Starting Dose for Febuxostat
The recommended starting dose of febuxostat is 40 mg once daily, which can be increased to 80 mg once daily after 2 weeks if serum uric acid levels remain ≥6 mg/dL. 1, 2, 3
Initial Dosing Strategy
Begin febuxostat at 40 mg orally once daily regardless of renal function status (mild to moderate impairment does not require dose adjustment). 1, 4, 2
After 2 weeks of treatment, check serum uric acid levels; if the level is not below 6 mg/dL, increase the dose to 80 mg once daily. 1, 2
The target serum uric acid level is <6 mg/dL for all gout patients, with a lower target of <5 mg/dL for those with severe disease (tophi, chronic arthropathy, or frequent attacks). 5
Mandatory Flare Prophylaxis
Always initiate concomitant anti-inflammatory prophylaxis when starting febuxostat to prevent treatment-induced gout flares, using colchicine (0.5–1.2 mg daily), NSAIDs with gastroprotection, or low-dose prednisone (<10 mg/day). 5, 6
Continue prophylaxis for at least 3–6 months after febuxostat initiation, extending the duration if flares persist during treatment. 5
Colchicine 0.6 mg daily is the preferred first-line prophylactic agent unless contraindicated by severe renal impairment (GFR <30 mL/min) or concurrent use of strong CYP3A4/P-glycoprotein inhibitors. 6
Renal Dosing Considerations
No dosage adjustment is required for mild to moderate renal impairment (creatinine clearance 30–89 mL/min), which is a key advantage of febuxostat over allopurinol. 1, 4, 2, 3
Data are limited on the safety of febuxostat in severe renal impairment (creatinine clearance <30 mL/min); use with caution in this population. 2
Monitoring and Follow-Up
Check serum uric acid levels every 2–4 weeks during dose titration to implement a treat-to-target strategy. 5
Once the target serum uric acid level is achieved and stable, monitor every 6 months. 5
Monitor for adverse effects including liver function abnormalities (most common), nausea, arthralgias, and rash during treatment. 1, 4, 2
Cardiovascular Safety Considerations
Be aware that cardiovascular thromboembolic events occurred more frequently in randomized trials with febuxostat compared to allopurinol, though a causal relationship has not been definitively established. 1
Monitor patients for signs and symptoms of myocardial infarction and stroke, particularly in those with pre-existing cardiovascular disease. 1
Clinical Context and Positioning
Febuxostat is generally considered a second-line urate-lowering therapy after allopurinol, or as an alternative for patients who cannot tolerate allopurinol due to hypersensitivity, intolerance, or lack of efficacy. 1, 2
Febuxostat 80 mg/day achieves superior serum uric acid reduction compared to conventionally dosed allopurinol (300 mg/day), with 67% vs 42% of patients reaching target levels <6 mg/dL. 7, 3
The main advantage of febuxostat is its consistent dosing without renal adjustment in mild-to-moderate kidney disease, whereas allopurinol requires dose reduction and careful titration in renal impairment. 4, 2
Common Pitfalls to Avoid
Do not start febuxostat without concurrent flare prophylaxis, as initiating urate-lowering therapy precipitates acute gout attacks in the majority of patients. 5, 6
Do not assume the 40 mg dose will be sufficient; approximately half of patients require dose escalation to 80 mg to achieve target serum uric acid levels. 2, 3
Do not discontinue febuxostat during an acute gout flare; continue the medication with appropriate anti-inflammatory treatment, as stopping does not improve flare outcomes and delays definitive urate control. 6