What are the best ways to prevent gout with medication, specifically xanthine oxidase inhibitors (XOI) like allopurinol (Zyloprim) and febuxostat (Uloric), and other pharmacological interventions?

Best Medications for Gout Prevention

Allopurinol is strongly recommended as the first-line medication for preventing gout, with a starting dose of 100 mg daily (or 50 mg in CKD stage ≥3) and gradual titration to achieve a serum urate level below 6 mg/dL. 1, 2

First-Line Therapy: Xanthine Oxidase Inhibitors

Allopurinol

• Start at low dose: 100 mg/day (50 mg/day in stage 4 or worse CKD) 1, 3
• Gradually titrate upward by 100 mg every 2-5 weeks until target serum urate is achieved 1, 2
• Maximum dose can exceed 300 mg daily even with renal impairment, with proper monitoring 1
• Target serum urate level: <6 mg/dL for most patients, <5 mg/dL for those with tophi 2
• Consider HLA-B*5801 screening before initiating in high-risk populations (Koreans with CKD stage ≥3, Han Chinese, Thai) 1, 2

Febuxostat

• Alternative when allopurinol is not tolerated or ineffective 1
• Start at 40 mg/day with subsequent dose titration 1
• More effective than fixed-dose allopurinol (300 mg) in lowering serum urate 4
• Should not be used in combination with allopurinol 1

Second-Line Therapy: Uricosuric Agents

Probenecid

• First choice among uricosurics for monotherapy 1
• Not recommended as first-line therapy in patients with creatinine clearance <50 ml/min 1
• Start at low dose (500 mg once or twice daily) with dose titration 1
• Contraindicated in patients with history of urolithiasis 1

Other Uricosuric Options

• Fenofibrate and losartan have clinically significant uricosuric effects and can be useful as part of a comprehensive strategy 1
• Measure urinary uric acid before and during uricosuric therapy 1

Refractory Gout Management

Combination Therapy

• Adding a uricosuric agent to XOI or vice versa is effective for refractory cases 1

Pegloticase

• Reserved for patients with severe gout burden who are refractory to or intolerant of conventional ULT 1
• Not recommended as first-line therapy 1
• Oral ULT should be discontinued during pegloticase therapy 1

Flare Prevention During ULT Initiation

• Strongly recommended: Initiate concomitant anti-inflammatory prophylaxis when starting ULT 1
• Options include colchicine, NSAIDs, or prednisone/prednisolone 1
• Continue prophylaxis for 3-6 months 1

Monitoring Protocol

1. Check serum urate every 2-4 weeks during dose titration 2
2. Once target is achieved, monitor every 6 months 2
3. Monitor renal function regularly, especially in patients with CKD 2, 3
4. Watch for signs of drug toxicity (rash, pruritis, elevated liver enzymes) 1, 3

Important Considerations

• Increase fluid intake to at least 2 liters daily 3
• Maintain neutral or slightly alkaline urine to prevent stone formation 3
• Acute gout flares may increase during early ULT initiation, even with normal serum urate levels 3
• Optimal benefit of allopurinol may be delayed for 2-6 weeks 3

Common Pitfalls to Avoid

• Starting with too high a dose of allopurinol (increases risk of hypersensitivity reactions)
• Failure to titrate dose to achieve target serum urate level
• Discontinuing ULT during acute flares (should be continued)
• Inadequate duration of prophylaxis when initiating ULT
• Not monitoring serum urate levels regularly
• Stopping therapy once symptoms resolve (ULT is typically lifelong)

By following these evidence-based recommendations, gout can be effectively managed with appropriate medication to prevent recurrent flares, reduce tophi, and improve quality of life.