Nilotinib (brand name Tasigna) is an oral medication used to treat chronic myelogenous leukemia (CML) which has the Philadelphia chromosome. It may be used both in initial cases of chronic phase CML as well as in accelerated and chronic phase CML that has not responded to imatinib.
Nilotinib is a Bcr-Abl tyrosine kinase inhibitor and works by interfering with signalling within the cancer cell. It was approved for medical use in the United States in 2007.
Structurally related to imatinib, it is 10–30 time more potent than imatinib in inhibiting Bcr-Abl tyrosine kinase activity and proliferation of Bcr-Abl expressing cells.
Nilotinib was developed by Novartis, based on the structure of the Abl-imatinib complex to address imatinib intolerance and resistance.
Nilotinib Side Effects
Nilotinib has a number of adverse side effects including 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 high blood pressure, various types of arrhythmia, and prolonged QT interval. Nilotinib can also affect the body’s electrolyte and glucose balance.
Though lung-related adverse effects are rare when compared with imatinib and dasatinib, there is a case report of acute respiratory failure from diffuse alveolar hemorrhage in people taking nilotinib3.
Nilotinib carries a black box warning in the United States for possible heart complications. Contraindications include long QT syndrome, hypokalaemia, hypomagnesaemia, pregnancy, planned pregnancy, lactation and galactose/lactose intolerance.
Dose reduction has been recommended in people with liver problems which involves recommendation of lower starting dose and monitoring of any hepatic function abnormalities.
Hepatitis B virus reactivation may also occur.
Weisberg E, Manley P, Mestan J, Cowan-Jacob S, Ray A, Griffin JD (2006). AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. Br. J. Cancer. 94 (12): 1765–9. ↩︎
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 (BBA) – Proteins and Proteomics. 1804 (3): 445–53. ↩︎
Donatelli, Christopher; Chongnarungsin, Daych; Ashton, Rendell (2014). Acute respiratory failure from nilotinib-associated diffuse alveolar hemorrhage. Leukemia & Lymphoma. 55 (10): 1–6. ↩︎