Peringatan Keamanan

Oral lowest published toxic dose (TDLO) in humans is 1.82 mg/kg/14D (intermittent).L13056 Oral LD50 is 300 mg/kg in mice, 3200 mg/kg in rabbits, and 980 mg/kg in rats.L32273

No dose-limiting toxicities were observed with febuxostat administered at doses up to 300 mg daily for seven days in healthy subjects. There are no reports of overdose of febuxostat in clinical studies and there is no known antidote. Overdose should be managed by symptomatic and supportive care.L32238

Febuxostat

DB04854

small molecule approved

Deskripsi

Febuxostat is a non-purine xanthine oxidase (XO) inhibitor.A39743 In early 2008, febuxostat was granted marketing authorization by the European Commission for the treatment of chronic hyperuricemia and gout.A230548 In the following year, the FDA for approved febuxostat for use in the chronic management of hyperuricemia in adult patients with gout who have an inadequate response or intolerance to allopurinol.L32238 Gout is a form of arthritis that is caused by the accumulation of uric acid crystal in or around a joint, leading to inflammation and further deposition of uric acid crystal deposition in bones, joints, tissues, and other organs in the long term. Gout is closely associated with hyperuricemia. Febuxostat works by inhibiting the activity of an enzyme that is responsible for the synthesis of uric acid, thereby reducing serum uric acid levels.A230548

In February 2019, a black box warning for febuxostat was added, based on the findings of a post-market clinical study (the CARES trial) where there was an increased risk of cardiovascular (CV) fatal outcomes in patients with gout and known cardiovascular disease treated with febuxostat, when compared to those treated with allopurinol. The manufacturer and the FDA advise health professionals to limit the use of febuxostat to second-line therapy in patients who have inadequate response or intolerance to allopurinol, and to avoid the use of febuxostat in patients with cardiovascular diseases.A2742, L13056

Struktur Molekul 2D

Berat 316.375
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The apparent mean terminal elimination half-life of approximately 5 to 8 hours.[L32238]
Volume Distribusi The apparent steady-state volume of distribution (V<sub>ss</sub>/F) of febuxostat ranges from 29 to 75 L, indicating a low to medium volume of distribution.[A230598]
Klirens (Clearance) Following oral administration of single doses of 10 to 240 mg, the mean apparent total clearance ranged from 10 to 12 L/h.[A230548]

Absorpsi

After oral administration, about 85% of febuxostat is absorbed rapidly.A230548 Tmax ranges from 1 to 1.5 hours. Following once-daily oral administration, Cmax was approximately 1.6 ± 0.6 mcg/mL at a dose of 40 mg febuxostat and 2.6 ± 1.7 mcg/mL at a dose of 80 mg febuxostat.L32238 A high-fat meal decreased Cmax by 49% and AUC by 18%, but there were no clinically significant changes in the ability of febuxostat to decrease serum uric acid concentrations.L32238

Metabolisme

Febuxostat is metabolized in the liver by UDP-glucuronosyltransferase (UGT) and Cytochrome P450 (CYP) enzymes, with the relative contribution of each enzyme isoform in the metabolism of febuxostat not fully elucidated. UGT1A1, UGT1A3, UGT1A9, and UGT2B7 mediate conjugation of febuxostat,L32238 which approximately accounts for 22–44% of the metabolism of the total dose administered, to produce the acyl-glucuronide metabolite.A230548 CYP1A2, CYP2C8, CYP2C9, and non-P450 enzymes are responsible for the oxidation reaction, which accounts for 2-8% of the metabolism of the dose.A230548 Oxidation reaction produces 67M-1, 67M-2, and 67M-4, which are pharmacologically active metabolites. 67M-1, 67M-2, and 67M-4 can further undergo glucuronidation and sulfation.A230598 Hydroxy metabolites are present in human plasma at much lower concentrations than the parent drug.L32238

