How to Initiate Allopurinol and Which NSAID to Use for Gout Flare Prophylaxis
Start allopurinol at 100 mg daily (or 50 mg daily if CKD stage ≥3), titrate by 100 mg every 2–4 weeks until serum urate is <6 mg/dL, and provide mandatory anti-inflammatory prophylaxis with colchicine 0.5–1 mg daily (or any NSAID at low dose if colchicine is contraindicated) for at least 3–6 months. 1
Allopurinol Initiation Protocol
Starting Dose
- Begin at 100 mg daily in patients with normal renal function 1
- Begin at 50 mg daily (or lower) in patients with CKD stage ≥3 1
- The low starting dose reduces the risk of allopurinol hypersensitivity syndrome and minimizes gout flares during initiation 1
Dose Titration Strategy
- Increase by 100 mg increments every 2–4 weeks until target serum urate is achieved 1
- Measure serum urate every 2–5 weeks during titration to guide dose adjustments 1
- Target serum urate: <6 mg/dL (360 μmol/L) for all patients 1
- For severe gout with tophi or chronic arthropathy, target <5 mg/dL until resolution, then maintain <6 mg/dL 1
- Most patients require doses >300 mg daily to reach target; maximum FDA-approved dose is 800 mg daily 1, 2
Timing of Initiation
You can start allopurinol during an acute gout flare—you do not need to wait for the flare to resolve 1, 3, 4. Two randomized controlled trials demonstrated that starting allopurinol during an acute attack does not prolong flare duration or increase severity 1, 3. This approach improves adherence because patients are highly motivated during symptomatic episodes 1, 3.
Mandatory Anti-Inflammatory Prophylaxis
First-Line Prophylaxis Options
Colchicine 0.5–1 mg daily is the preferred prophylactic agent 1
- Reduce dose in renal impairment 1
- Avoid in patients receiving strong P-glycoprotein or CYP3A4 inhibitors (cyclosporin, clarithromycin) 1
- Monitor for neurotoxicity and muscle toxicity, especially with concurrent statin use 1
Alternative Prophylaxis (if colchicine contraindicated or not tolerated)
Any NSAID at low dose can be used for prophylaxis 1
Low-dose oral corticosteroids (e.g., prednisone/prednisolone) are an alternative 1
Duration of Prophylaxis
- Continue for at least 3–6 months after starting allopurinol 1
- Prophylaxis <3 months is associated with significantly higher flare rates 1, 3
- Extend beyond 6 months if patient continues experiencing flares 1
Which NSAID to Use
Any NSAID is acceptable for gout flare prophylaxis at low doses—the choice depends on patient-specific contraindications rather than superiority of one agent over another 1. Common options include:
- Naproxen 250 mg twice daily
- Indomethacin 25 mg twice daily
- Ibuprofen 400 mg twice daily
For acute gout flares (not prophylaxis), use full anti-inflammatory NSAID doses plus proton pump inhibitor 1.
Treatment of Concurrent Acute Flare
If starting allopurinol during an active flare, treat the acute attack separately with therapeutic doses of anti-inflammatory medication 3:
- Colchicine: 1 mg loading dose, then 0.5 mg one hour later (within 12 hours of flare onset) 1
- NSAIDs: Full anti-inflammatory doses (e.g., naproxen 500 mg twice daily, indomethacin 50 mg three times daily) 1
- Oral corticosteroids: 30–35 mg prednisolone equivalent daily for 3–5 days 1
Critical Pitfalls to Avoid
- Never stop allopurinol during a gout flare if the patient is already taking it—this causes serum urate fluctuations that can trigger additional flares 3
- Never start at 300 mg daily—this increases flare risk and hypersensitivity reactions 1
- Never omit prophylaxis—starting allopurinol without prophylaxis dramatically increases flare risk in the first 3–6 months 1, 3
- Never accept serum urate ≥6 mg/dL as adequate—this allows continued crystal deposition 1
- Never assume 300 mg is the maximum dose—most patients require higher doses, and allopurinol can be safely titrated to 800 mg daily with monitoring 1, 2
- Do not be misled by "normal" serum urate during an acute flare—urate often drops transiently during attacks and does not reflect true baseline hyperuricemia 3