Peringatan Keamanan

Based on findings from animal studies and its mechanism of action, quizartinib can cause embryo-fetal harm when administered to a pregnant woman.L47426

There are no available data on quizartinib use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, oral administration of quizartinib to pregnant rats during organogenesis resulted in adverse developmental outcomes including structural abnormalities and alterations to growth at maternal exposures approximately 3 times those in patients at the maximum recommended human dose (MRHD) of 53 mg/day (see Data). Advise pregnant women of the potential risk to a fetus.L47426

Carcinogenicity studies have not been conducted with quizartinib.L47426

Quizartinib was mutagenic in a bacterial reverse mutation (Ames) assay and not mutagenic in an in vivo transgenic rat mutation assay. Quizartinib was not genotoxic in vitro in mouse lymphoma thymidine kinase mutation and human lymphocyte chromosome aberration assays, or in an in vivo rat bone marrow micronucleus assay.L47426

Fertility studies in animals have not been conducted with quizartinib. However, adverse findings in male and female reproductive systems were observed in repeat dose toxicity studies in rats and monkeys. Findings in female animals (rats or monkeys) included ovarian cysts, vaginal mucosal modifications, and atrophy of the uterus, ovary, and vagina, starting at exposures (AUC) approximately 0.2 times the MRHD of 53 mg/day. In male animals (rats and monkeys), findings included testicular seminiferous tubular degeneration, failure of sperm release, germ cell depletion in the testes, and oligospermia/aspermia, starting at exposures approximately 0.4 times the MRHD. After approximately one month of recovery period, all these findings except the vaginal mucosal modifications in the female rats were reversible.L47426

Quizartinib

DB12874

small molecule approved investigational

Deskripsi

Quizartinib is an oral and potent fms-like tyrosine kinase 3 (FLT3) inhibitor and it is the first drug developed specifically targeting FLT3, as other agents with FLT3 inhibition activities were investigated with other targets in mind.A260641 Additionally, quizartinib also demonstrates inhibitory activity toward FLT3 with internal tandem duplication (ITD), although with a 10-fold lower affinity compared to wild-type FLT3.L47426 FLT3-ITD mutation is present in 75% of FLT3-mutated AML, leading to constitutively active FLT3 and thus poorer overall survival and higher risk of relapse.A260646 Multiple clinical trials have demonstrated quizartinib's efficacy in relapsed/refractory FLT3-ITD mutant AML.A260651 Therefore, quizartinib is proven to be a beneficial addition to the current AML treatment regimen, although serious side effects such as QT prolongation necessitates further research to optimize quizartinib's addition to AML standard of care.A260641

Quizartinib was approved by the FDA in July 2023 and developed under the brand name VANFLYTA by Daiichi Sankyo.L47436 The FDA approval was based on positive results from the QuANTUM-First trial for FLT3-ITD positive AML, where quizartinib combined with standard cytarabine and anthracycline induction and standard cytarabine consolidation, followed by a maintenance monotherapy resulted in a 22% reduction in the risk of death.L47436

Struktur Molekul 2D

Berat 560.67
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 (SD) effective half-lives (t1/2) in patients with newly diagnosed AML for quizartinib and AC886 during maintenance therapy are 81 hours (±73) and 136 hours (±113), respectively.[L47426]
Volume Distribusi Volume of distribution at steady state in healthy subjects was estimated to be 275 L (17%).[L47426]
Klirens (Clearance) Total body clearance of quizartinib in healthy subjects was estimated to be 2.23 L/hour (29%).[L47426]

Absorpsi

The mean (SD) absolute bioavailability of quizartinib from the tablet formulation was 71% (±7%) in healthy subjects. After oral administration under fasted conditions, time to peak concentration (median Tmax) of quizartinib and AC886 measured post dose was approximately 4 hours (range 2 to 8 hours) and 5 to 6 hours (range 4 to 120 hours), respectively, in healthy subjects. Following the administration of 35.4 mg quizartinib once daily in patients with newly diagnosed acute myeloid leukemia, the Cmax and AUC0-24h were calculated to be 140 ng/mL (71%) and 2,680 ng.h/mL (85%) respectively during the induction therapy and 204 ng/mL (64%) and 3,930 ng.h/mL (78%) respectively during the consolidation therapy.L47426 For the metabolite AC886, the Cmax and AUC0-24h were estimated to be 163 ng/mL (52%) and 3,590 ng.h/mL (51%) respectively during the induction therapy and 172 ng/mL (47%) and 3,800 ng.h/mL (46%) respectively during the consolidation therapy.L47426 Increasing the once daily dose of quizartinib to 53 mg also increases the Cmax and AUC0-24h of quizartinib to 529 ng/mL (60%) and 10,200 ng.h/mL (75%) respectively at steady state. The Cmax and AUC0-24h of the metabolite AC886 also increases to 262 ng/mL (48%) and 5,790 ng•h/mL (46%) respectively.L47426 No clinically significant differences in the pharmacokinetics of quizartinib were observed when administered with a high-fat, high-calorie meal.L47426

