Is febuxostat (febuxostat) used for treating hyperuricemia (elevated uric acid levels) in gout patients?

Is Febuxostat Used for Treating Hyperuricemia in Gout Patients?

Yes, febuxostat is used as a first-line xanthine oxidase inhibitor for treating hyperuricemia in gout patients, though allopurinol is generally preferred initially due to cost considerations. 1

First-Line Urate-Lowering Therapy

The American College of Rheumatology recommends xanthine oxidase inhibitor (XOI) therapy with either allopurinol or febuxostat as first-line pharmacologic urate-lowering therapy for gout patients. 1 The panel did not preferentially recommend one XOI over the other from a purely clinical efficacy standpoint. 1

However, in practical clinical application, allopurinol is typically initiated first due to substantially lower cost, with febuxostat reserved for patients who have contraindications, intolerance, or inadequate response to allopurinol. 1, 2

When to Use Febuxostat

Febuxostat should be considered in the following scenarios:

• Drug intolerance or adverse events with allopurinol: Febuxostat can be substituted after allopurinol intolerance, including hypersensitivity reactions. 1

• Failure of upward dose titration of allopurinol: After attempting to maximize allopurinol dosing to achieve target serum urate, febuxostat substitution is appropriate. 1

• Moderate-to-severe chronic kidney disease (CKD stage ≥3): Febuxostat does not require dose adjustment in mild-to-moderate renal impairment, unlike allopurinol which requires careful dose calibration. 2, 3

• High-risk populations for allopurinol hypersensitivity: Consider febuxostat in Koreans with stage 3 or worse CKD, and Han Chinese and Thai patients who test positive for HLA-B*5801. 2

Dosing Protocol

Start febuxostat at 40 mg once daily to minimize gout flares during therapy initiation. 2, 4

• If serum uric acid is not <6 mg/dL after 2-4 weeks, increase to 80 mg once daily. 4, 5

• Always initiate concomitant anti-inflammatory prophylaxis (colchicine, NSAIDs, or prednisone) for 3-6 months when starting febuxostat to prevent acute gout flares. 2, 4

Target Serum Urate Levels

• Minimum target: <6 mg/dL for all gout patients. 1, 2

• For severe gout (tophi, chronic arthropathy, frequent attacks): target <5 mg/dL. 1, 2

• Monitor serum urate every 2-4 weeks initially, then every 3-6 months once stable to ensure target levels are maintained. 4

Comparative Efficacy

Febuxostat 80 mg/day is more effective than allopurinol 300 mg/day at decreasing serum urate levels. 6, 7 In clinical trials, 67% of patients on febuxostat 80 mg/day achieved serum urate <6 mg/dL compared to 42% on allopurinol 300 mg/day. 8 However, the doses of allopurinol used in these comparisons (100-300 mg/day) are in the lower range of approved doses, and allopurinol can be titrated above 300 mg/day to achieve target serum urate. 1

Critical Safety Considerations

Cardiovascular safety concerns exist with febuxostat. The CARES trial showed higher risk of cardiovascular-related death compared to allopurinol. 6 The FDA issued a black box warning for cardiovascular risk. 4

• Assess cardiovascular disease history before prescribing febuxostat. 4

• Use shared decision-making when prescribing to patients at high cardiovascular risk. 4

• If a cardiovascular event occurs during treatment, consider switching to alternative urate-lowering therapy. 4

Important Contraindications and Warnings

• Febuxostat should NOT be used in combination with allopurinol as both are xanthine oxidase inhibitors working through the same mechanism. 1, 6

• Febuxostat is NOT indicated for asymptomatic hyperuricemia. 2, 4

• During pegloticase therapy (third-line agent for refractory gout), febuxostat and all oral urate-lowering agents should be discontinued to avoid masking loss of pegloticase efficacy. 1

Common Adverse Events

The most frequently reported adverse events with febuxostat include liver function abnormalities, nausea, arthralgias, diarrhea, and rash. 5, 9 These occur at rates comparable to allopurinol. 3, 7

Common Pitfalls to Avoid

• Failing to provide anti-inflammatory prophylaxis when initiating febuxostat, leading to increased gout flares. 2

• Starting with too high a dose (80 mg) instead of 40 mg, which increases flare risk. 2

• Using febuxostat as first-line therapy without considering cost when allopurinol would be appropriate. 2

• Not monitoring serum urate levels to ensure target achievement. 2

• Discontinuing therapy prematurely once target urate is achieved; urate-lowering therapy should be maintained lifelong. 2