What to do for gout attacks in a patient already taking allopurinol (xanthine oxidase inhibitor)?

Management of Gout Flares in Patients Already Taking Allopurinol

Continue allopurinol at the current dose and treat the acute flare with anti-inflammatory therapy (NSAIDs, colchicine, or corticosteroids), then reassess and uptitrate the allopurinol dose after the flare resolves to achieve target serum urate <6 mg/dL. 1, 2, 3

Acute Flare Management

Do Not Stop Allopurinol

• Continue allopurinol without interruption during the acute gout attack 2, 4
• Starting or continuing allopurinol during an acute attack does not significantly prolong the duration of the flare when appropriate anti-inflammatory treatment is provided 2, 4
• A randomized controlled trial demonstrated no statistically significant difference in days to resolution between patients who started allopurinol during an acute attack (15.4 days) versus placebo (13.4 days, p=0.5) 4

Treat the Acute Inflammation

• Use standard anti-inflammatory therapy: NSAIDs, colchicine, or corticosteroids to manage the acute attack 1, 2, 3
• The choice of anti-inflammatory agent should be based on patient comorbidities (e.g., corticosteroids may be preferred in patients with renal impairment) 5

Post-Flare Dose Optimization

Assess Why the Flare Occurred

• The occurrence of a gout flare while on allopurinol indicates inadequate urate lowering 1, 6
• Check serum urate level—the target is <6 mg/dL for all gout patients, or <5 mg/dL for those with severe gout (tophi, chronic arthropathy, frequent attacks) 1
• Common causes of inadequate response include: insufficient dosing (most common), poor adherence, or rarely, partial resistance to allopurinol 6

Uptitrate Allopurinol Dose

• Increase allopurinol by 100 mg increments every 2-5 weeks until serum urate target is achieved 7, 1, 3
• The American College of Rheumatology emphasizes that doses above 300 mg/day are often necessary, as allopurinol ≤300 mg/day fails to achieve target urate levels in more than half of gout patients 1
• Maximum FDA-approved dose is 800 mg/day 1, 3
• In a study of allopurinol uptitration, 97% of patients achieved target urate levels with a median final dose of 300 mg daily, and the mean fall in urate after a single 100 mg dose increase was 71 µmol/L (1.2 mg/dL) 8

Reinitiate or Continue Prophylaxis During Uptitration

• Anti-inflammatory prophylaxis (colchicine, NSAIDs, or prednisone) must be continued or restarted when adjusting allopurinol dose 1, 2, 3
• Prophylaxis should continue for at least 3-6 months with ongoing evaluation, and longer if flares persist 1, 2
• The FDA label specifically states that maintenance doses of colchicine should be given prophylactically when allopurinol is begun or adjusted 3

Special Considerations

Renal Impairment

• Allopurinol remains the preferred agent even in moderate-to-severe CKD (stage ≥3) 5
• Dose titration above 300 mg/day is supported even in renal impairment with careful monitoring 1, 5
• For CKD stage 4 or worse, consider starting at 50 mg/day if initiating therapy 1
• With creatinine clearance 10-20 mL/min, use 200 mg daily; <10 mL/min, do not exceed 100 mg daily 3

Monitoring During Dose Escalation

• Monitor serum urate every 2-5 weeks during dose titration 1
• Once target is achieved, monitor serum urate every 6 months 1
• Watch for hypersensitivity reactions (rash, pruritis, elevated liver enzymes, eosinophilia) during dose escalation 1
• A randomized controlled trial of allopurinol dose escalation showed no difference in renal function changes or serious adverse events between dose escalation and control groups 9

Common Pitfalls to Avoid

• Do not discontinue allopurinol during an acute flare—this is outdated practice and can worsen long-term urate control 2, 4
• Do not leave patients on 300 mg allopurinol without checking if they've achieved target serum urate—this fixed-dose approach fails in over 50% of patients 1
• Do not uptitrate allopurinol without adequate anti-inflammatory prophylaxis—this increases flare frequency 1, 3
• Ensure adequate hydration (at least 2 liters daily urinary output) to prevent xanthine calculi and renal urate precipitation 3