Peringatan Keamanan

There is limited clinical information on the overdose from upacitinib: in clinical trials, once-daily administration of 60 mg in extended-release formulations were well tolerated. In case of an overdose, it is recommended that the patient is monitored for signs and symptoms of adverse reactions and treated with appropriate symptomatic treatment.L10896

The oral LD50 in rats is 14500 mg/kg.L10911

Upadacitinib

DB15091

small molecule approved investigational

Deskripsi

Upadacitinib is an oral Janus kinase (JAK)1-selective inhibitor and a disease-modifying antirheumatic drug (DMARD) used in the treatment of rheumatoid arthritis to slow down disease progression. Rheumatoid arthritis is a chronic autoimmune inflammatory disease affecting the peripheral joints. It is characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage damage and bone destruction, leading to co-morbidities.A189165 Despite a variety of therapeutic agents available for treatment, up to 40% of the patients do not respond to current therapies, including biological therapies.A189171 The etiology of the disease is mostly unknown; however, the role of JAK as a driver of immune-mediated conditions was discovered, leading to the use of JAK as therapeutic targets for rheumatoid arthritis.A189168 To reduce dose-related toxicity (as seen with some pan-JAK inhibitors) without significantly affecting efficacy, more selective JAK1 inhibitors, upadacitinib and filgotinib, were developed.A189165

The FDA approved upadacitinib in August 2019 and it is used for the treatment of active rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, and ankylosing spondylitis.L10896 In December 2019, it was additionally approved by the European Commission and Health Canada.L10899,L42540 Upadacitinib is marketed under the brand name RINVOQ for oral administration.L10896

Struktur Molekul 2D

Berat 380.375
Wujud liquid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The mean terminal elimination half-life of upadacitinib ranged from 8 to 14 hours following administration of the extended-release formulation.[L10896,L10905] In clinical trials, approximately 90% of upadacitinib in the systemic circulation was eliminated within 24 hours of dosing.[L10896]
Volume Distribusi The volume of distribution of upadacitinib in a patient with rheumatoid arthritis and a body weight of 74 kg is estimated to be 224 L following oral administration of an extended-release formula.[L10905] In a pharmacokinetic study consisting of healthy volunteers receiving the extended-release formulation, the steady-state volume of distribution was 294 L.[A184043] Upadacitinib partitions similarly between plasma and blood cellular components with a blood to plasma ratio of 1.0.[L10896]
Klirens (Clearance) The apparent oral clearance of upadacitinib in healthy volunteers receiving the extended-release formulation was 53.7 L/h.[A184043]

Absorpsi

Upadacitinib displays a dose-proportional pharmacokinetic profile over the therapeutic dose range. Following oral administration, the median time to reach Cmax (Tmax) ranges from 2 to 4 hours. The steady-state plasma concentrations of upadacitinib are reached within 4 days following multiple once-daily administrations, with minimal accumulation.L10896 Food intake has no clinically relevant effect on the AUC, Cmax, and Cmin of upadacitinib from the extended-release formulation.A189162

Metabolisme

Upadacitinib predominantly undergoes CYP3A4-mediated metabolism;L10896 however, upadacitinib is a nonsensitive substrate of CYP3A4.A189162 It is also metabolized by CYP2D6 to a lesser extent.L10896 In a human radio-labelled study, about 79% of the total plasma radioactivity accounted for the parent drug, and about 13% of the total plasma radioactivity accounted for the main metabolite produced from mono-oxidation, followed by glucuronidation.L10896 There are no known active metabolites of upadacitinib.L10905

Rute Eliminasi

Following administration of a single radio-labelled dose from the immediate-release formulation, approximately 53% of the total dose was excreted in the feces where 38% of the excreted dose was an unchanged parent drug. About 43% of the total dose was excreted in the urine, where 24% of that dose was in the unchanged parent drug form.L10905 Approximately 34% of the total dose of upadacitinib dose was excreted as metabolites.L10896

Interaksi Makanan

3 Data
  • 1. Avoid grapefruit products. Upadacitinib exposure is increased when a strong CYP3A4 inhibitor such as grapefruit is used, which may increase the risk for drug-related adverse events.
  • 2. Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of upadacitinib.
  • 3. Take with or without food. Food does not significantly affect drug concentrations.

