Peringatan Keamanan

There is not currently any data on carcinogenicity, effect on human fertility, or on early embryonic development. However, based on its mechanism of action, ceritinib may cause fetal harm when administered to pregnant women and should therefore be administered with effective contraception during treatment. Diarrhea, nausea, vomiting, or abdominal pain occurred in 96% of 255 patients including severe cases in 14% of patients. Drug-induced hepatotoxicity also occurred in 27% of 255 patients, presenting as alanine aminotransferase (ALT) levels greater than 5 times the upper limit of normal (ULN). Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis, hyperglycaemia, and bradycardia have also been reported.

Ceritinib

DB09063

small molecule approved

Deskripsi

Ceritinib is used for the treatment of adults with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) following failure (secondary to resistance or intolerance) of prior crizotinib therapy. About 4% of patients with NSCLC have a chromosomal rearrangement that generates a fusion gene between EML4 (echinoderm microtubule-associated protein-like 4) and ALK (anaplastic lymphoma kinase), which results in constitutive kinase activity that contributes to carcinogenesis and seems to drive the malignant phenotype. Ceritinib exerts its therapeutic effect by inhibiting autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells. Following treatment with crizotinib (a first-generation ALK inhibitor), most tumours develop drug resistance due to mutations in key "gatekeeper" residues of the enzyme. This occurrence led to development of novel second-generation ALK inhibitors such as ceritinib to overcome crizotinib resistance. The FDA approved ceritinib in April 2014 due to a surprisingly high response rate (56%) towards crizotinib-resistant tumours and has designated it with orphan drug status.

Struktur Molekul 2D

Berat 558.135
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 is 41 hours.
Volume Distribusi The apparent volume of distribution (Vd/F) is 4230 L following a single 750 mg dose.
Klirens (Clearance) The geometric mean apparent clearance (CL/F) of ceritinib was lower at steady-state (33.2 L/h) after 750 mg daily dosing than after a single 750 mg dose (88.5 L/h).

Absorpsi

After oral administration of ceritinib, peak concentrations were achieved after approximately 4 to 6 hours.

Metabolisme

In vitro studies demonstrated that CYP3A was the major enzyme involved in the metabolic clearance of ceritinib. Following oral administration of a single 750 mg radiolabeled ceritinib dose, ceritinib as the parent compound was the main circulating component (82%) in human plasma.

Rute Eliminasi

Following oral administration of a single 750 mg radiolabeled ceritinib dose, 92.3% of the administered dose was recovered in the feces (with 68% as unchanged parent compound) while 1.3% of the administered dose was recovered in the urine.

Interaksi Makanan

3 Data
  • 1. Avoid grapefruit products. Grapefruit inhibits the CYP3A metabolism of ceritinib, which may increase its serum concentration.
  • 2. Avoid St. John's Wort. This herb induces the CYP3A metabolism of ceritinib and may reduce its serum concentration.
  • 3. Take with food. Food increases the bioavailability of ceritinib. Taking ceritinib in a fasted state increases the risk of adverse gastrointestinal effects like nausea, vomiting, and abdominal pain.

