What medications are used to prevent gout?

Medications for Gout Prevention

Allopurinol is the strongly recommended first-line medication for preventing gout, starting at a low dose (≤100 mg/day) and gradually titrating upward to achieve a serum uric acid level below 6 mg/dL. 1

First-Line Urate-Lowering Therapy (ULT)

Allopurinol

• Starting dose: 100 mg/day (lower in patients with CKD stage ≥3)
• Titration: Increase by 100 mg increments every 2-4 weeks until target uric acid level is reached 1
• Target: Serum uric acid (SUA) <6 mg/dL (360 μmol/L) for most patients
• Lower target: SUA <5 mg/dL (300 μmol/L) for patients with severe gout (tophi, chronic arthropathy, frequent attacks) 1
• Maximum FDA-approved dose: 800 mg/day 1

Safety considerations for allopurinol:

• For patients of Southeast Asian descent (Han Chinese, Korean, Thai), HLA-B*5801 testing is recommended prior to starting allopurinol due to increased risk of severe hypersensitivity reactions 1
• In patients with renal impairment, start with even lower doses and adjust maximum dosage according to creatinine clearance 1

Second-Line Options (if allopurinol fails or cannot be tolerated)

Febuxostat

• Starting dose: ≤40 mg/day
• Titration: Increase dose as needed to reach target SUA
• Caution: Consider switching to alternative ULT in patients with history of cardiovascular disease 1

Uricosuric Agents

• Probenecid:
  • Starting dose: 500 mg once or twice daily 1
  • Gradually increase as needed
  • Less effective in patients with CKD stage ≥3 1
  • Requires good hydration and may require urine alkalinization to prevent stone formation 2

Combination Therapy

• If SUA target cannot be reached with allopurinol alone, consider:
  • Switching to febuxostat
  • Combining allopurinol with a uricosuric agent 1

Anti-inflammatory Prophylaxis

When starting any ULT, concomitant anti-inflammatory prophylaxis is strongly recommended to prevent gout flares:

• Colchicine: 0.6 mg once or twice daily 3
• NSAIDs: At low anti-inflammatory doses
• Low-dose corticosteroids: Option for those who cannot take colchicine or NSAIDs

Prophylaxis should be continued for 3-6 months after achieving target SUA levels 1

Special Considerations

Patients with Renal Impairment

• Xanthine oxidase inhibitors (allopurinol or febuxostat) are strongly preferred over uricosurics 1
• For severe CKD with debilitating tophaceous gout, pegloticase may be considered if other options fail 1

Concomitant Medications

• Diuretics: Consider substituting if possible, as they can increase uric acid levels
• Hypertension: Losartan may be preferred as it has uricosuric effects
• Hyperlipidemia: Consider statins or fenofibrate 1

Duration of Therapy

• ULT should be maintained lifelong to keep SUA <6 mg/dL (360 μmol/L) 1
• Discontinuation typically results in return of hyperuricemia and gout attacks

Common Pitfalls to Avoid

1. Starting with too high a dose: This increases risk of acute flares and allopurinol hypersensitivity syndrome 4
2. Failing to provide prophylaxis: Always prescribe anti-inflammatory prophylaxis when initiating ULT 1
3. Inadequate dose titration: Many patients require doses higher than 300 mg/day of allopurinol to reach target SUA 5
4. Stopping ULT during acute flares: ULT can actually be initiated during an acute attack with appropriate prophylaxis 6
5. Not monitoring SUA levels: Regular monitoring is essential for dose adjustment and ensuring target levels are maintained 1

By following these evidence-based recommendations, gout can be effectively prevented and managed, reducing the frequency of painful attacks and preventing long-term joint damage.