What is the recommended use and dosage of febuxostat (febuxostat) for patients with gout or hyperuricemia?

Febuxostat for Gout and Hyperuricemia Management

Febuxostat is recommended as a second-line urate-lowering therapy for patients with gout who are intolerant to allopurinol or in whom allopurinol is contraindicated or ineffective, starting at 40 mg daily with potential titration to 80 mg daily to achieve target serum uric acid levels below 6 mg/dL. 1

Indications for Use

Febuxostat is indicated for:

• Patients with gout who cannot tolerate allopurinol due to hypersensitivity or intolerance 1
• Patients who fail to achieve target serum uric acid levels with appropriate doses of allopurinol 1
• Patients with moderate-to-severe chronic kidney disease (CKD stage ≥3) who cannot use allopurinol 1, 2

Dosing Protocol

Initial Dosing

• Start at 40 mg once daily 1, 3
• Can be used without dose adjustment in mild to moderate renal impairment 2, 4

Dose Titration

• Check serum uric acid levels 2-4 weeks after starting therapy 2
• If serum uric acid remains ≥6 mg/dL after two weeks, increase to 80 mg once daily 3
• Continue monitoring serum uric acid levels to ensure target is maintained 1

Target Levels

• Primary target: serum uric acid <6 mg/dL (360 μmol/L) 1
• For severe gout (tophi, chronic arthropathy, frequent attacks): consider lower target of <5 mg/dL (300 μmol/L) until resolution 1

Efficacy

Febuxostat has demonstrated superior urate-lowering efficacy compared to fixed-dose allopurinol:

• 80 mg febuxostat achieved target serum urate in 67% of patients vs. 42% with allopurinol 300 mg 5
• 120 mg febuxostat achieved target serum urate in 62% of patients vs. 21% with allopurinol 300 mg 6
• Greater efficacy in patients with renal impairment compared to allopurinol 4

Flare Prophylaxis

• Always initiate prophylaxis against gout flares when starting febuxostat 1
• Options include:
  • Colchicine (0.5-1.0 mg daily with dose adjustment for renal function)
  • NSAIDs (if not contraindicated)
  • Low-dose prednisone/prednisolone
• Continue prophylaxis for 3-6 months after achieving target serum uric acid 1, 2

Safety Considerations

Common Adverse Events

• Liver function abnormalities (4.6-6.6%) 5
• Nausea (1.1-1.3%) 5
• Arthralgias (0.7-1.1%) 5
• Rash (0.5-1.6%) 5

Important Precautions

• Monitor for cardiovascular thromboembolic events (higher incidence reported in clinical trials, though causal relationship not established) 3
• Monitor liver function periodically, especially during the first few months of therapy 4
• No dosage adjustment needed for elderly patients or those with mild to moderate renal or hepatic impairment 3

Advantages Over Allopurinol

• No dosage adjustment required in mild to moderate renal impairment 4
• More potent urate-lowering effect at approved doses 6, 5
• Alternative for patients with HLA-B*5801 allele who are at high risk for allopurinol hypersensitivity syndrome 1, 2

Clinical Pearls

• Initiate febuxostat at a low dose (40 mg) to reduce risk of precipitating acute gout flares 1
• Always use with concomitant anti-inflammatory prophylaxis when initiating therapy 1
• Long-term treatment (up to 4 years) has been shown to reduce gout flare incidence to near zero 7
• Febuxostat should not be used as first-line therapy due to higher cost and potential cardiovascular concerns 1
• Discontinue if rash or other signs of hypersensitivity develop 3

By following these guidelines for febuxostat use, clinicians can effectively manage hyperuricemia in patients with gout while minimizing adverse effects and optimizing outcomes.