Peringatan Keamanan

The oral LD50 was 250 mg/kg.L31953

Single doses of ruxolitinib up to 200 mg were tolerated well. Higher doses than recommended repeat doses are associated with myelosuppression, including leukopenia, anemia, and thrombocytopenia. There is no known antidote for overdoses with ruxolitinib: it is recommended that patients are given appropriate supportive treatment. Hemodialysis is not expected to enhance the elimination of ruxolitinib.L31938

Ruxolitinib

DB08877

small molecule approved

Deskripsi

Ruxolitinib, formerly known as INCB018424 or INC424, is an anticancer drug and a Janus kinase (JAK) inhibitor. It is a potent and selective inhibitor of JAK1 and JAK2,A229698 which are tyrosine kinases involved in cytokine signalling and hematopoiesis.A7450 Myeloproliferative neoplasms, such as myelofibrosis and polycythemia vera, are often characterized by aberrant activation of the JAK-STAT pathway, leading to abnormal blood cell counts and thrombotic complications. By inhibiting JAK1 and JAK2, ruxolitinib works to block the dysregulated cell signalling pathways and prevents abnormal blood cell proliferation.A229708 Due to a large number of patients with myeloproliferative neoplasms who have JAK2 mutations, ruxolitinib was the first ATP-competitive inhibitor of JAK1 and JAK2 ever developed.A229938

Ruxolitinib was first approved for the treatment of adult patients with myelofibrosis by the FDA in 2011, followed by EMA's approval in 2012.A229708 In 2014, it was approved for the treatment of polycythemia vera in adults who have an inadequate response to or are intolerant of hydroxyurea and in 2019, ruxolitinib was approved for use in steroid-refractory acute graft-versus-host disease in adults and children.L31958 The topical formulation of ruxolitinib is used to treat atopic dermatitis and vitiligo.L39125 It is being investigated for other inflammatory skin conditions.A229883

Ruxolitinib has been investigated to treat patients with coronavirus disease 2019 (COVID-19) accompanied by severe systemic hyperinflammation. In phase II clinical trials, ruxolitinib improved chest computed tomography and improved recovery in patients with lymphopenia.A229713, A229718 However, phase III clinical trials later determined that ruxolitinib was inadequate in meeting its primary endpoint of reducing the number of hospitalized COVID-19 patients who experienced severe complications L31968 thus the drug was not approved as a treatment for COVID-19.

Struktur Molekul 2D

Berat 306.365
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The mean elimination half-life of ruxolitinib is approximately 3 hours and the mean half-life of its metabolites is approximately 5.8 hours.[L31938]
Volume Distribusi The mean volume of distribution (%coefficient of variation) at steady-state is 72 L (29%) in patients with myelofibrosis and 75 L (23%) in patients with polycythemia vera.[L31938] It is not known whether ruxolitinib crosses the blood-brain barrier.[L14787]
Klirens (Clearance) Ruxolitinib clearance (% coefficient of variation) is 17.7 L/h in women and 22.1 L/h in men with myelofibrosis. Drug clearance was 12.7 L/h (42%) in patients with polycythemia vera and 11.9 L/h (43%) in patients with acute graft-versus-host disease.[L31938]

Absorpsi

Following oral administration, ruxolitinib undergoes rapid absorption A229753 and the peak concentrations are reached within one hour after administration.A229703 Over a single-dose range of 5 mg to 200 mg, the mean maximal plasma concentration (Cmax) increases proportionally. Cmax ranged from 205 nM to 7100 nM and AUC ranged from 862 nM x hr to 30700 nM x hr. Tmax ranges from one to two hours following oral administration. Oral bioavailability is at least 95%.L31938

Metabolisme

More than 99% of orally-administered ruxolitinib undergoes metabolismA229703 mediated by CYP3A4 and, to a lesser extent, CYP2C9.L31938 The major circulating metabolites in human plasma were M18 formed by 2-hydroxylation, and M16 and M27 (stereoisomers) formed by 3-hydroxylation. Other identified metabolites include M9 and M49, which are formed by hydroxylation and ketone formation. Not all metabolite structures are fully characterized and it is speculated that many metabolites exist in stereoisomers.A229753 Metabolites of ruxolitinib retain inhibitory activity against JAK1 and JAk2 to a lesser degree than the parent drug.A38590

