Febuxostat
Encyclopedia
Febuxostat is a urate lowering drug, an inhibitor of xanthine oxidase
that is indicated for use in the treatment of hyperuricemia
and gout
.
Febuxostat received marketing approval by the European Medicines Agency
on April 21, 2008 and was approved by the U.S. Food and Drug Administration on February 16, 2009.
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
.
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.
. 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.
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.
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.
Xanthine oxidase
Xanthine oxidase Xanthine oxidase Xanthine oxidase (XO (sometimes 'XAO'), a form of xanthine oxidoreductase that generates reactive oxygen species. Is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid...
that is indicated for use in the treatment of hyperuricemia
Hyperuricemia
Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L for women and 400 µmol/L for men.-Causes:...
and gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
.
Febuxostat received marketing approval by the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
on April 21, 2008 and was approved by the U.S. Food and Drug Administration on February 16, 2009.
A study comparing febuxostat to allopurinol
Allopurinol
Allopurinol is a drug used primarily to treat hyperuricemia and its complications, including chronic gout.- Mechanism of action :...
found that more individuals treated with febuxostat had decreased levels of uric acid, but there was no difference in the amount of initial gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
flares or the surface area of gout tophi
Tophus
A tophus is a deposit of monosodium urate crystals in people with longstanding high levels of uric acid in the blood. Tophi are pathognomonic for the disease gout...
.
A committee of the British National Institute for Health and Clinical Excellence
National Institute for Health and Clinical Excellence
The National Institute for Health and Clinical Excellence is a special health authority of the English National Health Service , serving both English NHS and the Welsh NHS...
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.
Mechanism of action
Febuxostat is a non-purine selective inhibitor of xanthine oxidaseXanthine oxidase
Xanthine oxidase Xanthine oxidase Xanthine oxidase (XO (sometimes 'XAO'), a form of xanthine oxidoreductase that generates reactive oxygen species. Is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid...
. 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
Hypoxanthine
Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids where it is present in the anticodon of tRNA in the form of its nucleoside inosine. It has a tautomer known as 6-Hydroxypurine. Hypoxanthine is a necessary additive in certain cell,...
and xanthine
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....
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.
Clinical efficacy
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.
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.