Interaksi Obat

1199 Data
Modafinil The metabolism of Ceritinib can be increased when combined with Modafinil.
Armodafinil The metabolism of Ceritinib can be increased when combined with Armodafinil.
Lomitapide The metabolism of Lomitapide can be decreased when combined with Ceritinib.
Ranolazine The serum concentration of Ceritinib can be increased when it is combined with Ranolazine.
Octreotide Octreotide may increase the bradycardic activities of Ceritinib.
Esmolol Esmolol may increase the bradycardic activities of Ceritinib.
Betaxolol Betaxolol may increase the bradycardic activities of Ceritinib.
Midodrine Midodrine may increase the bradycardic activities of Ceritinib.
Pregabalin Pregabalin may increase the bradycardic activities of Ceritinib.
Metoprolol Metoprolol may increase the bradycardic activities of Ceritinib.
Isradipine Isradipine may increase the bradycardic activities of Ceritinib.
Atenolol Atenolol may increase the bradycardic activities of Ceritinib.
Diltiazem Diltiazem may increase the bradycardic activities of Ceritinib.
Trimethadione Trimethadione may increase the bradycardic activities of Ceritinib.
Timolol Timolol may increase the bradycardic activities of Ceritinib.
Amlodipine Amlodipine may increase the bradycardic activities of Ceritinib.
Digoxin Digoxin may increase the bradycardic activities of Ceritinib.
Nimodipine Nimodipine may increase the bradycardic activities of Ceritinib.
Nisoldipine Nisoldipine may increase the bradycardic activities of Ceritinib.
Bendroflumethiazide Bendroflumethiazide may increase the bradycardic activities of Ceritinib.
Sotalol Sotalol may increase the bradycardic activities of Ceritinib.
Lercanidipine Lercanidipine may increase the bradycardic activities of Ceritinib.
Lamotrigine Lamotrigine may increase the bradycardic activities of Ceritinib.
Cinnarizine Cinnarizine may increase the bradycardic activities of Ceritinib.
Propranolol Propranolol may increase the bradycardic activities of Ceritinib.
Clonidine Clonidine may increase the bradycardic activities of Ceritinib.
Ethosuximide Ethosuximide may increase the bradycardic activities of Ceritinib.
Labetalol Labetalol may increase the bradycardic activities of Ceritinib.
Bisoprolol Bisoprolol may increase the bradycardic activities of Ceritinib.
Nicardipine Nicardipine may increase the bradycardic activities of Ceritinib.
Dexmedetomidine Dexmedetomidine may increase the bradycardic activities of Ceritinib.
Magnesium sulfate Magnesium sulfate may increase the bradycardic activities of Ceritinib.
Verapamil Verapamil may increase the bradycardic activities of Ceritinib.
Galantamine Galantamine may increase the bradycardic activities of Ceritinib.
Tizanidine Tizanidine may increase the bradycardic activities of Ceritinib.
Sufentanil Sufentanil may increase the bradycardic activities of Ceritinib.
Alfentanil Alfentanil may increase the bradycardic activities of Ceritinib.
Levomenthol Levomenthol may increase the bradycardic activities of Ceritinib.
Loperamide Loperamide may increase the bradycardic activities of Ceritinib.
Donepezil Donepezil may increase the bradycardic activities of Ceritinib.
Alprenolol Alprenolol may increase the bradycardic activities of Ceritinib.
Remifentanil Remifentanil may increase the bradycardic activities of Ceritinib.
Zonisamide Zonisamide may increase the bradycardic activities of Ceritinib.
Pindolol Pindolol may increase the bradycardic activities of Ceritinib.
Methyldopa Methyldopa may increase the bradycardic activities of Ceritinib.
Rivastigmine Rivastigmine may increase the bradycardic activities of Ceritinib.
Guanfacine Guanfacine may increase the bradycardic activities of Ceritinib.
Felodipine Felodipine may increase the bradycardic activities of Ceritinib.
Nitrendipine Nitrendipine may increase the bradycardic activities of Ceritinib.
Perhexiline Perhexiline may increase the bradycardic activities of Ceritinib.
Nifedipine Nifedipine may increase the bradycardic activities of Ceritinib.
Amiodarone Amiodarone may increase the bradycardic activities of Ceritinib.
Carvedilol Carvedilol may increase the bradycardic activities of Ceritinib.
Bretylium Bretylium may increase the bradycardic activities of Ceritinib.
Propafenone Propafenone may increase the bradycardic activities of Ceritinib.
Acebutolol Acebutolol may increase the bradycardic activities of Ceritinib.
Nadolol Nadolol may increase the bradycardic activities of Ceritinib.
Bepridil Bepridil may increase the bradycardic activities of Ceritinib.
Bevantolol Bevantolol may increase the bradycardic activities of Ceritinib.
Practolol Practolol may increase the bradycardic activities of Ceritinib.
Penbutolol Penbutolol may increase the bradycardic activities of Ceritinib.
Mibefradil Mibefradil may increase the bradycardic activities of Ceritinib.
Oxprenolol Oxprenolol may increase the bradycardic activities of Ceritinib.
Nimesulide Nimesulide may increase the bradycardic activities of Ceritinib.
Prenylamine Prenylamine may increase the bradycardic activities of Ceritinib.
Cyclandelate Cyclandelate may increase the bradycardic activities of Ceritinib.
Flunarizine Flunarizine may increase the bradycardic activities of Ceritinib.
Fluspirilene Fluspirilene may increase the bradycardic activities of Ceritinib.
Celiprolol Celiprolol may increase the bradycardic activities of Ceritinib.
Dronedarone Dronedarone may increase the bradycardic activities of Ceritinib.
Nebivolol Nebivolol may increase the bradycardic activities of Ceritinib.
Lucinactant Lucinactant may increase the bradycardic activities of Ceritinib.
Clevidipine Clevidipine may increase the bradycardic activities of Ceritinib.
Methsuximide Methsuximide may increase the bradycardic activities of Ceritinib.
Seletracetam Seletracetam may increase the bradycardic activities of Ceritinib.
Nylidrin Nylidrin may increase the bradycardic activities of Ceritinib.
Lacosamide Lacosamide may increase the bradycardic activities of Ceritinib.
Calfactant Calfactant may increase the bradycardic activities of Ceritinib.
Dotarizine Dotarizine may increase the bradycardic activities of Ceritinib.
Pasireotide Pasireotide may increase the bradycardic activities of Ceritinib.
Nilvadipine Nilvadipine may increase the bradycardic activities of Ceritinib.
Bufuralol Bufuralol may increase the bradycardic activities of Ceritinib.
Beractant Beractant may increase the bradycardic activities of Ceritinib.
Lanreotide Lanreotide may increase the bradycardic activities of Ceritinib.
Tranilast Tranilast may increase the bradycardic activities of Ceritinib.
Bopindolol Bopindolol may increase the bradycardic activities of Ceritinib.
Bupranolol Bupranolol may increase the bradycardic activities of Ceritinib.
Agmatine Agmatine may increase the bradycardic activities of Ceritinib.
Crizotinib Crizotinib may increase the bradycardic activities of Ceritinib.
Fingolimod Fingolimod may increase the bradycardic activities of Ceritinib.
Tofacitinib Tofacitinib may increase the bradycardic activities of Ceritinib.
Regorafenib Regorafenib may increase the bradycardic activities of Ceritinib.
Indenolol Indenolol may increase the bradycardic activities of Ceritinib.
Fendiline Fendiline may increase the bradycardic activities of Ceritinib.
Eperisone Eperisone may increase the bradycardic activities of Ceritinib.
Ivabradine Ivabradine may increase the bradycardic activities of Ceritinib.
Trimebutine Trimebutine may increase the bradycardic activities of Ceritinib.
Pinaverium Pinaverium may increase the bradycardic activities of Ceritinib.
Poractant alfa Poractant alfa may increase the bradycardic activities of Ceritinib.
Arotinolol Arotinolol may increase the bradycardic activities of Ceritinib.

Target Protein

ALK tyrosine kinase receptor ALK

Referensi & Sumber

Synthesis reference: Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y, Liu B, Tuntland T, Cui X, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY: Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulf onyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013 Jul 25;56(14):5675-90. doi: 10.1021/jm400402q. Epub 2013 Jun 26. Pubmed(http://www.ncbi.nlm.nih.gov/pubmed/23742252)
Artikel (PubMed)
  • PMID: 24670165
    Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA: Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. doi: 10.1056/NEJMoa1311107.
  • PMID: 26020125
    Nishio M, Murakami H, Horiike A, Takahashi T, Hirai F, Suenaga N, Tajima T, Tokushige K, Ishii M, Boral A, Robson M, Seto T: Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors. J Thorac Oncol. 2015 Jul;10(7):1058-66. doi: 10.1097/JTO.0000000000000566.
  • PMID: 17185414
    Galkin AV, Melnick JS, Kim S, Hood TL, Li N, Li L, Xia G, Steensma R, Chopiuk G, Jiang J, Wan Y, Ding P, Liu Y, Sun F, Schultz PG, Gray NS, Warmuth M: Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5. Epub 2006 Dec 21.
  • PMID: 23742252
    Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y, Liu B, Tuntland T, Cui X, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY: Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulf onyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013 Jul 25;56(14):5675-90. doi: 10.1021/jm400402q. Epub 2013 Jun 26.
  • PMID: 25971657
    Mano H: The EML4-ALK oncogene: targeting an essential growth driver in human cancer. Proc Jpn Acad Ser B Phys Biol Sci. 2015;91(5):193-201. doi: 10.2183/pjab.91.193.

Contoh Produk & Brand

Produk: 9 • International brands: 1
Produk
  • Zykadia
    Capsule • 150 mg/1 • Oral • US • Approved
  • Zykadia
    Tablet, film coated • 150 mg/1 • Oral • US • Approved
  • Zykadia
    Capsule • 150 mg • Oral • Canada • Approved
  • Zykadia
    Capsule • 150 mg • Oral • EU • Approved
  • Zykadia
    Capsule • 150 mg • Oral • EU • Approved
  • Zykadia
    Capsule • 150 mg • Oral • EU • Approved
  • Zykadia
    Tablet, film coated • 150 mg • Oral • EU • Approved
  • Zykadia
    Capsule • 150 mg • Oral • EU • Approved
Menampilkan 8 dari 9 produk.
International Brands
  • Zykadia

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
© 2025 Digital Pharmacy Research - Universitas Esa Unggul