Rute Eliminasi

Febuxostat is eliminated via both hepatic and renal pathways. Following oral administration of 80 mg radiolabeled febuxostat, approximately 49% of the dose was recovered in the urine. In urine, about 3% of the recovered dose accounted for unchanged febuxostat, 30% accounted for the acyl glucuronide metabolite, 13% accounted for oxidative metabolites and their conjugates, and 3% accounted for unidentified metabolites.L32238 Approximately 45% of the total dose was recovered in the feces, where 12% of the dose accounted for the unchanged parent drug. About 1% accounted for the acyl glucuronide metabolite, 25% accounted for oxidative metabolites and their conjugates, and 7% accounted for unidentified metabolites.L32238

Interaksi Makanan

1 Data
  • 1. Take with or without food. A high fat meal decreases Cmax and AUC in a clinically insignificant way.

Interaksi Obat

209 Data
Porfimer sodium Febuxostat may increase the photosensitizing activities of Porfimer sodium.
Verteporfin Febuxostat may increase the photosensitizing activities of Verteporfin.
Caffeine The serum concentration of the active metabolites of Caffeine can be increased when Caffeine is used in combination with Febuxostat.
Theophylline The serum concentration of the active metabolites of Theophylline can be increased when Theophylline is used in combination with Febuxostat.
Dyphylline The serum concentration of the active metabolites of Dyphylline can be increased when Dyphylline is used in combination with Febuxostat.
Pentoxifylline The serum concentration of the active metabolites of Pentoxifylline can be increased when Pentoxifylline is used in combination with Febuxostat.
Aminophylline The serum concentration of the active metabolites of Aminophylline can be increased when Aminophylline is used in combination with Febuxostat.
Oxtriphylline The serum concentration of the active metabolites of Oxtriphylline can be increased when Oxtriphylline is used in combination with Febuxostat.
Theobromine The serum concentration of the active metabolites of Theobromine can be increased when Theobromine is used in combination with Febuxostat.
Fenethylline The serum concentration of the active metabolites of Fenethylline can be increased when Fenethylline is used in combination with Febuxostat.
8-azaguanine The serum concentration of the active metabolites of 8-azaguanine can be increased when 8-azaguanine is used in combination with Febuxostat.
7,9-Dimethylguanine The serum concentration of the active metabolites of 7,9-Dimethylguanine can be increased when 7,9-Dimethylguanine is used in combination with Febuxostat.
Xanthine The serum concentration of the active metabolites of Xanthine can be increased when Xanthine is used in combination with Febuxostat.
7-Deazaguanine The serum concentration of the active metabolites of 7-Deazaguanine can be increased when 7-Deazaguanine is used in combination with Febuxostat.
Guanine The serum concentration of the active metabolites of Guanine can be increased when Guanine is used in combination with Febuxostat.
9-Methylguanine The serum concentration of the active metabolites of 9-Methylguanine can be increased when 9-Methylguanine is used in combination with Febuxostat.
Peldesine The serum concentration of the active metabolites of Peldesine can be increased when Peldesine is used in combination with Febuxostat.
Hypoxanthine The serum concentration of the active metabolites of Hypoxanthine can be increased when Hypoxanthine is used in combination with Febuxostat.
9-Deazaguanine The serum concentration of the active metabolites of 9-Deazaguanine can be increased when 9-Deazaguanine is used in combination with Febuxostat.
Propentofylline The serum concentration of the active metabolites of Propentofylline can be increased when Propentofylline is used in combination with Febuxostat.
Valomaciclovir The serum concentration of the active metabolites of Valomaciclovir can be increased when Valomaciclovir is used in combination with Febuxostat.
3-isobutyl-1-methyl-7H-xanthine The serum concentration of the active metabolites of 3-isobutyl-1-methyl-7H-xanthine can be increased when 3-isobutyl-1-methyl-7H-xanthine is used in combination with Febuxostat.
