|Systematic (IUPAC) name|
|4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)- 5-(trifluoromethyl)phenyl]-3- [(4-pyridin-3-ylpyrimidin-2-yl) amino]benzamide|
|Licence data||EMA: , US FDA:|
|Pregnancy cat.||D (AU) D (US)|
|Legal status||Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US)|
|Metabolism||Hepatic (mostly CYP3A4-mediated)|
|Mol. mass||529.5245 g/mol|
|(what is this?)|
Nilotinib (AMN107, trade name Tasigna), in the form of the hydrochloride monohydrate salt, is a small molecule tyrosine kinase inhibitor approved for the treatment of imatinib-resistant chronic myelogenous leukemia.
It is FDA- (29 October 2007), EMA- (29 September 2009), MHRA- (19 November 2007) and TGA- (17 January 2008) approved for use as a treatment for Philadelphia Chromosome (Ph+)-positive Chronic myelogenous leukaemia. In June 2006, a Phase I clinical trial found nilotinib has a relatively favorable safety profile and shows activity in cases of CML resistant to treatment with imatinib, another tyrosine kinase inhibitor currently used as a first-line treatment. In that study 92% of patients (already resistant or unresponsive to imatinib) achieved a normal white blood cell counts after five months of treatment. The drug carries a black box warning for possible heart complications. The use of low doses of nilotinib is being investigated for use for Parkinson's and Alzheimer's disease, as well as for ALS, dementia and Huntington's disease. Novartis announced on April 11, 2011 that it is discontinuing a Phase III trial of Tasigna® (nilotinib) for investigational use in the first-line treatment of gastrointestinal stromal tumor (GIST) based on the recommendation of an independent data monitoring committee. Interim results showed Tasigna is unlikely to demonstrate superiority compared to Novartis's Glivec® (imatinib)*, the current standard of care in this setting.
- Tumour lysis syndrome
- Liver impairment
- History of pancreatitis
- Check serum lipase periodically in order to detect pancreatitis
- Total gastrectomy
- Avoid pregnancy or impregnating women
Nilotinib has a number of adverse effects typical of anti-cancer drugs. These include headache, fatigue, gastrointestinal problems such as nausea, vomiting, diarrhea and constipation, muscle and joint pain, rash and other skin conditions, flu-like symptoms, and reduced blood cell count. Less typical side effects are those of the cardiovascular system, such as hypertension (high blood pressure), various types of arrhythmia, and prolonged QT interval. Nilotinib can also effect the body's electrolyte and glucose balance. Though pulmonary-related adverse effects are rare when compare with imatinib and dasatinib. There is a case report of acute respiratory failure from diffuse alveolar hemorrhage in patient taking nilotinib.
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- Kantarjian H et al.; Giles, Francis; Wunderle, Lydia; Bhalla, Kapil; O'Brien, Susan; Wassmann, Barbara; Tanaka, Chiaki; Manley, Paul; Rae, Patricia; Mietlowski, William; Bochinski, Kathy; Hochhaus, Andreas; Griffin, James D.; Hoelzer, Dieter; Albitar, Maher; Dugan, Margaret; Cortes, Jorge; Alland, Leila; Ottmann, Oliver G. (2006). "Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL". N Engl J Med 354 (24): 2542–51. doi:10.1056/NEJMoa055104. PMID 16775235.
- "Patients with treatment-resistant leukemia achieve high responses to Tasigna (nilotinib) in first published clinical trial results". MediaReleases (Novartis). 2006-06-14. Retrieved 2009-08-04.
- "FDA Approves Tasigna for Treatment of Philadelphia Chromosome Positive Chronic Myeloid Leukemia". U.S. Food and Drug Administration. 2007-10-30. Retrieved 2009-08-04.
- "Prescribing information for Tasigna (nilotinib) Capsules" (PDF). NDA 022068. U.S. FDA. 2007-10-29. Retrieved 2009-08-04.
- Donatelli, Christopher, Daych Chongnarungsin, and Rendell Ashton. "Acute respiratory failure from nilotinib-associated diffuse alveolar hemorrhage." Leukemia & Lymphoma 0 (2014): 1-6.
- Weisberg E, Manley P, Mestan J, Cowan-Jacob S, Ray A, Griffin JD (June 2006). "AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL". Br. J. Cancer 94 (12): 1765–9. doi:10.1038/sj.bjc.6603170. PMC 2361347. PMID 16721371.
- Manley, PW; Drueckes, P; Fendrich, G; Furet, P; Liebetanz, J; Martiny-Baron, G; Mestan, J; Trappe, J et al. (2010). "Extended kinase profile and properties of the protein kinase inhibitor nilotinib". Biochimica et Biophysica Acta 1804 (3): 445–53. doi:10.1016/j.bbapap.2009.11.008. PMID 19922818.
- Discovery and development of Bcr-Abl tyrosine kinase inhibitors
- New drug information/Abbreviated Scientific Narrative
- Highlights of Prescription information Nilotinib (August 2007) Novartis Pharmaceuticals Corporation (USA)
- Summary of Product Characteristics Nilotinib (November 2007) Novartis AG (Europe)