Newly diagnosed adults with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. Chronic and accelerated phase Ph+ CML in adults resistant or intolerant to imatinib.
Take on an empty stomach. Swallow whole. Newly diagnosed Ph+ CML: 300mg every 12 hours. Hepatic impairment (mild, moderate, severe): initially 200mg twice daily, followed by dose increase to 300mg twice daily if tolerated. Resistant or intolerant Ph+ CML: 400mg every 12 hours. Hepatic impairment (mild or moderate): initially 300mg twice daily, followed by dose increase to 400mg twice daily if tolerated; severe: initially 200mg twice daily, followed by sequential dose increase to 300mg twice daily, and then 400mg twice daily if tolerated. See literature for dose adjustments for QT prolongation, hematological and non-hematological toxicities, concomitant strong CYP3A4 inhibitors and inducers.
Hypokalemia. Hypomagnesemia. Long QT syndrome.
Prolongs QT interval, sudden deaths have been reported; correct electrolyte abnormalities (hypokalemia, hypomagnesemia) before starting; monitor. Monitor ECG at baseline, after 7 days, then periodically and after dose changes. Hereditary galactose intolerance, severe lactase deficiency, glucose-galactose malabsorption: not recommended. Hepatic impairment. History of pancreatitis. Uncontrolled cardiovascular or renal disease. Monitor for myelosuppression; withhold or reduce dose if occurs; perform CBCs every 2 weeks for 1st 2 months then once monthly. Monitor serum lipase, liver function. Total gastrectomy (monitor frequently); consider dose increase or alternative therapy. Tumor lysis syndrome possible; maintain adequate hydration, correct uric acid levels prior to initiating therapy. Pregnancy (Cat.D) (use adequate contraception), nursing mothers: not recommended.
Avoid concomitant food, antiarrhythmics, or other drugs that can cause QT prolongation. Avoid strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), grapefruit. Avoid strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital), St. John's wort; adjust nilotinib dose if unavoidable. May affect, or be affected by, other drugs metabolized by CYP3A4, 2B6, 2C8, 2C9, 2D6, UGT1A1, p-glycoprotein. Caution with drugs that affect gastric pH (eg, proton pump inhibitors, H2 blockers).
Rash, pruritus, GI upset, fatigue, headache, constipation, reversible myelosuppression (thrombocytopenia, neutropenia, anemia), pneumonia, febrile neutropenia, leukopenia, intracranial hemorrhage, elevated serum lipase, pyrexia, electrolyte disturbances (hypophosphatemia, hypo- and hyperkalemia, hypocalcemia, hyponatremia); QT prolongation, arrhythmias, sudden death, hepatotoxicity.
Testing considerations: BCR-Abl t(9;22)