Peringatan Keamanan

Based on animal embryo-fetal toxicity studies, enasidenib can cause fetal harm when administered to a pregnant woman. There are no available data on enasidenib use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal embryo-fetal toxicity studies, oral administration of enasidenib to pregnant rats and rabbits during organogenesis was associated with embryo-fetal mortality and alterations to growth starting at 0.1 times the steady-state clinical exposure based on the AUC at the recommended human dose. Advise pregnant women of the potential risk to a fetus.L49981

Carcinogenicity studies have not been performed with enasidenib.L49981

Enasidenib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay. Enasidenib was not clastogenic in an in vitro human lymphocyte chromosomal aberration assay, or in an in vivo rat bone marrow micronucleus assay.L49981

Fertility studies in animals have not been conducted with enasidenib. In repeat-dose toxicity studies with twice daily oral administration of enasidenib in rats up to 90 days in duration, changes were reported in male and female reproductive organs including seminiferous tubular degeneration, hypospermia, atrophy of the seminal vesicle and prostate, decreased corpora lutea and increased atretic follicles in the ovaries, and atrophy in the uterus.L49981

Enasidenib

DB13874

small molecule approved investigational

Deskripsi

Enasidenib is an orally available treatment for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with specific mutations in the isocitrate dehydrogenase 2 (IDH2) gene, which is a recurrent mutation detected in 12-20% of adult patients with AML A20344, A20345. Patients eligible for this treatment are selected by testing the presence of IDH2 mutations in the blood or bone marrow. This small molecule acts as an allosteric inhibitor of mutant IDH2 enzyme to prevent cell growth, and it also has shown to block several other enzymes that play a role in abnormal cell differentiation. First developed by Agios Pharmaceuticals and licensed to Celgene, enasidenib was approved by U.S. Food and Drug Administration on August 1, 2017.

Struktur Molekul 2D

Berat 473.383
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Enasidenib has a terminal half-life of 7.9 days.[L49981]
Volume Distribusi The mean volume of distribution (Vd) of enasidenib is 55.8 L (CV% 29).[L49981]
Klirens (Clearance) Enasidenib has a mean total body clearance (CL/F) of 0.70 L/hour (CV% 62.5).[L49981]

Absorpsi

The peak plasma concentration (Cmax) is 1.4 mcg/mL coefficient of variation (CV%) 50% after a single dose of 100 mg, and 13.1 mcg/mL (CV% 45%) at steady state for 100 mg daily. The area under concentration-time curve (AUC) of enasidenib increases in an approximately dose-proportional manner from 50 mg (0.5 times approved recommended dosage) to 450 mg (4.5 times approved recommended dosage) daily dose. Steady-state plasma levels are reached within 29 days of once-daily dosing. Accumulation is approximately 10-fold when administered once daily.L49981 The absolute bioavailability after a 100 mg oral dose of enasidenib is approximately 57%. After a single oral dose, the median time to Cmax (Tmax) is 4 hours.L49981

Metabolisme

Metabolism of enasidenib is mediated by multiple cytochrome P450 (CYP) enzymes (e.g.,CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4), and by multiple UDP glucuronosyl transferases (UGTs) (e.g., UGT1A1, UGT1A3, UGT1A4, UGT1A9, UGT2B7, and UGT2B15) in vitro. Further metabolism of the metabolite AGI-16903 is also mediated by multiple enzymes (e.g., CYP1A2, CYP2C19, CYP3A4, UGT1A1, UGT1A3, and UGT1A9) in vitro. Enasidenib accounted for 89% of the radioactivity in circulation and AGI-16903, the N-dealkylated metabolite, represented 10% of the circulating radioactivity.L49981

Rute Eliminasi

Eighty-nine percent (89%) of enasidenib is eliminated in feces and 11% in the urine. Excretion of unchanged enasidenib accounts for 34% of the radiolabeled drug in the feces and 0.4% in the urine.L49981

Interaksi Makanan

5 Data
  • 1. Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of enasidenib; however, CYP3A4 is one of many enzymes involved in enasidenib metabolism.
  • 2. Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of enasidenib; however, CYP3A4 is one of many enzymes involved in enasidenib metabolism.
  • 3. Take at the same time every day.
  • 4. Take with a full glass of water.
  • 5. Take with or without food.

