What is the recommended dosage of febuxostat (Uloric) for treating gout?

Febuxostat Dosage for 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 maximum FDA-approved dose being 80 mg/day in the United States (though 120 mg/day is approved internationally for refractory cases). 1

Initial Dosing Strategy

• Begin with febuxostat 40 mg orally once daily to minimize the risk of gout flares during initiation 1, 2
• After 2 weeks, increase to 80 mg once daily if serum urate levels remain ≥6 mg/dL 2, 3
• The FDA-approved maximum dose in the United States is 80 mg daily 1

Dose Escalation for Refractory Disease

• For patients with active disease refractory to standard oral therapy, febuxostat may be increased to 120 mg daily, a dose approved in many countries outside the USA 1
• This higher dose should only be considered when the 80 mg dose fails to achieve target serum urate levels and disease remains symptomatic 1

Mandatory Flare Prophylaxis

• Always initiate concomitant anti-inflammatory prophylaxis when starting febuxostat, using colchicine, NSAIDs, or prednisone/prednisolone 1
• Continue prophylaxis for 3-6 months after initiating therapy, with ongoing evaluation and extended prophylaxis if flares persist 1
• This approach significantly reduces the risk of gout attacks during the initial treatment period 1

Dosing in Special Populations

Chronic Kidney Disease

• No dosage adjustment is required for mild to moderate renal impairment, unlike allopurinol 4, 3
• Febuxostat maintains efficacy in patients with CKD and may be preferred when renal function limits allopurinol dosing 4, 3
• However, data on severe renal impairment remain limited 3

Hepatic Impairment

• No dosage adjustment needed for mild to moderate hepatic impairment 2, 5

Treatment Target and Monitoring

• Titrate dose to achieve serum urate <6 mg/dL using a treat-to-target strategy 1
• For patients with severe gout (tophi, chronic arthropathy), consider a lower target of <5 mg/dL until crystal dissolution is complete 6
• Monitor serum urate levels regularly during dose titration to guide therapy 1

Clinical Context and Positioning

• The 2020 American College of Rheumatology guidelines strongly recommend allopurinol over febuxostat as first-line therapy for all patients with gout 1
• Febuxostat serves as an appropriate alternative when allopurinol is not tolerated, contraindicated, or fails to achieve target serum urate levels despite appropriate dosing 1, 2
• At 80 mg daily, febuxostat demonstrates greater urate-lowering efficacy than allopurinol 300 mg daily in head-to-head trials 1, 4

Common Pitfalls to Avoid

• Do not start at higher doses (80 mg) initially, as this increases the risk of gout flares during initiation 1
• Never initiate febuxostat without anti-inflammatory prophylaxis, as this significantly increases flare risk 1
• Do not discontinue therapy prematurely—long-term studies show that sustained treatment for 3-5 years maintains target urate levels and nearly eliminates gout flares 4, 7
• Be aware that cardiovascular thromboembolic events were more common in febuxostat-treated patients in some trials, though causality remains unestablished; monitor patients for signs of myocardial infarction and stroke 2

Adverse Effects

• Most common adverse events include liver function abnormalities, diarrhea, nausea, arthralgias, and rash 4, 2, 3
• Most treatment-related adverse events are mild to moderate in severity 7
• Cardiovascular safety continues to be evaluated in ongoing large trials 4