What medications are used for gout prevention?

Medications for Gout Prevention

Xanthine oxidase inhibitors (XOIs), specifically allopurinol or febuxostat, are the first-line pharmacologic treatments for gout prevention, with allopurinol being the recommended initial therapy for most patients. 1

First-Line Therapy: Allopurinol

Indications for Urate-Lowering Therapy

• Urate-lowering therapy is indicated in patients with:
  • Recurrent acute gout attacks
  • Arthropathy
  • Tophi
  • Radiographic changes of gout 2

Dosing and Titration

• Starting dose:
  • ≤100 mg/day for most patients
  • ≤50 mg/day in patients with stage 4 or worse chronic kidney disease 1
  • Start at 1.5 mg per unit of estimated GFR to reduce risk of allopurinol hypersensitivity syndrome 3
• Gradual dose increase:
  • Increase by 100 mg every 2-5 weeks until target serum urate is reached 1, 4
  • Maximum dose up to 800 mg daily with appropriate monitoring 1

Target Serum Urate Levels

• <6 mg/dL (360 μmol/L) for most patients
• <5 mg/dL (300 μmol/L) for patients with severe tophaceous gout 1, 2

Alternative and Second-Line Therapies

Febuxostat

• Alternative when allopurinol is not tolerated or contraindicated 1
• More effective than allopurinol 300 mg daily in achieving target serum urate levels 5

Uricosuric Agents

1. Probenecid:

   • First choice among uricosurics for monotherapy 1
   • Contraindications:
     • Creatinine clearance <50 ml/minute
     • History of urolithiasis
     • Elevated urine uric acid 1, 6

2. Benzbromarone:

   • Can be used in patients with mild to moderate renal insufficiency 2
   • Very effective at doses of 50-100 mg/day 7
   • Small risk of hepatotoxicity 2

Combination Therapy

• For refractory cases, a uricosuric agent can be added to an XOI 1
• Other medications with uricosuric effects that can be used in combination therapy:
  • Fenofibrate (for patients with hyperlipidemia)
  • Losartan (for patients with hypertension) 2, 1

Prophylaxis Against Acute Flares

When initiating urate-lowering therapy, prophylaxis against acute flares is essential:

• First choice: Colchicine 0.5-1.2 mg daily 2, 1
• Alternatives (if colchicine is contraindicated or not tolerated):
  • NSAIDs (with gastroprotection if indicated)
  • Low-dose glucocorticoids 2, 1

Special Considerations

Renal Impairment

• For moderate renal impairment (eGFR 66 mL/min/1.73m²), consider reducing allopurinol dose to 100-200 mg daily 1
• In CKD stage ≥3, start at lower doses (≤50 mg/day) 1
• Benzbromarone can be used in patients with mild to moderate renal insufficiency 2

Genetic Testing

• HLA-B*5801 screening should be considered before initiating allopurinol in high-risk populations:
  • Koreans with stage 3 or worse CKD
  • Han Chinese and Thai patients regardless of renal function 1
• If HLA-B*58:01 positive, allopurinol is contraindicated and alternative therapy should be considered 1

Monitoring

• Serum urate should be checked every 2-5 weeks during dose titration
• Once target is achieved, check every 6 months
• Regular monitoring of renal function and liver function tests 1

Important Drug Interactions

• Allopurinol and febuxostat should not be used in combination 1
• Patients taking azathioprine/mercaptopurine require 65-75% dose reduction when taking allopurinol 1
• Salicylates antagonize the uricosuric action of probenecid 6
• Probenecid may prolong or enhance the action of oral sulfonylureas, increasing risk of hypoglycemia 6

Lifestyle Modifications as Adjunctive Therapy

• Weight loss if appropriate
• Limiting alcohol (especially beer)
• Avoiding sugar-sweetened drinks
• Limiting meat and seafood intake
• Encouraging low-fat dairy products
• Regular exercise 1, 2

Long-term adherence to urate-lowering therapy is essential, as discontinuing therapy prematurely can lead to loss of serum urate control and increased risk of gout flares 1.