Allopurinol

1. Indications
   1. Gout Prophylaxis
      1. Uric Acid over-producers (Uric Acid > 750 mg/24h)
      2. Used in Uric Acid under-excreters as well
   2. Criteria
      1. Recurrent episode of gout (>3 attacks per year)
      2. Tophaceous gout
      3. Nephrolithiasis
2. Precautions
   1. Avoid in acute gout attack (wait at least 4-6 weeks after acute attack)
   2. Avoid use with Azathioprine (causes toxic levels)
   3. Avoid in Renal Failure (or use low dose)
   4. Do not use for asymptomatic Hyperuricemia
3. Mechanism: Xanthine oxidase inhibitor
   1. Inhibits Uric Acid formation
4. Dosing
   1. Use concurrent antiinflammatory agent when starting to prevent triggering attack
      1. Wait to start Allopurinol until at least 6-8 weeks symptom-free from last attack
      2. Antiinflammatory agent options to start concurrently with Allopurinol (continue for first 3-6 months)
         1. NSAIDS (avoid in Chronic Kidney Disease, heart disease or liver disease)
            1. Aleve 220 mg (OTC) orally twice daily or
            2. Naprosyn 250 mg orally twice daily or
            3. Indomethacin 25 mg orally twice daily
         2. Prednisone (if NSAIDs contraindicated)
            1. Maintenance: 10 mg orally daily, then 5 mg orally daily for 3-6 months
            2. Acute Exacerbation (start at first symptoms of gout recurrence): 40 mg orally for 1-3 days
               1. Have available as emergency prescription
         3. Colchicine
            1. Colchicine was a first line agent for this until generic preparations were removed from market (now too expensive)
            2. Colchicine 0.6 mg PO daily to twice daily
   2. Allopurinol 100-300 mg/day
      1. Use lowest dose to keep Uric Acid <6 mg/dl
      2. Initiating dose
         1. Start: 100 mg daily for 2 weeks
         2. Next: 200 mg daily for 2 weeks
         3. Next: 300 mg daily (most effective dose for most patients)
         4. Some patients require higher doses (up to 800 mg/day) to maintain Uric Acid <6 mg/dl
      3. Adjust for Renal Function
         1. GFR >90 ml/min: 300 mg daily
         2. GFR 60-89 ml/min: 200 mg daily
         3. GFR 30-59 ml/min: 100 mg daily
         4. GFR 10-29 ml/min (or Cr >1.5): 50-100 mg daily
         5. GFR <10 ml/minute: Avoid or use with caution
5. Monitoring: Obtain 6 weeks after starting Allopurinol
   1. Complete Blood Count (CBC)
   2. Alanine Aminotransferase (ALT)
   3. Serum Creatinine
   4. Serum Uric Acid
6. Adverse effects
   1. May precipitate acute gout attack (never start during active gout attack)
      1. See Dosing above for protocol using NSAIDs or Colchicine concurrently
   2. Hypersensitivity Syndrome (presents as dermatitis)
      1. Varies from mild rash to Stevens Johnson Syndrome
   3. Toxic Hepatitis
   4. Nausea
   5. Diarrhea
   6. Cytopenias
7. Drug Interactions
   1. Azathioprine (toxicity)
   2. Warfarin (Allopurinal increases INR)