What medications are used for gout prevention?

Medications for Gout Prevention

Allopurinol is the strongly recommended first-line urate-lowering therapy (ULT) for gout prevention in all patients, including those with chronic kidney disease (CKD). 1

First-Line Urate-Lowering Therapies

• Allopurinol should be started at a low dose (100 mg/day or lower in patients with CKD) and gradually titrated upward by 100 mg increments every 2-4 weeks until the target serum uric acid (SUA) level is reached 1
• The maximum FDA-approved dose of allopurinol is 800 mg/day, and doses above 300 mg/day are often required to achieve target SUA levels 1
• In patients with renal impairment, allopurinol starting dose should be adjusted based on creatinine clearance, but may still require titration above 300 mg/day to achieve SUA targets 1

Second-Line Urate-Lowering Therapies

• If SUA target cannot be reached with allopurinol or if allopurinol is not tolerated, febuxostat should be considered as an alternative 1
• Febuxostat should be started at a low dose (≤40 mg/day) and titrated upward to reach target SUA levels 1
• Uricosuric agents (probenecid, benzbromarone) can be used as alternatives or in combination with xanthine oxidase inhibitors when target SUA levels are not achieved 1
• Probenecid should be started at 500 mg once or twice daily and titrated upward as needed 1, 2
• Uricosuric agents are relatively contraindicated in patients with urolithiasis or renal impairment 1

Treatment Targets and Monitoring

• The target SUA level should be maintained below 6 mg/dL (360 μmol/L) for most patients with gout 1
• A lower SUA target (<5 mg/dL; 300 μmol/L) is recommended for patients with severe gout (tophi, chronic arthropathy, frequent attacks) until crystal dissolution occurs 1
• SUA levels should be monitored regularly and ULT maintained lifelong to prevent crystal formation 1
• Long-term maintenance of SUA <3 mg/dL is not recommended 1

Anti-inflammatory Prophylaxis

• Concomitant anti-inflammatory prophylaxis is strongly recommended when initiating ULT to prevent gout flares 1
• Colchicine (up to 1.2 mg daily) is commonly used for prophylaxis 1, 3
• NSAIDs or low-dose corticosteroids can be used as alternatives if colchicine is contraindicated or not tolerated 1
• Prophylaxis should be continued for 3-6 months after starting ULT or until target SUA is achieved 1

Special Considerations

• Pegloticase is strongly recommended against as first-line therapy but may be indicated in patients with severe tophaceous gout who have failed other ULT options 1, 4
• When gout occurs in patients receiving diuretics, consider substituting the diuretic if possible 1
• For hypertension management in gout patients, consider losartan (which has uricosuric effects) or calcium channel blockers 1, 5
• For hyperlipidemia in gout patients, consider statins or fenofibrate 1

Non-pharmacological Approaches

• All patients with gout should receive lifestyle advice including weight loss if appropriate, regular exercise, and dietary modifications 1
• Patients should avoid or limit alcohol (especially beer and spirits), sugar-sweetened drinks, and excessive intake of meat and seafood 1, 5
• Low-fat dairy products should be encouraged as they are associated with lower urate levels 1

Common Pitfalls to Avoid

• Starting ULT at too high a dose, which increases the risk of allopurinol hypersensitivity syndrome, especially in patients with renal impairment 6, 1
• Failing to provide anti-inflammatory prophylaxis when initiating ULT, which can lead to increased flares 1
• Discontinuing ULT during acute gout attacks, which is unnecessary and may delay achieving therapeutic targets 7, 8
• Inadequate dose titration of ULT, leading to failure to achieve target SUA levels 1
• Stopping ULT once SUA levels normalize, as this will lead to recurrence of gout 1