What are the indications for Febuxostat (febuxostat) therapy?

Febuxostat Indications

Febuxostat is indicated for the treatment of chronic hyperuricemia in patients with gout where urate deposition has already occurred. 1, 2

Primary Indications

• Febuxostat is a non-purine selective inhibitor of xanthine oxidase used for urate-lowering therapy (ULT) in patients with gout 1
• It is effective in both uric acid overproducers and underexcretors 3
• Febuxostat is particularly indicated in patients with:
  • Recurrent gout flares 1
  • Tophi 1
  • Urate arthropathy 1
  • Uric acid renal stones 1

Special Populations

• Febuxostat is preferred in patients with moderate to severe renal impairment (eGFR <60 ml/min) 1, 4
  • Unlike allopurinol, febuxostat does not require dosage adjustment in patients with mild to moderate renal impairment 2, 5
  • Febuxostat remains effective in patients with severely impaired renal function (eGFR <30 ml/min) where allopurinol would require significant dose reduction 4
• Febuxostat can be considered when allopurinol is not tolerated or contraindicated 1
  • Particularly in patients with history of allopurinol hypersensitivity syndrome 1
  • In patients with the HLA-B*5801 allele who are at higher risk for severe cutaneous adverse reactions with allopurinol 1

Dosing Considerations

• Febuxostat is available in 40 mg and 80 mg doses (doses >80 mg/day are not FDA-approved) 1
• Treatment should be initiated at a low dose (40 mg/day) with subsequent titration to achieve target serum urate levels 1
• Target serum urate level should be <6 mg/dL for most patients 1
• A lower target (<5 mg/dL) may be recommended for patients with severe gout (tophi, chronic arthropathy, frequent attacks) 1

Efficacy Considerations

• Febuxostat 80 mg/day is more effective than allopurinol 300 mg/day at decreasing serum urate levels 1
• No major differences in outcomes or total adverse events between allopurinol 300 mg/day and febuxostat 40 mg/day 1
• In clinical trials, febuxostat achieved target serum urate levels (<6.0 mg/dL) in 56% of patients at 40 mg dose and 76% at 80 mg dose 6

Important Precautions

• Cardiovascular risk: The American College of Rheumatology conditionally recommends switching to an alternative urate-lowering therapy for patients taking febuxostat with a history of cardiovascular disease or new cardiovascular events 4
• Prophylaxis against acute gout flares should be provided when initiating febuxostat, typically with colchicine or low-dose NSAIDs if not contraindicated 1
• Gout flares may increase during initial therapy due to mobilization of urate crystals 1, 6

Treatment Algorithm

1. Confirm diagnosis of gout with hyperuricemia 1
2. Consider febuxostat as first-line therapy in patients with renal impairment 4, 2
3. Consider febuxostat as second-line therapy after allopurinol in patients with normal renal function 1
4. Start at low dose (40 mg) and titrate as needed to achieve target serum urate level 1
5. Monitor serum urate levels regularly to ensure target achievement 1
6. Provide prophylaxis against gout flares during initiation 1