When to Start Allopurinol in Gout
Allopurinol should be initiated in patients with recurrent gout flares (≥2 per year), tophi, urate arthropathy, renal stones, or serum uric acid >8.0 mg/dL, and can be started even during an acute flare rather than waiting for resolution. 1
Specific Indications for Starting Allopurinol
Absolute indications where allopurinol should be started include: 1
- Recurrent gout flares: Two or more attacks per year 1
- Tophi: Presence of any tophaceous deposits 1
- Chronic gouty arthritis (urate arthropathy) 1
- Renal stones 1
- Very high serum uric acid: >8.0 mg/dL (>480 μmol/L) 1
Additional indications that warrant starting therapy: 1
- Young age at onset: <40 years old 1
- Significant comorbidities: Renal impairment, hypertension, ischemic heart disease, or heart failure 1
The 2020 ACR guidelines conditionally recommend initiating urate-lowering therapy even after the first gout flare in patients who meet any of the above criteria. 1 EULAR recommends discussing urate-lowering therapy with every patient from the first presentation of definite gout. 1
Timing: Starting During vs. After an Acute Flare
You can and should start allopurinol during an acute gout flare if the patient meets indications for urate-lowering therapy. 2, 1 The ACR conditionally recommends starting ULT during a flare rather than waiting for it to resolve. 2, 1 A randomized controlled trial demonstrated that initiating allopurinol during an acute treated gout attack did not prolong the attack (15.4 days with allopurinol vs 13.4 days with placebo, p=0.5). 3
Initial Dosing Strategy
Start low and titrate slowly to minimize hypersensitivity risk and acute flares: 2, 4
For patients with normal renal function:
- Start at ≤100 mg daily 2, 4
- Increase by 100 mg increments every 2-4 weeks 4
- Titrate until serum uric acid <6 mg/dL is achieved 4
- Maximum FDA-approved dose is 800 mg/day 2
For patients with CKD (stage ≥3):
- Start at ≤50 mg daily 2, 4, 5
- With creatinine clearance 10-20 mL/min: use 200 mg daily maximum 6
- With creatinine clearance <10 mL/min: do not exceed 100 mg daily 6
- Starting dose should be ≤1.5 mg per unit of estimated GFR (mg/ml/minute) to reduce hypersensitivity risk 7
The low starting dose is critical because starting doses >1.5 mg per unit of estimated GFR increase the risk of allopurinol hypersensitivity syndrome 23-fold. 7
Mandatory Flare Prophylaxis
Always initiate concomitant anti-inflammatory prophylaxis when starting allopurinol. 2, 4, 6 This is strongly recommended to prevent paradoxical flares that occur with urate mobilization. 2, 4
- Colchicine: 0.5-1 mg/day 4
- Low-dose NSAIDs 4
- Prednisone/prednisolone: Low-dose (5-10 mg daily preferred in CKD) 5
Duration of prophylaxis: Continue for 3-6 months after starting allopurinol, with ongoing evaluation and extended prophylaxis if flares persist. 2, 4, 5
Target Serum Urate Levels
Standard target: Maintain serum uric acid <6 mg/dL (360 μmol/L) 1, 4
Lower target for severe disease: <5 mg/dL (300 μmol/L) for patients with tophi, chronic arthropathy, or frequent attacks until crystal dissolution is complete 1, 4, 5
Monitor serum uric acid levels regularly to guide dose titration until target is reached. 4 Most patients require doses >300 mg/day to achieve target urate levels. 2
Allopurinol as First-Line Therapy
Allopurinol is strongly recommended as the preferred first-line urate-lowering agent for all patients with gout, including those with moderate-to-severe CKD (stage ≥3). 2, 4 This recommendation is based on its efficacy when dosed appropriately, tolerability, safety profile, and lower cost compared to alternatives. 2
Pegloticase as first-line therapy is strongly recommended against due to cost, safety concerns, and the favorable benefit-to-harm ratio of other options. 2
Critical Pitfalls to Avoid
Do not use standard dosing in CKD patients without dose adjustment—always start low and titrate slowly based on renal function. 5, 6
Do not start high-dose allopurinol without prophylaxis—this dramatically increases the risk of paradoxical flares. 5, 6
Do not discontinue allopurinol once started—this is lifelong therapy, as discontinuation leads to recurrence of gout flares in approximately 87% of patients within 5 years. 1, 4
Do not rely on the traditional 300 mg/day ceiling—doses up to 800 mg/day are often necessary and well-tolerated to achieve target serum urate levels. 2, 8