Interaksi Obat

1319 Data
Afatinib The serum concentration of Afatinib can be increased when it is combined with Enasidenib.
Armodafinil The metabolism of Enasidenib can be increased when combined with Armodafinil.
Modafinil The metabolism of Enasidenib can be increased when combined with Modafinil.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Enasidenib.
Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Enasidenib.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Enasidenib.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Enasidenib.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Enasidenib.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Enasidenib.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Enasidenib.
Silodosin The excretion of Silodosin can be decreased when combined with Enasidenib.
Topotecan The serum concentration of Topotecan can be increased when it is combined with Enasidenib.
Aripiprazole The metabolism of Aripiprazole can be increased when combined with Enasidenib.
Aripiprazole lauroxil The metabolism of Aripiprazole lauroxil can be increased when combined with Enasidenib.
Cilostazol The serum concentration of Cilostazol can be increased when it is combined with Enasidenib.
Deferasirox The serum concentration of Enasidenib can be increased when it is combined with Deferasirox.
Peginterferon alfa-2b The serum concentration of Enasidenib can be increased when it is combined with Peginterferon alfa-2b.
Leflunomide The serum concentration of Enasidenib can be decreased when it is combined with Leflunomide.
Teriflunomide The serum concentration of Enasidenib can be decreased when it is combined with Teriflunomide.
Dabrafenib The serum concentration of Enasidenib can be decreased when it is combined with Dabrafenib.
Eliglustat The metabolism of Eliglustat can be decreased when combined with Enasidenib.
Ibrutinib The metabolism of Ibrutinib can be decreased when combined with Enasidenib.
Everolimus The serum concentration of Everolimus can be increased when it is combined with Enasidenib.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Enasidenib.
Luliconazole The serum concentration of Enasidenib can be increased when it is combined with Luliconazole.
Colchicine The serum concentration of Colchicine can be increased when it is combined with Enasidenib.
Iloperidone The metabolism of Iloperidone can be decreased when combined with Enasidenib.
Retapamulin The metabolism of Retapamulin can be decreased when combined with Enasidenib.
Tofacitinib The metabolism of Tofacitinib can be decreased when combined with Enasidenib.
Vardenafil The metabolism of Vardenafil can be decreased when combined with Enasidenib.
Zopiclone The metabolism of Zopiclone can be decreased when combined with Enasidenib.
Irinotecan The risk or severity of neutropenia can be increased when Enasidenib is combined with Irinotecan.
Lovastatin The metabolism of Lovastatin can be decreased when combined with Enasidenib.
Metreleptin The metabolism of Enasidenib can be increased when combined with Metreleptin.
Zolmitriptan The metabolism of Zolmitriptan can be decreased when combined with Enasidenib.
Alfuzosin The metabolism of Alfuzosin can be decreased when combined with Enasidenib.
Alprazolam The metabolism of Alprazolam can be decreased when combined with Enasidenib.
Mifepristone The serum concentration of Enasidenib can be increased when it is combined with Mifepristone.
Atomoxetine The metabolism of Atomoxetine can be decreased when combined with Enasidenib.
Succinic acid The excretion of Succinic acid can be decreased when combined with Enasidenib.
Citrulline The excretion of Citrulline can be decreased when combined with Enasidenib.
Oseltamivir The excretion of Oseltamivir can be decreased when combined with Enasidenib.
Cefotiam The excretion of Cefotiam can be decreased when combined with Enasidenib.
Piperacillin The excretion of Piperacillin can be decreased when combined with Enasidenib.
Aminohippuric acid The excretion of Aminohippuric acid can be decreased when combined with Enasidenib.
Trifluridine The excretion of Trifluridine can be decreased when combined with Enasidenib.
Cefdinir The excretion of Cefdinir can be decreased when combined with Enasidenib.
Valaciclovir The excretion of Valaciclovir can be decreased when combined with Enasidenib.
Levocarnitine The excretion of Levocarnitine can be decreased when combined with Enasidenib.
Leucovorin The excretion of Leucovorin can be decreased when combined with Enasidenib.
Fluorescein The excretion of Fluorescein can be decreased when combined with Enasidenib.
Cefaclor The excretion of Cefaclor can be decreased when combined with Enasidenib.
Quinapril The excretion of Quinapril can be decreased when combined with Enasidenib.
Bumetanide The excretion of Bumetanide can be decreased when combined with Enasidenib.
Dinoprostone The excretion of Dinoprostone can be decreased when combined with Enasidenib.
Benzylpenicillin The excretion of Benzylpenicillin can be decreased when combined with Enasidenib.
Cefazolin The excretion of Cefazolin can be decreased when combined with Enasidenib.
Ceftizoxime The excretion of Ceftizoxime can be decreased when combined with Enasidenib.
Cefacetrile The excretion of Cefacetrile can be decreased when combined with Enasidenib.
Ceftibuten The excretion of Ceftibuten can be decreased when combined with Enasidenib.
Tazobactam The excretion of Tazobactam can be decreased when combined with Enasidenib.
Cyclic adenosine monophosphate The excretion of Cyclic adenosine monophosphate can be decreased when combined with Enasidenib.
Cholic Acid The excretion of Cholic Acid can be decreased when combined with Enasidenib.
Glutaric Acid The excretion of Glutaric Acid can be decreased when combined with Enasidenib.
Oxalic Acid The excretion of Oxalic Acid can be decreased when combined with Enasidenib.
Doripenem The excretion of Doripenem can be decreased when combined with Enasidenib.
Saxagliptin The excretion of Saxagliptin can be decreased when combined with Enasidenib.
Ellagic acid The excretion of Ellagic acid can be decreased when combined with Enasidenib.
Cefaloridine The excretion of Cefaloridine can be decreased when combined with Enasidenib.
Avibactam The excretion of Avibactam can be decreased when combined with Enasidenib.
Relebactam The excretion of Relebactam can be decreased when combined with Enasidenib.
Captopril The excretion of Captopril can be decreased when combined with Enasidenib.
Hydrochlorothiazide The excretion of Hydrochlorothiazide can be decreased when combined with Enasidenib.
Taurocholic acid The excretion of Taurocholic acid can be decreased when combined with Enasidenib.
Oxytetracycline The excretion of Oxytetracycline can be decreased when combined with Enasidenib.
Polythiazide The excretion of Polythiazide can be decreased when combined with Enasidenib.
Tenofovir The excretion of Tenofovir can be decreased when combined with Enasidenib.
Acamprosate The excretion of Acamprosate can be decreased when combined with Enasidenib.
Ifosfamide The metabolism of Ifosfamide can be increased when combined with Enasidenib.
Perampanel The metabolism of Perampanel can be increased when combined with Enasidenib.
Warfarin The serum concentration of Warfarin can be increased when it is combined with Enasidenib.
Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Enasidenib.
(R)-warfarin The serum concentration of (R)-warfarin can be increased when it is combined with Enasidenib.
R,S-Warfarin alcohol The serum concentration of R,S-Warfarin alcohol can be increased when it is combined with Enasidenib.
S,R-Warfarin alcohol The serum concentration of S,R-Warfarin alcohol can be increased when it is combined with Enasidenib.
(S)-Warfarin The serum concentration of (S)-Warfarin can be increased when it is combined with Enasidenib.
Midazolam The serum concentration of Midazolam can be increased when it is combined with Enasidenib.
Tacrolimus The serum concentration of Tacrolimus can be increased when it is combined with Enasidenib.
Crizotinib The metabolism of Enasidenib can be decreased when combined with Crizotinib.
Atorvastatin The metabolism of Atorvastatin can be decreased when combined with Enasidenib.
Mirabegron The serum concentration of Enasidenib can be increased when it is combined with Mirabegron.
Abiraterone The metabolism of Enasidenib can be decreased when combined with Abiraterone.
Eluxadoline The serum concentration of Eluxadoline can be increased when it is combined with Enasidenib.
Vincristine The excretion of Vincristine can be decreased when combined with Enasidenib.
Cyproterone acetate The metabolism of Enasidenib can be increased when combined with Cyproterone acetate.
Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Enasidenib.
Lumacaftor The serum concentration of Enasidenib can be decreased when it is combined with Lumacaftor.
Erlotinib The serum concentration of Erlotinib can be decreased when it is combined with Enasidenib.
Albendazole The metabolism of Enasidenib can be increased when combined with Albendazole.
Desipramine The metabolism of Enasidenib can be decreased when combined with Desipramine.

