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Febuxostat

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Febuxostat, Uloric

  • See Also
  1. Gouty Arthritis
  2. Allopurinol
  • Indications
  1. Gouty Arthritis (refractory to Allopurinol at maximal doses)
  • Contraindications
  1. See Drug Interactions below
  2. Avoid in known cardiovascular disease (Allopurinol is preferred instead)
  3. Avoid (or caution) in severe renal Impairment (see Renal Dosing below)
  4. Avoid (or caution) in severe hepatic Impairment
  • Mechanism
  1. Xanthine oxidase
    1. Enzyme that converts oxypurines (including Nucleic Acids) to Uric Acid
  2. Xanthine Oxidase Inhibitor
    1. Febuxostat is a selective, noncompetitive inhibitor of xanthine oxidase
    2. Febuxostat is a non-Purine inhibitor of xanthine oxidase
      1. Contrast with Allopurinol which is an isomer of hypoxanthine and a substrate for xanthine oxidase
    3. As with Allopurinol, Febuxostat increases renal xanthine excretion (since it is not converted to Uric Acid)
      1. Renal xanthines may crystallize in the renal tubules resulting in obstructive uropathy
  • Medications
  1. Febuxostat tablets: 40 mg, 80 mg
  • Dosing
  1. Adult: 40 mg orally daily
  2. May increase up to 80 mg/day if Uric Acid still >6 mg/dl after 2 weeks of therapy
  3. Maximum dose 40 mg in GFR 15 to 29 ml/min
  • Adverse Effects
  1. Increased risk of cardiovascular related death in known CV disease (NNH 91)
    1. Risk is increased compared with Allopurinol
    2. White (2018) N Engl J Med 378:1200-10 [PubMed]
  2. Hepatotoxicity (transaminase increase)
    1. Obtain baseline Liver Function Tests
  3. Gout Flare
    1. As with Allopurinol, use gout prophylaxis (e.g. concurrent NSAID) when starting Febuxostat
  4. Severe Hypersensitivity Syndrome with Skin Reaction (presents as dermatitis, Pruritus)
    1. As with Allopurinol, varies from mild rash to Stevens Johnson Syndrome
    2. Stop Febuxostat if this occurs
  • Safety
  1. Unknown safety in pregnancy
  2. Unknown safety in Lactation
  • Drug Interactions
  1. Agents to avoid inc combination with Febuxostat
    1. Azathioprine (Imuran)
    2. Mercaptopurine
    3. Theophylline
  • Resources
  1. Febuxostat (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14f1555c-2565-42c7-b3f5-dd5f03fed67a