II. Indications

  1. Gouty Arthritis (refractory to Allopurinol at maximal doses)

III. 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

IV. 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

V. Medications

  1. Febuxostat tablets: 40 mg, 80 mg

VI. 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

VII. 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

VIII. Safety

  1. Unknown safety in pregnancy
  2. Unknown safety in Lactation

IX. Drug Interactions

  1. Agents to avoid inc combination with Febuxostat
    1. Azathioprine (Imuran)
    2. Mercaptopurine
    3. Theophylline

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Related Studies

Cost: Medications

febuxostat (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
FEBUXOSTAT 40 MG TABLET Generic $0.64 each
FEBUXOSTAT 80 MG TABLET Generic $0.80 each
uloric (on 4/20/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ULORIC 40 MG TABLET Generic $0.64 each

Ontology: febuxostat (C0249529)

Definition (NCI) An orally available, non-purine inhibitor of xanthine oxidase with uric acid lowering activity. Upon oral administration, febuxostat selectively and noncompetitively inhibits the activity of xanthine oxidase, an enzyme that converts oxypurines, including hypoxanthine and xanthine, into uric acid. By inhibiting xanthine oxidase, uric acid production is reduced and serum uric acid levels are lowered. Febuxostat may provide protection against acute renal failure caused by the excessive release of uric acid that occurs upon massive tumor cell lysis resulting from the treatment of some malignancies.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C084623
SnomedCT 441610003, 441743008
English 5-Thiazolecarboxylic acid, 2-(3-cyano-4-(2-methylpropoxy)phenyl)-4-methyl-, 2-(3-Cyano-4-(2-methylpropoxy)phenyl)-4-methylthiazole-5-carboxylic Acid, Febuxostat (product), Febuxostat, Febuxostat (substance), febuxostat [Chemical/Ingredient], FEBUXOSTAT, febuxostat
Spanish febuxostat, febuxostat (producto), febuxostat (sustancia)