Alternative Maintenance Medications for Gout Besides Allopurinol
Febuxostat is the preferred first-line alternative to allopurinol for gout maintenance therapy, followed by uricosuric agents (probenecid, benzbromarone) depending on renal function. 1, 2
First-Line Alternative: Febuxostat
Febuxostat should be your go-to alternative when allopurinol cannot be used, whether due to hypersensitivity, intolerance, or failure to achieve target serum uric acid levels. 1
Start febuxostat at 40 mg daily and increase to 80 mg after 2 weeks if serum uric acid remains ≥6 mg/dL. 3, 4
Febuxostat requires no dose adjustment in mild-to-moderate renal impairment (eGFR 30-59 mL/min/1.73m²), making it particularly advantageous over allopurinol in patients with kidney disease. 1, 5
In clinical trials, febuxostat 80 mg achieved target serum uric acid <6 mg/dL in 48-53% of patients compared to only 21-22% with allopurinol 300 mg. 6
Critical Caveat with Febuxostat
Febuxostat carries cardiovascular risk concerns - the ACR conditionally recommends switching from febuxostat to alternative therapy in patients with established cardiovascular disease or new cardiovascular events. 2, 5
Monitor patients for signs of myocardial infarction and stroke, though a definitive causal relationship has not been established. 4
Second-Line Alternatives: Uricosuric Agents
Probenecid
Use probenecid in patients with normal renal function (eGFR >60 mL/min) as an alternative when febuxostat is contraindicated or not preferred. 1, 2
Probenecid is contraindicated in patients with urolithiasis due to increased kidney stone formation risk. 1, 7
Probenecid is not effective when glomerular filtration rate is ≤30 mL/min. 7
Avoid concurrent salicylate use as it antagonizes the uricosuric effect. 7
Benzbromarone
Benzbromarone is the preferred uricosuric in patients with mild-to-moderate renal impairment where febuxostat cannot be used. 1, 2
Benzbromarone requires no dose adjustment in renal insufficiency and demonstrates superior uric acid reduction compared to allopurinol in patients with kidney disease. 1, 2
Important warning: Benzbromarone carries a small risk of hepatotoxicity and is available only on a named-patient basis in many countries. 1
Do not use benzbromarone in patients with eGFR <30 mL/min. 1
Sulphinpyrazone
Sulphinpyrazone is a less potent alternative, reducing serum uric acid by approximately 3.3 mg/dL compared to 4.6 mg/dL with allopurinol. 1
Like probenecid, it requires normal renal function and is contraindicated in urolithiasis. 1
Treatment Algorithm
For patients with normal renal function (eGFR >60):
- First choice: Febuxostat 40-80 mg daily 1, 2
- Second choice: Probenecid (if no history of kidney stones and no cardiovascular disease concerns with febuxostat) 1, 2
For patients with mild-moderate renal impairment (eGFR 30-59):
- First choice: Febuxostat 40-80 mg daily (no dose adjustment needed) 1, 5
- Second choice: Benzbromarone (where available, if febuxostat contraindicated) 1, 2
For patients with severe renal impairment (eGFR <30):
- Febuxostat remains an option but data are limited 3
- Avoid benzbromarone 1
- Consider pegloticase for severe, refractory tophaceous gout 1
Essential Prophylaxis During Initiation
Always provide flare prophylaxis when starting any urate-lowering therapy with colchicine 0.5-1.2 mg daily, NSAIDs, or low-dose glucocorticoids for at least 6 months. 1
Reduce colchicine dose to 0.5 mg daily in patients with renal impairment. 5
Special Consideration: Allopurinol Desensitization
If febuxostat and uricosurics all fail or are contraindicated, allopurinol desensitization can be attempted only in patients with prior mild allergic reactions. 1, 2
Never attempt desensitization in patients with severe reactions or allopurinol hypersensitivity syndrome. 1, 2