Peringatan Keamanan

There is limited information regarding the LD50 or overdose of ivosidenib.

Ivosidenib is associated with a risk of differentiation syndrome, Guillain-Barre syndrome, and embryo-fetal toxicity.A248750,L41870

Ivosidenib

DB14568

small molecule approved investigational

Deskripsi

Ivosidenib is a first-in-class isocitrate dehydrogenase-1 (IDH1) inhibitor. IDH1 is an enzyme that is often mutated and overexpressed in some cancers, leading to aberrant cell growth and proliferation.A248750 Ivosidenib inhibits mutated IDH1, blocking the enzymatic activity and further differentiation of cancer cells.A248745

Ivosidenib was granted accelerated approval by the FDA in July 2018 for the treatment of relapsed of refractory acute myeloid leukemia in adults.A248745 It is currently approved to also treat newly diagnosed acute myeloid leukemia in older adults in combination azacitidine or as monotherapy, as well as locally advanced or metastatic cholangiocarcinoma and relapsed or refractory myelodysplastic syndromes in adults. The drug is only effective in patients with a susceptible IDH1 mutation.L48781

In February 2023, the EMA's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion of ivosidenib and recommended it be granted marketing authorization for the treatment of acute myeloid leukemia and cholangiocarcinoma.L46287 It was fully approved by the EMA in May 2023.L46596

Struktur Molekul 2D

Berat 582.97
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal half-life at steady state is 58 hours in patients with relapsed or refractory AML, 98 hours in patients with newly diagnosed AML who were also treated with azacitidine, and 129 hours in patients with cholangiocarcinoma.[L41870]
Volume Distribusi The apparent volume of distribution at steady state is 403 L in patients with relapsed or refractory AML, 504 L in patients with newly diagnosed AML who were also treated with azacitidine, and 706 L in patients with cholangiocarcinoma.[L41870]
Klirens (Clearance) The apparent clearance at steady state is 5.6 L/h in patients with relapsed or refractory AML, 4.6 L/h in patients with newly diagnosed AML who were also treated with azacitidine, and 6.1 L/h in patients with cholangiocarcinoma.[L41870]

Absorpsi

Following oral administration, ivosidenib is rapidly absorbed.A248755 The Cmax following a single oral dose is 4503 ng/mL in patients with relapsed or refractory AML, 4820 ng/mL in patients with newly diagnosed AML who were also treated with azacitidine, and 4060 ng/mL in patients with cholangiocarcinoma. The steady-state was reached within 14 days. The steady-state Cmax is 6551 ng/mL in patients with relapsed or refractory AML, 6145 ng/mL in patients with newly diagnosed AML who were also treated with azacitidine, and 4799 ng/mL in patients with cholangiocarcinoma. The Tmax ranges from two to three hours.L41870 A high-fat meal increases ivosidenib exposure.L41870

Metabolisme

Ivosidenib is predominantly metabolized by CYP3A4 via oxidation. The exact chemical structures of the metabolites formed from CYP3A4-mediated oxidation have not been fully characterized. Ivosidenib can also undergo N-dealkylation and hydrolysis as minor metabolic pathways.A248755,A248760,L41870

Rute Eliminasi

Following oral administration of ivosidenib, about 77% of the dose was eliminated in feces, where 67% was in the form of unchanged parent drug. About 17% of the dose was excreted in urine, where 10% was in the form of unchanged ivosidenib.L41870

Interaksi Makanan

5 Data
  • 1. Do not take with or immediately after a high-fat meal. Administration of ivosidenib with a high-fat meal increases the Cmax and AUC of ivosidenib by 98 and 25%, respectively.
  • 2. Exercise caution with grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of ivosidenib. Dose adjustment may be necessary if co-administered.
  • 3. Exercise caution with St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of ivosidenib.
  • 4. Take at the same time every day.
  • 5. Take with or without food.

