What is the management for hyperuricemia?

Management of Elevated Uric Acid (Hyperuricemia)

The management of hyperuricemia requires both non-pharmacologic and pharmacologic approaches, with allopurinol or febuxostat as first-line pharmacologic therapy to reduce serum urate levels below 6 mg/dL to prevent gout attacks and complications. 1

Initial Assessment

• Perform a thorough clinical evaluation of disease activity through history and physical examination for symptoms of arthritis, presence of tophi, and signs of acute or chronic synovitis 1
• Screen for causes of hyperuricemia, including medications (thiazides, loop diuretics, niacin, calcineurin inhibitors) and comorbidities (obesity, metabolic syndrome, hypertension, kidney disease) 1
• Consider urine uric acid evaluation for patients with gout onset before age 25 or history of urolithiasis to screen for uric acid overproduction 1, 2

Non-Pharmacologic Management

• Limit consumption of purine-rich meats and seafood to reduce uric acid levels 1, 3
• Reduce consumption of alcohol, particularly beer, and avoid alcohol overuse 1
• Avoid high fructose corn syrup sweetened beverages and energy drinks 1
• Encourage consumption of low-fat or non-fat dairy products 1, 4
• Maintain adequate hydration with fluid intake sufficient to yield daily urinary output of at least 2 liters 5
• Achieve and maintain healthy weight through appropriate diet and exercise 1, 4

Pharmacologic Management

When to Initiate Urate-Lowering Therapy (ULT)

• Initiate ULT in patients with recurrent gout attacks, tophi, chronic gouty arthritis, or joint damage 1
• High-quality evidence shows that ULT reduces serum urate levels but does not reduce gout attacks within the first 6 months; however, longer-term therapy (>1 year) reduces gout flares 1

First-Line Therapy

• Allopurinol is recommended as a first-line xanthine oxidase inhibitor (XOI) 1, 5

  • Start at 100 mg daily and increase by 100 mg every 2-5 weeks until target serum urate is achieved 5
  • Average dosage is 200-300 mg/day for mild gout and 400-600 mg/day for moderately severe tophaceous gout 5
  • Maximum recommended dosage is 800 mg daily 5
  • Adjust dose in renal impairment: 200 mg daily with creatinine clearance 10-20 mL/min; 100 mg daily with clearance <10 mL/min 5

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

  • Consider in patients who cannot tolerate allopurinol or have contraindications to its use 1

Alternative Therapies

• Probenecid is recommended as an alternative first-line therapy when XOIs are contraindicated or not tolerated 1

  • Not recommended as monotherapy in patients with creatinine clearance <50 mL/min 1
  • Risk of urolithiasis (approximately 10%) and multiple drug interactions 1

• Pegloticase is reserved for patients with refractory disease who have failed maximum appropriate doses of XOI and uricosuric combination therapy 1

Monitoring and Target Levels

• Monitor serum urate every 2-5 weeks during ULT titration and continue measurements every 6 months once target is achieved 2
• Target serum urate level should be below 6 mg/dL for all gout patients 1, 5
• For patients with greater disease severity and urate burden (e.g., tophi, chronic tophaceous gout), target serum urate below 5 mg/dL 1

Special Considerations

• In patients with chronic kidney disease, XOIs are preferred over uricosuric agents, but dose adjustment is necessary 5, 6
• Continue colchicine and/or anti-inflammatory agents during initiation of ULT until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months 5
• Persons with the HLA-B*5801 haplotype (prevalent in Asian persons) may have increased risk for serious adverse effects with allopurinol 1
• For hyperuricemia associated with tumor lysis syndrome, rasburicase is recommended for rapid reduction of uric acid levels 1, 2

Common Pitfalls to Avoid

• Relying on a single serum uric acid determination; technical factors can affect measurement 5
• Expecting immediate resolution of symptoms; it may take weeks to months of ULT to achieve target levels and reduce flares 1
• Discontinuing ULT during acute gout attacks; continue therapy while treating the acute attack 5
• Underestimating the importance of dietary and lifestyle modifications alongside pharmacologic therapy 1
• Failing to address comorbidities that contribute to hyperuricemia (hypertension, obesity, metabolic syndrome) 1, 7

Remember that diet and lifestyle measures alone typically provide insufficient serum urate-lowering effects for many patients with gout and should be combined with pharmacologic therapy when indicated 1.