Rute Eliminasi

Following oral administration of a single radiolabeled dose of ruxolitinib, the drug was mainly eliminated through metabolism. About 74% of the total dose was excreted in urine and 22% was excreted in feces,L31938 mostly in the form of hydroxyl and oxo metabolites of ruxolitinib.A229753 The unchanged parent drug accounted for less than 1% of the excreted total radioactivity.L31938

Interaksi Makanan

3 Data
  • 1. Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of ruxolitinib.
  • 2. Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum levels of ruxolitinib.
  • 3. Take with or without food. A high-fat, high-calorie meal had negligible effects on the pharmacokinetics of ruxolitinib.

Interaksi Obat

1662 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Ruxolitinib.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Ruxolitinib.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Ruxolitinib.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Ruxolitinib.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Ruxolitinib.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Ruxolitinib.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Ruxolitinib.
Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Ruxolitinib.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Ruxolitinib.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Ruxolitinib.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Ruxolitinib.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Ruxolitinib.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Ruxolitinib.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Ruxolitinib.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Ruxolitinib.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Ruxolitinib.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Ruxolitinib.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Ruxolitinib.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Ruxolitinib.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Ruxolitinib.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Ruxolitinib.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Ruxolitinib.
Cladribine Ruxolitinib may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Carmustine is combined with Ruxolitinib.
Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Ruxolitinib.
Bleomycin The risk or severity of adverse effects can be increased when Bleomycin is combined with Ruxolitinib.
Chlorambucil The risk or severity of adverse effects can be increased when Chlorambucil is combined with Ruxolitinib.
Raltitrexed The risk or severity of adverse effects can be increased when Raltitrexed is combined with Ruxolitinib.
Mitomycin The risk or severity of adverse effects can be increased when Mitomycin is combined with Ruxolitinib.
Vindesine The risk or severity of adverse effects can be increased when Vindesine is combined with Ruxolitinib.
Tioguanine The risk or severity of adverse effects can be increased when Tioguanine is combined with Ruxolitinib.
Vinorelbine The risk or severity of adverse effects can be increased when Vinorelbine is combined with Ruxolitinib.
Dexrazoxane The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Ruxolitinib.
Streptozocin The risk or severity of adverse effects can be increased when Streptozocin is combined with Ruxolitinib.
Trifluridine The risk or severity of adverse effects can be increased when Trifluridine is combined with Ruxolitinib.
Gemcitabine The risk or severity of adverse effects can be increased when Gemcitabine is combined with Ruxolitinib.
Epirubicin The risk or severity of adverse effects can be increased when Epirubicin is combined with Ruxolitinib.
Lenalidomide The risk or severity of adverse effects can be increased when Lenalidomide is combined with Ruxolitinib.
Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Ruxolitinib.
Cisplatin The risk or severity of adverse effects can be increased when Cisplatin is combined with Ruxolitinib.
Oxaliplatin The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Ruxolitinib.
Vincristine The risk or severity of adverse effects can be increased when Vincristine is combined with Ruxolitinib.
Pentostatin The risk or severity of adverse effects can be increased when Pentostatin is combined with Ruxolitinib.
Methotrexate The risk or severity of adverse effects can be increased when Methotrexate is combined with Ruxolitinib.
Linezolid The risk or severity of adverse effects can be increased when Linezolid is combined with Ruxolitinib.
Clofarabine The risk or severity of adverse effects can be increased when Clofarabine is combined with Ruxolitinib.
Prednisone The risk or severity of adverse effects can be increased when Prednisone is combined with Ruxolitinib.
Pemetrexed The risk or severity of adverse effects can be increased when Pemetrexed is combined with Ruxolitinib.
Fludrocortisone The risk or severity of adverse effects can be increased when Fludrocortisone is combined with Ruxolitinib.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Ruxolitinib.
Irinotecan The risk or severity of adverse effects can be increased when Irinotecan is combined with Ruxolitinib.
Sulfasalazine The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Ruxolitinib.
Dacarbazine The risk or severity of adverse effects can be increased when Dacarbazine is combined with Ruxolitinib.
