What is the protocol for prescribing febuxostat (febuxostat) in patients with hyperuricemia?

Protocol for Prescribing Febuxostat in Hyperuricemia

When to Prescribe Febuxostat

Febuxostat is recommended as a second-line urate-lowering therapy after allopurinol for patients with symptomatic gout and hyperuricemia, particularly when allopurinol is contraindicated, not tolerated, or ineffective. 1, 2

Do NOT Prescribe for Asymptomatic Hyperuricemia

• Febuxostat should not be initiated for asymptomatic hyperuricemia, even when serum uric acid levels are elevated or crystal deposition is detected on imaging 3, 2
• Treatment is only warranted when patients develop gout symptoms, subcutaneous tophi, radiographic damage, or frequent gout flares 3

Specific Indications for Febuxostat

• Allopurinol intolerance or contraindication: Primary indication when first-line therapy cannot be used 1, 2
• Inadequate response to allopurinol: After appropriate trial of allopurinol at optimized doses 2
• Chronic kidney disease (CKD stage ≥3): Febuxostat is particularly useful as it requires no dose adjustment in renal impairment, unlike allopurinol 4, 2, 5
• High-risk populations for allopurinol hypersensitivity: Consider in patients of Han Chinese, Korean, or Thai descent, or African Americans who test positive for HLA-B*5801 1, 2

Cardiovascular Risk Assessment (Critical Step)

Before prescribing febuxostat, assess cardiovascular disease (CVD) history, as febuxostat carries an FDA black box warning for cardiovascular risk. 1, 4

• If history of CVD or new cardiovascular event: Conditionally recommend switching to an alternative urate-lowering therapy if available 1, 4
• Shared decision-making required: Discuss cardiovascular risks with patients at high risk for CVD before initiating febuxostat 4
• If febuxostat is chosen despite CVD history, close monitoring for cardiovascular events is essential 1

Dosing Protocol

Starting Dose

Always start febuxostat at 40 mg once daily to minimize the risk of gout flares during therapy initiation. 4, 2

Dose Titration

• If target serum uric acid level (<6 mg/dL) is not achieved after 2-4 weeks, increase to 80 mg once daily 2, 5
• Maximum dose is 80 mg daily in most patients; some severe cases may require up to 120 mg daily 4, 5
• No dose adjustment required for any stage of CKD, which is a key advantage over allopurinol 4, 2, 5

Mandatory Gout Flare Prophylaxis

Always initiate concomitant anti-inflammatory prophylaxis when starting febuxostat to prevent acute gout flares. 4, 2

Prophylaxis Options

• Colchicine (preferred, dose-adjusted for renal function) 4, 2
• Low-dose NSAIDs (if not contraindicated) 4, 2
• Prednisone/prednisolone (if colchicine and NSAIDs contraindicated) 4, 2

Duration of Prophylaxis

• Continue prophylaxis for 3-6 months after initiating febuxostat 4, 2
• This prolonged prophylaxis is necessary as gout flares can occur for an extended period with aggressive urate lowering 2, 6

Target Serum Uric Acid Levels

The therapeutic goal is to achieve and maintain serum uric acid levels below 6 mg/dL at minimum. 4, 2

• For patients with severe gout (tophi, chronic arthropathy, frequent attacks), target levels below 5 mg/dL 2
• Regular monitoring of serum uric acid levels is required to ensure target levels are achieved and maintained 2

Monitoring Protocol

Baseline Assessment

• Measure baseline serum uric acid level 4
• Evaluate renal function (eGFR, creatinine clearance) 4
• Assess cardiovascular disease history 1, 4
• Check liver function tests 6

Ongoing Monitoring

• Monitor serum uric acid levels regularly (every 2-4 weeks initially, then every 3-6 months once stable) to ensure target levels are maintained 2
• Monitor for cardiovascular events, especially in patients with CVD history 1
• Monitor liver function tests periodically, as hepatotoxicity has been reported more frequently with febuxostat than allopurinol 7, 6

Common Pitfalls to Avoid

• Starting with too high a dose: Always begin at 40 mg/day to reduce flare risk 2
• Failing to provide anti-inflammatory prophylaxis: This leads to increased gout flares and treatment discontinuation 2, 7
• Using febuxostat as first-line therapy: Allopurinol remains the preferred first-line agent due to efficacy, safety profile, and lower cost 2
• Discontinuing therapy prematurely: Urate-lowering therapy should be maintained lifelong once target levels are achieved to prevent recurrence 1, 2
• Not monitoring serum urate levels: Regular monitoring is essential to confirm therapeutic targets are met 2
• Ignoring cardiovascular risk: Always assess CVD history before prescribing and consider alternatives in high-risk patients 1, 4

Special Populations

Chronic Kidney Disease

• Febuxostat is preferred in patients with eGFR <60 mL/min as it does not require dose adjustment 4, 2
• Start at 40 mg daily and titrate to 80 mg if needed, regardless of CKD stage 4
• Allopurinol would require significant dose reduction in severe renal impairment, potentially limiting efficacy 4

Patients with Prior Allopurinol Hypersensitivity

• Febuxostat is an appropriate alternative for patients who experienced allergic reactions to allopurinol 2
• Consider in high-risk ethnic groups (Han Chinese, Korean, Thai, African American) with positive HLA-B*5801 testing 1, 2