Interaksi Obat

452 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Upadacitinib.
Etanercept The risk or severity of adverse effects can be increased when Etanercept is combined with Upadacitinib.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Upadacitinib.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Upadacitinib.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Upadacitinib.
Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Upadacitinib.
Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Upadacitinib.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Upadacitinib.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Upadacitinib.
Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Upadacitinib.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Upadacitinib.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Upadacitinib.
Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Upadacitinib.
Infliximab The risk or severity of adverse effects can be increased when Infliximab is combined with Upadacitinib.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Upadacitinib.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Upadacitinib.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Upadacitinib.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Upadacitinib.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Upadacitinib.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Upadacitinib.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Upadacitinib.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Upadacitinib.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Upadacitinib.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Upadacitinib.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Upadacitinib.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Upadacitinib.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Upadacitinib.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Upadacitinib.
Flunisolide The risk or severity of adverse effects can be increased when Flunisolide is combined with Upadacitinib.
Bortezomib The risk or severity of adverse effects can be increased when Bortezomib is combined with Upadacitinib.
Cladribine Upadacitinib may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Carmustine is combined with Upadacitinib.
Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Upadacitinib.
Bleomycin The risk or severity of adverse effects can be increased when Bleomycin is combined with Upadacitinib.
Chlorambucil The risk or severity of adverse effects can be increased when Chlorambucil is combined with Upadacitinib.
Raltitrexed The risk or severity of adverse effects can be increased when Raltitrexed is combined with Upadacitinib.
Mitomycin The risk or severity of adverse effects can be increased when Mitomycin is combined with Upadacitinib.
Bexarotene The risk or severity of adverse effects can be increased when Bexarotene is combined with Upadacitinib.
Vindesine The risk or severity of adverse effects can be increased when Vindesine is combined with Upadacitinib.
Floxuridine The risk or severity of adverse effects can be increased when Floxuridine is combined with Upadacitinib.
Fluorometholone The risk or severity of adverse effects can be increased when Fluorometholone is combined with Upadacitinib.
Indomethacin The risk or severity of adverse effects can be increased when Indomethacin is combined with Upadacitinib.
Tioguanine The risk or severity of adverse effects can be increased when Tioguanine is combined with Upadacitinib.
Vinorelbine The risk or severity of adverse effects can be increased when Vinorelbine is combined with Upadacitinib.
Dexrazoxane The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Upadacitinib.
Beclomethasone dipropionate The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Upadacitinib.
Sorafenib The risk or severity of adverse effects can be increased when Sorafenib is combined with Upadacitinib.
Streptozocin The risk or severity of adverse effects can be increased when Streptozocin is combined with Upadacitinib.
Trifluridine The risk or severity of adverse effects can be increased when Trifluridine is combined with Upadacitinib.
Gemcitabine The risk or severity of adverse effects can be increased when Gemcitabine is combined with Upadacitinib.
Betamethasone The risk or severity of adverse effects can be increased when Betamethasone is combined with Upadacitinib.
Teniposide The risk or severity of adverse effects can be increased when Teniposide is combined with Upadacitinib.
Epirubicin The risk or severity of adverse effects can be increased when Epirubicin is combined with Upadacitinib.
Chloramphenicol The risk or severity of adverse effects can be increased when Chloramphenicol is combined with Upadacitinib.
Lenalidomide The risk or severity of adverse effects can be increased when Lenalidomide is combined with Upadacitinib.
Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Upadacitinib.
Zidovudine The risk or severity of adverse effects can be increased when Zidovudine is combined with Upadacitinib.
Cisplatin The risk or severity of adverse effects can be increased when Cisplatin is combined with Upadacitinib.
Oxaliplatin The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Upadacitinib.
Cyclophosphamide The risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Upadacitinib.
Vincristine The risk or severity of adverse effects can be increased when Vincristine is combined with Upadacitinib.
Fluorouracil The risk or severity of adverse effects can be increased when Fluorouracil is combined with Upadacitinib.
Desoximetasone The risk or severity of adverse effects can be increased when Desoximetasone is combined with Upadacitinib.
Propylthiouracil The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Upadacitinib.
Pentostatin The risk or severity of adverse effects can be increased when Pentostatin is combined with Upadacitinib.
Methotrexate The risk or severity of adverse effects can be increased when Methotrexate is combined with Upadacitinib.
Vinblastine The risk or severity of adverse effects can be increased when Vinblastine is combined with Upadacitinib.
Fluticasone propionate The risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Upadacitinib.
Fluocinolone acetonide The risk or severity of adverse effects can be increased when Fluocinolone acetonide is combined with Upadacitinib.
Linezolid The risk or severity of adverse effects can be increased when Linezolid is combined with Upadacitinib.
Imatinib The risk or severity of adverse effects can be increased when Imatinib is combined with Upadacitinib.
Triamcinolone The risk or severity of adverse effects can be increased when Triamcinolone is combined with Upadacitinib.
Clofarabine The risk or severity of adverse effects can be increased when Clofarabine is combined with Upadacitinib.
Prednisone The risk or severity of adverse effects can be increased when Prednisone is combined with Upadacitinib.
Pemetrexed The risk or severity of adverse effects can be increased when Pemetrexed is combined with Upadacitinib.
Fludrocortisone The risk or severity of adverse effects can be increased when Fludrocortisone is combined with Upadacitinib.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Upadacitinib.
Daunorubicin The risk or severity of adverse effects can be increased when Daunorubicin is combined with Upadacitinib.
Irinotecan The risk or severity of adverse effects can be increased when Irinotecan is combined with Upadacitinib.
Mometasone The risk or severity of adverse effects can be increased when Mometasone is combined with Upadacitinib.
Etoposide The risk or severity of adverse effects can be increased when Etoposide is combined with Upadacitinib.
Sulfasalazine The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Upadacitinib.
Dacarbazine The risk or severity of adverse effects can be increased when Dacarbazine is combined with Upadacitinib.
Temozolomide The risk or severity of adverse effects can be increased when Temozolomide is combined with Upadacitinib.
Penicillamine The risk or severity of adverse effects can be increased when Penicillamine is combined with Upadacitinib.
Prednisolone The risk or severity of adverse effects can be increased when Prednisolone is combined with Upadacitinib.
Sirolimus The risk or severity of adverse effects can be increased when Sirolimus is combined with Upadacitinib.
Mechlorethamine The risk or severity of adverse effects can be increased when Mechlorethamine is combined with Upadacitinib.
Azacitidine The risk or severity of adverse effects can be increased when Azacitidine is combined with Upadacitinib.
Carboplatin The risk or severity of adverse effects can be increased when Carboplatin is combined with Upadacitinib.
Methylprednisolone The risk or severity of adverse effects can be increased when Methylprednisolone is combined with Upadacitinib.
Dactinomycin The risk or severity of adverse effects can be increased when Dactinomycin is combined with Upadacitinib.
Cytarabine The risk or severity of adverse effects can be increased when Cytarabine is combined with Upadacitinib.
Azathioprine The risk or severity of adverse effects can be increased when Azathioprine is combined with Upadacitinib.
Doxorubicin The risk or severity of adverse effects can be increased when Doxorubicin is combined with Upadacitinib.
Hydroxyurea The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Upadacitinib.
Busulfan The risk or severity of adverse effects can be increased when Busulfan is combined with Upadacitinib.
Clobetasol propionate The risk or severity of adverse effects can be increased when Clobetasol propionate is combined with Upadacitinib.
Mycophenolic acid The risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Upadacitinib.
Topotecan The risk or severity of adverse effects can be increased when Topotecan is combined with Upadacitinib.