Target Protein

Isocitrate dehydrogenase [NADP] cytoplasmic IDH1
Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial IDH3A
Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial IDH3B
Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial IDH3G
Isocitrate dehydrogenase [NADP], mitochondrial IDH2

Referensi & Sumber

Artikel (PubMed)
  • PMID: 27721426
    Medeiros BC, Fathi AT, DiNardo CD, Pollyea DA, Chan SM, Swords R: Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia. 2017 Feb;31(2):272-281. doi: 10.1038/leu.2016.275. Epub 2016 Oct 10.
  • PMID: 28588020
    Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, Stone RM, DeAngelo DJ, Levine RL, Flinn IW, Kantarjian HM, Collins R, Patel MR, Frankel AE, Stein A, Sekeres MA, Swords RT, Medeiros BC, Willekens C, Vyas P, Tosolini A, Xu Q, Knight RD, Yen KE, Agresta S, de Botton S, Tallman MS: Enasidenib in mutant-IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017 Jun 6. pii: blood-2017-04-779405. doi: 10.1182/blood-2017-04-779405.
  • PMID: 28588019
    Amatangelo MD, Quek L, Shih A, Stein EM, Roshal M, David MD, Marteyn B, Rahnamay Farnoud N, de Botton S, Bernard OA, Wu B, Yen KE, Tallman MS, Papaemmanuil E, Penard-Lacronique V, Thakurta A, Vyas P, Levine RL: Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response. Blood. 2017 Jun 6. pii: blood-2017-04-779447. doi: 10.1182/blood-2017-04-779447.

Contoh Produk & Brand

Produk: 4 • International brands: 0
Produk
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Sekuens Gen/Protein (FASTA)

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