What are the treatment options for hyperuricemia?

Treatment Options for Hyperuricemia

The treatment of hyperuricemia should begin with lifestyle modifications, followed by pharmacologic therapy with xanthine oxidase inhibitors (allopurinol or febuxostat) as first-line medications when serum uric acid levels remain elevated above target levels despite lifestyle changes. 1

Non-Pharmacological Management

Dietary Modifications

• Limit consumption of purine-rich foods (red meat, seafood) 2, 1
• Reduce intake of high-fructose corn syrup sweetened beverages and energy drinks 2, 1
• Encourage consumption of low-fat or non-fat dairy products 2, 1
• Maintain adequate fluid intake to yield at least 2 liters of daily urinary output 3
• Maintain neutral or slightly alkaline urine 3

Lifestyle Changes

• Reduce alcohol consumption, particularly beer, but also wine and spirits 2, 1
• Complete abstinence from alcohol during periods of active gout arthritis 2, 1
• Weight reduction if obese 2
• Regular exercise 4

Pharmacological Management

First-Line Therapy

• Xanthine Oxidase Inhibitors (XOIs) are the first-line medications for hyperuricemia management 1
  • Allopurinol:
    • Starting dose: 100 mg/day 1, 3
    • Gradually titrate upward to achieve target uric acid level 1, 3
    • Dose adjustment required in renal impairment 3:
      • Creatinine clearance 10-20 mL/min: 200 mg/day
      • Creatinine clearance <10 mL/min: ≤100 mg/day
      • Extreme renal impairment (clearance <3 mL/min): Extend dosing interval
  • Febuxostat:
    • Alternative first-line agent, especially in patients with renal impairment or allopurinol intolerance 1
    • Can be used without dose adjustment in mild to moderate renal impairment 1

Second-Line Therapy

• Uricosuric Agents:
  • Probenecid: Indicated for hyperuricemia associated with gout and gouty arthritis 5
  • Not recommended as first-line monotherapy in patients with creatinine clearance <50 mL/min 1
  • Consider when XOIs are contraindicated or not tolerated 1

Refractory Cases

• Pegloticase: Reserved for severe refractory gout when other treatments have failed 1

Treatment Targets and Monitoring

Target Serum Uric Acid Levels

• <6 mg/dL for most patients 1
• <5 mg/dL for patients with tophi or chronic tophaceous gout 1

Monitoring

• Check serum uric acid every 2-5 weeks during dose titration 1
• Once target is achieved, check every 6 months 1
• Use serum uric acid level as an index for dose adjustments 3

Prophylaxis During Initiation of Urate-Lowering Therapy

• Colchicine (up to 1.2 mg daily) is preferred for prophylaxis against acute flares when initiating urate-lowering therapy 1
• NSAIDs or low-dose glucocorticoids if colchicine is contraindicated 1

Special Considerations

Comorbidity Management

• Address associated comorbidities such as hyperlipidemia, hypertension, hyperglycemia, and obesity 2
• Consider eliminating non-essential medications that elevate serum urate (e.g., thiazide and loop diuretics, niacin, calcineurin inhibitors) 2
• Low-dose aspirin (≤325 mg daily) may be continued for cardiovascular prophylaxis despite its modest effect on serum urate 2

Asymptomatic Hyperuricemia

• Pharmacological treatment is generally not recommended for asymptomatic hyperuricemia to prevent gout, renal disease, or cardiovascular events 1

Combination Therapy

• Adding a uricosuric agent to allopurinol may be useful in some patients to achieve minimum serum uric acid levels, provided total urinary uric acid load does not exceed renal function capacity 3

The evidence clearly supports a structured approach to hyperuricemia management, beginning with lifestyle modifications and progressing to pharmacologic therapy when needed, with xanthine oxidase inhibitors being the cornerstone of treatment for achieving target serum uric acid levels and preventing complications.