Interaksi Obat

1235 Data
Ivabradine The risk or severity of QTc prolongation can be increased when Ivabradine is combined with Ivosidenib.
Modafinil The metabolism of Modafinil can be increased when combined with Ivosidenib.
Armodafinil The metabolism of Ivosidenib can be increased when combined with Armodafinil.
Bosutinib The metabolism of Bosutinib can be increased when combined with Ivosidenib.
Brentuximab vedotin The metabolism of Brentuximab vedotin can be increased when combined with Ivosidenib.
Colchicine The metabolism of Colchicine can be increased when combined with Ivosidenib.
Naloxegol The metabolism of Naloxegol can be increased when combined with Ivosidenib.
Pazopanib The metabolism of Pazopanib can be increased when combined with Ivosidenib.
Prucalopride The metabolism of Prucalopride can be increased when combined with Ivosidenib.
Silodosin The metabolism of Silodosin can be increased when combined with Ivosidenib.
Aripiprazole The metabolism of Aripiprazole can be increased when combined with Ivosidenib.
Aripiprazole lauroxil The metabolism of Aripiprazole lauroxil can be increased when combined with Ivosidenib.
Everolimus The metabolism of Everolimus can be increased when combined with Ivosidenib.
Metreleptin The metabolism of Ivosidenib can be increased when combined with Metreleptin.
Saxagliptin The metabolism of Saxagliptin can be increased when combined with Ivosidenib.
Conjugated estrogens The metabolism of Conjugated estrogens can be increased when combined with Ivosidenib.
Indomethacin The metabolism of Indomethacin can be increased when combined with Ivosidenib.
Zidovudine The metabolism of Zidovudine can be increased when combined with Ivosidenib.
Estradiol The metabolism of Estradiol can be increased when combined with Ivosidenib.
Ifosfamide The metabolism of Ifosfamide can be increased when combined with Ivosidenib.
Perampanel The metabolism of Perampanel can be increased when combined with Ivosidenib.
Warfarin The metabolism of Warfarin can be increased when combined with Ivosidenib.
Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Ivosidenib.
(R)-warfarin The metabolism of (R)-warfarin can be increased when combined with Ivosidenib.
R,S-Warfarin alcohol The metabolism of R,S-Warfarin alcohol can be increased when combined with Ivosidenib.
S,R-Warfarin alcohol The metabolism of S,R-Warfarin alcohol can be increased when combined with Ivosidenib.
(S)-Warfarin The metabolism of (S)-Warfarin can be increased when combined with Ivosidenib.
Crizotinib The metabolism of Ivosidenib can be decreased when combined with Crizotinib.
Vincristine The metabolism of Vincristine can be increased when combined with Ivosidenib.
Doxorubicin The metabolism of Doxorubicin can be increased when combined with Ivosidenib.
Lumacaftor The metabolism of Ivosidenib can be increased when combined with Lumacaftor.
Erlotinib The risk or severity of QTc prolongation can be increased when Erlotinib is combined with Ivosidenib.
Anagrelide The risk or severity of QTc prolongation can be increased when Anagrelide is combined with Ivosidenib.
Disopyramide The risk or severity of QTc prolongation can be increased when Disopyramide is combined with Ivosidenib.
Clemastine The risk or severity of QTc prolongation can be increased when Clemastine is combined with Ivosidenib.
Ibutilide The risk or severity of QTc prolongation can be increased when Ibutilide is combined with Ivosidenib.
Grepafloxacin The risk or severity of QTc prolongation can be increased when Grepafloxacin is combined with Ivosidenib.
Sotalol The risk or severity of QTc prolongation can be increased when Sotalol is combined with Ivosidenib.
Toremifene The risk or severity of QTc prolongation can be increased when Toremifene is combined with Ivosidenib.
Thioridazine The risk or severity of QTc prolongation can be increased when Thioridazine is combined with Ivosidenib.
Trovafloxacin The risk or severity of QTc prolongation can be increased when Trovafloxacin is combined with Ivosidenib.
Cocaine The risk or severity of QTc prolongation can be increased when Cocaine is combined with Ivosidenib.
Procainamide The risk or severity of QTc prolongation can be increased when Procainamide is combined with Ivosidenib.
Arsenic trioxide The risk or severity of QTc prolongation can be increased when Arsenic trioxide is combined with Ivosidenib.
Escitalopram The risk or severity of QTc prolongation can be increased when Escitalopram is combined with Ivosidenib.
Domperidone The risk or severity of QTc prolongation can be increased when Domperidone is combined with Ivosidenib.
Sparfloxacin The risk or severity of QTc prolongation can be increased when Sparfloxacin is combined with Ivosidenib.
Halofantrine The risk or severity of QTc prolongation can be increased when Halofantrine is combined with Ivosidenib.
Bepridil The risk or severity of QTc prolongation can be increased when Bepridil is combined with Ivosidenib.
Paliperidone The risk or severity of QTc prolongation can be increased when Paliperidone is combined with Ivosidenib.
Lithium cation The risk or severity of QTc prolongation can be increased when Lithium cation is combined with Ivosidenib.
Temafloxacin The risk or severity of QTc prolongation can be increased when Temafloxacin is combined with Ivosidenib.
