What is the recommended dose of febuxostat (xanthine oxidase inhibitor) for treating hyperuricemia?

Febuxostat Dosing for Hyperuricemia in Gout

Start febuxostat at 40 mg once daily, then increase to 80 mg daily after 2 weeks if serum urate remains ≥6 mg/dL, with the FDA-approved maximum dose being 80 mg/day in the United States. 1, 2

Initial Dosing Strategy

• Begin at 40 mg once daily rather than higher doses to minimize the risk of gout flares during treatment initiation 1, 2, 3
• After 2 weeks, increase to 80 mg once daily if serum urate levels have not reached the target of <6 mg/dL 2, 3, 4
• The maximum FDA-approved dose in the United States is 80 mg daily 1

Dose Escalation for Refractory Disease

• For patients with severe, refractory gout who fail to achieve target serum urate on standard oral therapy, febuxostat may be increased to 120 mg daily—a dose approved in many countries outside the USA 1
• This higher dose is specifically recommended by the American College of Rheumatology for active disease refractory to appropriately dosed oral urate-lowering therapy 1

Mandatory Flare Prophylaxis

Always initiate concomitant anti-inflammatory prophylaxis when starting febuxostat, as lowering serum urate rapidly triggers gout flares 2, 5:

• Use colchicine (0.5-1 mg/day), NSAIDs, or low-dose corticosteroids 1
• Continue prophylaxis for at least 6 months after initiating urate-lowering therapy 1, 2
• Extend prophylaxis duration if flares persist beyond 6 months 2

Treatment Target and Monitoring

• Titrate dose to achieve serum urate <6 mg/dL using a treat-to-target strategy 1, 2
• For patients with severe gout (tophi, chronic arthropathy, frequent attacks), consider a lower target of <5 mg/dL until complete crystal dissolution occurs 1, 2
• Monitor serum urate every 2-5 weeks during dose titration, then every 6 months once target is achieved 1
• Do not allow serum urate to fall below 3 mg/dL long-term 1

Renal Impairment Considerations

• No dose adjustment is required for mild-to-moderate renal impairment (CKD stages 2-3) 3, 4
• Febuxostat offers an advantage over allopurinol in patients with renal insufficiency, as allopurinol requires dose reduction based on creatinine clearance 1
• Limited safety data exist for severe renal impairment (eGFR <30 mL/min); use with caution 3

Clinical Positioning

The 2020 American College of Rheumatology guidelines strongly recommend allopurinol over febuxostat as first-line therapy for all patients with gout, including those with moderate-to-severe CKD 1, 2. However, febuxostat is appropriate when:

• Allopurinol is contraindicated or not tolerated 1
• Target serum urate cannot be achieved with appropriately dosed allopurinol (up to 800 mg/day) 1
• At 80 mg daily, febuxostat demonstrates superior urate-lowering efficacy compared to allopurinol 300 mg daily 2, 6

Common Pitfalls to Avoid

• Never start at 80 mg daily—this significantly increases the risk of gout flares during initiation 1, 2
• Never initiate febuxostat without anti-inflammatory prophylaxis—this is a critical error that leads to preventable flares 2, 5
• Do not discontinue febuxostat after achieving symptom control, as this leads to recurrence of hyperuricemia and gout flares 5
• Monitor for cardiovascular events, particularly in patients with pre-existing cardiovascular disease, as some trials showed increased thromboembolic events with febuxostat 4
• Watch for liver function abnormalities, nausea, arthralgias, and rash—the most common adverse effects 3, 4, 7