* Therapeutic indications:
Tasigna is indicated for the treatment of adult patients with:
– newly diagnosed Philadelphia chromosome positive chronic myelogenous leukaemia (CML) in the chronic phase,
– chronic phase and accelerated phase Philadelphia chromosome positive CML with resistance or intolerance to prior therapy including imatinib. Efficacy data in patients with CML in blast crisis are not available.
* Pharmacotherapeutic group:
Antineoplastic agents, protein kinase inhibitors, ATC code: L01XE08
* Mechanism of Action:
Nilotinib is a potent inhibitor of the ABL tyrosine kinase activity of the BCR-ABL oncoprotein both in cell lines and in primary Philadelphia-chromosome positive leukaemia cells. The substance binds with high affinity to the ATP-binding site in such a manner that it is a potent inhibitor of wild-type BCR-ABL and maintains activity against 32/33 imatinib-resistant mutant forms of BCR-ABL. As a consequence of this biochemical activity, nilotinib selectively inhibits the proliferation and induces apoptosis in cell lines and in primary Philadelphia-chromosome positive leukaemia cells from CML patients. In murine models of CML, as a single agent nilotinib reduces tumour burden and prolongs survival following oral administration.
Nilotinib has little or no effect against the majority of other protein kinases examined, including Src, except for the PDGF, KIT and Ephrin receptor kinases, which it inhibits at concentrations within the range achieved following oral administration at therapeutic doses recommended for the treatment of CML.