What are the indications for prescribing allopurinol (xanthine oxidase inhibitor) versus febuxostat (Xanthine Oxidase inhibitor) for patients with hyperuricemia?

From the Guidelines

Allopurinol should be the first-line urate-lowering therapy (ULT) for gout management, with febuxostat reserved for patients who cannot tolerate allopurinol or have contraindications to its use. When deciding between allopurinol and febuxostat, consider the patient's renal function, as allopurinol requires dose adjustment in patients with chronic kidney disease (CKD) stage 4 or worse 1. Start allopurinol at a low dose (100mg daily, or 50mg daily in patients with CKD stage 4 or worse) and gradually titrate upward every 2-4 weeks based on serum urate levels and tolerance, with a typical maintenance dose of 300-600mg daily 1. Febuxostat (40-80mg daily) can be used without dose adjustment in patients with mild to moderate renal impairment, but should be used cautiously in patients with cardiovascular disease due to a potentially higher risk of cardiovascular events 1. For either medication, start prophylaxis with colchicine, NSAIDs, or low-dose prednisone for the first 3-6 months to prevent gout flares during initiation of therapy, and continue treatment indefinitely to maintain target serum urate levels below 6 mg/dL 1.

Some key points to consider when choosing between allopurinol and febuxostat include:

• Patient's renal function and ability to tolerate allopurinol
• Presence of contraindications to allopurinol, such as hypersensitivity reactions
• Patient's cardiovascular disease status and potential risk of cardiovascular events with febuxostat
• Ability to achieve target serum urate levels with allopurinol, and consideration of febuxostat if targets are not met
• Importance of prophylaxis with colchicine, NSAIDs, or low-dose prednisone during initiation of ULT to prevent gout flares.

It is essential to individualize treatment based on patient-specific factors and to monitor serum urate levels and renal function regularly to adjust therapy as needed 1.

From the FDA Drug Label

Allopurinol tablets reduce serum and urinary uric acid concentrations. The dosage of allopurinol tablets to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease.

The decision to give allopurinol vs febuxostat is not directly addressed in the provided drug labels, as there is no mention of febuxostat.

• Allopurinol is indicated for the management of patients with signs and symptoms of primary or secondary gout, leukemia, lymphoma, and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels, and for the management of patients with recurrent calcium oxalate calculi 2 2. The FDA drug label does not answer the question.

From the Research

Deciding Between Allopurinol and Febuxostat

When deciding between allopurinol and febuxostat for gout management, several factors should be considered:

• Patient's renal function: Allopurinol dosing should be adjusted according to creatinine clearance to minimize the risk of allopurinol hypersensitivity syndrome (AHS) 3, 4.
• Starting dose: A starting dose of 1.5 mg per unit of estimated GFR may be associated with a reduced risk of AHS 3.
• Dose titration: Allopurinol dose can be gradually increased to achieve target serum urate levels in patients who tolerate the initial dose 3, 4.
• Chronic kidney disease (CKD): Patients with CKD may require lower doses of allopurinol to achieve similar serum urate lowering compared to patients with normal kidney function 5.
• Dialysis: Allopurinol dosing practices, oxypurinol pharmacokinetics, and effectiveness in gout patients receiving dialysis are complex and require careful consideration 6.

Comparative Effectiveness

A double-blind noninferiority trial compared the effectiveness of allopurinol and febuxostat in gout management:

• Allopurinol was noninferior to febuxostat in controlling flares 7.
• Both treatments achieved serum urate goals in patients with gout, including those with stage 3 chronic kidney disease 7.
• There were no significant differences in serious adverse events, including cardiovascular events, between the two treatments 7.

Key Considerations

When choosing between allopurinol and febuxostat, consider the following:

• Patient's individual characteristics, such as renal function and comorbidities.
• The potential risks and benefits of each treatment, including the risk of AHS with allopurinol.
• The need for careful dose titration and monitoring to achieve target serum urate levels and minimize adverse events.