Generic Name and Formulations:
Nilotinib (as HCl monohydrate) 50mg, 150mg, 200mg; caps; contains lactose.
Novartis Pharmaceuticals Corp
Indications for TASIGNA:
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.
Take on an empty stomach. Swallow whole with water; if unable, may disperse capsule contents in 1 tsp of applesauce, then take immediately (within 15 mins). Newly diagnosed Ph+ CML: 300mg every 12hrs. 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 12hrs. 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. Concomitant strong CYP3A4 inhibitors (newly diagnosed): if unavoidable, reduce to 200mg once daily; (resistant or intolerant): if unavoidable, reduce to 300mg once daily; monitor for QT prolongation. May give concomitant hematopoietic growth factors, hydroxyurea, or anagrelide if clinically indicated. Dose modifications for QT prolongation, hematological and non-hematological toxicities, and criteria for treatment discontinuation and re-initiation: see full labeling.
<1yr: not established. Take on an empty stomach. Swallow whole with water; if unable, may disperse capsule contents in 1 tsp of applesauce, then take immediately (within 15 mins). ≥1yr: Newly diagnosed, resistant or intolerant Ph+ CML-CP: 230mg/m2 every 12hrs (round to the nearest 50mg); max 400mg/dose. Continue if clinically beneficial or until unacceptable toxicity. May give concomitant hematopoietic growth factors, hydroxyurea, or anagrelide if clinically indicated. Dose modifications for QT prolongation, hematological and non-hematological toxicities, and criteria for treatment discontinuation and re-initiation: see full labeling.
Hypokalemia. Hypomagnesemia. Long QT syndrome.
QT prolongation. Sudden deaths.
QT prolongation, sudden deaths have been reported; correct electrolyte abnormalities prior to initiating; monitor periodically. Obtain ECGs at baseline, after 7 days, then periodically and after dose adjustments. Cardiovascular status should be evaluated; monitor cardiovascular risk factors and actively manage during therapy. Uncontrolled or significant CVD (eg, recent MI, CHF, unstable angina, significant bradycardia). History of pancreatitis. 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 monthly or as clinically indicated. Monitor lipids and glucose periodically during first year, then yearly. 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. Monitor for signs/symptoms of bleeding. Hereditary galactose intolerance, severe lactase deficiency, glucose-galactose malabsorption: not recommended. Monitor BCR-ABL transcript levels in patients eligible for treatment discontinuation or those who re-initiate treatment due to loss of molecular response, using an FDA authorized test (see full labeling). Monitor growth and development in children. Hepatic impairment: reduce dose. Embryo-fetal toxicity. Pregnancy: exclude status prior to initiation. Females of reproductive potential should use effective contraception during and for at least 14 days after last dose. Nursing mothers: not recommended (during and for at least 14 days after last 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.
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).
Testing considerations: BCR-Abl t(9;22)
Caps 50mg—120; 150mg, 200mg—28, 112