How to safely discontinue allopurinol (xanthine oxidase inhibitor) in patients with a history of gout?

How to Safely Discontinue Allopurinol in Patients with Gout

Allopurinol discontinuation should be accompanied by prophylactic anti-inflammatory therapy for at least 3-6 months to prevent gout flares, as stopping allopurinol leads to rising serum urate levels and increased risk of acute attacks. 1

Indications for Discontinuation

• Allopurinol should be discontinued when the potential for overproduction of uric acid is no longer present, as stated in the FDA label 2
• Discontinuation is mandatory if a patient develops a rash, which could indicate the onset of allopurinol hypersensitivity syndrome (AHS) 3
• Allopurinol should be stopped before pregnancy due to associations with cleft palate and other facial anomalies 3

Discontinuation Protocol

Step 1: Risk Assessment

• Evaluate the patient's risk for gout flares after discontinuation based on:
  • Recent gout flares (especially in the past month) 4
  • Presence of tophi 1
  • Baseline serum uric acid level (higher levels indicate greater risk) 1
  • History of frequent gout attacks (≥2/year) 3

Step 2: Prophylactic Therapy

• Initiate prophylactic anti-inflammatory therapy before discontinuing allopurinol:
  • First-line: Colchicine 0.6 mg once or twice daily (adjust for renal function) 3, 5
  • Alternative if colchicine is contraindicated: Low-dose NSAIDs 3
  • For patients who cannot take colchicine or NSAIDs: Consider low-dose prednisone 3

Step 3: Gradual Discontinuation

• For patients on high doses (>300 mg/day), consider tapering the dose gradually over 2-4 weeks rather than abrupt discontinuation 6
• Monitor serum urate levels during the tapering process 1

Step 4: Post-Discontinuation Monitoring

• Schedule follow-up visits at 1,3, and 6 months after discontinuation 4
• Monitor for:
  • Acute gout flares 5
  • Rising serum urate levels 1
  • Development of tophi 3

Special Considerations

Patients with Chronic Kidney Disease

• Patients with CKD stage ≥3 are at higher risk for flares after discontinuation and may require longer prophylaxis 3
• Consider using losartan for hypertension management in these patients, as it has uricosuric effects 3

Patients with Cardiovascular Disease

• If discontinuing allopurinol to switch to febuxostat, be aware of the cardiovascular risk associated with febuxostat 7
• Consider alternative urate-lowering therapies like probenecid if appropriate 8

Common Pitfalls to Avoid

• Discontinuing prophylactic anti-inflammatory therapy too early (should continue for at least 3-6 months) 5, 4
• Failing to monitor serum urate levels after discontinuation 1
• Not providing clear instructions to patients about when to seek medical attention for acute flares 3
• Discontinuing allopurinol in patients with severe gout (tophi, chronic arthropathy) without a plan for alternative urate-lowering therapy 3

When to Consider Alternative Therapy Instead of Discontinuation

• For patients with frequent gout flares (≥2/year), consider switching to an alternative urate-lowering therapy rather than complete discontinuation 3
• Options include:
  • Febuxostat (with caution in patients with cardiovascular disease) 8, 7
  • Probenecid (if normal renal function) 8
  • Benzbromarone (where available, especially in patients with renal impairment) 8, 9

Remember that once allopurinol is discontinued, serum urate levels will rise, potentially leading to recurrent gout attacks. Careful monitoring and prophylactic therapy are essential to manage this transition safely.