Metabolisme

In vitro quizartinib is primarily metabolized via oxidation by CYP3A4/5 and AC886 is formed and metabolized by CYP3A4/5.L47426

Rute Eliminasi

Following a single radiolabeled dose of quizartinib 53 mg to healthy subjects, 76.3% of the total radioactivity was recovered in feces (4% unchanged) and 1.64% in urine.L47426

Interaksi Makanan

1 Data
  • 1. Take with or without food.

Interaksi Obat

844 Data
Darbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Quizartinib.
Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Quizartinib.
Peginesatide The risk or severity of Thrombosis can be increased when Peginesatide is combined with Quizartinib.
Methoxy polyethylene glycol-epoetin beta The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Quizartinib.
Lidocaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Lidocaine.
Ropivacaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Ropivacaine.
Bupivacaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Bupivacaine.
Cinchocaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Cinchocaine.
Dyclonine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Dyclonine.
Procaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Procaine.
Prilocaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Prilocaine.
Proparacaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Proparacaine.
Meloxicam The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Meloxicam.
Oxybuprocaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Oxybuprocaine.
Cocaine The risk or severity of QTc prolongation can be increased when Cocaine is combined with Quizartinib.
Mepivacaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Mepivacaine.
Levobupivacaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Levobupivacaine.
Diphenhydramine The risk or severity of QTc prolongation can be increased when Diphenhydramine is combined with Quizartinib.
Benzocaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Benzocaine.
Chloroprocaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Chloroprocaine.
Phenol The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Phenol.
Tetrodotoxin The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Tetrodotoxin.
Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Benzyl alcohol.
Capsaicin The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Capsaicin.
Etidocaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Etidocaine.
Articaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Articaine.
Tetracaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Tetracaine.
Propoxycaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Propoxycaine.
Pramocaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Pramocaine.
Butamben The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Butamben.
Butacaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Butacaine.
Oxetacaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Oxetacaine.
Ethyl chloride The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Ethyl chloride.
Butanilicaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Butanilicaine.
Metabutethamine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Metabutethamine.
Quinisocaine The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Quinisocaine.
Ambroxol The risk or severity of methemoglobinemia can be increased when Quizartinib is combined with Ambroxol.
Nelfinavir The serum concentration of Quizartinib can be increased when it is combined with Nelfinavir.
Indinavir The serum concentration of Quizartinib can be increased when it is combined with Indinavir.
Terfenadine The serum concentration of Quizartinib can be increased when it is combined with Terfenadine.
Ritonavir The serum concentration of Quizartinib can be increased when it is combined with Ritonavir.
Voriconazole The serum concentration of Quizartinib can be increased when it is combined with Voriconazole.
Efavirenz The serum concentration of Quizartinib can be increased when it is combined with Efavirenz.
Ergotamine The serum concentration of Quizartinib can be increased when it is combined with Ergotamine.
Amprenavir The serum concentration of Quizartinib can be increased when it is combined with Amprenavir.
Delavirdine The serum concentration of Quizartinib can be increased when it is combined with Delavirdine.
Methimazole The serum concentration of Quizartinib can be increased when it is combined with Methimazole.
Conivaptan The serum concentration of Quizartinib can be increased when it is combined with Conivaptan.
Tipranavir The serum concentration of Quizartinib can be increased when it is combined with Tipranavir.
Telithromycin The serum concentration of Quizartinib can be increased when it is combined with Telithromycin.
Ketoconazole The serum concentration of Quizartinib can be increased when it is combined with Ketoconazole.
Atazanavir The serum concentration of Quizartinib can be increased when it is combined with Atazanavir.
Amiodarone The serum concentration of Quizartinib can be increased when it is combined with Amiodarone.
Econazole The serum concentration of Quizartinib can be increased when it is combined with Econazole.
Nefazodone The serum concentration of Quizartinib can be increased when it is combined with Nefazodone.
Itraconazole The serum concentration of Quizartinib can be increased when it is combined with Itraconazole.
Clarithromycin The serum concentration of Quizartinib can be increased when it is combined with Clarithromycin.
Saquinavir The serum concentration of Quizartinib can be increased when it is combined with Saquinavir.
Posaconazole The serum concentration of Quizartinib can be increased when it is combined with Posaconazole.
Darunavir The serum concentration of Quizartinib can be increased when it is combined with Darunavir.
Danazol The serum concentration of Quizartinib can be increased when it is combined with Danazol.
Lopinavir The serum concentration of Quizartinib can be increased when it is combined with Lopinavir.
Ditiocarb The serum concentration of Quizartinib can be increased when it is combined with Ditiocarb.
Nilotinib The serum concentration of Quizartinib can be increased when it is combined with Nilotinib.
Telaprevir The serum concentration of Quizartinib can be increased when it is combined with Telaprevir.
Levoketoconazole The serum concentration of Quizartinib can be increased when it is combined with Levoketoconazole.
Lonafarnib The serum concentration of Quizartinib can be increased when it is combined with Lonafarnib.
Midostaurin The serum concentration of Quizartinib can be increased when it is combined with Midostaurin.
Boceprevir The serum concentration of Quizartinib can be increased when it is combined with Boceprevir.
Cobicistat The serum concentration of Quizartinib can be increased when it is combined with Cobicistat.
Elvitegravir The serum concentration of Quizartinib can be increased when it is combined with Elvitegravir.
Stiripentol The metabolism of Quizartinib can be decreased when combined with Stiripentol.
Curcumin The serum concentration of Quizartinib can be increased when it is combined with Curcumin.
Ribociclib The serum concentration of Quizartinib can be increased when it is combined with Ribociclib.
Danoprevir The serum concentration of Quizartinib can be increased when it is combined with Danoprevir.
Troleandomycin The serum concentration of Quizartinib can be increased when it is combined with Troleandomycin.
Phenytoin The serum concentration of Quizartinib can be decreased when it is combined with Phenytoin.
Pentobarbital The serum concentration of Quizartinib can be decreased when it is combined with Pentobarbital.
Carbamazepine The serum concentration of Quizartinib can be decreased when it is combined with Carbamazepine.
Mitotane The serum concentration of Quizartinib can be decreased when it is combined with Mitotane.
Primidone The serum concentration of Quizartinib can be decreased when it is combined with Primidone.
Rimexolone The serum concentration of Quizartinib can be decreased when it is combined with Rimexolone.
Rifampin The serum concentration of Quizartinib can be decreased when it is combined with Rifampicin.
Phenobarbital The serum concentration of Quizartinib can be decreased when it is combined with Phenobarbital.
Rifapentine The serum concentration of Quizartinib can be decreased when it is combined with Rifapentine.
Dexamethasone The serum concentration of Quizartinib can be decreased when it is combined with Dexamethasone.
Fosphenytoin The serum concentration of Quizartinib can be decreased when it is combined with Fosphenytoin.
St. John's Wort The serum concentration of Quizartinib can be decreased when it is combined with St. John's Wort.
Enzalutamide The serum concentration of Quizartinib can be decreased when it is combined with Enzalutamide.
Lumacaftor The serum concentration of Quizartinib can be decreased when it is combined with Lumacaftor.
Apalutamide The serum concentration of Quizartinib can be decreased when it is combined with Apalutamide.
Leuprolide The risk or severity of QTc prolongation can be increased when Leuprolide is combined with Quizartinib.
Goserelin The risk or severity of QTc prolongation can be increased when Goserelin is combined with Quizartinib.
Octreotide The risk or severity of QTc prolongation can be increased when Octreotide is combined with Quizartinib.
Oxytocin The risk or severity of QTc prolongation can be increased when Oxytocin is combined with Quizartinib.
Esmolol The risk or severity of QTc prolongation can be increased when Esmolol is combined with Quizartinib.
Bortezomib The risk or severity of QTc prolongation can be increased when Bortezomib is combined with Quizartinib.
Betaxolol The risk or severity of QTc prolongation can be increased when Betaxolol is combined with Quizartinib.
Fluconazole The risk or severity of QTc prolongation can be increased when Fluconazole is combined with Quizartinib.
Erythromycin The serum concentration of Quizartinib can be increased when it is combined with Erythromycin.