Zuclopenthixol The risk or severity of QTc prolongation can be increased when Zuclopenthixol is combined with Ivosidenib.
Tetrabenazine The risk or severity of QTc prolongation can be increased when Tetrabenazine is combined with Ivosidenib.
Iloperidone The risk or severity of QTc prolongation can be increased when Iloperidone is combined with Ivosidenib.
Asenapine The risk or severity of QTc prolongation can be increased when Asenapine is combined with Ivosidenib.
Artemether The risk or severity of QTc prolongation can be increased when Artemether is combined with Ivosidenib.
Glasdegib The risk or severity of QTc prolongation can be increased when Glasdegib is combined with Ivosidenib.
Deutetrabenazine The risk or severity of QTc prolongation can be increased when Deutetrabenazine is combined with Ivosidenib.
Macimorelin The risk or severity of QTc prolongation can be increased when Macimorelin is combined with Ivosidenib.
Terodiline The risk or severity of QTc prolongation can be increased when Terodiline is combined with Ivosidenib.
Eliglustat The risk or severity of QTc prolongation can be increased when Eliglustat is combined with Ivosidenib.
Cisapride The risk or severity of QTc prolongation can be increased when Cisapride is combined with Ivosidenib.
Lumefantrine The risk or severity of QTc prolongation can be increased when Lumefantrine is combined with Ivosidenib.
Leuprolide The risk or severity of QTc prolongation can be increased when Leuprolide is combined with Ivosidenib.
Goserelin The risk or severity of QTc prolongation can be increased when Goserelin is combined with Ivosidenib.
Moxifloxacin The risk or severity of QTc prolongation can be increased when Moxifloxacin is combined with Ivosidenib.
Sulfisoxazole The risk or severity of QTc prolongation can be increased when Sulfisoxazole is combined with Ivosidenib.
Sulpiride The risk or severity of QTc prolongation can be increased when Sulpiride is combined with Ivosidenib.
Promazine The metabolism of Promazine can be increased when combined with Ivosidenib.
Droperidol The risk or severity of QTc prolongation can be increased when Droperidol is combined with Ivosidenib.
Oxaliplatin The risk or severity of QTc prolongation can be increased when Oxaliplatin is combined with Ivosidenib.
Fluorouracil The risk or severity of QTc prolongation can be increased when Fluorouracil is combined with Ivosidenib.
Perflutren The risk or severity of QTc prolongation can be increased when Perflutren is combined with Ivosidenib.
Cinnarizine The metabolism of Cinnarizine can be increased when combined with Ivosidenib.
Atropine The risk or severity of QTc prolongation can be increased when Atropine is combined with Ivosidenib.
Adenosine The risk or severity of QTc prolongation can be increased when Adenosine is combined with Ivosidenib.
Pentamidine The risk or severity of QTc prolongation can be increased when Pentamidine is combined with Ivosidenib.
Gadobenic acid The risk or severity of QTc prolongation can be increased when Gadobenic acid is combined with Ivosidenib.
Carbinoxamine The risk or severity of QTc prolongation can be increased when Carbinoxamine is combined with Ivosidenib.
Dolasetron The metabolism of Dolasetron can be increased when combined with Ivosidenib.
Nalidixic acid The risk or severity of QTc prolongation can be increased when Nalidixic acid is combined with Ivosidenib.
Cinoxacin The risk or severity of QTc prolongation can be increased when Cinoxacin is combined with Ivosidenib.
Granisetron The metabolism of Granisetron can be increased when combined with Ivosidenib.
Levosimendan The risk or severity of QTc prolongation can be increased when Levosimendan is combined with Ivosidenib.
Mesoridazine The risk or severity of QTc prolongation can be increased when Mesoridazine is combined with Ivosidenib.
Desloratadine The risk or severity of QTc prolongation can be increased when Desloratadine is combined with Ivosidenib.
Lomefloxacin The risk or severity of QTc prolongation can be increased when Lomefloxacin is combined with Ivosidenib.
Dimenhydrinate The risk or severity of QTc prolongation can be increased when Dimenhydrinate is combined with Ivosidenib.
Papaverine The risk or severity of QTc prolongation can be increased when Papaverine is combined with Ivosidenib.
Chlorpheniramine The metabolism of Chlorpheniramine can be increased when combined with Ivosidenib.
Gemifloxacin The risk or severity of QTc prolongation can be increased when Gemifloxacin is combined with Ivosidenib.
Ofloxacin The risk or severity of QTc prolongation can be increased when Ofloxacin is combined with Ivosidenib.
Flecainide The risk or severity of QTc prolongation can be increased when Flecainide is combined with Ivosidenib.
Probucol The risk or severity of QTc prolongation can be increased when Probucol is combined with Ivosidenib.
Aceprometazine The risk or severity of QTc prolongation can be increased when Aceprometazine is combined with Ivosidenib.
Terlipressin The risk or severity of QTc prolongation can be increased when Terlipressin is combined with Ivosidenib.
Prenylamine The metabolism of Prenylamine can be increased when combined with Ivosidenib.
Fluspirilene The metabolism of Fluspirilene can be increased when combined with Ivosidenib.
Lofexidine The risk or severity of QTc prolongation can be increased when Lofexidine is combined with Ivosidenib.

