Nilotinib inhibits the tyrosine kinase activity of the BCR-ABL protein. Nilotinib fits into the ATP-binding site of the BCR-ABL protein with higher affinity than imatinib, over-riding resistance caused by mutations. The ability of AMN107 to inhibit TEL-platelet-derived growth factor receptor-beta (TEL-PDGFRbeta), which causes chronic myelomonocytic leukaemia, and FIP1-like-1-PDGFRalpha, which causes hypereosinophilic syndrome, suggests potential use of AMN107 for myeloproliferative diseases characterised by these kinase fusions 

Absorption

Peak Plasma Concentration: 1540 ng/ml
Peak Plasma Time: 3 hr

Distribution

Protein Bound: 98% 

Metabolism

Oxidation and hydroxylation by liver CYP3A4

 

Elimination

Half-life: 17hr

Total body clearance: 29 L/hr

Excretion: Feces 93%; urine 22%

 

For the potential treatment of various leukemias, including chronic myeloid leukemia (CML).

 

Missed dose

• Patients should not take 2 doses at the same time to make up for a missed dose.

Avoid concomitant food (for at least 2hrs before and 1hr after dose), antiarrhythmics, or other drugs that may prolong QT interval. Avoid strong CYP3A4 inhibitors (eg, ketoconazole), grapefruit, grapefruit juice; see Adults. Avoid strong CYP3A4 inducers (eg, rifampicin), St. John's wort. Concomitant proton pump inhibitors: not recommended. Administer H₂-blockers at least 10hrs before or 2hrs after nilotinib dose. Separate dosing of antacids by at least 2hrs of nilotinib dose.

Newly diagnosed chronic phase (CP) Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in adults and children. Chronic and accelerated phase Ph+ CML in adults resistant or intolerant to prior imatinib. Chronic phase Ph+ CML in children resistant or intolerant to prior tyrosine-kinase inhibitor therapy.

Hypokalemia. Hypomagnesemia. Long QT syndrome

Nausea, rash, headache, fatigue, pruritus, vomiting, diarrhea, cough, constipation, arthralgia, nasopharyngitis, pyrexia, night sweats, myelosuppression (thrombocytopenia, neutropenia, anemia); QT prolongation, elevated serum lipase, electrolyte abnormalities (hypophosphatemia, hypo- and hyperkalemia, hypocalcemia, hyponatremia), hemorrhage, hepatotoxicity, cardiac and arterial vascular occlusive events, severe fluid retention (monitor).