Peringatan Keamanan

Gilteritinib is not reported to be mutagenic in bacterial mutagenesis assays nor clastogenic in aberration test assays in Chinese hamster lung cells. However, it resulted positive for the induction of micronuclei in mouse bone marrow and for the degeneration and necrosis of germ cells and spermatid giant cell formation in testis as well as single cell necrosis of the epididymal duct epithelia.FDA label

Gilteritinib

DB12141

small molecule approved investigational

Deskripsi

Gilteritinib, also known as ASP2215, is a small molecule part of the FLT3 tyrosine kinase inhibitors that presented a greater selectivity and potency when compared with other agents from this group.A40036 It is a pyrazinecarboxamide derivative that showed high selectivity to FLT3 preventing the c-Kit -driven myelosuppression observed in other therapies.A40044 Gilteritinib was developed by Astellas Pharma and FDA approved on November 28, 2018. This drug was approved after being designed as an orphan drug with a fast track and priority review status.L4830

Struktur Molekul 2D

Berat 552.724
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The reported median half-life of gilteritinib was of approximate 45-159 hours.[L4833]
Volume Distribusi The estimated apparent central and peripheral volume of distribution is 1092 L and 1100 L respectively. This value indicated an extensive tissue distribution.[L4834]
Klirens (Clearance) The estimated clearance of gilteritinib is 14.85 L/h.[L4834]

Absorpsi

In preclinical trials, the maximal plasma concentration of gilteritinib was observed 2 hours after oral administration and followed by a maximal intratumor concentration after 4-8 hours. The maximum concentration, as well as the AUC, were modified correspondingly with the dose and were reported to be 374 ng/ml and 6943 ng.h/ml, respectively.A40048 The steady-state plasma level is reached within 15 days of dosing with an approximate 10-fold bioaccumulation.L4833 In a fasted state in humans, the tmax is reported to be of 4-6 hours. The Cmax and AUC were decreased by 26% and 10% respectively by the co-ingestion of a high-fat meal with a tmax delay of 2 hours.L4834

Metabolisme

Gilteritinib is primarily metabolized in the liver by the activity of CYP3A4. Its metabolism is driven by reactions of N-dealkylation and oxidation which forms the metabolite M17, M16 and M10. From the plasma concentration, the major form is the unchanged drug.L4835

Rute Eliminasi

From the administered dose, gilteritinib is mainly excreted in feces which represents 64.5% of the administered dose while 16.4% is recovered in urine either as the unchanged drug or as its metabolites.L4835

Interaksi Makanan

4 Data
  • 1. Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of gilteritinib.
  • 2. Avoid St. John's Wort. This herb induces CYP3A4 and p-glycoprotein, which may reduce the serum concentration of gilteritinib.
  • 3. Take at the same time every day.
  • 4. Take with or without food.

