Nilotinib

Nilotinib capsules are a kinase inhibitor indicated for the treatment of: Adult and pediatric patients greater than or equal to 1 year of age with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. ( 1.1 ) Adult patients with chronic phase (CP) and accelerated phase (AP) Ph+ CML resistant to or intolerant to prior therapy that included imatinib. ( 1.2 ) Pediatric patients greater than or equal to 1 year of age with Ph+ CML-CP resistant or intolerant to prior tyrosine-kinase inhibitor (TKI) therapy.

12.1 Mechanism of Action Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of ABL protein. In vitro , nilotinib inhibited BCR-ABL mediated proliferation of murine leukemic cell lines and human cell lines derived from patients with Ph+ CML. Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from BCR-ABL kinase mutations, in 32 out of 33 mutations tested.

Clinical clearance of Nilotinib (Kinase Inhibitor) relies on dual hepatorenal clearance pathway combining glucuronidation and urinary filtration of nilotinib with a Mean elimination half-life of 4 to 11 hours across adult Nilotinib dosing half-life; patients absorbing at Oral fraction absorbed ranges from 46% to 58% (Nilotinib 150) bioavailability typically observe target onset around oral tmax achieved within 2 to 3 hours following nilotinib ingestion.

FDA clinical labeling for Nilotinib restricts administration in nilotinib is contraindicated in patients with hypokalemia, hypomagnesemia, or long qt syndrome .; nilotinib is contraindicated in patients with hypokalemia, hypomagnesemia, or long qt syndrome. across 150 mg/1 Capsule, 95 mg/1 Tablet, 50 mg/1 Capsule, 200 mg/1 Capsule, 71 mg/1 Tablet, with self-reported patient tracking dominated by nausea (10.9% of reports), headache (9.5% of reports), fatigue (8.6% of reports).