What is the recommended treatment for hyperuricemia?

Treatment of Hyperuricemia with Uric Acid Level of 9 mg/dL

Start allopurinol 100 mg daily and titrate upward by 100 mg every 2-5 weeks until serum uric acid is below 6 mg/dL, while simultaneously implementing dietary modifications including limiting purine-rich meats, seafood, and alcohol. 1, 2, 3

Immediate Pharmacologic Management

Allopurinol is the first-line urate-lowering therapy (ULT) for hyperuricemia. 1, 2, 4, 3

Allopurinol Dosing Strategy

• Start at 100 mg daily to minimize risk of acute gout flares 3
• Increase by 100 mg increments every 2-5 weeks based on serum urate monitoring 1, 3
• Target dose typically ranges from 200-600 mg daily depending on disease severity 3
• Maximum recommended dose is 800 mg daily 3
• Take following meals for better tolerability 3

Target Serum Urate Level

• Achieve and maintain serum uric acid below 6 mg/dL (360 μmol/L) 2, 4, 5
• For patients who develop tophi or chronic tophaceous gout, target below 5 mg/dL (300 μmol/L) 1, 2
• Avoid targeting levels below 3 mg/dL for long-term therapy 5

Monitoring Protocol

• Check serum urate every 2-5 weeks during dose titration 1, 2, 4
• Once target achieved, monitor every 6 months to assess adherence 1, 2
• Assess creatinine clearance before initiating therapy, as this affects dosing 1, 3

Alternative Pharmacologic Options

Febuxostat

• Use when allopurinol is contraindicated, not tolerated, or fails to achieve target uric acid 1, 2, 4
• Similar efficacy to allopurinol as a xanthine oxidase inhibitor 1, 2
• Note: Limited safety data in stage 4 or worse chronic kidney disease 1

Probenecid

• Consider as alternative first-line therapy when xanthine oxidase inhibitors are contraindicated or not tolerated 1, 4
• Do not use if creatinine clearance is below 50 mL/min 1

Pegloticase

• Reserved only for refractory disease after failure of maximum doses of xanthine oxidase inhibitors and uricosuric combination therapy 2, 4

Essential Non-Pharmacologic Interventions

These dietary modifications provide approximately 10-18% reduction in serum urate but are insufficient as monotherapy for a uric acid of 9 mg/dL. 1

Dietary Modifications

• Limit purine-rich meats (red meat, organ meats) and seafood 1, 2, 5
• Avoid high fructose corn syrup sweetened beverages and energy drinks 1, 2, 5
• Encourage low-fat or non-fat dairy products 1, 2, 5
• Reduce animal protein, sodium, and refined sugars 3

Alcohol Management

• Reduce alcohol consumption, particularly beer, but also wine and spirits 1, 2, 5
• Avoid alcohol overuse in all patients with hyperuricemia 1, 2
• Complete abstinence during acute gout attacks 1, 2

Weight and Hydration

• Achieve weight reduction if overweight or obese 2, 5
• Maintain fluid intake sufficient for at least 2 liters daily urinary output 3
• Maintain neutral or slightly alkaline urine 3

Special Considerations and Renal Dosing

Chronic Kidney Disease Adjustments

• With creatinine clearance 10-20 mL/min: maximum 200 mg daily 3
• With creatinine clearance <10 mL/min: maximum 100 mg daily 3
• With creatinine clearance <3 mL/min: lengthen interval between doses 3
• Xanthine oxidase inhibitors are preferred over uricosuric agents in CKD 2, 4

Screening Before Treatment

• Evaluate for medications elevating uric acid: thiazides, loop diuretics, niacin, calcineurin inhibitors 2, 4, 5
• Screen for comorbidities: obesity, hypertension, hyperlipidemia, diabetes, kidney disease 4, 5
• Consider 24-hour urine uric acid if gout onset before age 25 or history of kidney stones 2, 4, 5

Critical Pitfalls to Avoid

• Do not treat asymptomatic hyperuricemia without prior gout attacks, tophi, or other complications - allopurinol is not indicated for asymptomatic hyperuricemia alone 3
• Do not start with high-dose allopurinol - this increases risk of acute gout flares 3
• Do not use probenecid in patients with reduced kidney function (CrCl <50 mL/min) 1
• Do not rely on dietary modifications alone for a uric acid of 9 mg/dL - pharmacologic therapy is required 1
• Do not stop colchicine or anti-inflammatory prophylaxis abruptly when starting ULT - continue until serum urate normalized and freedom from attacks for several months 3

Acute Flare Prophylaxis

• ULT can be started during an acute gout attack if effective anti-inflammatory management is instituted 1
• Continue colchicine or anti-inflammatory agents during ULT dose titration until uric acid normalized and patient has been attack-free for several months 3