Does initiating allopurinol (xanthine oxidase inhibitor) therapy increase the risk of acute gout attacks?

Managing Acute Gout Flares When Starting Allopurinol

Yes, initiating allopurinol therapy does increase the risk of acute gout attacks, particularly during the early stages of treatment. This occurs even when normal or subnormal serum uric acid levels have been attained 1.

Mechanism of Allopurinol-Induced Flares

• Allopurinol lowers serum uric acid by inhibiting xanthine oxidase, which can cause mobilization of urate crystals from tissue deposits, leading to fluctuations in serum uric acid levels that trigger acute gout attacks 1
• These mobilization-related flares typically occur during the early stages of treatment, even when the medication is effectively lowering serum urate levels 2, 1

Prevention of Flares When Starting Allopurinol

Prophylactic Medication

• Administering concomitant anti-inflammatory prophylaxis therapy is strongly recommended when initiating allopurinol 2
• Options for prophylaxis include:
  • Colchicine (most commonly used)
  • NSAIDs
  • Prednisone/prednisolone 2, 3
• Prophylaxis should be continued for 3-6 months after starting allopurinol, with ongoing evaluation and continued prophylaxis as needed if the patient continues to experience flares 2

"Start Low, Go Slow" Dosing Strategy

• Begin allopurinol at a low dose of 100 mg daily (or 50 mg daily in patients with stage 4 or worse CKD) 2, 3
• Gradually increase the dose by 100 mg increments every 2-4 weeks until reaching the target serum urate level of <6 mg/dL 2, 3
• This gradual titration approach reduces the risk of flares associated with treatment initiation 2

Risk Factors for Flares When Starting Allopurinol

Recent research has identified specific risk factors that increase the likelihood of experiencing gout flares when starting allopurinol:

• Having a gout flare in the month before starting allopurinol (odds ratio 2.65) 4
• Starting at a dose of 100 mg daily (odds ratio 3.21) compared to lower doses 4
• Higher starting doses relative to renal function 5

Duration of Flare Risk

• The risk of flares is highest during the first few months of therapy 2, 1
• Attacks typically become shorter and less severe after several months of therapy 1
• It may take several months of allopurinol therapy to deplete the uric acid pool sufficiently to achieve control of acute attacks 1

Targeted Prophylaxis Approach

Anti-inflammatory prophylaxis may be best targeted at:

• Patients who have had a gout flare in the month before starting allopurinol 4
• Those starting at allopurinol 100 mg daily (versus lower doses) 4
• Patients with higher urate burden (tophi, frequent attacks) 2

Special Considerations

• For patients with ongoing gout flares during the first six months of allopurinol who have not yet achieved target serum urate levels, a longer period of prophylaxis may be required 4
• Adequate hydration (at least 2 liters of urine output daily) and maintaining neutral or slightly alkaline urine can help prevent complications 1

Timing of Allopurinol Initiation

• Traditionally, allopurinol was not started during an acute gout attack
• Recent small studies suggest that starting allopurinol during an acute attack does not significantly prolong the duration of the flare when appropriate anti-inflammatory treatment is provided 6
• However, the 2016 EULAR guidelines note that these studies were small and results may not be generalizable to all patients or more potent urate-lowering drugs 2