Can a patient with gout take allopurinol during an acute gout attack?

Can Patients Take Allopurinol During Gout Attacks?

Yes, allopurinol can and should be started during an acute gout attack rather than waiting for the flare to resolve, provided that effective anti-inflammatory treatment is established simultaneously. 1

Current Guideline Recommendations

The 2020 American College of Rheumatology conditionally recommends starting urate-lowering therapy (ULT) during a gout flare rather than delaying until after the flare has resolved. 1 This represents a significant shift from traditional practice, which historically avoided initiating allopurinol during acute attacks due to concerns about prolonging the painful arthritis. 2

For patients already taking allopurinol when a flare occurs, continue the medication without interruption. 1 Stopping allopurinol during a flare can lead to fluctuations in serum urate levels that may trigger additional attacks. 1

Essential Requirements When Starting During a Flare

Anti-Inflammatory Prophylaxis (Mandatory)

• Concomitant anti-inflammatory prophylaxis is strongly recommended when initiating allopurinol, regardless of whether started during or after a flare. 1
• Prophylaxis options include colchicine (0.5-1 mg/day), NSAIDs, or prednisone/prednisolone. 1
• Continue prophylaxis for 3-6 months after initiating ULT to minimize flare risk. 1, 3
• The FDA label recommends continuing colchicine and/or anti-inflammatory agents until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months. 4

Treat the Acute Flare Separately

• The acute flare itself requires therapeutic doses of anti-inflammatory medication (NSAIDs at full anti-inflammatory doses, colchicine 1.2 mg followed by 0.6 mg one hour later, or corticosteroids), which is distinct from the prophylactic therapy used to prevent future flares. 1

Low-Dose Initiation Strategy

• Start allopurinol at 100 mg daily (or 50 mg daily in CKD stage ≥4), even when initiating during a flare. 1, 4
• The FDA label specifically recommends starting with a low dose of 100 mg daily and increasing at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained. 4
• Titrate gradually every 2-5 weeks to minimize flare risk. 1, 3
• The goal is to achieve serum urate <6 mg/dL, often requiring 300-600 mg daily. 1

Supporting Evidence

Three randomized controlled trials directly addressed this question and found no significant harm from immediate initiation:

• A 2015 trial (31 patients) showed no statistically significant difference in days to resolution between allopurinol and placebo groups (15.4 vs 13.4 days, p=0.5) when allopurinol was started at 100 mg daily during acute attacks. 2
• A 2012 trial (51 patients) using allopurinol 300 mg daily found no significant difference in daily pain scores or subsequent flares compared to placebo. 5
• A 2022 trial (115 patients) comparing early versus late allopurinol initiation found no significant difference in median time to complete resolution (6 days in both groups, p=0.14). 6

The EULAR guidelines acknowledge this evolving evidence, noting that small trials suggested no harm from immediate initiation. 1

Practical Implementation Algorithm

Step 1: Confirm the Patient Meets Criteria for ULT

• Frequent gout flares (≥2/year), presence of tophi, radiographic damage, or first flare with comorbidities (CKD stage ≥3, serum urate >9 mg/dL, or history of urolithiasis). 1

Step 2: Establish Anti-Inflammatory Treatment

• Start therapeutic doses for the acute flare (NSAIDs, colchicine, or corticosteroids). 1
• Simultaneously initiate prophylactic anti-inflammatory therapy (colchicine 0.5-1 mg/day or low-dose NSAID). 1, 3

Step 3: Initiate Allopurinol at Low Dose

• Begin allopurinol 100 mg daily during the flare visit. 1, 4
• Do not wait for flare resolution. 1

Step 4: Titrate to Target

• Increase by 100 mg every 2-5 weeks until serum urate <6 mg/dL is achieved. 1, 4
• Monitor serum uric acid every 2-5 weeks during titration. 1

Step 5: Maintain Prophylaxis

• Continue prophylactic anti-inflammatory therapy for at least 3-6 months. 1, 3
• Studies show that discontinuing prophylaxis at 8 weeks results in a spike in acute attacks. 7

Common Pitfalls to Avoid

• Starting allopurinol without simultaneous prophylaxis significantly increases the risk of further attacks. 3 The FDA label notes that past experience suggested acute gout attacks occurred in 6% of patients when allopurinol was initiated, though current usage with gradual initiation has reduced this to less than 1%. 4
• Using too high a starting dose (>100 mg) increases the risk of triggering attacks and hypersensitivity reactions. 3
• Stopping prophylaxis too early (<6 months) reduces benefit. 3 Both the FACT and APEX trials showed a spike in attacks after discontinuing prophylaxis at 8 weeks. 7
• Stopping at 300 mg allopurinol without checking if target is achieved. More than half of patients do not reach the uric acid target with ≤300 mg. 3 The FDA label allows doses up to 800 mg daily. 4
• Discontinuing allopurinol if a patient develops a flare while already on therapy. Continue the current dose and treat the flare separately. 1

Important Caveats

• The recommendation to start during a flare is conditional, meaning individual patient factors may reasonably support delaying initiation in some cases, such as concerns about medication complexity or patient preference. 1
• The supporting trials used allopurinol doses of 200-300 mg, so findings may not generalize to higher initial doses or more potent urate-lowering strategies. 1, 3
• Initiating allopurinol during the flare visit prevents the risk of patients not returning for delayed initiation, and patients experiencing acute symptoms are highly motivated to start long-term preventive therapy. 1