What is the first‑line medication and dosing for an adult with elevated serum uric acid and normal renal function?

First-Line Medication for Elevated Uric Acid

Allopurinol is the preferred first-line medication for adults with elevated serum uric acid and normal renal function, starting at 100 mg daily and titrating upward every 2-5 weeks to achieve a target serum urate <6 mg/dL. 1, 2

When to Initiate Urate-Lowering Therapy

Strong indications (treat regardless of serum urate level):

• One or more subcutaneous tophi 1, 2
• Frequent gout flares (≥2 per year) 1, 2
• Radiographic joint damage from gout 1, 2
• Chronic tophaceous gouty arthropathy 2

Conditional indications (consider after first gout flare):

• Chronic kidney disease stage ≥3 (eGFR <60 mL/min) 1, 2
• Serum urate >9 mg/dL 2
• History of urolithiasis (kidney stones) 1, 2

Do NOT treat asymptomatic hyperuricemia (elevated uric acid without gout symptoms), as current evidence shows limited benefit relative to potential risks. 2

Allopurinol Dosing Protocol

Starting dose:

• 100 mg daily for normal renal function 1, 2
• 50 mg daily for CKD stage 4 or worse 1, 2

Titration strategy:

• Increase by 100 mg every 2-5 weeks based on serum urate monitoring 1, 2
• Target serum urate <6 mg/dL for all patients 1, 2
• For severe gout (tophi, chronic arthropathy, frequent attacks), target <5 mg/dL until crystal dissolution 1, 2
• Maximum FDA-approved dose is 800 mg daily 2

Critical point: Allopurinol can be safely titrated above 300 mg daily, even with renal impairment, as long as accompanied by adequate patient education and monitoring for drug toxicity (pruritis, rash, elevated hepatic transaminases). 1 Most patients require doses >300 mg daily to achieve target serum urate. 1, 2

Mandatory Flare Prophylaxis

You must provide anti-inflammatory prophylaxis when initiating allopurinol to prevent acute gout flares:

• Colchicine 0.5-1 mg daily for at least 6 months 1, 2
• If colchicine contraindicated: low-dose NSAIDs or low-dose glucocorticoids 1, 2
• Reduce colchicine dose in renal impairment and avoid with strong P-glycoprotein/CYP3A4 inhibitors 1

Failing to provide prophylaxis is a major cause of treatment failure and patient non-adherence. 2

Monitoring Schedule

During dose titration:

• Check serum urate every 2-5 weeks until target achieved 1, 2

After achieving target:

• Monitor serum urate every 6 months to assess adherence 1, 2

Alternative First-Line Options

Febuxostat is appropriate as first-line therapy if allopurinol is contraindicated or not tolerated:

• Start at 40 mg daily, titrate to 80 mg daily as needed 2, 3
• No dose adjustment required in mild-to-moderate CKD 4, 3
• Caution: FDA black box warning for cardiovascular risk—consider alternative in patients with established cardiovascular disease 4, 3

Probenecid (uricosuric agent) is an alternative first-line option when at least one xanthine oxidase inhibitor is contraindicated or not tolerated:

• Contraindicated if creatinine clearance <50 mL/min 1, 2, 3
• Contraindicated with history of urolithiasis 1, 3
• Requires measurement of urinary uric acid before initiation 1

Common Pitfalls to Avoid

1. Undertreating with fixed 300 mg allopurinol dose: Most patients need higher doses to reach target serum urate <6 mg/dL. 1, 2

2. Omitting flare prophylaxis: This leads to acute flares during initiation and treatment abandonment. 2

3. Stopping allopurinol during acute flare: Continue urate-lowering therapy and add anti-inflammatory treatment. 2

4. Treating asymptomatic hyperuricemia: No indication unless patient has had gout symptoms or meets conditional criteria above. 2

5. Inadequate monitoring: Check serum urate regularly during titration to guide dose adjustments. 1, 2