Uric acid The serum concentration of the active metabolites of Uric acid can be increased when Uric acid is used in combination with Febuxostat.
Doxofylline The serum concentration of the active metabolites of Doxofylline can be increased when Doxofylline is used in combination with Febuxostat.
6-O-benzylguanine The serum concentration of the active metabolites of 6-O-benzylguanine can be increased when 6-O-benzylguanine is used in combination with Febuxostat.
Lisofylline The serum concentration of the active metabolites of Lisofylline can be increased when Lisofylline is used in combination with Febuxostat.
Lobucavir The serum concentration of the active metabolites of Lobucavir can be increased when Lobucavir is used in combination with Febuxostat.
Cafedrine The serum concentration of the active metabolites of Cafedrine can be increased when Cafedrine is used in combination with Febuxostat.
Theodrenaline The serum concentration of the active metabolites of Theodrenaline can be increased when Theodrenaline is used in combination with Febuxostat.
Bamifylline The serum concentration of the active metabolites of Bamifylline can be increased when Bamifylline is used in combination with Febuxostat.
Proxyphylline The serum concentration of the active metabolites of Proxyphylline can be increased when Proxyphylline is used in combination with Febuxostat.
Acefylline The serum concentration of the active metabolites of Acefylline can be increased when Acefylline is used in combination with Febuxostat.
Etamiphylline The serum concentration of the active metabolites of Etamiphylline can be increased when Etamiphylline is used in combination with Febuxostat.
Pentifylline The serum concentration of the active metabolites of Pentifylline can be increased when Pentifylline is used in combination with Febuxostat.
Bufylline The serum concentration of the active metabolites of Bufylline can be increased when Bufylline is used in combination with Febuxostat.
Bromotheophylline The serum concentration of the active metabolites of Bromotheophylline can be increased when Bromotheophylline is used in combination with Febuxostat.
Furafylline The serum concentration of the active metabolites of Furafylline can be increased when Furafylline is used in combination with Febuxostat.
8-chlorotheophylline The serum concentration of the active metabolites of 8-chlorotheophylline can be increased when 8-chlorotheophylline is used in combination with Febuxostat.
PCS-499 The serum concentration of the active metabolites of PCS-499 can be increased when PCS-499 is used in combination with Febuxostat.
Nelfinavir The metabolism of Febuxostat can be increased when combined with Nelfinavir.
Phenytoin The metabolism of Febuxostat can be increased when combined with Phenytoin.
Desogestrel The metabolism of Febuxostat can be increased when combined with Desogestrel.
Lamotrigine The metabolism of Febuxostat can be increased when combined with Lamotrigine.
Carbamazepine The metabolism of Febuxostat can be increased when combined with Carbamazepine.
Efavirenz The metabolism of Febuxostat can be increased when combined with Efavirenz.
Primidone The metabolism of Febuxostat can be increased when combined with Primidone.
Tipranavir The metabolism of Febuxostat can be increased when combined with Tipranavir.
Ethinylestradiol The metabolism of Febuxostat can be increased when combined with Ethinylestradiol.
Rifampin The metabolism of Febuxostat can be increased when combined with Rifampicin.
Phenobarbital The metabolism of Febuxostat can be increased when combined with Phenobarbital.
Testosterone propionate The metabolism of Febuxostat can be increased when combined with Testosterone propionate.
Didanosine The serum concentration of Didanosine can be increased when it is combined with Febuxostat.
Azathioprine The metabolism of Azathioprine can be decreased when combined with Febuxostat.
Mercaptopurine The serum concentration of Mercaptopurine can be increased when it is combined with Febuxostat.
Pegloticase The risk or severity of adverse effects can be increased when Febuxostat is combined with Pegloticase.
Adenine The metabolism of Febuxostat can be decreased when combined with Adenine.
Indinavir The metabolism of Febuxostat can be decreased when combined with Indinavir.
