Peringatan Keamanan

There is no known antidote for lusutrombopag: hemodialysis is not expected to enhance the elimination of lusutrombopag from the plasma as there is high protein binding. Overdose may be characterized by excessive platelet counts that may result in thrombotic and thromboembolic complications. In the event of overdose, closely monitor patients and platelet count and treat thrombotic complications in accordance with standard of care FDA Label.

In animal and in vitro studies, lusutrombopag did not display any carcinogenicity, genotoxicity, or reproductive toxicity FDA Label.

Lusutrombopag

DB13125

small molecule approved investigational

Deskripsi

Lusutrombopag is an orally bioavailable thrombopoietin receptor (TPOR) agonist developed by Shionogi & Company (Osaka, Japan). TPOR is a regulatory target site for endogenous thrombopoietin, which acts as a primary cytokine to promote megakaryocyte proliferation and differentiation, and affect other hematopoietic lineages as well, including erythroid, granulocytic and lymphoid lineages A36736. Thrombocytopenia, which indicates abnormally low levels of platelets, is a common complication related to chronic liver disease. This hematological abnormality, especially in cases of severe thrombocytopenia (platelet count <50,000/?L), creates challenges to patients requiring invasive medical procedures where there is a significant risk for spontaneous bleeding A36732. Lusutrombopag binds to the transmembrane domain of TPOR expressed on megakaryocytes, and causes the proliferation and differentiation of megakaryocytic progenitor cells from hematopoietic stem cells FDA Label.

In September 2015, lusutrombopag received its first global approval in Japan to reduce the need for platelet transfusion in adults with chronic liver disease and thrombocytopenia who are schedule to undergo an invasive medical procedure A36730. Lusutrombopag was approved by the FDA on July 31st, 2018 for the same therapeutic indication under the market name Mulpleta. In two randomized, double-blind, placebo-controlled trials, patients with chronic liver disease and severe thrombocytopenia who were undergoing an invasive procedure with a platelet count less than 50 x 10^9/L were administered lusutrombopag orally L4166. Higher percentages (65-78%) of the patients receiving lusutrombopag required no platelet transfusion prior to the primary invasive procedure compared to those receiving placebo L4166. Lusutrombopag is currently in phase III development in various European countries including Austria, Belgium, Germany, and the UK A36730.

Struktur Molekul 2D

Berat 591.54
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) In healthy adult subjects, the terminal elimination half?life (t1/2) was approximately 27 hours [FDA Label].
Volume Distribusi The mean (%CV) lusutrombopag apparent volume of distribution in healthy adult subjects was 39.5 (23.5) L [FDA Label].
Klirens (Clearance) The approximate mean (%CV) clearance of lusutrombopag in patients with chronic liver disease is estimated to be 1.1 (36.1) L/hr [FDA Label].

Absorpsi

Lusutrombopag is rapidly absorbed following oral administration A36730. It exhibited a dose?proportional pharmacokinetic profile over the single dose range of 1 mg to 50 mg, which was similar in both healthy subjects and those with chronic liver disease. A geometric mean (%CV) maximal concentration (Cmax) and area under the curve (AUC) in healthy subjects receiving 3 mg of lusutrombopag were 111 (20.4) ng/mL and 2931 (23.4) ng.hr/mL FDA Label. The accumulation ratios of Cmax and AUC were approximately 2 with once?daily multiple?dose administration, and steady?state plasma lusutrombopag concentrations were achieved after Day 5. The time to reach peak plasma concentrations (Tmax) were approximately 6 to 8 hours after oral administration in patients with chronic liver disease FDA Label. Food consumption is not reported to affect the absorption and bioavailability of lusutrombopag FDA Label.

Metabolisme

CYP4 enzymes predominantly contribute to the metabolism of lusutrombopag, especially CYP4A11 FDA Label. Lusutrombopag is reported to mainly undergo ?- and ?-oxidation, as well as glucuronidation A36730.

Rute Eliminasi

About 1% of the administered dose of lusutrombopag undergoes urinary excretion. Fecal excretion accounted for 83% of the total dose, where 16% of the dose was excreted as unchanged parent compound A36730.

