What is the treatment for hyperuricemia?

Treatment for Hyperuricemia

The first-line pharmacologic treatment for hyperuricemia is xanthine oxidase inhibitors (XOIs), with allopurinol being the preferred initial agent, starting at 100 mg daily and titrating upward every 2-5 weeks to achieve a target serum urate level below 6 mg/dL. 1

Initial Assessment and Evaluation

• 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 comorbidities (obesity, hypertension, diabetes, hyperlipidemia) and medications that can elevate uric acid (thiazides, loop diuretics, niacin, calcineurin inhibitors) 1, 2
• Consider urine uric acid evaluation for patients with gout onset before age 25 or history of urolithiasis to screen for uric acid overproduction 1

Non-Pharmacologic Management

• Limit consumption of purine-rich meats and seafood to reduce uric acid levels 1, 3
• Avoid high fructose corn syrup sweetened beverages and energy drinks 1
• Encourage consumption of low-fat or non-fat dairy products, which may have antihyperuricemic effects 1, 3
• Reduce alcohol consumption, particularly beer, and avoid alcohol overuse 1, 3
• Complete abstinence from alcohol during periods of active gout arthritis 1
• Aim for weight reduction if obese, as controlled weight management can lower serum urate similarly to low purine diets 1, 3
• Consider increasing intake of vegetables, water, and vitamin C sources 4

Pharmacologic Treatment

First-Line Therapy: Xanthine Oxidase Inhibitors

• Allopurinol is recommended as the first-line XOI 1, 5

  • Start at 100 mg daily and titrate upward every 2-5 weeks to reach target serum urate level 1, 5
  • Dosing should be adjusted based on renal function: for creatinine clearance 10-20 mL/min, use 200 mg daily; for <10 mL/min, do not exceed 100 mg daily 5
  • Allopurinol works by inhibiting xanthine oxidase, reducing the production of uric acid 5

• Febuxostat is an alternative XOI with similar efficacy when allopurinol is not tolerated or contraindicated 1

Alternative Therapies

• Probenecid (uricosuric agent) is recommended as an alternative first-line therapy when XOIs are contraindicated or not tolerated 1, 6
• Combination therapy with XOI and uricosuric agent may be considered for patients not achieving target urate levels on monotherapy 5
• 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 to monitor adherence 1
• The 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 (tophi, chronic tophaceous gout), target serum urate below 5 mg/dL 1

Special Considerations

Renal Impairment

• In patients with chronic kidney disease, xanthine oxidase inhibitors are preferred over uricosuric agents, but dose adjustment is necessary 1, 5
• For acute gout flares in CKD patients, low-dose colchicine or glucocorticoids are preferable to NSAIDs 1

Tumor Lysis Syndrome

• For hyperuricemia associated with tumor lysis syndrome, rasburicase is recommended for rapid reduction of uric acid levels 2
• Rasburicase affects rapid and complete degradation of uric acid to allantoin, allowing prompt continuation of chemotherapy 2

Heart Failure

• Hyperuricemia confers a poor prognosis in heart failure patients 2
• In acute gout with heart failure, a short course of colchicine may be considered, while NSAIDs should be avoided 2

Common Pitfalls and Caveats

• 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
• Poor adherence to ULT is a common problem in gout patients; regular monitoring helps address this issue 1
• Failure to titrate allopurinol to appropriate doses often leads to suboptimal outcomes; many patients require doses above 300 mg daily 1
• Initiating ULT at high doses increases risk of adverse events; always start at low doses and titrate upward 1, 5
• Neglecting prophylaxis against acute flares when initiating ULT can lead to poor medication adherence 1
• Urine alkalinization has traditionally been used but has drawbacks including increased precipitation of calcium phosphate and reduced xanthine solubility 2