Valproic acid The metabolism of Febuxostat can be decreased when combined with Valproic acid.
Amitriptyline The metabolism of Febuxostat can be decreased when combined with Amitriptyline.
Indomethacin The metabolism of Febuxostat can be decreased when combined with Indomethacin.
Erlotinib The metabolism of Febuxostat can be decreased when combined with Erlotinib.
Flurbiprofen The metabolism of Febuxostat can be decreased when combined with Flurbiprofen.
Propofol The metabolism of Febuxostat can be decreased when combined with Propofol.
Ketoconazole The metabolism of Febuxostat can be decreased when combined with Ketoconazole.
Probenecid The metabolism of Febuxostat can be decreased when combined with Probenecid.
Atazanavir The metabolism of Febuxostat can be decreased when combined with Atazanavir.
Regorafenib The metabolism of Febuxostat can be decreased when combined with Regorafenib.
Dasabuvir The metabolism of Febuxostat can be decreased when combined with Dasabuvir.
Sodium aurothiomalate The metabolism of Febuxostat can be decreased when combined with Sodium aurothiomalate.
Paritaprevir The metabolism of Febuxostat can be decreased when combined with Paritaprevir.
Silibinin The metabolism of Febuxostat can be decreased when combined with Silibinin.
Fostamatinib The metabolism of Febuxostat can be decreased when combined with Fostamatinib.
Pexidartinib The metabolism of Febuxostat can be decreased when combined with Pexidartinib.
Mefenamic acid The metabolism of Febuxostat can be decreased when combined with Mefenamic acid.
Diflunisal The metabolism of Febuxostat can be decreased when combined with Diflunisal.
Fosphenytoin The metabolism of Febuxostat can be decreased when combined with Fosphenytoin.
Methylene blue The metabolism of Febuxostat can be decreased when combined with Methylene blue.
Isavuconazole The metabolism of Febuxostat can be decreased when combined with Isavuconazole.
Umifenovir The metabolism of Febuxostat can be decreased when combined with Umifenovir.
Niflumic acid The metabolism of Febuxostat can be decreased when combined with Niflumic acid.
Cannabidiol The metabolism of Febuxostat can be decreased when combined with Cannabidiol.
Gemfibrozil The metabolism of Febuxostat can be decreased when combined with Gemfibrozil.
Flunitrazepam The metabolism of Febuxostat can be decreased when combined with Flunitrazepam.
Deferasirox The metabolism of Febuxostat can be decreased when combined with Deferasirox.
Dovitinib The metabolism of Febuxostat can be decreased when combined with Dovitinib.
Eltrombopag The metabolism of Febuxostat can be decreased when combined with Eltrombopag.
Chenodeoxycholic acid The metabolism of Febuxostat can be decreased when combined with Chenodeoxycholic acid.
Alpelisib The serum concentration of Alpelisib can be increased when it is combined with Febuxostat.
Ubrogepant The serum concentration of Ubrogepant can be increased when it is combined with Febuxostat.
Rimegepant The serum concentration of Rimegepant can be increased when it is combined with Febuxostat.
Methyclothiazide The therapeutic efficacy of Febuxostat can be decreased when used in combination with Methyclothiazide.
Bendroflumethiazide The therapeutic efficacy of Febuxostat can be decreased when used in combination with Bendroflumethiazide.
Benzthiazide The therapeutic efficacy of Febuxostat can be decreased when used in combination with Benzthiazide.
Cyclothiazide The therapeutic efficacy of Febuxostat can be decreased when used in combination with Cyclothiazide.
Hydroflumethiazide The therapeutic efficacy of Febuxostat can be decreased when used in combination with Hydroflumethiazide.
Chlorothiazide The therapeutic efficacy of Febuxostat can be decreased when used in combination with Chlorothiazide.
Hydrochlorothiazide The therapeutic efficacy of Febuxostat can be decreased when used in combination with Hydrochlorothiazide.
Trichlormethiazide The therapeutic efficacy of Febuxostat can be decreased when used in combination with Trichlormethiazide.
Polythiazide The therapeutic efficacy of Febuxostat can be decreased when used in combination with Polythiazide.
Mebutizide The therapeutic efficacy of Febuxostat can be decreased when used in combination with Mebutizide.

