Febuxostat Dosing and Treatment Plan 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, and always initiate concomitant anti-inflammatory prophylaxis for at least 8 weeks to prevent gout flares. 1, 2
Initial Dosing Strategy
- Begin with febuxostat 40 mg once daily rather than starting at a higher dose to minimize the risk of precipitating acute gout flares 1, 2
- After 2 weeks, check serum urate levels and increase to 80 mg daily if the target of <6 mg/dL has not been achieved 2, 3, 4
- The maximum FDA-approved dose is 80 mg daily in the United States 1
- For refractory disease outside the U.S., doses up to 120 mg daily may be considered where approved 1
- No dosage adjustment is required for mild-to-moderate renal impairment (CrCl 30-89 mL/min), which is a key advantage over allopurinol 5, 4
Mandatory Flare Prophylaxis
You must initiate anti-inflammatory prophylaxis when starting febuxostat to prevent the paradoxical increase in gout flares that occurs with urate-lowering therapy 1, 2:
- Colchicine 0.5-1 mg daily, OR
- Low-dose NSAIDs, OR
- Low-dose prednisone/prednisolone 6
Continue prophylaxis for more than 8 weeks—studies that discontinued prophylaxis at 8 weeks experienced a spike in acute gout attacks 1, 2. Consider extending prophylaxis for 3-6 months or longer if flares persist 6.
When to Use Febuxostat
Febuxostat is not first-line therapy—allopurinol remains the strongly recommended initial agent for all patients with gout 1:
- Use febuxostat when allopurinol is not tolerated, causes hypersensitivity, or fails to achieve target serum urate despite appropriate dose titration 1
- Febuxostat is appropriate for patients with moderate-to-severe chronic kidney disease (stage ≥3) who cannot tolerate adequate allopurinol dosing 1
- Do not use febuxostat as first-line therapy in patients with established cardiovascular disease due to potential CV safety concerns 2
Indications for Long-Term Treatment
Initiate urate-lowering therapy only in patients with:
- Recurrent gout (≥2 episodes per year), OR
- Problematic gout including tophi, chronic kidney disease, or urolithiasis 2
Do not initiate febuxostat after a first gout attack or in patients with infrequent attacks (<2 per year) 2. Importantly, do not treat asymptomatic hyperuricemia—the number needed to treat is 24 patients for 3 years to prevent a single gout flare 1.
Monitoring and Target Goals
- Target serum urate <6 mg/dL (360 μmol/L) for most patients 2, 6
- For severe gout with tophi, consider a lower target of <5 mg/dL (300 μmol/L) until crystal dissolution is complete 6
- Check serum urate levels after initiating therapy and during dose titration to ensure target achievement 2
- Long-term monitoring of serum urate is recommended, though optimal frequency is not definitively established 2
Comparative Efficacy
Febuxostat 80 mg daily is more effective than allopurinol 300 mg daily at lowering serum urate levels 1, 2, 5, while febuxostat 40 mg daily is equally effective to allopurinol 300 mg daily 1, 2. However, this comparison is somewhat misleading since allopurinol 300 mg is often underdosed—allopurinol can be titrated up to 800 mg daily to achieve target urate levels 1.
Duration of Therapy
Febuxostat is lifelong therapy—discontinuation leads to recurrence of gout flares in approximately 87% of patients within 5 years 6. Long-term studies demonstrate that sustained urate reduction over 3-5 years results in near-elimination of gout flares and progressive tophus resolution 1, 5, 7.
Critical Pitfalls to Avoid
- Never start febuxostat without concurrent anti-inflammatory prophylaxis—this dramatically increases the risk of acute flares 2
- Do not discontinue febuxostat after achieving symptom control—this will lead to recurrent flares 2
- Avoid febuxostat as first-line therapy in patients with cardiovascular disease—consider switching to allopurinol in these patients 2
- Do not use febuxostat in severe renal impairment (CrCl <30 mL/min)—safety data are lacking 8
Adverse Effects
Monitor for liver function abnormalities, diarrhea, nausea, arthralgias, and rash 2, 5, 3. Cardiovascular thromboembolic events were the most common serious adverse events in clinical trials, though causality has not been definitively established 5, 3.