What medication to prescribe for hyperuricemia?

Management of Hyperuricemia

For patients with hyperuricemia, xanthine oxidase inhibitors (XOIs) such as allopurinol or febuxostat are the first-line pharmacologic treatment options, with the goal of achieving serum urate levels below 6 mg/dL. 1

Initial Assessment and Treatment Decision

• Evaluate for the presence of gout symptoms (arthritis attacks), tophi, and signs of chronic synovitis to determine disease burden 2
• Consider secondary causes of hyperuricemia including obesity, hypertension, diabetes, and medications such as thiazides and loop diuretics 2
• Pharmacologic treatment is indicated for:
  • Patients with recurrent gout attacks (≥2 attacks/year) 1
  • Presence of tophi on physical examination or imaging 1
  • Chronic kidney disease stage 2 or worse 1
  • History of urolithiasis 1

First-Line Pharmacologic Treatment

• Allopurinol is recommended as a first-line XOI therapy: 1, 2

  • Start at low dose (100 mg/day or less) to reduce risk of hypersensitivity reactions 1, 3
  • Gradually titrate upward every 2-5 weeks until target serum urate is achieved 1, 2
  • Dose adjustment required in renal impairment: 3
    • Creatinine clearance 10-20 mL/min: maximum 200 mg/day
    • Creatinine clearance <10 mL/min: maximum 100 mg/day

• Febuxostat is an alternative first-line XOI with similar efficacy to allopurinol 1

  • Consider in patients with allopurinol intolerance or contraindications 1
  • May be preferred in patients with moderate renal impairment 1

Alternative Pharmacologic Options

• Probenecid is recommended as an alternative first-line option when: 1, 4

  • XOIs are contraindicated or not tolerated
  • Not recommended as monotherapy if creatinine clearance is below 50 mL/min 1

• Combination therapy with an XOI plus a uricosuric agent should be considered when: 1, 2

  • Target serum urate is not achieved with appropriate dosing of an XOI alone

• Pegloticase is reserved for patients with severe tophaceous gout who have failed maximum appropriate doses of XOI and uricosuric combination therapy 1, 2

Treatment Targets and Monitoring

• The minimum serum urate target is <6 mg/dL for all gout patients 1
• A lower target (<5 mg/dL) is recommended for patients with severe disease (tophi, chronic arthropathy) 1, 2
• Monitor serum urate every 2-5 weeks during ULT titration and every 6 months once target is achieved 1, 2

Adjunctive Non-Pharmacologic Measures

• Limit consumption of purine-rich meats and seafood 1, 2
• Avoid high-fructose corn syrup sweetened beverages 1, 2
• Reduce alcohol consumption, particularly beer 1, 2
• Encourage consumption of low-fat dairy products 1, 2
• Maintain adequate hydration with at least 2 liters of fluid daily 3

Common Pitfalls to Avoid

• Diet and lifestyle measures alone typically provide only 10-18% decrease in serum urate, which is insufficient for most patients with sustained hyperuricemia above 7 mg/dL 1, 2
• Failure to titrate allopurinol to appropriate doses often leads to suboptimal outcomes 2
• Starting ULT at high doses increases risk of adverse events, particularly allopurinol hypersensitivity syndrome 1, 2
• Poor medication adherence is common in gout patients and requires regular monitoring and patient education 1, 2
• Neglecting prophylaxis against acute flares when initiating ULT can lead to poor medication adherence 2