Allopurinol is the Preferred First-Line Urate-Lowering Therapy Over Febuxostat for Gout
Allopurinol is strongly recommended as the preferred first-line urate-lowering therapy over febuxostat for patients with gout, including those with chronic kidney disease stage ≥3. 1, 2
Comparative Efficacy and Safety
- Allopurinol is recommended as first-line therapy due to its proven efficacy when dosed appropriately, tolerability, safety profile, and lower cost compared to febuxostat 1
- While febuxostat may be more effective at lowering serum urate levels (70% vs 38% achieving target levels with allopurinol), this does not translate to better clinical outcomes in terms of gout flare reduction 3, 4
- Recent evidence from the STOP Gout Trial shows that patients with CKD had fewer gout flares with allopurinol compared to febuxostat (32% vs 45%), despite similar achievement of serum urate goals 5
- Both medications have similar safety profiles with no significant difference in withdrawals due to adverse events (7% with allopurinol versus 8% with febuxostat) 6
Dosing Recommendations
- For allopurinol, start at a low dose (≤100 mg/day, even lower in CKD patients) with subsequent dose titration to achieve target serum urate <6 mg/dL 1, 7
- For febuxostat, if used as an alternative, start at ≤40 mg/day with subsequent dose titration 1, 2
- Patients may require allopurinol doses above 300 mg/day (up to the FDA-approved maximum of 800 mg/day) to achieve serum urate targets, even in those with CKD 1, 7
Special Considerations for CKD Patients
- Both allopurinol and febuxostat are strongly recommended over probenecid for patients with CKD stage ≥3 1, 7
- The traditional concern about limiting allopurinol dosing in CKD has been challenged by evidence supporting dose titration above 300 mg/day when needed to achieve target serum urate levels 7, 2
- The risk of allopurinol hypersensitivity syndrome (AHS) is associated with higher starting doses and CKD, emphasizing the importance of starting with low doses 7, 2
Prophylaxis Recommendations
- Concomitant anti-inflammatory prophylaxis (colchicine, NSAIDs, or prednisone/prednisolone) is strongly recommended when initiating any urate-lowering therapy to prevent gout flares 1, 2
- Prophylaxis should be continued for 3-6 months after initiating urate-lowering therapy 7, 2
Common Pitfalls and Caveats
- Starting with too high a dose of allopurinol, especially in CKD patients, increases the risk of allopurinol hypersensitivity syndrome 7
- Underdosing allopurinol (staying at 300 mg/day) may lead to failure to achieve target serum urate levels in many patients 1, 7
- Focusing solely on serum urate levels rather than clinical outcomes (gout flares, tophi regression) may lead to inappropriate medication selection 5
- Not providing prophylaxis when initiating urate-lowering therapy significantly increases the risk of gout flares 1, 2