What is the recommended dose and administration of allopurinol (xanthine oxidase inhibitor) for preventing hyperuricemia in patients undergoing chemotherapy?

Allopurinol Dosing for Prevention of Hyperuricemia in Patients Undergoing Chemotherapy

For patients undergoing chemotherapy, allopurinol should be administered at 100 mg/m²/dose every 8 hours (10 mg/kg/day divided every 8 hours) orally with a maximum of 800 mg/day, or 200-400 mg/m²/day in 1-3 divided doses intravenously with a maximum of 600 mg/day. 1

Dosing Considerations

• Start allopurinol 1-2 days before initiating chemotherapy and continue for 3-7 days afterward, based on ongoing risk of tumor lysis syndrome (TLS) development 1
• Reduce dose by at least 50% in patients with renal insufficiency 1, 2
• For oral administration in high-risk TLS patients, the recommended dose is 100 mg/m² three times daily (maximum 800 mg/day) 1
• Intravenous administration should be considered when oral administration is not feasible 1

Risk Stratification and Treatment Approach

High-Risk Patients

• Patients with high tumor burden (e.g., high-grade lymphomas, acute lymphoblastic leukemia) 1
• Patients with elevated LDH (>2 times upper normal limit) 1
• Patients receiving intensive polychemotherapy 1

Treatment recommendation for high-risk patients:

• Rasburicase is preferred over allopurinol for initial management 1
• After rasburicase treatment, transition to oral allopurinol for maintenance 1

Intermediate-Risk Patients

• If hyperuricemia develops despite prophylactic allopurinol, consider switching to rasburicase 1

Low-Risk Patients

• Oral allopurinol with hydration and urine alkalinization is recommended 1

Important Drug Interactions

• Reduce 6-mercaptopurine and/or azathioprine doses by 65-75% when used concomitantly with allopurinol 1, 2
• Consider dose adjustments when allopurinol is used with:
  • Dicumarol 1
  • Thiazide diuretics 1
  • Chlorpropamide 1
  • Cyclosporine 1, 2
  • Cytotoxic agents 2

Monitoring and Safety Considerations

• Monitor serum uric acid, electrolytes (potassium, phosphate, calcium), and renal function every 12 hours for the first three days, then every 24 hours 1
• Be aware of the risk of xanthine crystal deposition in renal tubules, which can cause acute obstructive uropathy 1, 3
• Consider HLA-B*5801 testing before initiating allopurinol in high-risk ethnic groups (Han-Chinese, Korean, Thai populations) due to increased risk of allopurinol hypersensitivity syndrome (AHS) 2, 4
• Patients with hematological malignancies may develop AHS even without known risk factors 4

Hydration Protocol

• Start hydration at least 48 hours before chemotherapy when possible 1
• Maintain urine output of at least 100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 1
• Loop diuretics may be required to maintain adequate urine output, except in patients with obstructive uropathy or hypovolemia 1

Special Considerations

• Do not administer allopurinol concurrently with rasburicase to avoid xanthine accumulation and lack of substrate for rasburicase 1
• In patients with G6PD deficiency (where rasburicase is contraindicated), use allopurinol with hydration and urine alkalinization 1
• For patients with preexisting hyperuricemia (>7.5 mg/dL), rasburicase is preferred over allopurinol 1

By following these guidelines, hyperuricemia can be effectively prevented in patients undergoing chemotherapy, reducing the risk of tumor lysis syndrome and associated complications.