Allopurinol, Zyloprim, Xanthine Oxidase Inhibitor

  1. Gout Prophylaxis (first-line agent)
    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 (>=2 attacks per year, and consider for 1 gout flare/year)
    2. Tophaceous gout
    3. Radiographic damage attributable to gout
    4. Nephrolithiasis
  • Precautions
  1. Avoid use with Azathioprine (causes toxic levels)
  2. Avoid in Renal Failure (or use low dose)
  3. Do not use for asymptomatic Hyperuricemia
  4. Genetic Testing (HLA B5801)
    1. Obtain prior to use if risk of severe Hypersensitivity skin reaction
    2. Risks include southeast asian (esp. Hans Chinese, Thai, Korean) and African American
  5. Avoid in acute gout attack (wait at least 4-6 weeks after acute attack)
    1. However, more recent data suggests safety in starting during acute attack (per email, Dr. John Rasor)
      1. Eminaga (2016) Rheumatol Int 36(12):1747-52 +PMID:27761603 [PubMed]
      2. Hill (2015) J Clin Rheumatol 21(3):120-5 +PMID:25807090 [PubMed]
      3. Taylor (2012) Am J Med 125(11):1126-1134 +PMID:23098865 [PubMed]
  • Mechanism
  1. Xanthine Oxidase Inhibitor
  2. Inhibits Uric Acid formation
  • 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
      1. However, see precautions above for recent data suggesting safety in starting with acute 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 Allopurinol initiation (but now too expensive)
          1. Generic preparations were removed from market
        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 (<5 mg/dl if symptomatic)
      1. Probenacid may be used with Allopurinol if GFR>50 ml/min and normal Urine Uric Acid normal
      2. Duzallo (Allopurinol with Lesinurad) is an expensive alternative to Probenacid and Allopurinol
    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 starting dose 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 mg daily (maximum dose 300 mg/day)
      5. GFR <10 ml/minute: Avoid or use with caution
  • Monitoring
  • Obtain 6 weeks after starting Allopurinol
  • Adverse effects (more common with renal dysfunction)
  1. May precipitate acute gout attack (never start during active gout attack)
    1. See Dosing above for protocol using NSAIDs or Colchicine concurrently
  2. Severe Hypersensitivity Syndrome (presents as dermatitis, Pruritus)
    1. Varies from mild rash to Stevens Johnson Syndrome
    2. Genetic Testing (HLA B5801) prior to use if Hans Chinese, Thai or if CKD 3, Korean
    3. Stop Allopurinol if this occurs
  3. Toxic Hepatitis
  4. Nausea
  5. Diarrhea
  6. Cytopenias
  • Drug Interactions
  1. Azathioprine (toxicity)
  2. Warfarin (Allopurinal increases INR)