Generic Name and Formulations:
Nilotinib (as HCl monohydrate) 150mg, 200mg; caps; contains lactose.
Novartis Pharmaceuticals Corp
Indications for TASIGNA:
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 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. May give concomitant hematopoietic growth factors, hydroxyurea, or anagrelide if clinically indicated. See full labeling for dose adjustments in QT prolongation, hematological and non-hematological toxicities, concomitant strong CYP3A4 inhibitors/inducers, and criteria for treatment discontinuation and re-initiation.
Hypokalemia. Hypomagnesemia. Long QT syndrome.
Prolongs QT interval, 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. History of pancreatitis. Monitor for myelosuppression; withhold or reduce dose if occurs; perform CBCs every 2 weeks for 1st 2 months then once monthly. Hepatic impairment. 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. 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 (eg, amiodarone, disopyramide, procainamide, quinidine, sotalol), or other drugs that may prolong QT interval (eg, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, pimozide). Avoid strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), grapefruit; if necessary, interrupt therapy or consider dose reduction of nilotinib; if unavoidable, monitor closely for QT prolongation. Avoid strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John's wort. May affect, or be affected by, other drugs metabolized by CYP3A4, 2B6, 2C8, 2C9, 2D6, UGT1A1, P-glycoprotein. 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.
Rash, pruritus, headache, nausea, fatigue, alopecia, myalgia, upper abdominal pain, nasopharyngitis, constipation, diarrhea, vomiting, arthralgia, pyrexia, night sweats, upper respiratory tract infection, back pain, cough, asthenia, pneumonia, febrile neutropenia, leukopenia, intracranial hemorrhage, reversible myelosuppression (thrombocytopenia, neutropenia, anemia); QT prolongation, elevated serum lipase, electrolyte disturbances (hypophosphatemia, hypo- and hyperkalemia, hypocalcemia, hyponatremia), sudden death, hepatotoxicity, cardiac and arterial vascular occlusive events, severe fluid retention (monitor).
Testing considerations: BCR-Abl t(9;22)
Blister pack (28 caps)—1, 4