What is a suitable long-term medication for managing gout in patients who cannot take febuxostat (febuxostat) due to drug-drug interactions?

Alternative Long-Term Urate-Lowering Therapy When Febuxostat is Contraindicated

Allopurinol is the recommended first-line alternative for long-term gout management when febuxostat cannot be used due to drug-drug interactions. 1

Primary Recommendation: Allopurinol

Allopurinol should be initiated as the preferred alternative urate-lowering therapy (ULT) in patients who cannot take febuxostat. 1

Initiation Strategy

• Start allopurinol at 100 mg daily (or 50 mg daily if creatinine clearance <30 mL/min or stage 4+ CKD) 1
• Titrate upward by 100 mg increments every 2-4 weeks until serum uric acid target is achieved 1
• Target serum uric acid <6 mg/dL (360 μmol/L) for standard gout management 1
• For severe gout with tophi or chronic arthropathy, target <5 mg/dL (300 μmol/L) until crystal dissolution occurs 1

Dosing Considerations

• Doses above 300 mg daily are frequently necessary and appropriate to achieve target uric acid levels 1, 2
• FDA-approved doses extend up to 800 mg daily 2
• In renal impairment, adjust maximum dosage according to creatinine clearance 1, 3

Mandatory Prophylaxis

• Initiate colchicine (0.5-1 mg daily) or NSAID prophylaxis at least 1 week before starting allopurinol 1, 4
• Continue prophylaxis for at least 3-6 months to prevent acute gout flares 1, 4

Second-Line Alternatives: Uricosuric Agents

If allopurinol is contraindicated or not tolerated, uricosuric agents represent the next therapeutic option. 1

Probenecid

• Use as alternative first-line therapy if xanthine oxidase inhibitors are contraindicated or not tolerated 1
• Requires normal renal function (creatinine clearance ≥50 mL/min) 1
• Relatively contraindicated in patients with history of urolithiasis 1
• Dose: 1-2 g/day 1

Benzbromarone

• Can be used in patients with mild to moderate renal insufficiency 1
• Available on named-patient basis in some countries 1
• Carries small risk of hepatotoxicity requiring monitoring 1

Third-Line Option: Pegloticase

For patients with severe debilitating chronic tophaceous gout who fail to achieve target serum uric acid with all other available drugs at maximal dosages (including combinations), pegloticase is indicated. 1

Key Characteristics

• Reserved for refractory, severe disease with poor quality of life 1
• Administered intravenously in healthcare settings 3
• Requires discontinuation of all oral urate-lowering agents before initiation 3
• High risk of anaphylaxis (requiring pretreatment with antihistamines and corticosteroids) and infusion reactions 3

Critical Pitfalls to Avoid

Underdosing Allopurinol

• More than half of gout patients fail to achieve target uric acid levels on standard 300 mg allopurinol dose 2
• Titrate to effect rather than stopping at arbitrary dose limits 1

Premature Discontinuation

• Lifelong therapy is required; discontinuation leads to recurrence in approximately 87% of patients within 5 years 2, 4
• Maintain therapy even after achieving symptom control 2

Inadequate Prophylaxis

• Initiating ULT without concurrent anti-inflammatory prophylaxis dramatically increases acute flare risk 1, 4
• Prophylaxis duration of less than 3 months is often insufficient 4

HLA-B*5801 Screening

• Consider rapid PCR-based HLA-B*5801 screening before initiating allopurinol in high-risk populations (Southeast Asian descent, Korean, Han Chinese, Thai) where allele frequency is elevated 1
• This screening helps prevent severe cutaneous adverse reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis 5

Monitoring Requirements

• Check serum uric acid levels during dose titration to guide adjustments 1
• Once target achieved, monitor serum uric acid every 6 months 2, 4
• Monitor renal function every 6 months as allopurinol dosing may require adjustment if renal function changes 2
• Assess for adverse effects including rash, hepatotoxicity, and gastrointestinal symptoms 5