What is the treatment for hyperuricemia?

Treatment of Hyperuricemia

Allopurinol should be the first-line urate-lowering therapy for hyperuricemia, starting at a low dose of 100 mg daily (or 50 mg in renal impairment) and gradually titrating upward every 2-5 weeks to achieve a target serum urate level below 6 mg/dL. 1, 2, 3

Initial Assessment and Management Approach

• Evaluate for underlying causes of hyperuricemia including comorbidities (obesity, hypertension, hyperlipidemia, diabetes) and medications (thiazides, loop diuretics, niacin, calcineurin inhibitors) that may elevate uric acid levels 2, 4
• Consider urine uric acid evaluation for patients with early-onset hyperuricemia (before age 25) or history of urolithiasis to screen for uric acid overproduction 2
• Implement lifestyle modifications as first-line intervention alongside pharmacologic therapy:
  • Limit consumption of purine-rich foods (red meat, seafood) 2, 5
  • Avoid high fructose corn syrup sweetened beverages and excessive alcohol intake 2, 5
  • Encourage weight loss if overweight or obese 4, 6
  • Increase intake of low-fat dairy products, vegetables, and vitamin C sources 5

Pharmacologic Management Algorithm

First-Line Therapy

• Start allopurinol at 100 mg daily (50 mg in stage 4 or worse CKD) 1, 3
• Gradually titrate dose upward every 2-5 weeks to achieve target serum urate level 1, 3
• Consider HLA-B*5801 testing before initiating allopurinol in high-risk populations (Koreans with stage 3 or worse CKD; Han Chinese and Thai patients) 1
• Monitor serum urate every 2-5 weeks during dose titration 2

Alternative First-Line Options

• Febuxostat can be used as an alternative first-line agent when allopurinol is contraindicated or not tolerated 1, 2
• Probenecid is an alternative first-line option, particularly in patients with normal renal function who are uric acid under-excreters 1, 7
• Avoid probenecid in patients with creatinine clearance <50 mL/minute or history of urolithiasis 1

Refractory Hyperuricemia Management

• If target serum urate is not achieved with maximum appropriate dose of a single agent, consider combination therapy:
  • Add a uricosuric agent (probenecid, fenofibrate, or losartan) to an XOI 1
  • Monitor for potential drug interactions and adverse effects 1
• For severe, refractory cases where combination therapy fails, consider pegloticase 1, 2

Target Serum Urate Levels and Monitoring

• Maintain serum urate below 6 mg/dL (0.36 mmol/L) for all patients with hyperuricemia 1, 2
• For patients with tophaceous gout or greater disease severity, target serum urate below 5 mg/dL (0.30 mmol/L) 1, 2
• Continue monitoring serum urate every 6 months once target is achieved to ensure adherence 2
• ULT should be continued indefinitely to prevent recurrence 4

Special Considerations

Renal Impairment

• In mild-moderate renal impairment, allopurinol can be used with close monitoring, starting at a low dose (50-100 mg daily) 1, 3
• With creatinine clearance of 10-20 mL/min, daily dosage of 200 mg is suitable; with clearance <10 mL/min, do not exceed 100 mg daily 3
• Febuxostat is an alternative that can be used without dose adjustment in mild-moderate renal impairment 1

Prophylaxis During ULT Initiation

• When starting ULT, consider prophylaxis with colchicine (up to 1.2 mg daily) to prevent acute gout flares 1
• If colchicine is contraindicated or not tolerated, low-dose NSAIDs or glucocorticoids may be used as alternatives 1
• Duration of prophylaxis depends on individual factors such as flare frequency and gout duration 1

Common Pitfalls and Caveats

• Avoid treating asymptomatic hyperuricemia to prevent gouty arthritis, renal disease, or cardiovascular events unless there are specific indications 1, 8
• Do not rely on a single serum uric acid determination due to potential technical difficulties in estimation 3
• Maintain adequate fluid intake (at least 2 liters of urine output daily) and slightly alkaline urine to prevent crystallization 3
• When transferring from a uricosuric agent to allopurinol, gradually reduce the dose of the uricosuric agent over several weeks while gradually increasing allopurinol 3
• Recognize that ULT may initially increase the frequency of acute gout attacks, highlighting the importance of prophylaxis 1