Temozolomide The risk or severity of adverse effects can be increased when Temozolomide is combined with Ruxolitinib.
Penicillamine The risk or severity of adverse effects can be increased when Penicillamine is combined with Ruxolitinib.
Mechlorethamine The risk or severity of adverse effects can be increased when Mechlorethamine is combined with Ruxolitinib.
Azacitidine The risk or severity of adverse effects can be increased when Azacitidine is combined with Ruxolitinib.
Carboplatin The risk or severity of adverse effects can be increased when Carboplatin is combined with Ruxolitinib.
Dactinomycin The risk or severity of adverse effects can be increased when Dactinomycin is combined with Ruxolitinib.
Cytarabine The risk or severity of adverse effects can be increased when Cytarabine is combined with Ruxolitinib.
Azathioprine The risk or severity of adverse effects can be increased when Azathioprine is combined with Ruxolitinib.
Hydroxyurea The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Ruxolitinib.
Mycophenolic acid The risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Ruxolitinib.
Mercaptopurine The risk or severity of adverse effects can be increased when Mercaptopurine is combined with Ruxolitinib.
Melphalan The risk or severity of adverse effects can be increased when Melphalan is combined with Ruxolitinib.
Fludarabine The risk or severity of adverse effects can be increased when Fludarabine is combined with Ruxolitinib.
Flucytosine The risk or severity of adverse effects can be increased when Flucytosine is combined with Ruxolitinib.
Trilostane The risk or severity of adverse effects can be increased when Trilostane is combined with Ruxolitinib.
Procarbazine The risk or severity of adverse effects can be increased when Procarbazine is combined with Ruxolitinib.
Arsenic trioxide The risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Ruxolitinib.
Estramustine The risk or severity of adverse effects can be increased when Estramustine is combined with Ruxolitinib.
Lomustine The risk or severity of adverse effects can be increased when Lomustine is combined with Ruxolitinib.
Eculizumab The risk or severity of adverse effects can be increased when Eculizumab is combined with Ruxolitinib.
Decitabine The risk or severity of adverse effects can be increased when Decitabine is combined with Ruxolitinib.
Nelarabine The risk or severity of adverse effects can be increased when Nelarabine is combined with Ruxolitinib.
Ciclesonide The risk or severity of adverse effects can be increased when Ciclesonide is combined with Ruxolitinib.
Stepronin The risk or severity of adverse effects can be increased when Stepronin is combined with Ruxolitinib.
Hydroxychloroquine The risk or severity of adverse effects can be increased when Hydroxychloroquine is combined with Ruxolitinib.
Castanospermine The risk or severity of adverse effects can be increased when Castanospermine is combined with Ruxolitinib.
Vorinostat The risk or severity of adverse effects can be increased when Vorinostat is combined with Ruxolitinib.
2-Methoxyethanol The risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Ruxolitinib.
Brequinar The risk or severity of adverse effects can be increased when Brequinar is combined with Ruxolitinib.
Thiotepa The risk or severity of adverse effects can be increased when Thiotepa is combined with Ruxolitinib.
Aldosterone The risk or severity of adverse effects can be increased when Aldosterone is combined with Ruxolitinib.
Ixabepilone The risk or severity of adverse effects can be increased when Ixabepilone is combined with Ruxolitinib.
Pirfenidone The risk or severity of adverse effects can be increased when Pirfenidone is combined with Ruxolitinib.
Belinostat The risk or severity of adverse effects can be increased when Belinostat is combined with Ruxolitinib.
Interferon alfa The risk or severity of adverse effects can be increased when Interferon alfa is combined with Ruxolitinib.
Glatiramer The risk or severity of adverse effects can be increased when Glatiramer is combined with Ruxolitinib.
Briakinumab The risk or severity of adverse effects can be increased when Briakinumab is combined with Ruxolitinib.
Human interferon omega-1 The risk or severity of adverse effects can be increased when Human interferon omega-1 is combined with Ruxolitinib.
Panobinostat The risk or severity of adverse effects can be increased when Panobinostat is combined with Ruxolitinib.
Mepolizumab The risk or severity of adverse effects can be increased when Mepolizumab is combined with Ruxolitinib.
Abetimus The risk or severity of adverse effects can be increased when Abetimus is combined with Ruxolitinib.
Belatacept The risk or severity of adverse effects can be increased when Belatacept is combined with Ruxolitinib.
Bendamustine The risk or severity of adverse effects can be increased when Bendamustine is combined with Ruxolitinib.
Cabazitaxel The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Ruxolitinib.
Pralatrexate The risk or severity of adverse effects can be increased when Pralatrexate is combined with Ruxolitinib.
Wortmannin The risk or severity of adverse effects can be increased when Wortmannin is combined with Ruxolitinib.
Eribulin The risk or severity of adverse effects can be increased when Eribulin is combined with Ruxolitinib.