Interaksi Obat

1082 Data
Ivabradine Ivabradine may increase the QTc-prolonging activities of Gilteritinib.
Ranolazine The serum concentration of Gilteritinib can be increased when it is combined with Ranolazine.
Phenytoin The metabolism of Gilteritinib can be increased when combined with Phenytoin.
Fosphenytoin The metabolism of Gilteritinib can be increased when combined with Fosphenytoin.
Propacetamol The serum concentration of Propacetamol can be increased when it is combined with Gilteritinib.
Lumacaftor The serum concentration of Gilteritinib can be decreased when it is combined with Lumacaftor.
Anagrelide The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Anagrelide.
Disopyramide The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Disopyramide.
Clemastine The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Clemastine.
Ibutilide The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Ibutilide.
Valproic acid The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Valproic acid.
Grepafloxacin The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Grepafloxacin.
Quinine The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Quinine.
Sotalol The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Sotalol.
Erlotinib The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Erlotinib.
Toremifene The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Toremifene.
Imatinib The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Imatinib.
Trovafloxacin The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Trovafloxacin.
Mifepristone The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Mifepristone.
Cocaine The risk or severity of methemoglobinemia can be increased when Gilteritinib is combined with Cocaine.
Procainamide The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Procainamide.
Arsenic trioxide The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Arsenic trioxide.
Domperidone The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Domperidone.
Sparfloxacin The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Sparfloxacin.
Halofantrine The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Halofantrine.
Bepridil The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Bepridil.
Temafloxacin The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Temafloxacin.
Tetrabenazine The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Tetrabenazine.
Vandetanib The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Vandetanib.
Romidepsin The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Romidepsin.
Artemether The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Artemether.
Lumefantrine The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Lumefantrine.
Glasdegib The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Glasdegib.
Deutetrabenazine The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Deutetrabenazine.
Macimorelin The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Macimorelin.
Terodiline The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Terodiline.
Dofetilide The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Dofetilide.
Astemizole The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Astemizole.
Quinidine The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Quinidine.
Pimozide The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Pimozide.
Dronedarone The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Dronedarone.
Eliglustat The serum concentration of Gilteritinib can be increased when it is combined with Eliglustat.
Leuprolide The risk or severity of QTc prolongation can be increased when Leuprolide is combined with Gilteritinib.
Goserelin The risk or severity of QTc prolongation can be increased when Goserelin is combined with Gilteritinib.
Moxifloxacin The risk or severity of QTc prolongation can be increased when Moxifloxacin is combined with Gilteritinib.
Sulfisoxazole The risk or severity of QTc prolongation can be increased when Sulfisoxazole is combined with Gilteritinib.
Sulpiride The risk or severity of QTc prolongation can be increased when Sulpiride is combined with Gilteritinib.
Prochlorperazine The risk or severity of QTc prolongation can be increased when Prochlorperazine is combined with Gilteritinib.
Droperidol The risk or severity of QTc prolongation can be increased when Droperidol is combined with Gilteritinib.
Perflutren The risk or severity of QTc prolongation can be increased when Perflutren is combined with Gilteritinib.
Cinnarizine The risk or severity of QTc prolongation can be increased when Cinnarizine is combined with Gilteritinib.
Atropine The risk or severity of QTc prolongation can be increased when Atropine is combined with Gilteritinib.
Adenosine The risk or severity of QTc prolongation can be increased when Adenosine is combined with Gilteritinib.
Pentamidine The risk or severity of QTc prolongation can be increased when Pentamidine is combined with Gilteritinib.
Gadobenic acid The risk or severity of QTc prolongation can be increased when Gadobenic acid is combined with Gilteritinib.
Carbinoxamine The risk or severity of QTc prolongation can be increased when Carbinoxamine is combined with Gilteritinib.
Roxithromycin The risk or severity of QTc prolongation can be increased when Roxithromycin is combined with Gilteritinib.
Nalidixic acid The risk or severity of QTc prolongation can be increased when Nalidixic acid is combined with Gilteritinib.
Cinoxacin The risk or severity of QTc prolongation can be increased when Cinoxacin is combined with Gilteritinib.
Levosimendan The risk or severity of QTc prolongation can be increased when Levosimendan is combined with Gilteritinib.
Desloratadine The risk or severity of QTc prolongation can be increased when Desloratadine is combined with Gilteritinib.
Lomefloxacin The risk or severity of QTc prolongation can be increased when Lomefloxacin is combined with Gilteritinib.
Dimenhydrinate The risk or severity of QTc prolongation can be increased when Dimenhydrinate is combined with Gilteritinib.
Papaverine The risk or severity of QTc prolongation can be increased when Papaverine is combined with Gilteritinib.
Gemifloxacin The risk or severity of QTc prolongation can be increased when Gemifloxacin is combined with Gilteritinib.
Ofloxacin The risk or severity of QTc prolongation can be increased when Ofloxacin is combined with Gilteritinib.
Flecainide The risk or severity of QTc prolongation can be increased when Flecainide is combined with Gilteritinib.
Probucol The risk or severity of QTc prolongation can be increased when Probucol is combined with Gilteritinib.
Aceprometazine The risk or severity of QTc prolongation can be increased when Aceprometazine is combined with Gilteritinib.
Terlipressin The risk or severity of QTc prolongation can be increased when Terlipressin is combined with Gilteritinib.
Prenylamine The risk or severity of QTc prolongation can be increased when Prenylamine is combined with Gilteritinib.
Azimilide The risk or severity of QTc prolongation can be increased when Azimilide is combined with Gilteritinib.
Pracinostat The risk or severity of QTc prolongation can be increased when Pracinostat is combined with Gilteritinib.
Technetium Tc-99m ciprofloxacin The risk or severity of QTc prolongation can be increased when Technetium Tc-99m ciprofloxacin is combined with Gilteritinib.
Garenoxacin The risk or severity of QTc prolongation can be increased when Garenoxacin is combined with Gilteritinib.
Tedisamil The risk or severity of QTc prolongation can be increased when Tedisamil is combined with Gilteritinib.
Tucidinostat The risk or severity of QTc prolongation can be increased when Tucidinostat is combined with Gilteritinib.
Telavancin The risk or severity of QTc prolongation can be increased when Telavancin is combined with Gilteritinib.
Nemonoxacin The risk or severity of QTc prolongation can be increased when Nemonoxacin is combined with Gilteritinib.
Nilvadipine The risk or severity of QTc prolongation can be increased when Nilvadipine is combined with Gilteritinib.
Antazoline The risk or severity of QTc prolongation can be increased when Antazoline is combined with Gilteritinib.
Bedaquiline The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Bedaquiline.
Fendiline The risk or severity of QTc prolongation can be increased when Fendiline is combined with Gilteritinib.
Eperisone The risk or severity of QTc prolongation can be increased when Eperisone is combined with Gilteritinib.
Melperone The risk or severity of QTc prolongation can be increased when Melperone is combined with Gilteritinib.
Benidipine The risk or severity of QTc prolongation can be increased when Benidipine is combined with Gilteritinib.
Dexchlorpheniramine maleate The risk or severity of QTc prolongation can be increased when Dexchlorpheniramine maleate is combined with Gilteritinib.
Amifampridine The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Gilteritinib.
Mocetinostat The risk or severity of QTc prolongation can be increased when Mocetinostat is combined with Gilteritinib.
Entinostat The risk or severity of QTc prolongation can be increased when Entinostat is combined with Gilteritinib.
CUDC-101 The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with CUDC-101.
Simendan The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Simendan.
Ricolinostat The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Ricolinostat.
Mizolastine The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Mizolastine.
Abexinostat The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Abexinostat.
Oxatomide The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Oxatomide.
Sitafloxacin The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Sitafloxacin.
Sultopride The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Sultopride.
Otilonium The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Otilonium.
Nizofenone The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Nizofenone.

