What medication should be given to a patient with hyperuricemia (elevated uric acid level)?

Management of Hyperuricemia with Uric Acid Level of 8.5 mg/dL

For a patient presenting with a uric acid level of 8.5 mg/dL, you should NOT initiate urate-lowering therapy unless the patient has symptomatic gout (acute attacks, tophi, joint destruction) or specific high-risk conditions such as active malignancy with tumor lysis risk or recurrent calcium oxalate kidney stones with high urinary uric acid excretion. 1

Critical First Step: Determine If Treatment Is Indicated

The FDA label explicitly states that allopurinol "is not recommended for the treatment of asymptomatic hyperuricemia" and "is not an innocuous drug." 1 Treatment should only be initiated for:

• Symptomatic gout: Patients with acute attacks, tophi, joint destruction, uric acid kidney stones, or gout nephropathy 1
• Malignancy-related hyperuricemia: Patients with leukemia, lymphoma, or other cancers receiving chemotherapy causing elevated uric acid 1
• Recurrent calcium oxalate stones: Male patients excreting >800 mg/day or female patients >750 mg/day of urinary uric acid 1

A uric acid level of 8.5 mg/dL alone, without symptoms or these specific conditions, does not warrant pharmacologic treatment. 1

If Treatment IS Indicated: Medication Selection Algorithm

Step 1: Assess Renal Function and Comorbidities

• Check creatinine clearance/eGFR before selecting medication 2, 3
• Screen for cardiovascular disease history as this affects medication choice 3, 4
• Consider HLA-B*5801 testing in high-risk populations (Koreans with CKD stage 3 or worse, Han Chinese, Thai patients) before starting allopurinol 2

Step 2: Choose Initial Urate-Lowering Therapy

For Normal Renal Function (eGFR ≥60 mL/min):

Start with allopurinol as first-line therapy 2, 4:

• Initial dose: 100 mg daily (or 50 mg daily if stage 4 or worse CKD) 2, 1
• Titrate upward by 100 mg every 2-5 weeks until target serum uric acid <6 mg/dL is achieved 2, 1
• Maximum dose: 800 mg daily (can exceed 300 mg/day even with renal impairment if monitored closely for toxicity) 2, 1

For Impaired Renal Function (eGFR <60 mL/min):

Febuxostat is preferred over allopurinol 3:

• Initial dose: 40 mg daily 3
• Titrate to maximum 80 mg daily (up to 120 mg in severe cases) 3
• No dose adjustment required regardless of CKD stage 3
• CRITICAL CAVEAT: Febuxostat carries an FDA black box warning for cardiovascular risk; if the patient has cardiovascular disease history, strongly consider switching to alternative therapy or using allopurinol with careful dose adjustment instead 3, 4

Step 3: Mandatory Gout Flare Prophylaxis

Always initiate anti-inflammatory prophylaxis when starting urate-lowering therapy 3, 4:

• Colchicine (dose-adjusted for renal function), OR
• Low-dose NSAIDs (if not contraindicated), OR
• Prednisone/prednisolone 3
• Continue prophylaxis for 3-6 months after initiating therapy 3

Step 4: Dose Adjustment Based on Renal Function (If Using Allopurinol)

Allopurinol requires strict renal dose adjustment 2, 1:

• CrCl 10-20 mL/min: Maximum 200 mg daily 1
• CrCl <10 mL/min: Maximum 100 mg daily 1
• CrCl <3 mL/min: Extend dosing interval beyond daily 1

The rationale is that decreased renal clearance leads to accumulation of oxypurinol (allopurinol's metabolite), increasing risk of severe cutaneous adverse reactions with 25-30% mortality 3.

Target Serum Uric Acid Level

Treat to target of <6 mg/dL for most patients 2, 3, 4, 1:

• For severe tophaceous gout, target <5 mg/dL 4
• Monitor serum uric acid levels and adjust dosing every 2-5 weeks until target achieved 2, 1

Important Considerations Before Starting Therapy

Eliminate Contributing Medications (If Medically Appropriate)

Discontinue non-essential medications that elevate uric acid 2:

• Thiazide and loop diuretics
• Niacin
• Calcineurin inhibitors
• Do NOT discontinue low-dose aspirin (≤325 mg daily) for cardiovascular prophylaxis despite modest uric acid elevation 2

Screen for Uric Acid Overproduction

Measure 24-hour urinary uric acid in patients with 2:

• Gout onset before age 25
• History of kidney stones

If urinary uric acid is elevated (indicating overproduction), uricosuric agents are contraindicated 2.

Common Pitfalls to Avoid

1. Never combine allopurinol and febuxostat - both are xanthine oxidase inhibitors working through the same mechanism 4

2. Do not start urate-lowering therapy during an acute gout flare - wait until the flare resolves, but ensure prophylaxis is in place before initiating 2

3. Do not use febuxostat as first-line in patients with cardiovascular disease due to increased cardiovascular mortality risk shown in the CARES trial 4

4. Avoid rapid dose escalation - this increases risk of precipitating acute gout flares 2, 1

5. Do not forget to reduce 6-mercaptopurine or azathioprine doses by 65-75% if patient is on these medications when starting allopurinol 2

If First-Line Therapy Fails

For refractory hyperuricemia despite maximum tolerated xanthine oxidase inhibitor dose 2, 4:

• Add a uricosuric agent (probenecid) to the xanthine oxidase inhibitor 2
• Switch from allopurinol to febuxostat (or vice versa) if drug intolerance occurs 2
• Consider pegloticase for severe refractory gout with high disease burden (discontinue all oral urate-lowering agents during pegloticase therapy) 2, 4

Special Populations

Tumor Lysis Syndrome Risk (Malignancy Patients)

For patients with rapidly proliferating malignancies at high risk for tumor lysis syndrome 2:

• Rasburicase is preferred over allopurinol for preexisting hyperuricemia ≥7.5 mg/dL 2
• Allopurinol dosing: 200-400 mg/m²/day IV (maximum 600 mg/day) or 100 mg/m²/dose PO every 8 hours (maximum 800 mg/day) 2
• Screen for G6PD deficiency before rasburicase - it is contraindicated in G6PD-deficient patients 2