Febuxostat

316.37500

316.37

101V0R1N2E

758874

DTXSID8048650

C65629

M04AA03|M - Musculo-skeletal system

2934100090

111.45000

3.9

Crystalline Solid

1.31 g/cm3

238-239ºC

536.6ºC at 760 mmHg

278.3ºC

1.605

2.41E-12mmHg at 25°C

180.6 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

P264, P270, P273, P301+P312, P330, P501

H302

|Warning|H302 (92.86%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P273, P301+P312, P330, and P501|Aggregated GHS information provided by 15 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The FDA adverse event reporting system database, AERS, indicated potential signals of febuxostat-associated cardiovascular thromboembolic events. AERS is not capable of establishing the causal link and detecting the true frequency of an adverse event associated with a drug. The positive IC value found in this study merits continued surveillance and assessment of cardiovascular thromboembolic events associated with Febuxostat.

Liver test abnormalities have been reported to occur in 2% to 13% (average ~3.5%) of patients receiving febuxostat, but the levels are generally mild-to-moderate and self-limited. The height, nature and timing of these abnormalities have not been described. However, liver test elevations were the major reason for febuxostat discontinuation for adverse events (~2%) in clinical trials, despite the fact that no cases of jaundice or acute hepatitis were reported. Since its approval and more wide-scale use, there have been several individual case reports of liver injury attributed to febuxostat. Most cases have been marked by serum aminotransferase elevations without jaundice arising within days of starting febuxostat, including enzyme elevations in the setting of DRESS syndrome. At least one instance of a mixed-cholestatic hepatitis without immunoallergic features, arising after several months of treatment has been described. The product label for febuxostat lists hepatic steatosis, hepatitis and hepatomegaly as potential side effects. Furthermore, several cases of acute liver failure during febuxostat therapy have been reported to pharmacovigilance databases. Another unrelated, nonpurine xanthine oxidase inhibitor (benzbromarone) was not approved for use in the United States because of its potential for hepatic toxicity.

99.2%

For the treatment of hyperuricemia in patients with gout.|FDA Label|Febuxostat Mylan is indicated for the prevention and treatment of hyperuricaemia in adult patients undergoing chemotherapy for haematologic malignancies at intermediate to high risk of Tumor Lysis Syndrome (TLS).Febuxostat Mylan is indicated for the treatment of chronic hyperuricaemia in conditions where urate deposition has already occurred (including a history, or presence of, tophus and/or gouty arthritis).Febuxostat Mylan is indicated in adults.|Febuxostat Krka is indicated for the treatment of chronic hyperuricaemia in conditions where urate deposition has already occurred (including a history, or presence of, tophus and/or gouty arthritis).Febuxostat Krka is indicated in adults.|80 mg strength:Treatment of chronic hyperuricaemia in conditions where urate deposition has already occurred (including a history, or presence of, tophus and/or gouty arthritis).Adenuric is indicated in adults.120 mg strength:Adenuric is indicated for the treatment of chronic hyperuricaemia in conditions where urate deposition has already occurred (including a history, or presence of, tophus and/or gouty arthritis).Adenuric is indicated for the prevention and treatment of hyperuricaemia in adult patients undergoing chemotherapy for haematologic malignancies at intermediate to high risk of Tumor Lysis Syndrome (TLS).Adenuric is indicated in adults.|Prevention of hyperuricaemia

Febuxostat is a newly introduced nonpurine xanthine oxidase inhibitor used for the treatment of gout. Chronic febuxostat therapy has been associated with minor serum aminotransferase elevations, but has yet to be linked to cases of clinically apparent acute liver injury.

Antigout Agents/Gout Suppressants

Febuxostat (ULORIC) is a novel, xanthine oxidase/dehydrogenase (XO/XDH) inhibitor being developed by Teijin, TAP Pharmaceuticals, and Ipsen for the treatment of gout. The currently available XO inhibitor, allopurinol, has been associated with serious instances of severe hypersensitivity, in some cases leading to fatalities. There is some suggestion that febuxostat is less prone to excacerbate systemic inflammatory events in animal studies.

Agents that increase uric acid excretion by the kidney (URICOSURIC AGENTS), decrease uric acid production (antihyperuricemics), or alleviate the pain and inflammation of acute attacks of gout. (See all compounds classified as Gout Suppressants.)

>49%|Febuxostat is eliminated primarily through both hepatic and renal pathways.|The mean apparent steady state volume of distribution (Vss/F) of febuxostat was approximately 50 L (CV ~40%)

Febuxostat is extensively metabolized by both conjugation via uridine diphosphate glucuronosyltransferase (UGT) enzymes including UGT1A1, UGT1A3, UGT1A9, and UGT2B7 and oxidation via cytochrome P450 (CYP) enzymes including CYP1A2, 2C8 and 2C9 and non-P450 enzymes. The relative contribution of each enzyme isoform in the metabolism of febuxostat is not clear. The oxidation of the isobutyl side chain leads to the formation of four pharmacologically active hydroxy metabolites, all of which occur in plasma of humans at a much lower extent than febuxostat. In urine and feces, acyl glucuronide metabolites of febuxostat (~35% of the dose), and oxidative metabolites, 67M-1 (~10% of the dose), 67M-2 (~11% of the dose), and 67M-4, a secondary metabolite from 67M-1 (~14% of the dose), appeared to be the major metabolites of febuxostat in vivo.

~5-8 hours.

Febuxostat, a xanthine oxidase inhibitor, achieves its therapeutic effect by decreasing serum uric acid. Febuxostat is not expected to inhibit other enzymes involved in purine and pyrimidine synthesis and metabolism at therapeutic concentrations.

2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid

Human drugs -> Febuxostat Mylan -> EMA Drug Category|Antigout preparations -> Human pharmacotherapeutic group|Human drugs -> Febuxostat Krka -> EMA Drug Category|Human drugs -> Adenuric -> EMA Drug Category|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients