Ceritinib
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| Clinical data | |
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| Pronunciation | /səˈrɪtɪnɪb/ sə-RIT-i-nib |
| Trade names | Zykadia |
| AHFS/Drugs.com | Multum Consumer Information |
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| Routes of administration | By mouth (capsules) |
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| Pharmacokinetic data | |
| Bioavailability | Not determined |
| Protein binding | 97% |
| Metabolism | CYP3A |
| Biological half-life | 41 hours |
| Excretion | Feces (92.3%), urine (1.3%)[1] |
| Identifiers | |
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| Synonyms | LDK378 |
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| Formula | C28H36ClN5O3S |
| Molar mass | 558.14 g/mol |
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Ceritinib (INN,[2] trade name Zykadia /zaɪˈkeɪdiːə/ zy-KAY-dee-ə) is a drug for the treatment of a specific type of lung cancer.[3] It is an anaplastic lymphoma kinase (ALK) inhibitor.[4] It was developed by Novartis. It was approved in April 2014 by the Food and Drug Administration for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC) in patients that failed treatment with crizotinib.[3] It is a more effective, but more toxic, alternative to traditional platinum-based chemotherapies.[5]
Mechanism
Ceritinib was found at physiological concentrations to inhibit ALK, insulin-like growth factor 1 receptor (IGF-1R), and ROS1.
Adverse effects
Serious adverse effects include gastrointestinal toxicity, hepatotoxicity, interstitial lung disease, prolonged QT syndrome, hyperglycemia, bradycardia, and pancreatitis. The most commonly reported side effects were diarrhea, nausea, elevated liver enzymes, vomiting, abdominal pain, fatigue, decreased appetite, and constipation.[6]
More than half of patients in clinical trials experienced adverse events that necessitated a reduction in dose.[7]
History
Ceritinib was granted breakthrough status in March 2013 for ALK-positive NSCLC unresponsive to crizotinib, and FDA approval in April 2014 for the same indication.[8]
See also
References
- ↑ "Zykadia (ceritinib) Capsules, for Oral Use. Full Prescribing Information" (PDF). Novartis Pharmaceuticals Corporation. Retrieved 14 February 2017.
- ↑ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 71" (PDF). World Health Organization. 2014. p. 79. Retrieved 14 February 2017.
- 1 2 "FDA Approves Ceritinib for ALK-Positive Lung Cancer". Medscape. April 29, 2014.
- ↑ 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 (27 March 2014). "Ceritinib in ALK-Rearranged Non-Small-Cell Lung Cancer". The New England Journal of Medicine. 370 (13): 1189–97. PMC 4079055
. PMID 24670165. doi:10.1056/NEJMoa1311107. - ↑ http://www.nature.com/nrclinonc/journal/vaop/ncurrent/full/nrclinonc.2017.20.html
- ↑ https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/zykadia.pdf
- ↑ https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/zykadia.pdf
- ↑ http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm395386.htm