For the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (CML) in adult patients resistant or intolerant to prior therapy that included imatinib.

Nilotinib monohydrochloride, a selective tyrosine kinase inhibitor, binds to and stabilizes the inactive conformation of the kinase domain of Abl protein. Bcr-Abl is the oncogenic tyrosine kinase expressed by Philadelphia chromosome-positive (Ph+) stem cells, directly involved in the pathogenesis of chronic myeloid leukemia (CML). Nilotinib inhibits the autophosphorylation of Bcr-Abl, PDGFR, and c-Kit, thereby reducing the tumor size. The effectiveness of Nilotinib is based on hematologic and cytogenetic response rates

Bioavailability: Increased 82% when administered 30 minutes after a high-fat meal; Time to peak: 3 hours; Protein binding: ~98%; Metabolism: Hepatic; oxidation and hydroxylation, via CYP3A4 to primarily inactive metabolites; Excretion: Feces (93%; 69% as parent drug); Elimination Half-life: ~15-17 hours

Do not use in patients with hypokalemia, hypomagnesemia, or long QT syndrom

D

Excretion in breast milk unknown/not recommended

Rash (28% to 33%), pruritus (20% to 29%), headache, fatigue, fever, nausea, diarrhea, constipation, vomiting, lipase increased, abdominal pain, neutropenia (grades 3/4: 28% to 37%; median duration: 15 days), thrombocytopenia (grade 3: 7% to 11%; grade 4: 17% to 30%; median duration: 22 days), anemia (grades 3/4: 8% to 23%), arthralgia, limb pain, myalgia, weakness, muscle spasm, bone pain, back pain, cough, nasopharyngitis, dyspnea, peripheral edema

400 mg twice daily, ~12 hours apart. Swallow capsules whole with water. Administer on an empty stomach, at least 1 hour before or 2 hours after food. Avoid grapefruit juice. The concomitant use of a strong CYP3A4 inhibitor or strong CYP3A4 inducer with nilotinib is not recommended.