

• Allopurinol increases xanthine and hypoxanthine levels, which have lower solubility than uric acid 1, 2
• This can cause xanthine crystal deposition in renal tubules, leading to acute obstructive uropathy 1
• Risk is highest in patients with high tumor burden and aggressive hydration 2

Never administer allopurinol concurrently with rasburicase:

• This combination causes dangerous xanthine accumulation 2, 3
• After completing rasburicase (typically 3-5 days), transition to oral allopurinol 2, 3
• Maintain at least a 4-hour separation between the last rasburicase dose and first allopurinol dose 2

Essential Supportive Measures

Combine allopurinol with:

• Aggressive IV hydration targeting urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 2, 3
• Ideally start hydration 48 hours before chemotherapy 2, 3
• Monitor electrolytes, uric acid, creatinine, and LDH every 6-12 hours initially 3