Target Protein

Xanthine dehydrogenase/oxidase XDH

Referensi & Sumber

Synthesis reference: EPO Patent Report(https://data.epo.org/publication-server/rest/v1.0/publication-dates/20101229/patents/EP2266966NWA1/document.pdf)
Artikel (PubMed)
  • PMID: 23352248
    Gandhi PK, Gentry WM, Bottorff MB: Cardiovascular thromboembolic events associated with febuxostat: investigation of cases from the FDA adverse event reporting system database. Semin Arthritis Rheum. 2013 Jun;42(6):562-6. doi: 10.1016/j.semarthrit.2012.11.002. Epub 2013 Jan 24.
  • PMID: 23286293
    Saban-Ruiz J, Alonso-Pacho A, Fabregate-Fuente M, de la Puerta Gonzalez-Quevedo C: Xanthine oxidase inhibitor febuxostat as a novel agent postulated to act against vascular inflammation. Antiinflamm Antiallergy Agents Med Chem. 2013;12(1):94-9.
  • PMID: 22995295
    Tsuda H, Kawada N, Kaimori JY, Kitamura H, Moriyama T, Rakugi H, Takahara S, Isaka Y: Febuxostat suppressed renal ischemia-reperfusion injury via reduced oxidative stress. Biochem Biophys Res Commun. 2012 Oct 19;427(2):266-72. doi: 10.1016/j.bbrc.2012.09.032. Epub 2012 Sep 17.
  • PMID: 19447778
    Edwards NL: Febuxostat: a new treatment for hyperuricaemia in gout. Rheumatology (Oxford). 2009 May;48 Suppl 2:ii15-ii19. doi: 10.1093/rheumatology/kep088.
  • PMID: 19337428
    Hu M, Tomlinson B: Febuxostat in the management of hyperuricemia and chronic gout: a review. Ther Clin Risk Manag. 2008 Dec;4(6):1209-20. doi: 10.2147/tcrm.s3310.
  • PMID: 25501928
    Nishino T, Okamoto K: Mechanistic insights into xanthine oxidoreductase from development studies of candidate drugs to treat hyperuricemia and gout. J Biol Inorg Chem. 2015 Mar;20(2):195-207. doi: 10.1007/s00775-014-1210-x. Epub 2014 Dec 12.
  • PMID: 31334959
    Gerriets V, Jialal I: Febuxostat .
  • PMID: 20354234
    Grabowski BA, Khosravan R, Vernillet L, Mulford DJ: Metabolism and excretion of 14C febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, in healthy male subjects. J Clin Pharmacol. 2011 Feb;51(2):189-201. doi: 10.1177/0091270010365549. Epub 2010 Mar 30.

Contoh Produk & Brand

Produk: 131 • International brands: 3
Produk
  • Adenuric
    Tablet, film coated • 80 mg • Oral • EU • Approved
  • Adenuric
    Tablet, film coated • 80 mg • Oral • EU • Approved
  • Adenuric
    Tablet, film coated • 120 mg • Oral • EU • Approved
  • Adenuric
    Tablet, film coated • 120 mg • Oral • EU • Approved
  • Adenuric
    Tablet, film coated • 80 mg • Oral • EU • Approved
  • Adenuric
    Tablet, film coated • 80 mg • Oral • EU • Approved
  • Adenuric
    Tablet, film coated • 80 mg • Oral • EU • Approved
  • Adenuric
    Tablet, film coated • 80 mg • Oral • EU • Approved
Menampilkan 8 dari 131 produk.
International Brands
  • Atenurix — Ajanta Pharma Phil
  • Barif — Square
  • Feburic — Teijin Pharma

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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