Target Protein

Receptor-type tyrosine-protein kinase FLT3 FLT3

Referensi & Sumber

Artikel (PubMed)
  • PMID: 25145428
    Levis M: Quizartinib for the treatment of FLT3/ITD acute myeloid leukemia. Future Oncol. 2014;10(9):1571-9. doi: 10.2217/fon.14.105.
  • PMID: 32772726
    Garcia-Horton A, Yee KW: Quizartinib for the treatment of acute myeloid leukemia. Expert Opin Pharmacother. 2020 Dec;21(17):2077-2090. doi: 10.1080/14656566.2020.1801637. Epub 2020 Aug 9.
  • PMID: 31114157
    Zhou F, Ge Z, Chen B: Quizartinib (AC220): a promising option for acute myeloid leukemia. Drug Des Devel Ther. 2019 Apr 8;13:1117-1125. doi: 10.2147/DDDT.S198950. eCollection 2019.

Contoh Produk & Brand

Produk: 7 • International brands: 0
Produk
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  • Vanflyta
    Tablet, film coated • 17.7 mg/1 • Oral • US • Approved
  • Vanflyta
    Tablet, film coated • 26.5 mg • Oral • EU
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    Tablet, film coated • 26.5 mg • Oral • EU
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    Tablet, film coated • 26.5 mg • Oral • EU

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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