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