When should allopurinol be started in patients with gout?

When to Start Allopurinol in Patients with Gout

Allopurinol should be strongly recommended for patients with frequent gout flares (≥2/year), presence of tophi, or radiographic damage attributable to gout, and conditionally recommended for patients with previous multiple flares even if infrequent (<2/year). 1

Strong Indications for Initiating Allopurinol

• Frequent gout flares (≥2 per year) - strongly recommended to start urate-lowering therapy (ULT) with allopurinol 1
• Presence of one or more subcutaneous tophi - strongly recommended to initiate ULT 1
• Radiographic damage attributable to gout (any imaging modality) - strongly recommended to start ULT 1
• Urate arthropathy - indicated for ULT initiation 1
• Renal stones - indicated for ULT initiation 1

Conditional Indications for Initiating Allopurinol

• Patients with >1 previous flare but infrequent attacks (<2/year) - conditionally recommended to start ULT 1
• First gout flare with comorbidities - conditionally recommended to start ULT if the patient has:
  • Chronic kidney disease stage ≥3 1
  • Serum urate >9 mg/dL (540 μmol/L) 1
  • History of urolithiasis 1
• Young patients (<40 years) with first gout flare - recommended to initiate ULT close to time of first diagnosis 1

When Not to Start Allopurinol

• First gout flare without complicating factors - conditionally recommended against initiating ULT 1
• Asymptomatic hyperuricemia (serum urate >6.8 mg/dL without prior gout flares or tophi) - conditionally recommended against initiating ULT 1

Starting Allopurinol During an Acute Flare

• Traditionally, allopurinol was not started during an acute gout attack
• Current evidence supports that allopurinol can be started during an acute gout flare - research shows it does not prolong the duration of the acute attack 2
• When starting during a flare, the ACR conditionally recommends initiating ULT while the patient is experiencing the gout flare 1

Dosing and Titration of Allopurinol

• Start at a low dose (100 mg/day) and increase by 100 mg increments every 2-4 weeks until target serum urate is reached 1, 3
• For patients with renal impairment, the maximum dosage should be adjusted according to creatinine clearance 1, 3
• Target serum urate level should be <6 mg/dL (360 μmol/L) 1
• For severe gout (tophi, chronic arthropathy, frequent attacks), a lower target of <5 mg/dL (300 μmol/L) is recommended until resolution 1
• Maintenance doses typically range from 200-300 mg/day for mild gout and 400-600 mg/day for moderately severe tophaceous gout 3

Prophylaxis When Starting Allopurinol

• Anti-inflammatory prophylaxis is strongly recommended when initiating allopurinol to prevent flares 1
• Prophylaxis should be continued for the first 3-6 months of ULT 1
• Recommended prophylactic treatment is colchicine (0.5-1 mg/day) with dose reduction in renal impairment 1
• If colchicine is not tolerated or contraindicated, low-dose NSAIDs can be considered if not contraindicated 1

Monitoring and Long-term Management

• Serum urate levels should be monitored and maintained at <6 mg/dL (360 μmol/L) lifelong 1
• An increase in acute gout attacks may occur during early stages of allopurinol treatment, even with normal or subnormal serum urate levels 3
• It may take several months of therapy to deplete the uric acid pool sufficiently to achieve control of acute attacks 3
• Adequate fluid intake (>2 liters/day) and maintaining neutral or slightly alkaline urine are recommended 3

Comparative Effectiveness

• Allopurinol is recommended as the first-line ULT for all patients, including those with CKD stage ≥3 1
• Recent evidence shows allopurinol is noninferior to febuxostat in controlling gout flares when properly dosed and titrated 4
• If target serum urate cannot be reached with appropriate allopurinol dosing, switching to febuxostat or adding a uricosuric should be considered 1