Febuxostat for Gout Patients Intolerant to Allopurinol
Febuxostat is strongly recommended as the treatment of choice for gout patients who are intolerant to allopurinol, with a starting dose of 40 mg daily that can be increased to 80 mg daily if target serum urate levels are not achieved. 1, 2
Treatment Algorithm for Allopurinol-Intolerant Patients
Initial Treatment
- Start febuxostat at 40 mg once daily
- Initiate concomitant anti-inflammatory prophylaxis therapy for 3-6 months:
- Colchicine (0.6 mg once or twice daily) OR
- Low-dose prednisone/prednisolone OR
- NSAIDs (if renal function permits)
Monitoring and Dose Titration
- Check serum urate levels 2-4 weeks after starting therapy
- If serum urate remains ≥6 mg/dL after 2 weeks, increase febuxostat to 80 mg daily 2, 3
- Continue monitoring serum urate every 2-4 weeks until target level is achieved
- Target serum urate level: <6 mg/dL (<360 μmol/L)
Advantages of Febuxostat in Allopurinol-Intolerant Patients
Efficacy
- More effective than allopurinol 300 mg in lowering serum urate levels below 6 mg/dL 4
- In clinical trials, 53-62% of patients receiving febuxostat (80-120 mg) achieved target serum urate levels compared to only 21% with allopurinol 300 mg 4
Renal Considerations
- No dose adjustment required in mild to moderate renal impairment (CrCl ≥30 mL/min) 2, 3
- Can be used in patients with renal insufficiency, where allopurinol requires significant dose reduction 2
- Limited data available for severe renal impairment (CrCl <30 mL/min) 3
Special Considerations
Anti-inflammatory Prophylaxis
- Strong recommendation to provide prophylaxis against gout flares when initiating febuxostat 1
- Continue prophylaxis for 3-6 months after achieving target urate level 1, 2
- Early mobilization flares are common when starting urate-lowering therapy 5
Monitoring for Adverse Effects
- Most common adverse effects: liver function abnormalities, rash, nausea, and arthralgias 3
- Monitor liver function periodically
- Incidence of adverse events similar to allopurinol in clinical trials 5
Important Precautions
- Not recommended for co-administration with azathioprine or 6-mercaptopurine 5
- Cardiovascular events were numerically higher with febuxostat than allopurinol in some studies, though not statistically significant 5
Long-term Management
- Continue febuxostat indefinitely once target urate level is achieved
- Long-term studies (up to 5 years) show sustained reduction in serum urate levels and nearly complete elimination of gout flares with continued therapy 3
- Regular monitoring of serum urate levels (every 6 months) to ensure continued efficacy
Alternative Options if Febuxostat Fails
- Consider probenecid (uricosuric agent) if febuxostat is ineffective or not tolerated, but avoid in patients with CKD stage ≥3 or urolithiasis 1, 2
- Pegloticase should be considered only after failure of other urate-lowering therapies 1, 2
Febuxostat represents an effective alternative for patients who cannot tolerate allopurinol, with the advantage of not requiring dose adjustment in mild to moderate renal impairment and demonstrating superior efficacy in achieving target serum urate levels compared to standard-dose allopurinol.