What is the appropriate treatment and dosage of allopurinol for an adult patient with gout and no significant renal impairment?

Allopurinol Treatment for Gout

Yes, a patient with gout can and should take allopurinol, which is the preferred first-line urate-lowering therapy for all patients with gout, including those with moderate to severe chronic kidney disease. 1

Primary Indications for Allopurinol

Allopurinol is indicated for patients with: 1

• Recurrent acute gout attacks (more than 1 attack per year)
• Presence of tophi
• Gouty arthropathy
• Radiographic changes of gout

Starting Dose and Titration Strategy

Start low and titrate up—this is critical to avoid triggering acute flares: 1, 2

• Initial dose: 100 mg daily 1, 2
• Titration schedule: Increase by 100 mg every 2-4 weeks (guidelines recommend 2-4 weeks; FDA label suggests weekly intervals are acceptable) 1, 2
• Target serum uric acid: <6 mg/dL (360 μmol/L) for most patients 1, 3
• Lower target for severe gout: <5 mg/dL (300 μmol/L) until complete crystal dissolution occurs in patients with tophi or chronic arthropathy 1, 4
• Maximum dose: 800 mg daily 2

Dosing for Typical Gout Severity

The FDA label provides clear guidance on expected dosing: 2

• Mild gout: Average 200-300 mg/day
• Moderately severe tophaceous gout: Average 400-600 mg/day
• Doses >300 mg: Should be administered in divided doses

Common pitfall: Relying solely on the standard 300 mg dose fails to achieve target urate levels in more than half of gout patients. 1, 3 Most patients require dose titration beyond 300 mg to reach therapeutic goals.

Mandatory Prophylaxis During Initiation

Concomitant anti-inflammatory prophylaxis is strongly recommended during the first 3-6 months of allopurinol therapy to prevent acute gout flares. 1, 2 Options include:

• Colchicine (preferred)
• NSAIDs
• Low-dose corticosteroids

This is essential because initiating urate-lowering therapy mobilizes urate from tissue deposits, paradoxically triggering acute attacks even as serum uric acid normalizes. 2

Can Allopurinol Be Started During an Acute Attack?

Yes, allopurinol can be initiated during an acute gout attack without prolonging the attack, provided the acute inflammation is adequately treated. 5 The 2012 American College of Rheumatology guidelines support this approach, and a randomized trial found no significant prolongation of acute attacks when allopurinol was started during the acute phase (15.4 days to resolution with allopurinol versus 13.4 days with placebo, p=0.5). 5

Renal Dose Adjustments

For patients with renal impairment, dose adjustments are necessary: 2

• CrCl 10-20 mL/min: Maximum 200 mg daily
• CrCl <10 mL/min: Maximum 100 mg daily
• CrCl <3 mL/min: May need to lengthen dosing intervals

However, the American College of Rheumatology still recommends allopurinol as the preferred first-line agent even in moderate to severe chronic kidney disease, with appropriate dose adjustments. 1

Monitoring Requirements

During dose titration: 1

• Check serum uric acid regularly to guide dose adjustments
• Monitor for hypersensitivity reactions (rash, pruritus, elevated liver enzymes, eosinophilia)

Once target achieved: 1, 3

• Serum uric acid every 6 months
• Renal function every 6 months
• Assess for adherence and adverse effects

Duration of Therapy

Lifelong therapy is recommended. 1, 3 Discontinuing allopurinol after achieving symptom control leads to recurrence of gout flares in approximately 87% of patients within 5 years. 1, 3, 4 This is one of the most critical pitfalls to avoid—temporary symptomatic improvement does not justify stopping therapy.

Supportive Measures

The FDA label recommends: 2

• Fluid intake sufficient to yield at least 2 liters of daily urinary output
• Maintain neutral or slightly alkaline urine pH
• These measures help prevent xanthine calculi formation and renal urate precipitation

Comparison with Alternative Agents

Allopurinol versus febuxostat: 6

• Similar rates of acute gout attacks (21% with allopurinol versus 23% with febuxostat)
• Febuxostat 80 mg may be more effective at achieving target serum urate than allopurinol 300 mg (70% versus 38% achieving target)
• Similar withdrawal rates due to adverse events and serious adverse events
• However, most patients on allopurinol in these trials were limited to 300 mg; higher doses of allopurinol (up to 800 mg) can achieve comparable urate-lowering

Allopurinol versus benzbromarone: 6

• Similar efficacy in achieving target serum urate levels (58% with allopurinol versus 74% with benzbromarone)
• Similar safety profiles