What are the alternatives to allopurinol (xanthine oxidase inhibitor) for treating gout?

Alternatives to Allopurinol for Gout Treatment

Febuxostat is the most effective alternative to allopurinol for gout treatment, particularly for patients with allopurinol hypersensitivity or renal impairment. 1

First-Line Treatment and Alternatives

Allopurinol remains the recommended first-line urate-lowering therapy (ULT) for gout according to multiple guidelines 1. However, several alternatives are available when allopurinol cannot be used:

Xanthine Oxidase Inhibitors

• Febuxostat:
  • Most effective alternative to allopurinol
  • Advantages:
    • No dose adjustment required in mild-to-moderate renal impairment 1
    • More effective than allopurinol 300mg in achieving target serum urate levels 2, 3
    • Non-purine structure may reduce cross-reactivity in patients with allopurinol hypersensitivity 1
  • Starting dose: 40mg daily, titrated to achieve target serum urate 1

Uricosuric Agents

• Probenecid:

  • First-choice uricosuric agent 1
  • Contraindicated in:
    • Creatinine clearance <50 ml/min 1
    • History of urolithiasis 1
    • Uric acid overproduction 1
  • Starting dose: 500mg once or twice daily, with dose titration 1

• Benzbromarone:

  • More effective than probenecid
  • Can be used in mild-to-moderate renal impairment 1
  • Carries small risk of hepatotoxicity 1
  • Limited availability in some countries

Biologic Option

• Pegloticase:
  • Reserved for severe, refractory gout 1
  • Appropriate only after failure of or intolerance to conventional ULT 1
  • Not recommended as first-line therapy 1
  • Requires discontinuation of oral ULT during treatment 1

Treatment Algorithm for Selecting Alternatives

1. If allopurinol causes mild hypersensitivity reaction:

   • Consider febuxostat as first alternative 1
   • Monitor closely for adverse reactions

2. If patient has renal impairment (CKD stage ≥3):

   • Febuxostat is preferred over uricosuric agents 1
   • Benzbromarone can be considered if febuxostat is unavailable 1

3. If patient has normal renal function:

   • Either febuxostat or probenecid can be used 1
   • Consider patient-specific factors (cost, comorbidities)

4. For severe, refractory gout:

   • Consider combination therapy (xanthine oxidase inhibitor plus uricosuric) 1
   • Pegloticase for patients who fail all other options 1

Important Considerations

• Target serum urate level: <6 mg/dL (360 μmol/L) at minimum, often <5 mg/dL for patients with tophi 1

• Anti-inflammatory prophylaxis: Essential when initiating any ULT to prevent flares

  • Colchicine (up to 1.2 mg daily) is preferred 1
  • Continue prophylaxis for 3-6 months 1

• Adjunctive therapies: Fenofibrate and losartan have uricosuric effects and can be useful components of comprehensive ULT strategy 1

Common Pitfalls to Avoid

1. Inadequate dosing: Many patients receive suboptimal doses of ULT. All agents should be titrated to achieve target serum urate levels 4

2. Failure to provide flare prophylaxis: Always initiate prophylaxis when starting any ULT 1

3. Inappropriate discontinuation: ULT should be continued long-term to maintain target serum urate levels 1

4. Not monitoring urine uric acid: Essential before starting uricosuric therapy to rule out uric acid overproduction 1

5. Overlooking renal function: Crucial for selecting appropriate therapy and dosing 1

By following these evidence-based recommendations, clinicians can effectively manage gout when allopurinol cannot be used, prioritizing treatments that will reduce morbidity, mortality, and improve quality of life.