II. Indications: Uric Acid Lowering Therapy
- Gout Prophylaxis (first-line agent)
- Criteria
- Recurrent episode of gout (>=2 attacks per year, and consider for 1 gout flare/year)
- Tophaceous gout
- Radiographic damage attributable to gout
- Nephrolithiasis
III. Precautions
- Avoid use with Azathioprine (causes toxic levels)
- Avoid in Renal Failure (or use low dose)
- Do not use for asymptomatic Hyperuricemia
-
Genetic Testing (HLA B5801)
- Obtain prior to use if risk of severe Hypersensitivity skin reaction
- Risks include southeast asian (esp. Hans Chinese, Thai, Korean) and African American
- Avoid in acute gout attack (wait at least 4-6 weeks after acute attack)
- However, more recent data suggests safety in starting during acute attack (per email, Dr. John Rasor)
IV. Mechanism
- Xanthine Oxidase Inhibitor
- Inhibits Uric Acid formation
V. Dosing
- Use concurrent antiinflammatory agent when starting to prevent triggering attack
- Wait to start Allopurinol until at least 6-8 weeks symptom-free from last attack
- However, see precautions above for recent data suggesting safety in starting with acute attack
- Antiinflammatory agent options to start concurrently with Allopurinol (continue for first 3-6 months)
- NSAIDS (avoid in Chronic Kidney Disease, heart disease or liver disease)
- Aleve 220 mg (OTC) orally twice daily or
- Naprosyn 250 mg orally twice daily or
- Indomethacin 25 mg orally twice daily
- Prednisone (if NSAIDs contraindicated)
- Maintenance: 10 mg orally daily, then 5 mg orally daily for 3-6 months
- Acute Exacerbation (start at first symptoms of gout recurrence): 40 mg orally for 1-3 days
- Have available as emergency prescription
- Colchicine
- Colchicine was a first line agent for Allopurinol initiation (but now too expensive)
- Generic preparations were removed from market
- Colchicine 0.6 mg PO daily to twice daily
- Colchicine was a first line agent for Allopurinol initiation (but now too expensive)
- NSAIDS (avoid in Chronic Kidney Disease, heart disease or liver disease)
- Wait to start Allopurinol until at least 6-8 weeks symptom-free from last attack
- Allopurinol 100-300 mg/day
- Use lowest dose to keep Uric Acid <6 mg/dl (<5 mg/dl if symptomatic)
- Probenacid may be used with Allopurinol if GFR>50 ml/min and normal Urine Uric Acid normal
- Duzallo (Allopurinol with Lesinurad) is an expensive alternative to Probenacid and Allopurinol
- Initiating dose
- Start: 100 mg daily for 2 weeks
- Next: 200 mg daily for 2 weeks
- Next: 300 mg daily (most effective dose for most patients)
- Some patients require higher doses (up to 800 mg/day) to maintain Uric Acid <6 mg/dl
- Adjust starting dose for Renal Function
- GFR >90 ml/min: 300 mg daily
- GFR 60-89 ml/min: 200 mg daily
- GFR 30-59 ml/min: 100 mg daily
- GFR 10-29 ml/min (or Cr >1.5): 50 mg daily (maximum dose 300 mg/day)
- GFR <10 ml/minute: Avoid or use with caution
- Use lowest dose to keep Uric Acid <6 mg/dl (<5 mg/dl if symptomatic)
VI. Monitoring: Obtain 6 weeks after starting Allopurinol
- Complete Blood Count (CBC)
- Alanine Aminotransferase (ALT)
- Serum Creatinine
- Serum Uric Acid
VII. Adverse effects (more common with renal dysfunction)
- May precipitate acute gout attack (never start during active gout attack)
- See Dosing above for protocol using NSAIDs or Colchicine concurrently
- Severe Hypersensitivity Syndrome (presents as dermatitis, Pruritus)
- Varies from mild rash to Stevens Johnson Syndrome
- Genetic Testing (HLA B5801) prior to use if Hans Chinese, Thai or if CKD 3, Korean
- Stop Allopurinol if this occurs
- Toxic Hepatitis
- Nausea
- Diarrhea
- Cytopenias
VIII. Drug Interactions
- Azathioprine (toxicity)
- Warfarin (Allopurinal increases INR)
IX. References
- (2018) Presc Lett 25(9):50-1
- Eggebeen (2007) Am Fam Physician 76:801-12 [PubMed]
- Hainer (2014) Am Fam Physician 90(12): 831-6 [PubMed]
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Related Studies
allopurinol (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
ALLOPURINOL 100 MG TABLET | Generic | $0.05 each |
ALLOPURINOL 300 MG TABLET | Generic | $0.07 each |