What are the indications and dosing guidelines for allopurinol in treating gout?

Indications for Allopurinol Prescription

Allopurinol should be prescribed as first-line urate-lowering therapy for patients with recurrent gout attacks (≥2 per year), tophi, chronic gouty arthropathy, radiographic erosions, or urolithiasis, with the goal of maintaining serum uric acid below 6 mg/dL (360 μmol/L). 1

Primary Indications

Allopurinol is indicated for:

• Recurrent acute gout attacks (typically ≥2 attacks per year) 1, 2
• Presence of tophi (subcutaneous urate deposits) 1, 2
• Chronic gouty arthropathy or joint damage 1, 2
• Radiographic evidence of erosions from gout 1
• History of urolithiasis (kidney stones) 2, 3
• Urate overproduction (>1000 mg in 24-hour urine collection) 3

Important: Allopurinol should NOT be prescribed for asymptomatic hyperuricemia alone, as pharmacological treatment of asymptomatic hyperuricemia is not recommended to prevent gouty arthritis, renal disease, or cardiovascular events. 1

Dosing Strategy

Start low and titrate to target:

• Initial dose: 100 mg daily (or 50 mg daily in stage 4 or worse chronic kidney disease) 1, 4, 2
• Titration: Increase by 100 mg increments every 2-4 weeks 1, 2
• Target serum uric acid: <6 mg/dL (360 μmol/L) for all patients 1
• Lower target for severe gout: <5 mg/dL (300 μmol/L) for patients with tophi or chronic arthropathy until crystal dissolution is complete 1, 5
• Maximum FDA-approved dose: 800 mg daily 2

Critical point: The standard 300 mg dose fails to achieve target uric acid levels in more than half of gout patients. 1 Doses above 300 mg daily are often necessary and appropriate, even in patients with renal impairment, provided there is adequate monitoring for adverse events. 1

Mandatory Flare Prophylaxis

Always initiate anti-inflammatory prophylaxis when starting allopurinol to prevent acute gout flares during the initial phase of urate-lowering therapy. 1, 4

Prophylaxis options:

• Colchicine 0.5-1 mg daily (first-line) 1, 4
• Low-dose NSAIDs (if colchicine contraindicated or not tolerated) 1, 4
• Low-dose prednisone/prednisolone (if both above contraindicated) 1, 4

Duration: Continue prophylaxis for at least 6 months after initiating allopurinol, or longer if flares persist. 1, 4

Special Populations

Renal impairment:

• Allopurinol can be used in mild-moderate renal impairment with close monitoring 1
• Start at 50-100 mg daily in stage 3 CKD 1, 4
• Start at 50 mg daily in stage 4 or worse CKD 1
• Doses can be titrated above 300 mg even with renal impairment, with careful monitoring 1
• With creatinine clearance 10-20 mL/min: maximum 200 mg daily 2
• With creatinine clearance <10 mL/min: maximum 100 mg daily 2

Hypersensitivity risk management:

• Consider HLA-B*5801 testing in high-risk populations (Korean descent with stage 3 or worse CKD, Han Chinese, or Thai extraction) before initiating allopurinol 1
• The low starting dose strategy (≤100 mg daily) reduces risk of allopurinol hypersensitivity syndrome 1
• Monitor for rash, pruritis, elevated hepatic transaminases, and eosinophilia 1

Timing of Initiation

Allopurinol can be started during an acute gout attack, provided effective anti-inflammatory therapy has been instituted. 1, 3 Research demonstrates that initiating allopurinol at low doses (100-200 mg daily) during an acute attack does not prolong the duration or worsen severity of the flare. 3

Monitoring Requirements

During dose titration:

• Check serum uric acid every 2-5 weeks until target is achieved 1
• Monitor renal function before starting and periodically during treatment 1, 4

Once target achieved:

• Monitor serum uric acid every 6 months 1, 6
• Assess clinical symptoms, medication adherence, and adverse effects 6
• Monitor renal function every 6 months 6

Duration of Therapy

Allopurinol is lifelong therapy. Discontinuation leads to recurrence of gout flares in approximately 87% of patients within 5 years. 6, 4, 5 Once the target serum uric acid is achieved and maintained, continue the effective dose indefinitely. 6

Common Pitfalls to Avoid

• Never discontinue allopurinol after achieving symptom control - this leads to recurrence in the vast majority of patients 6, 5
• Never rely solely on the 300 mg dose - this fails to achieve target in >50% of patients 1, 6
• Never start allopurinol without flare prophylaxis - this increases risk of acute attacks and poor adherence 1, 4
• Never use outdated renal dosing algorithms that cap allopurinol at 300 mg in renal impairment - doses can be safely increased with monitoring 1
• Never prescribe allopurinol for asymptomatic hyperuricemia alone - there is no evidence this prevents gout or other complications 1