What is the treatment for hyperuricemia?

Treatment of 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

Diagnosis and Assessment

Before initiating treatment, it's important to:

• Confirm hyperuricemia (serum uric acid >7 mg/dL in men, >6 mg/dL in premenopausal women) 2
• Determine if the patient has symptomatic gout or asymptomatic hyperuricemia
• Evaluate for secondary causes of hyperuricemia:
  • Medications (thiazide/loop diuretics, low-dose aspirin, calcineurin inhibitors)
  • Renal impairment
  • Obesity
  • Alcohol consumption (especially beer)
  • High purine diet

Treatment Approach

1. Non-Pharmacological Management

Start with lifestyle modifications for all patients with hyperuricemia:

• Diet modifications:

  • Limit purine-rich foods (red meat, seafood) 1, 3
  • Reduce high-fructose corn syrup and sweetened beverages 1, 3
  • Encourage low-fat dairy products 1, 3
  • Consider Mediterranean diet pattern 3

• Alcohol reduction:

  • Limit all alcohol, particularly beer 1, 4
  • Complete abstinence during acute gout attacks 1

• Weight management:

  • Weight reduction for overweight/obese patients 3
  • Regular moderate exercise (avoid strenuous exercise which may trigger attacks) 3

• Hydration:

  • Maintain adequate fluid intake (at least 2 liters daily) 2

2. Pharmacological Treatment

If serum uric acid remains elevated despite lifestyle modifications or in patients with symptomatic gout, initiate pharmacologic therapy:

First-line options:

• Xanthine Oxidase Inhibitors 1:
  • Allopurinol: Start at low dose (100 mg/day) and titrate upward to achieve target uric acid level
    • For renal impairment: 100 mg daily with CrCl <10 mL/min; 200 mg daily with CrCl 10-20 mL/min 2
  • Febuxostat: Alternative first-line agent, especially in patients with renal impairment or allopurinol intolerance

Alternative options:

• Uricosurics (e.g., probenecid, benzbromarone) 1:

  • Consider when XOI contraindicated or not tolerated
  • Not recommended as first-line monotherapy in patients with creatinine clearance <50 mL/min

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

3. Treatment Targets and Monitoring

• Target serum uric acid level: <6 mg/dL for most patients 1
• Lower target (<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 achieved, monitor every 6 months 1

Special Considerations

Asymptomatic Hyperuricemia

• Pharmacological treatment is generally not recommended for asymptomatic hyperuricemia to prevent gout, renal disease, or cardiovascular events 1
• Focus on lifestyle modifications and management of comorbidities

Renal Impairment

• Allopurinol can be used with dose adjustment based on creatinine clearance 2:
  • CrCl 10-20 mL/min: 200 mg/day
  • CrCl <10 mL/min: 100 mg/day
  • CrCl <3 mL/min: may need extended interval between doses
• Febuxostat can be used without dose adjustment in mild to moderate renal impairment 1

Flare Prophylaxis

When initiating urate-lowering therapy, consider prophylaxis against acute flares:

• Colchicine (up to 1.2 mg daily) is preferred 1
• NSAIDs or low-dose glucocorticoids if colchicine is contraindicated 1

Common Pitfalls to Avoid

1. Starting with high-dose allopurinol - This increases risk of hypersensitivity reactions; always start low and titrate up

2. Stopping urate-lowering therapy during acute flares - Continue ULT during flares with appropriate anti-inflammatory treatment

3. Inadequate dose titration - Failure to adjust medication doses until target uric acid level is achieved

4. Neglecting lifestyle modifications - Diet and alcohol reduction remain important even when on medication

5. Discontinuing treatment once uric acid normalizes - ULT typically requires lifelong therapy to prevent recurrence

By following this structured approach to hyperuricemia management, clinicians can effectively reduce serum uric acid levels, prevent gout attacks, and potentially mitigate associated comorbidities.