| Systematic (IUPAC) name | |
|---|---|
| 2-(3-cyano-4-isobutoxyphenyl)-4-methyl- 1,3-thiazole-5-carboxylic acid |
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| Clinical data | |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a609020 |
| Licence data | EMA:Link, US FDA:link |
| Pregnancy cat. | C |
| Legal status | ℞-only (US) |
| Routes | oral |
| Pharmacokinetic data | |
| Bioavailability | ~49% absorbed |
| Protein binding | ~99% to albumin |
| Metabolism | via CYP1A2, 2C8, 2C9, UGT1A1, 1A3, 1A9, 2B7 |
| Half-life | ~5-8 hours |
| Excretion | urine (~49% mostly as metabolites, 3% as unchanged drug); feces (~45% mostly as metabolites, 12% as unchanged drug) |
| Identifiers | |
| CAS number | 144060-53-7 |
| ATC code | M04AA03 |
| PubChem | CID 134018 |
| ChemSpider | 118173 |
| UNII | 101V0R1N2E |
| KEGG | D01206 |
| ChEMBL | CHEMBL1164729 |
| Chemical data | |
| Formula | C16H16N2O3S |
| Mol. mass | 316.374 g/mol |
| SMILES | eMolecules & PubChem |
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Febuxostat (INN; trade names Adenuric [EU], Febutaz [India] and Uloric [US]) is a urate lowering drug, an inhibitor of xanthine oxidase that is indicated for use in the treatment of hyperuricemia and gout.[1]
Febuxostat received marketing approval by the European Medicines Agency on April 21, 2008[2] and was approved by the U.S. Food and Drug Administration on February 16, 2009.[3]
A study comparing febuxostat to allopurinol found that more individuals treated with febuxostat had decreased levels of uric acid, but there was no difference in the amount of initial gout flares or the surface area of gout tophi.[4]
A committee of the British National Institute for Health and Clinical Excellence concluded that although febuxostat had been shown to be more effective than fixed-dose (300 mg) allopurinol in lowering serum uric acid concentration, it had not been shown to be clinically more efficacious or cost effective compared with allopurinol when taken to control uric acid levels (up to 900 mg). However, the committee recommended febuxostat for people who are intolerant of allopurinol.[5]
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Febuxostat is a non-purine selective inhibitor of xanthine oxidase. It works by non-competitively blocking the molybdenum pterin center which is the active site on xanthine oxidase. Xanthine oxidase is needed to successively oxidize both hypoxanthine and xanthine to uric acid. Hence, febuxostat inhibits xanthine oxidase, therefore reducing production of uric acid. Febuxostat inhibits both, oxidized as well as reduced form of xanthine oxidase because of which febuxostat cannot be easily displaced from the molybdenum pterin site.
Many long and short-term clinical trials have proved the efficacy of Febuxostat in the treatment of gout and lowering uric acid levels. In these studies Febuxostat was found to be superior to Allopurinol in reducing the serum uric acid levels. Some notable landmark clinical trials are FACT, APEX, EXCEL, FOCUS and CONFIRMS.
Febuxostat versus Allopurinol Controlled Trial (FACT): Serum urate levels were reduced below 6.0 mg/dL at the last three monthly observations in a significantly greater proportion of patients with gout and hyperuricaemia receiving febuxostat 80 or 120 mg once daily than in those receiving allopurinol 300 mg once daily in a 52-week, randomized, double-blind trial.[6]
Allopurinol Placebo controlled Efficacy study of febuXostat (APEX): Febuxostat 80, 120 or 240 mg once daily showed significantly greater urate-lowering efficacy than allopurinol 100 or 300 mg once daily in a 28-week, randomized, double-blind, placebo-controlled trial in patients with gout and hyperuricaemia.[6]
At least one CV AE was investigator-reported in 5% of all subjects: 5%, 5%, and 6% of subjects in the febuxostat 40 mg, febuxostat 80 mg, and allopurinol groups, respectively. No difference between treatment groups in specific CV AEs was detected. Pre-specified adjudication of all deaths and all AEs reported to be CV system-related identified a total of six subjects experiencing an adjudicated APTC (Antiplatelet Trialists Collaboration) event: zero in the febuxostat 40 mg group, three in the febuxostat 80 mg group and three in the allopurinol group. All subjects experiencing an adjudicated APTC event had prior medical histories of or underlying risk factors for CVD. Differences in the rates of adjudicated non-APTC CV events between treatment groups were not significant. [7]
For treatment of hyperuricemia in patients with gout, febuxostat is recommended at 40 mg or 80 mg once daily. No dose adjustment is necessary when administering febuxostat in patients with mild to moderate renal and hepatic impairment.[8]
The adverse effects associated with febuxostat therapy include nausea, diarrhea, arthralgia, headache, increased hepatic serum enzyme levels and rash.[8][9]
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