Target Protein

Isocitrate dehydrogenase [NADP] cytoplasmic IDH1

Referensi & Sumber

Artikel (PubMed)
  • PMID: 27621679
    Mondesir J, Willekens C, Touat M, de Botton S: IDH1 and IDH2 mutations as novel therapeutic targets: current perspectives. J Blood Med. 2016 Sep 2;7:171-80. doi: 10.2147/JBM.S70716. eCollection 2016.
  • PMID: 26700815
    Flavahan WA, Drier Y, Liau BB, Gillespie SM, Venteicher AS, Stemmer-Rachamimov AO, Suva ML, Bernstein BE: Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature. 2016 Jan 7;529(7584):110-4. doi: 10.1038/nature16490. Epub 2015 Dec 23.
  • PMID: 21130701
    Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF, Tallman MS, Sun Z, Wolniak K, Peeters JK, Liu W, Choe SE, Fantin VR, Paietta E, Lowenberg B, Licht JD, Godley LA, Delwel R, Valk PJ, Thompson CB, Levine RL, Melnick A: Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010 Dec 14;18(6):553-67. doi: 10.1016/j.ccr.2010.11.015. Epub 2010 Dec 9.
  • PMID: 29670690
    Popovici-Muller J, Lemieux RM, Artin E, Saunders JO, Salituro FG, Travins J, Cianchetta G, Cai Z, Zhou D, Cui D, Chen P, Straley K, Tobin E, Wang F, David MD, Penard-Lacronique V, Quivoron C, Saada V, de Botton S, Gross S, Dang L, Yang H, Utley L, Chen Y, Kim H, Jin S, Gu Z, Yao G, Luo Z, Lv X, Fang C, Yan L, Olaharski A, Silverman L, Biller S, Su SM, Yen K: Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers. ACS Med Chem Lett. 2018 Jan 19;9(4):300-305. doi: 10.1021/acsmedchemlett.7b00421. eCollection 2018 Apr 12.
  • PMID: 33457062
    Merchant SL, Culos K, Wyatt H: Ivosidenib: IDH1 Inhibitor for the Treatment of Acute Myeloid Leukemia. J Adv Pract Oncol. 2019 Jul;10(5):494-500. doi: 10.6004/jadpro.2019.10.5.7. Epub 2019 Jul 1.
  • PMID: 31644134
    Authors unspecified: Ivosidenib .
  • PMID: 30209701
    Dhillon S: Ivosidenib: First Global Approval. Drugs. 2018 Sep;78(14):1509-1516. doi: 10.1007/s40265-018-0978-3.
  • PMID: 30758648
    Prakash C, Fan B, Altaf S, Agresta S, Liu H, Yang H: Pharmacokinetics, absorption, metabolism, and excretion of (14)Civosidenib (AG-120) in healthy male subjects. Cancer Chemother Pharmacol. 2019 May;83(5):837-848. doi: 10.1007/s00280-019-03793-7. Epub 2019 Feb 13.

Contoh Produk & Brand

Produk: 4 • International brands: 0
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