What is the recommended dose of febuxostat (febuxostat) for a patient with hyperuricemia (elevated uric acid levels) and potentially impaired renal function?

Febuxostat Dosing for Hyperuricemia

Start febuxostat at 40 mg once daily, and if serum uric acid remains ≥6 mg/dL after 2-4 weeks, increase to 80 mg once daily—the maximum FDA-approved dose for hyperuricemia in gout. 1, 2, 3

Initial Dosing Strategy

• Begin with febuxostat 40 mg orally once daily as the standard starting dose for patients with hyperuricemia and gout 2, 3
• No dose adjustment is required for mild to moderate renal impairment (CrCl 30-89 mL/min), making febuxostat particularly advantageous over allopurinol in patients with impaired renal function 4, 5, 3
• In patients with severe renal impairment (eGFR 15-50 mL/min/1.73 m²), febuxostat 30 mg twice daily or 40 mg once daily has been studied and found safe and effective 5

Dose Titration Protocol

• Measure serum uric acid after 2 weeks of treatment 2, 3
• If serum uric acid is not <6 mg/dL, increase to 80 mg once daily 1, 2, 3
• The 80 mg dose is superior to allopurinol 300 mg daily, achieving target serum uric acid <6 mg/dL in 67% versus 42% of patients 6, 7, 3
• Monitor serum uric acid every 2-5 weeks during dose titration until target is achieved 4
• Once target serum uric acid <6 mg/dL is achieved, monitor every 6 months 4

Critical Mandatory Prophylaxis

Always initiate anti-inflammatory prophylaxis when starting febuxostat to prevent acute gout flares. 1, 4

• Provide colchicine 0.5-1 mg daily, low-dose NSAIDs, or prednisone/prednisolone for at least 6 months (preferably throughout the first 6 months of treatment) 6, 1, 4
• The American College of Rheumatology strongly recommends this prophylaxis, as discontinuation at 8 weeks was associated with a spike in acute gout attacks in clinical trials 6, 1
• Adjust colchicine dose for renal function if impaired 4

Special Considerations for Renal Impairment

Febuxostat is preferred over allopurinol in patients with moderate-to-severe CKD (eGFR <60 mL/min) because it does not require dose adjustment and avoids the risk of severe cutaneous adverse reactions associated with allopurinol in renal failure. 1, 4

• In CKD stage 3-5, febuxostat maintains efficacy without dose reduction, whereas allopurinol requires significant dose adjustment that may limit effectiveness 4, 5
• A 12-month study in patients with eGFR 15-50 mL/min showed febuxostat achieved serum uric acid <6 mg/dL without deterioration in renal function 5
• Allopurinol carries increased risk of severe cutaneous adverse reactions (mortality 25-30%) in renal failure due to accumulation of its metabolite oxypurinol 4

Maximum Dosing Limits

• The maximum FDA-approved dose is 80 mg once daily 2, 3
• Doses of 120 mg and 240 mg daily were studied in clinical trials and showed greater uric acid reduction, but these doses are not FDA-approved 6, 7
• Some guidelines note that in severe CKD cases, up to 120 mg daily may be required, though this exceeds standard FDA approval 4

Cardiovascular Warning and Monitoring

Febuxostat carries an FDA black box warning for cardiovascular risk—consider switching to allopurinol in patients with established cardiovascular disease or who experience new cardiovascular events. 4

• More cardiovascular thromboembolic events occurred in randomized trials with febuxostat compared to allopurinol 2
• The American College of Rheumatology conditionally recommends switching to alternative urate-lowering therapy for patients with history of cardiovascular disease 4
• Shared decision-making is essential when considering febuxostat in patients at high cardiovascular risk 4
• Monitor for signs and symptoms of myocardial infarction and stroke 2

Common Pitfalls to Avoid

• Never combine febuxostat with allopurinol—they have redundant mechanisms of action and increase toxicity risk without therapeutic benefit 4
• Never start febuxostat without anti-inflammatory prophylaxis—this leads to acute gout flares that worsen patient outcomes 1, 4
• Never stop urate-lowering therapy during an acute flare—continue febuxostat and treat the flare separately 1
• Never use the 40 mg dose as the final dose without checking serum uric acid—most patients require 80 mg to achieve target 6, 7

Monitoring Parameters

• Baseline: serum uric acid, comprehensive metabolic panel, liver function tests 2
• During titration: serum uric acid every 2-4 weeks until target achieved 4, 2
• Maintenance: serum uric acid every 6 months, liver function tests periodically 4, 2
• Watch for adverse events: liver enzyme elevations (most common at 4.6-6.6%), nausea, arthralgias, rash 2, 3

Target Serum Uric Acid Levels

• Standard target: <6 mg/dL for all gout patients 1, 4
• Lower target: <5 mg/dL for patients with tophi to facilitate tophus resolution 1
• Achieving target serum uric acid <6 mg/dL results in progressive decrease in gout flare risk to approximately 5% at 12 months and near zero at 32 months 6