What are the treatment options for hyperuricemia?

Treatment of Hyperuricemia

Allopurinol is the first-line pharmacologic treatment for hyperuricemia, starting at 100 mg daily and titrating upward every 2-5 weeks to achieve a target serum urate level below 6 mg/dL. 1, 2, 3

Initial Assessment

Before initiating treatment, perform a focused evaluation:

• Screen for secondary causes: Check for obesity, hypertension, diabetes, hyperlipidemia, and chronic kidney disease 1, 2, 3
• Review medications: Identify drugs that elevate uric acid including thiazide and loop diuretics, niacin, and calcineurin inhibitors 1, 2, 3
• Evaluate for uric acid overproduction: In patients with gout onset before age 25 or history of urolithiasis, obtain 24-hour urine uric acid measurement 1, 2, 3
• Assess disease burden: Document presence of tophi, acute or chronic synovitis, and frequency of gout attacks 1, 3

Lifestyle Modifications

Dietary and lifestyle changes alone typically provide only 10-18% reduction in serum urate, which is insufficient for most patients with sustained hyperuricemia above 7 mg/dL. 1 However, these modifications should still be implemented:

• Limit purine-rich foods: Reduce consumption of red meat and seafood 1, 2, 3
• Avoid fructose: Eliminate high fructose corn syrup sweetened beverages and energy drinks 1, 2, 3
• Increase dairy intake: Encourage low-fat or non-fat dairy products 1, 2, 3
• Reduce alcohol: Particularly beer and spirits; complete abstinence during acute gout attacks 1, 2, 3
• Weight reduction: If obese, aim for gradual weight loss 1, 2

Pharmacologic Treatment Algorithm

First-Line Therapy: Xanthine Oxidase Inhibitors

Allopurinol:

• Starting dose: 100 mg daily 1, 2, 4
• Titration: Increase by 100 mg every 2-5 weeks until target serum urate is achieved 1, 2, 4
• Renal dosing adjustments: 4
  • Creatinine clearance 10-20 mL/min: maximum 200 mg daily
  • Creatinine clearance <10 mL/min: maximum 100 mg daily
  • Creatinine clearance <3 mL/min: extend dosing interval beyond daily
• Take with food to improve tolerability 4
• Maintain adequate hydration: Ensure daily urinary output of at least 2 liters 4

Febuxostat:

• Alternative to allopurinol when allopurinol is contraindicated or not tolerated 1, 2, 3
• Provides similar efficacy as a selective xanthine oxidase inhibitor 1, 3

Second-Line Therapy: Uricosuric Agents

Probenecid:

• Use when xanthine oxidase inhibitors are contraindicated or not tolerated 1, 5
• Avoid in chronic kidney disease: Xanthine oxidase inhibitors are preferred over uricosurics in CKD patients 1, 3
• Can be combined with allopurinol if target not reached with monotherapy 4

Third-Line Therapy: Recombinant Uricase

Pegloticase:

• Reserved for refractory disease that has failed maximum appropriate doses of xanthine oxidase inhibitor and uricosuric combination therapy 1, 3

Target Serum Urate Levels

• Standard target: <6 mg/dL for all gout patients 1, 2, 3
• Aggressive target: <5 mg/dL for patients with tophi or chronic tophaceous gout 1, 3
• Avoid excessive lowering: Do not target levels <3 mg/dL for long-term therapy 2

Monitoring Strategy

• During titration: Check serum urate every 2-5 weeks 1, 3
• After reaching target: Monitor every 6 months to assess adherence 1, 3
• Continue indefinitely: Lifelong urate-lowering therapy is necessary to prevent recurrence 2

Critical Pitfalls to Avoid

• Inadequate allopurinol dosing: Many patients require doses above 300 mg daily; failure to titrate appropriately leads to suboptimal outcomes 1
• Starting at high doses: Always initiate at low doses and titrate upward to reduce risk of adverse events 1
• Neglecting flare prophylaxis: When initiating urate-lowering therapy, provide prophylaxis against acute flares to improve medication adherence 1
• Poor adherence: Regular monitoring helps identify and address non-adherence, which is common in gout patients 1
• Overreliance on diet alone: Dietary modifications are typically insufficient for adequate urate lowering in most patients 1

Special Populations

Chronic Kidney Disease:

• Prefer xanthine oxidase inhibitors over uricosuric agents 1, 3
• Adjust allopurinol dose based on creatinine clearance 4
• For acute flares, use low-dose colchicine or glucocorticoids rather than NSAIDs 1, 3

Tumor Lysis Syndrome Prevention:

• Allopurinol 600-800 mg daily for 2-3 days before chemotherapy 4
• Maintain high fluid intake 4

Recurrent Calcium Oxalate Stones with Hyperuricosuria:

• Allopurinol 200-300 mg daily in divided doses 4
• Adjust based on 24-hour urinary urate measurements 4