Interaksi Makanan

1 Data
  • 1. Take with or without food.

Interaksi Obat

291 Data
Ranolazine The serum concentration of Lusutrombopag can be increased when it is combined with Ranolazine.
Lumacaftor The serum concentration of Lusutrombopag can be decreased when it is combined with Lumacaftor.
Vemurafenib The serum concentration of Lusutrombopag can be increased when it is combined with Vemurafenib.
Apalutamide The serum concentration of Lusutrombopag can be decreased when it is combined with Apalutamide.
Pitolisant The serum concentration of Lusutrombopag can be increased when it is combined with Pitolisant.
Isavuconazole The serum concentration of Lusutrombopag can be increased when it is combined with Isavuconazole.
Isavuconazonium The serum concentration of Lusutrombopag can be increased when it is combined with Isavuconazonium.
Sulfasalazine Sulfasalazine may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Novobiocin Novobiocin may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Hesperetin Hesperetin may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Rabeprazole Rabeprazole may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Topiroxostat Topiroxostat may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Daidzin Daidzin may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Fusidic acid Fusidic acid may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Naringenin Naringenin may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Vandetanib Vandetanib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Eltrombopag Eltrombopag may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Safinamide Safinamide may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Teriflunomide Teriflunomide may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Cannabidiol Cannabidiol may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Palbociclib Palbociclib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Dacomitinib Dacomitinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Glasdegib Glasdegib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Fostamatinib Fostamatinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Gilteritinib Gilteritinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Brigatinib Brigatinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Nabiximols Nabiximols may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Fedratinib Fedratinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Istradefylline Istradefylline may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Caffeine Caffeine may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Pantoprazole Pantoprazole may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Nelfinavir Nelfinavir may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Diethylstilbestrol Diethylstilbestrol may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Gefitinib Gefitinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Beclomethasone dipropionate Beclomethasone dipropionate may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Progesterone Progesterone may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Lansoprazole Lansoprazole may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Imatinib Imatinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Estradiol Estradiol may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Buprenorphine Buprenorphine may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Telmisartan Telmisartan may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Dexamethasone Dexamethasone may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Sunitinib Sunitinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Genistein Genistein may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Quercetin Quercetin may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Vismodegib Vismodegib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Rilpivirine Rilpivirine may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Afatinib Afatinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Alectinib Alectinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Abemaciclib Abemaciclib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Estradiol acetate Estradiol acetate may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Estradiol benzoate Estradiol benzoate may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Estradiol cypionate Estradiol cypionate may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Estradiol dienanthate Estradiol dienanthate may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Estradiol valerate Estradiol valerate may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Cyclosporine Cyclosporine may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Pravastatin Pravastatin may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Erlotinib Erlotinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Dasatinib Dasatinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Taurocholic acid Taurocholic acid may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Dovitinib Dovitinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Dabrafenib Dabrafenib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Dasabuvir Dasabuvir may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Paritaprevir Paritaprevir may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Ripretinib Ripretinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Fostemsavir Fostemsavir may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Pralsetinib Pralsetinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Clofazimine Clofazimine may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Dexamethasone acetate Dexamethasone acetate may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Avanafil Avanafil may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Tivozanib Tivozanib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Belumosudil Belumosudil may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Fluconazole The serum concentration of Lusutrombopag can be increased when it is combined with Fluconazole.
Erythromycin The serum concentration of Lusutrombopag can be increased when it is combined with Erythromycin.
Sildenafil The serum concentration of Lusutrombopag can be increased when it is combined with Sildenafil.
Reserpine The serum concentration of Lusutrombopag can be increased when it is combined with Reserpine.
Sorafenib The serum concentration of Lusutrombopag can be increased when it is combined with Sorafenib.
Loxapine The serum concentration of Lusutrombopag can be increased when it is combined with Loxapine.
Quinine The serum concentration of Lusutrombopag can be increased when it is combined with Quinine.
Ritonavir Ritonavir may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Toremifene The serum concentration of Lusutrombopag can be increased when it is combined with Toremifene.
Simvastatin The serum concentration of Lusutrombopag can be increased when it is combined with Simvastatin.
Verapamil The serum concentration of Lusutrombopag can be increased when it is combined with Verapamil.
Tamoxifen The serum concentration of Lusutrombopag can be increased when it is combined with Tamoxifen.
Mifepristone The serum concentration of Lusutrombopag can be increased when it is combined with Mifepristone.
Vardenafil The serum concentration of Lusutrombopag can be increased when it is combined with Vardenafil.
Conivaptan The serum concentration of Lusutrombopag can be increased when it is combined with Conivaptan.
Zonisamide The serum concentration of Lusutrombopag can be increased when it is combined with Zonisamide.
Tipranavir The serum concentration of Lusutrombopag can be increased when it is combined with Tipranavir.
Ketoconazole The serum concentration of Lusutrombopag can be increased when it is combined with Ketoconazole.
Amiodarone The serum concentration of Lusutrombopag can be increased when it is combined with Amiodarone.
Carvedilol The serum concentration of Lusutrombopag can be increased when it is combined with Carvedilol.
Itraconazole Itraconazole may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Propafenone The serum concentration of Lusutrombopag can be increased when it is combined with Propafenone.
Clarithromycin The serum concentration of Lusutrombopag can be increased when it is combined with Clarithromycin.
Saquinavir Saquinavir may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Lapatinib The serum concentration of Lusutrombopag can be increased when it is combined with Lapatinib.
Paliperidone The serum concentration of Lusutrombopag can be increased when it is combined with Paliperidone.
Mibefradil The serum concentration of Lusutrombopag can be increased when it is combined with Mibefradil.
Lopinavir The serum concentration of Lusutrombopag can be increased when it is combined with Lopinavir.

