Allopurinol Dosing After Chemotherapy-Induced Tumor Lysis Syndrome
After completing rasburicase therapy for chemotherapy-induced TLS, transition to oral allopurinol at 100 mg/m² every 8 hours (maximum 800 mg/day orally) or 200-400 mg/m²/day IV in divided doses (maximum 600 mg/day), continuing for 3-7 days based on ongoing TLS risk, with mandatory 50% dose reduction in renal impairment. 1, 2
Sequencing: Rasburicase First, Then Allopurinol
Never administer allopurinol concurrently with rasburicase—this combination causes xanthine and hypoxanthine accumulation, leading to xanthine crystal deposition in renal tubules and acute obstructive uropathy. 2, 3
After completing the 3-5 day rasburicase course (0.20 mg/kg/day IV), transition to oral allopurinol for continued uric acid control. 2, 3
A multicenter phase III trial demonstrated that sequential rasburicase followed by allopurinol achieved 78% response rate with excellent tolerability, reducing uric acid within 4 hours (versus 27 hours for allopurinol alone). 2, 4
Standard Allopurinol Dosing Regimen
Oral dosing: 100 mg/m² every 8 hours (equivalent to 10 mg/kg/day divided every 8 hours), with a maximum daily dose of 800 mg/day. 1, 2
Intravenous dosing: For patients unable to take oral medication, use 200-400 mg/m²/day IV in 1-3 divided doses, with a maximum of 600 mg/day. 1, 5
Continue allopurinol for 3-7 days after chemotherapy initiation, adjusting duration based on ongoing TLS risk assessment. 1, 2
Mandatory Renal Dose Adjustment
Reduce allopurinol dose by at least 50% in any degree of renal insufficiency because the drug and its active metabolite oxipurinol are renally excreted and accumulate in renal failure. 1, 2, 5
With creatinine clearance 10-20 mL/min: maximum 200 mg daily. 5
With creatinine clearance <10 mL/min: maximum 100 mg daily. 5
With extreme renal impairment (creatinine clearance <3 mL/min): extend the interval between doses beyond daily administration. 5
Critical Drug Interactions
Reduce 6-mercaptopurine or azathioprine doses by 65-75% when co-administered with allopurinol, as allopurinol blocks purine degradation and causes toxic accumulation of these thiopurines. 1, 2
Monitor and potentially adjust doses of dicumarol, thiazide diuretics, chlorpropamide, and cyclosporine when used with allopurinol. 1
Supportive Measures During Allopurinol Therapy
Maintain aggressive IV hydration targeting urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg). 2, 3
Ensure daily urinary output of at least 2 liters with neutral or slightly alkaline urine. 5
Loop diuretics (not thiazides) may be required to achieve target urine output, but avoid in obstructive uropathy or hypovolemia. 2, 3
Monitoring Parameters
Monitor uric acid, electrolytes (potassium, phosphate, calcium), creatinine, BUN, and LDH every 6 hours for the first 24 hours, then every 12 hours for 3 days, then daily until stable. 3, 6
Maintain urine specific gravity at 1.010 to ensure adequate dilution. 1
Common Pitfalls to Avoid
Failure to reduce allopurinol dose in renal impairment leads to drug accumulation and toxicity—always check creatinine clearance before dosing. 2, 5
Starting allopurinol before completing rasburicase causes xanthine accumulation because rasburicase generates xanthine/hypoxanthine as intermediates while allopurinol blocks their further metabolism. 2
Allopurinol only prevents new uric acid formation and does not reduce pre-existing hyperuricemia—this is why rasburicase is preferred initially for patients with baseline uric acid >7.5 mg/dL. 1
Do not correct mild hypocalcemia with calcium gluconate during TLS management, as this promotes calcium-phosphate precipitation in tissues and kidneys. 2, 3
Criteria for Safe Chemotherapy Resumption
Uric acid <475 μmol/L (8 mg/dL). 6
Creatinine <141 μmol/L. 6
pH ≥7.0. 6
All electrolytes (potassium, phosphate, calcium) normalized. 6
Obtain nephrology consultation before restarting therapy in any patient with previous clinical TLS. 6
Implement prophylactic rasburicase for all subsequent chemotherapy cycles in patients with previous TLS, as they remain at high risk for recurrence. 6