Target Protein

Tyrosine-protein kinase JAK1 JAK1

Referensi & Sumber

Artikel (PubMed)
  • PMID: 30945116
    Klunder B, Mittapalli RK, Mohamed MF, Friedel A, Noertersheuser P, Othman AA: Population Pharmacokinetics of Upadacitinib Using the Immediate-Release and Extended-Release Formulations in Healthy Subjects and Subjects with Rheumatoid Arthritis: Analyses of Phase I-III Clinical Trials. Clin Pharmacokinet. 2019 Aug;58(8):1045-1058. doi: 10.1007/s40262-019-00739-3.
  • PMID: 30886973
    Parmentier JM, Voss J, Graff C, Schwartz A, Argiriadi M, Friedman M, Camp HS, Padley RJ, George JS, Hyland D, Rosebraugh M, Wishart N, Olson L, Long AJ: In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatol. 2018 Aug 28;2:23. doi: 10.1186/s41927-018-0031-x. eCollection 2018.
  • PMID: 29688617
    Mohamed MF, Zeng J, Marroum PJ, Song IH, Othman AA: Pharmacokinetics of Upadacitinib With the Clinical Regimens of the Extended-Release Formulation Utilized in Rheumatoid Arthritis Phase 3 Trials. Clin Pharmacol Drug Dev. 2019 Feb;8(2):208-216. doi: 10.1002/cpdd.462. Epub 2018 Apr 24.
  • PMID: 31692920
    Biggioggero M, Becciolini A, Crotti C, Agape E, Favalli EG: Upadacitinib and filgotinib: the role of JAK1 selective inhibition in the treatment of rheumatoid arthritis. Drugs Context. 2019 Oct 24;8:212595. doi: 10.7573/dic.212595. eCollection 2019.
  • PMID: 29282366
    Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ: JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017 Dec 28;17(1):78. doi: 10.1038/nrd.2017.267.
  • PMID: 29424301
    Rivellese F, Lobasso A, Barbieri L, Liccardo B, de Paulis A, Rossi FW: Novel Therapeutic Approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors. Curr Med Chem. 2019;26(16):2823-2843. doi: 10.2174/0929867325666180209145243.
  • PMID: 7537214
    Guschin D, Rogers N, Briscoe J, Witthuhn B, Watling D, Horn F, Pellegrini S, Yasukawa K, Heinrich P, Stark GR, et al.: A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. EMBO J. 1995 Apr 3;14(7):1421-9.
  • PMID: 30508136
    Choy EH: Clinical significance of Janus Kinase inhibitor selectivity. Rheumatology (Oxford). 2019 Jun 1;58(6):953-962. doi: 10.1093/rheumatology/key339.

Contoh Produk & Brand

Produk: 18 • International brands: 0
Produk
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