Target Protein

Receptor-type tyrosine-protein kinase FLT3 FLT3
Tyrosine-protein kinase receptor UFO AXL
ALK tyrosine kinase receptor ALK
Serotonin Receptors HTR1A

Referensi & Sumber

Artikel (PubMed)
  • PMID: 30466756
    Stone RM: What FLT3 inhibitor holds the greatest promise? Best Pract Res Clin Haematol. 2018 Dec;31(4):401-404. doi: 10.1016/j.beha.2018.09.008. Epub 2018 Sep 20.
  • PMID: 28000291
    Fathi AT, Chen YB: The role of FLT3 inhibitors in the treatment of FLT3-mutated acute myeloid leukemia. Eur J Haematol. 2017 Apr;98(4):330-336. doi: 10.1111/ejh.12841. Epub 2017 Jan 19.
  • PMID: 27775694
    Antar A, Otrock ZK, El-Cheikh J, Kharfan-Dabaja MA, Battipaglia G, Mahfouz R, Mohty M, Bazarbachi A: Inhibition of FLT3 in AML: a focus on sorafenib. Bone Marrow Transplant. 2017 Mar;52(3):344-351. doi: 10.1038/bmt.2016.251. Epub 2016 Oct 24.
  • PMID: 26279055
    Thom C: Preliminary data on ASP2215: tolerability and efficacy in acute myeloid leukemia patients. Future Oncol. 2015 Sep;11(18):2499-501. doi: 10.2217/fon.15.188. Epub 2015 Aug 17.
  • PMID: 27908881
    Lee LY, Hernandez D, Rajkhowa T, Smith SC, Raman JR, Nguyen B, Small D, Levis M: Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor. Blood. 2017 Jan 12;129(2):257-260. doi: 10.1182/blood-2016-10-745133. Epub 2016 Dec 1.
  • PMID: 28516360
    Mori M, Kaneko N, Ueno Y, Yamada M, Tanaka R, Saito R, Shimada I, Mori K, Kuromitsu S: Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia. Invest New Drugs. 2017 Oct;35(5):556-565. doi: 10.1007/s10637-017-0470-z. Epub 2017 May 17.

Contoh Produk & Brand

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