What is the recommended dose of allopurinol for treating gout?

Allopurinol Dosing for Gout Treatment

For gout treatment, allopurinol should be started at a low dose of 100 mg/day (50 mg/day in patients with CKD stage ≥4) and gradually titrated upward every 2-5 weeks until reaching the serum urate target of <6 mg/dL, with doses often requiring 300-600 mg/day for optimal effectiveness. 1, 2

Initial Dosing and Titration Strategy

• Start allopurinol at no greater than 100 mg/day for most patients 1
• For patients with stage 4 or worse chronic kidney disease (CKD), start at an even lower dose of 50 mg/day 1
• Gradually increase the dose by 100 mg increments every 2-5 weeks until reaching the target serum urate level 1
• Monitor serum urate levels every 2-5 weeks during dose titration to guide adjustments 1

Target Serum Urate Levels

• The primary goal is to achieve serum urate <6 mg/dL in all gout patients 1
• For patients with severe gout (tophi, chronic arthropathy, frequent attacks), consider a lower target of <5 mg/dL to facilitate faster crystal dissolution 1
• Continue monitoring serum urate every 6 months once target is achieved 1

Maintenance Dosing

• The average effective dose range is 200-300 mg/day for mild gout and 400-600 mg/day for moderately severe tophaceous gout 2
• Doses above 300 mg/day are often necessary, as allopurinol at ≤300 mg/day fails to achieve target urate levels in more than half of gout patients 1
• The maximum FDA-approved dose is 800 mg/day 1, 2
• Doses exceeding 300 mg should be administered in divided doses 2

Special Considerations

Renal Impairment

• Allopurinol remains the preferred first-line agent even in patients with moderate-to-severe CKD (stage ≥3) 1
• While traditional practice limited dosing in renal impairment, current guidelines support dose titration above 300 mg/day even in renal impairment if done with careful monitoring 1
• For patients with creatinine clearance 10-20 mL/min, a daily dose of 200 mg is suitable; with clearance <10 mL/min, do not exceed 100 mg/day 2

Safety Monitoring

• Monitor for drug hypersensitivity and adverse events (pruritis, rash, elevated liver enzymes, eosinophilia) during dose escalation 1
• Consider HLA-B*5801 testing prior to initiation in high-risk populations (Korean patients with stage ≥3 CKD, Han Chinese, or Thai patients regardless of renal function) 1
• The risk of allopurinol hypersensitivity syndrome (AHS) is highest in the first few months of therapy 1, 3

Clinical Pearls and Pitfalls

• Common Pitfall: Many practitioners limit allopurinol to 300 mg/day, which is often insufficient to reach target urate levels 1, 4
• Efficacy Evidence: Studies show that up-titration of allopurinol to doses up to 600 mg/day can achieve target urate levels in over 90% of patients 5, 6
• Safety Consideration: Starting at a higher dose increases risk of AHS; a starting dose of ≥1.5 mg per unit of estimated GFR is associated with increased risk 3
• Practical Approach: After a single 100-mg dose increase, mean fall in urate levels is approximately 71 μmol/L (1.2 mg/dL) 6
• Concurrent Therapy: Always initiate prophylaxis against gout flares (colchicine, NSAIDs, or prednisone) when starting allopurinol 1
• Treatment Timing: Contrary to traditional practice, allopurinol can be safely started during an acute gout attack if effective anti-inflammatory treatment is provided 7, 1