What is the recommended dose of allopurinol for treating gouty arthritis?

Allopurinol Dosing for Gouty Arthritis

Allopurinol should be started at a low dose of 100 mg daily and gradually increased by 100 mg increments every 2-4 weeks until achieving the target serum urate level of <6 mg/dL, with most patients requiring 300-600 mg/day for optimal effectiveness. 1, 2

Initial Dosing Strategy

• Start allopurinol at 100 mg daily for most patients with gouty arthritis 3, 1
• For patients with stage 4 or worse chronic kidney disease (CKD), start at an even lower dose of 50 mg daily 3, 1
• Increase the dose by 100 mg increments every 2-4 weeks until reaching the target serum urate level 3
• Monitor serum urate levels every 2-5 weeks during dose titration 1, 3

Target Serum Urate Levels

• The primary target is to maintain serum urate below 6 mg/dL (360 μmol/L) in all gout patients 3
• A lower target of <5 mg/dL (300 μmol/L) is recommended for patients with severe gout (tophi, chronic arthropathy, frequent attacks) until crystal dissolution and resolution of gout 3, 1
• Once the target is achieved, continue monitoring serum urate every 6 months 1

Maintenance Dosing

• The average effective dose ranges from 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 3, 1
• The maximum FDA-approved dose is 800 mg daily 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 renal impairment 1, 3
• For patients with creatinine clearance 10-20 mL/min, a daily dose of 200 mg is suitable 2
• When creatinine clearance is <10 mL/min, daily dosage should not exceed 100 mg 2
• With extreme renal impairment (creatinine clearance <3 mL/min), the interval between doses may also need to be lengthened 2

Safety Monitoring

• Monitor for drug hypersensitivity and adverse events (pruritus, rash, elevated liver enzymes, eosinophilia) during dose escalation 3, 1
• Consider HLA-B*5801 testing prior to initiation in high-risk populations (Korean patients with stage ≥3 CKD, Han Chinese, or Thai patients) 3, 1

Flare Prevention During Initiation

• Prophylaxis against gout flares is recommended during the first 6 months of allopurinol therapy 3
• Use colchicine 0.5-1 mg/day for prophylaxis, with dose reduction in patients with renal impairment 3
• If colchicine is not tolerated or contraindicated, low-dose NSAIDs can be used if not contraindicated 3

Clinical Pearls

• Allopurinol can be started during an acute gout attack if effective anti-inflammatory management has been instituted 3, 4
• The "go low, go slow" strategy of gradual dose titration helps reduce early gout flares and the incidence of toxicity 3, 1
• A dose of 1.5 mg per unit of estimated GFR or lower may be associated with reduced risk of allopurinol hypersensitivity syndrome 5
• In a randomized controlled trial, allopurinol dose escalation achieved target serum urate in 69% of patients compared to 32% in the control group, with similar safety profiles 6
• Maintain adequate fluid intake (at least 2 liters of urine output daily) and slightly alkaline urine to help prevent renal precipitation of urates 2