Target Protein

Urokinase plasminogen activator surface receptor PLAUR
Tyrosine-protein kinase JAK2 JAK2
Tyrosine-protein kinase JAK1 JAK1
Tyrosine-protein kinase JAK3 JAK3
Non-receptor tyrosine-protein kinase TYK2 TYK2

Referensi & Sumber

Artikel (PubMed)
  • PMID: 23514013
    Cervantes F, Martinez-Trillos A: Myelofibrosis: an update on current pharmacotherapy and future directions. Expert Opin Pharmacother. 2013 May;14(7):873-84. doi: 10.1517/14656566.2013.783019. Epub 2013 Mar 21.
  • PMID: 23061804
    Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000.
  • PMID: 24756798
    Becker H, Engelhardt M, von Bubnoff N, Wasch R: Ruxolitinib. Recent Results Cancer Res. 2014;201:249-57. doi: 10.1007/978-3-642-54490-3_16.
  • PMID: 21919691
    Ostojic A, Vrhovac R, Verstovsek S: Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol. 2011 Sep;7(9):1035-43. doi: 10.2217/fon.11.81.
  • PMID: 30069628
    Ajayi S, Becker H, Reinhardt H, Engelhardt M, Zeiser R, von Bubnoff N, Wasch R: Ruxolitinib. Recent Results Cancer Res. 2018;212:119-132. doi: 10.1007/978-3-319-91439-8_6.
  • PMID: 32470486
    Cao Y, Wei J, Zou L, Jiang T, Wang G, Chen L, Huang L, Meng F, Huang L, Wang N, Zhou X, Luo H, Mao Z, Chen X, Xie J, Liu J, Cheng H, Zhao J, Huang G, Wang W, Zhou J: Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol. 2020 Jul;146(1):137-146.e3. doi: 10.1016/j.jaci.2020.05.019. Epub 2020 May 26.
  • PMID: 32518419
    La Rosee F, Bremer HC, Gehrke I, Kehr A, Hochhaus A, Birndt S, Fellhauer M, Henkes M, Kumle B, Russo SG, La Rosee P: The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation. Leukemia. 2020 Jul;34(7):1805-1815. doi: 10.1038/s41375-020-0891-0. Epub 2020 Jun 9.
  • PMID: 32653055
    Rosmarin D, Pandya AG, Lebwohl M, Grimes P, Hamzavi I, Gottlieb AB, Butler K, Kuo F, Sun K, Ji T, Howell MD, Harris JE: Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial. Lancet. 2020 Jul 11;396(10244):110-120. doi: 10.1016/S0140-6736(20)30609-7.
Menampilkan 8 dari 15 artikel.

Contoh Produk & Brand

Produk: 25 • International brands: 0
Produk
  • Jakafi
    Tablet • 5.0 mg/1 • Oral • US • Approved
  • Jakafi
    Tablet • 10.0 mg/1 • Oral • US • Approved
  • Jakafi
    Tablet • 15.0 mg/1 • Oral • US • Approved
  • Jakafi
    Tablet • 20.0 mg/1 • Oral • US • Approved
  • Jakafi
    Tablet • 25.0 mg/1 • Oral • US • Approved
  • Jakavi
    Tablet • 5 mg • Oral • Canada • Approved
  • Jakavi
    Tablet • 15 mg • Oral • Canada • Approved
  • Jakavi
    Tablet • 20 mg • Oral • Canada • Approved
Menampilkan 8 dari 25 produk.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
© 2025 Digital Pharmacy Research - Universitas Esa Unggul