Do you start allopurinol (a xanthine oxidase inhibitor) during an initial gout flare?

Starting Allopurinol During an Initial Gout Flare

For patients experiencing their first gout flare, the 2020 American College of Rheumatology (ACR) guidelines conditionally recommend AGAINST initiating allopurinol, unless specific high-risk features are present. 1

When NOT to Start Allopurinol with First Flare

For uncomplicated first gout flares, defer allopurinol initiation because:

• Only 20% of patients with hyperuricemia progress to recurrent gout within 5 years 1
• The number needed to treat is 24 patients for 3 years to prevent a single additional flare 1
• The risks and costs of long-term therapy outweigh benefits for most patients who may never have another attack 1

Exceptions: When to START Allopurinol with First Flare

Conditionally recommend initiating allopurinol during a first flare if ANY of these high-risk features are present: 1

• Chronic kidney disease stage ≥3
• Serum urate >9 mg/dL
• History of urolithiasis (kidney stones)
• Young age (<40 years) 2

Timing: During vs. After the Flare Resolves

If the decision is made to start allopurinol, the ACR conditionally recommends initiating it DURING the acute flare rather than waiting for resolution. 1, 2 This recommendation is based on:

• No prolongation of flare duration: Two randomized controlled trials demonstrated that starting allopurinol during an acute attack does not significantly prolong pain or worsen severity compared to delayed initiation 3, 4
• Practical benefits: Patients experiencing acute symptoms are highly motivated to start preventive therapy, and initiating during the flare visit prevents the risk of patients not returning 2
• Earlier urate control: Addresses underlying hyperuricemia sooner without adverse consequences 2

Critical Requirements When Starting Allopurinol

1. Anti-inflammatory Prophylaxis (MANDATORY)

The ACR strongly recommends concomitant anti-inflammatory prophylaxis when initiating allopurinol, regardless of whether started during or after a flare. 1, 2, 5

Prophylaxis options: 1, 2

• Colchicine 0.5-1 mg daily (preferred, with dose reduction in renal impairment)
• NSAIDs
• Prednisone/prednisolone

Duration: Continue prophylaxis for 3-6 months after initiating allopurinol, with ongoing evaluation and continued prophylaxis as needed if flares persist 1, 2

Evidence supporting prophylaxis: Colchicine reduces total flares (0.52 vs 2.91 without prophylaxis, p=0.008), reduces flare severity, and decreases likelihood of recurrent flares 6

2. Start-Low Go-Slow Dosing Strategy

The ACR strongly recommends starting allopurinol at LOW doses with gradual titration, even when initiating during a flare. 1, 5

Initial dosing: 1, 2, 5

• 100 mg daily for most patients
• ≤50 mg daily for CKD stage ≥4
• Never start at 300 mg - this increases flare risk significantly (OR 3.21) 7

Titration schedule: 2, 5

• Increase by 100 mg increments every 2-4 weeks (or weekly per FDA label)
• Target serum urate <6 mg/dL (360 μmol/L)
• Maximum dose 800 mg daily
• For severe gout (tophi, chronic arthropathy), target <5 mg/dL until resolution 2

3. Acute Flare Treatment

Treat the acute flare itself with separate therapeutic-dose anti-inflammatory medication (NSAIDs, colchicine, or corticosteroids), distinct from the prophylactic doses used to prevent future flares 2, 5

Common Pitfalls to Avoid

• Starting at 300 mg daily: This triples flare risk compared to 100 mg starting dose 7
• Omitting prophylaxis: Increases flare frequency dramatically and is strongly discouraged 1, 6
• Stopping allopurinol if already taking it: If a patient is already on allopurinol when a flare occurs, continue the current dose without interruption 2
• Inadequate prophylaxis duration: Stopping prophylaxis before 3 months increases flare risk, especially if serum urate target not yet achieved 1, 7

Predictors of Flare Risk During Initiation

Patients at highest risk for flares when starting allopurinol: 8, 7

• Younger age
• Higher baseline serum urate
• Recent flare in the month before starting allopurinol (OR 2.65)
• Starting dose of 100 mg vs. lower doses (OR 3.21)
• Absence of tophi (paradoxically protective)

For patients with ongoing flares during the first 6 months who have not achieved serum urate target, extend prophylaxis beyond 6 months. 7

Allopurinol as First-Line Agent

When urate-lowering therapy is indicated, allopurinol is strongly recommended as the preferred first-line agent over all other options (febuxostat, probenecid, pegloticase) for all patients, including those with CKD stage ≥3. 1, 2 This is based on efficacy, tolerability, safety, and lower cost 1