What is the recommended dose of allopurinol based on estimated Glomerular Filtration Rate (eGFR)?

Allopurinol Dosing Based on eGFR

Start allopurinol at ≤100 mg/day for patients with eGFR ≥30 mL/min/1.73m² and at ≤50 mg/day for eGFR <30 mL/min/1.73m², then titrate upward every 2-5 weeks by 50-100 mg increments to achieve serum uric acid <6 mg/dL, regardless of renal function. 1

Initial Dosing Strategy by eGFR

For eGFR ≥30 mL/min/1.73m²:

• Start at 100 mg once daily 1
• This low starting dose significantly reduces the risk of allopurinol hypersensitivity syndrome (AHS), which carries a 20-25% mortality rate 1

For eGFR <30 mL/min/1.73m²:

• Start at 50 mg once daily 1, 2
• For severe renal impairment (creatinine clearance <10 mL/min), do not exceed 100 mg daily 3
• With creatinine clearance 10-20 mL/min, use 200 mg daily as the maximum 3
• With extreme renal impairment (creatinine clearance <3 mL/min), lengthen the interval between doses 3

Dose Titration Protocol

Regardless of renal function, titrate aggressively to target:

• Increase by 50-100 mg every 2-5 weeks based on serum uric acid monitoring 1, 2
• Target serum uric acid <6 mg/dL in all patients 1, 4
• For severe tophaceous gout, target may be <5 mg/dL 1, 4
• Doses can safely exceed 300 mg/day even in CKD stage ≥3, provided adequate patient education and monitoring occur 1, 2

This represents a paradigm shift from older FDA labeling recommendations that suggested strict dose caps based on creatinine clearance 3. Current American College of Rheumatology guidelines emphasize that the "start low, go slow" approach with careful monitoring allows safe dose escalation regardless of renal function 1, 2.

Critical Monitoring Requirements

During dose titration (weeks 0-24):

• Monitor serum uric acid every 2-5 weeks 1, 4
• Watch for hypersensitivity signs: rash, pruritus, elevated liver enzymes 1, 4
• The highest risk for severe hypersensitivity reactions occurs in the first few months 1, 4

After achieving target (maintenance phase):

• Monitor serum uric acid every 6 months 1, 4
• Continue vigilance for delayed hypersensitivity reactions 1

Risk Mitigation Strategies

HLA-B*5801 genetic testing should be considered before initiating allopurinol in:

• Korean patients with stage 3 or worse CKD 1, 2
• Han Chinese and Thai patients regardless of renal function 2

Avoid concurrent thiazide diuretics when possible:

• Thiazides increase risk of hypersensitivity syndrome 1, 4
• If unavoidable, implement closer monitoring 1

Common Pitfalls to Avoid

Do not rely on plasma creatinine alone to guide dosing:

• Plasma creatinine <2.0 mg/dL has only 13% sensitivity to detect creatinine clearance <50 mL/min 5
• One-third of patients with plasma creatinine 1.0-1.5 mg/dL and 90% with 1.5-2.0 mg/dL would receive excessive doses if dosing were based on plasma creatinine rather than calculated creatinine clearance 5
• Always calculate eGFR or creatinine clearance using the Cockcroft-Gault equation 5

Do not cap doses at 300 mg/day in patients with CKD:

• Older recommendations suggesting strict dose limitations based on renal function are outdated 1, 2
• Modern treat-to-target strategies demonstrate safety and efficacy of higher doses with appropriate monitoring 6

Alternative Therapy Considerations

If target serum uric acid cannot be achieved with appropriately dosed allopurinol:

• Consider febuxostat, which can be used without dose adjustment in mild to moderate renal impairment 1, 2
• Recent data from the STOP Gout trial showed allopurinol and febuxostat are similarly efficacious in CKD patients when used in a treat-to-target regimen, with actually fewer gout flares in the allopurinol group 6

Avoid uricosuric agents as first-line therapy:

• Contraindicated with creatinine clearance <50 mL/min due to increased risk of renal stone formation 2