Target Protein

Thrombopoietin receptor MPL

Referensi & Sumber

Artikel (PubMed)
  • PMID: 29274361
    Yoshida H, Yamada H, Nogami W, Dohi K, Kurino-Yamada T, Sugiyama K, Takahashi K, Gahara Y, Kitaura M, Hasegawa M, Oshima I, Kuwabara K: Development of a new knock-in mouse model and evaluation of pharmacological activities of lusutrombopag, a novel, nonpeptidyl small-molecule agonist of the human thrombopoietin receptor c-Mpl. Exp Hematol. 2018 Mar;59:30-39.e2. doi: 10.1016/j.exphem.2017.12.005. Epub 2017 Dec 20.
  • PMID: 26666417
    Kim ES: Lusutrombopag: First Global Approval. Drugs. 2016 Jan;76(1):155-8. doi: 10.1007/s40265-015-0525-4.
  • PMID: 28324272
    Sakamaki A, Watanabe T, Abe S, Kamimura K, Tsuchiya A, Takamura M, Kawai H, Yamagiwa S, Terai S: Lusutrombopag increases hematocytes in a compensated liver cirrhosis patient. Clin J Gastroenterol. 2017 Jun;10(3):261-264. doi: 10.1007/s12328-017-0735-2. Epub 2017 Mar 21.
  • PMID: 28943563
    Sato S, Miyake T, Kataoka M, Isoda K, Yazaki T, Tobita H, Ishimura N, Kinoshita Y: Efficacy of Repeated Lusutrombopag Administration for Thrombocytopenia in a Patient Scheduled for Invasive Hepatocellular Carcinoma Treatment. Intern Med. 2017 Nov 1;56(21):2887-2890. doi: 10.2169/internalmedicine.8791-16. Epub 2017 Sep 25.
  • PMID: 16480521
    Ninos JM, Jefferies LC, Cogle CR, Kerr WG: The thrombopoietin receptor, c-Mpl, is a selective surface marker for human hematopoietic stem cells. J Transl Med. 2006 Feb 16;4:9. doi: 10.1186/1479-5876-4-9.
  • PMID: 23821332
    Kuter DJ: The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013 Jul;98(1):10-23. doi: 10.1007/s12185-013-1382-0. Epub 2013 Jul 3.
  • PMID: 16322779
    Patel SR, Hartwig JH, Italiano JE Jr: The biogenesis of platelets from megakaryocyte proplatelets. J Clin Invest. 2005 Dec;115(12):3348-54. doi: 10.1172/JCI26891.

Contoh Produk & Brand

Produk: 1 • International brands: 0
Produk
  • Mulpleta
    Tablet, film coated • 3 mg/1 • Oral • US • Approved

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