When should allopurinol be started in patients with gout?

When to Start Allopurinol for Gout

Allopurinol should be initiated in all patients with recurrent gout flares (≥2/year), tophi, urate arthropathy, renal stones, or very high serum uric acid levels (>8.0 mg/dL), and should be considered and discussed with every patient with a definite diagnosis of gout from the first presentation. 1

Indications for Starting Allopurinol

Allopurinol should be started in patients with:

• Recurrent gout flares (two or more per year) 1
• Presence of tophi 1
• Urate arthropathy (chronic gouty arthritis) 1
• Renal stones 1
• Very high serum uric acid level (>8.0 mg/dL; 480 mmol/L) 1
• Young age at onset (<40 years) 1
• Comorbidities (renal impairment, hypertension, ischemic heart disease, heart failure) 1

Timing of Initiation

• The 2020 American College of Rheumatology (ACR) guidelines conditionally recommend initiating urate-lowering therapy (ULT) even after the first gout flare in patients meeting criteria for ULT 1
• The European League Against Rheumatism (EULAR) recommends discussing ULT with every patient with a definite diagnosis of gout from the first presentation 1
• For patients experiencing their first flare, ULT initiation should be considered if they have risk factors for recurrent or severe disease 1
• Traditionally, allopurinol was not started during an acute gout attack, but recent evidence suggests it may be initiated during a flare without prolonging the attack 2
• The ACR conditionally recommends starting ULT during a gout flare rather than waiting until it resolves 1

Starting Dose and Titration

• Start with a low dose (100 mg/day for most patients, 50 mg/day for patients with stage 4 or worse chronic kidney disease) 3, 4
• Increase by 100 mg increments every 2-4 weeks until reaching the serum urate target 1, 3, 4
• Monitor serum uric acid levels every 2-5 weeks during dose titration 3
• The maximum FDA-approved dose is 800 mg/day 3, 4
• 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, 5

Target Serum Urate Levels

• The therapeutic goal is to maintain serum uric acid below 6 mg/dL (360 μmol/L) 1, 6
• A lower target of <5 mg/dL (300 μmol/L) is recommended for patients with severe gout (tophi, chronic arthropathy, frequent attacks) 1, 3
• Once the target is achieved, monitor serum urate levels every 6 months 6, 3

Prophylaxis During Initiation

• Concomitant anti-inflammatory prophylaxis is strongly recommended when starting allopurinol to prevent flares 1, 4
• Options include colchicine (0.5-1 mg/day), low-dose NSAIDs, or prednisone/prednisolone 1
• Prophylaxis should be continued for 3-6 months after starting ULT 1
• Colchicine dose should be reduced in patients with renal impairment 1

Special Considerations

Renal Impairment

• Allopurinol remains the preferred first-line agent even in patients with moderate-to-severe chronic kidney disease (CKD) 1, 3
• Start at a lower dose (50 mg/day) in patients with severe renal impairment 3, 4
• Dose can be gradually increased with careful monitoring 3, 7

Safety Monitoring

• Monitor for drug hypersensitivity and adverse events (pruritus, rash, elevated liver enzymes) 3, 8
• Consider HLA-B*5801 testing prior to initiation in high-risk populations (Korean patients with stage ≥3 CKD, Han Chinese, or Thai patients) 3

Common Pitfalls to Avoid

• Starting at too high a dose, which increases risk of allopurinol hypersensitivity syndrome 8
• Relying solely on the standard 300 mg dose, which often fails to achieve target urate levels 3, 5
• Discontinuing allopurinol after achieving symptom control, which leads to recurrence of gout flares 6
• Underestimating the need for lifelong therapy 6, 9
• Not using prophylaxis when initiating allopurinol 1

Allopurinol dose escalation has been shown to be effective and well-tolerated in achieving target serum urate levels, even in patients with mild-to-moderate renal impairment 7. Lifelong therapy is recommended as discontinuation leads to recurrence of gout flares in approximately 87% of patients within 5 years 6.