What is the first line medication for gout prevention?

First-Line Medication for Gout Prevention

Allopurinol is strongly recommended as the preferred first-line medication for gout prevention over all other urate-lowering therapies. 1

Rationale for Allopurinol as First-Line Therapy

• Allopurinol is recommended as the preferred first-line agent for all patients, including those with chronic kidney disease (CKD) stage ≥3, based on moderate certainty of evidence 1, 2
• The recommendation for allopurinol is based on its proven efficacy when dosed appropriately, tolerability, safety, and lower cost compared to other options 1
• Xanthine oxidase inhibitors (allopurinol or febuxostat) are strongly recommended over probenecid for patients with CKD stage ≥3 1, 2
• Pegloticase is strongly recommended against as first-line therapy due to cost, safety concerns, and favorable benefit-to-harm ratios of other treatment options 1

Dosing Recommendations

• Start allopurinol at a low dose (≤100 mg/day and lower in patients with CKD) with subsequent dose titration to target serum urate levels 1, 2
• Lower starting doses (e.g., ≤50 mg/day) should be considered in patients with CKD 1
• Dose titration should aim to achieve and maintain a serum urate target of <6 mg/dL 1, 2
• Despite traditional concerns about dosing limitations in CKD, patients may require dose titration above 300 mg/day to achieve serum urate targets 1, 2
• The maximum FDA-approved dose of allopurinol is 800 mg/day 1, 3

Prophylaxis During Initiation

• When starting urate-lowering therapy, concomitant anti-inflammatory prophylaxis is strongly recommended to prevent gout flares 1, 2
• Options for prophylaxis include colchicine, NSAIDs, or prednisone/prednisolone, with the choice based on patient factors 1, 4
• Prophylaxis should be continued for 3-6 months after initiating urate-lowering therapy 1, 2
• Colchicine prophylaxis at a dose of 0.6 mg once or twice daily is effective for preventing flares during initiation of urate-lowering therapy 4

Alternative First-Line Options

• Febuxostat may be considered as an alternative first-line agent if allopurinol is not tolerated 2, 5
• Start febuxostat at a low dose (≤40 mg/day) with subsequent dose titration to target 1, 2
• Probenecid is conditionally recommended to start at a low dose (500 mg once or twice daily) with dose titration if needed 1
• For patients who cannot tolerate allopurinol or febuxostat, alternative options should be considered based on individual factors 2

Safety Considerations

• The risk of allopurinol hypersensitivity syndrome (AHS) is associated with higher starting doses and CKD, emphasizing the importance of starting with low doses 1, 2
• Testing for HLA-B*5801 is conditionally recommended prior to starting allopurinol for patients of Southeast Asian descent (e.g., Han Chinese, Korean, Thai) to reduce the risk of severe cutaneous adverse reactions 1
• For patients with gout taking febuxostat with a history of cardiovascular disease or a new cardiovascular event, switching to an alternative urate-lowering therapy agent is conditionally recommended 1

Timing of Initiation

• When the decision is made that urate-lowering therapy is indicated while the patient is experiencing a gout flare, it is conditionally recommended to start urate-lowering therapy during the gout flare rather than waiting until the flare resolves 1, 6
• Starting allopurinol during an acute gout attack does not significantly prolong the duration of the attack when appropriate anti-inflammatory treatment is used 6