Nilotinib

Tasigna is a kinase inhibitor indicated for the treatment of: Adult and pediatric patients greater than or equal to 1 year of age with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. Adult patients with chronic phase (CP) and accelerated phase (AP) Ph+ CML resistant to or intolerant to prior therapy that included imatinib. Pediatric patients greater than or equal to 1 year of age with Ph+ CML-CP and CML-AP resistant or intolerant to prior tyrosine-kinase inhibitor (TKI) therapy.

Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of ABL protein. In vitro, nilotinib inhibited BCR-ABL mediated proliferation of murine leukemic cell lines and human cell lines derived from patients with Ph+ CML. Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from BCR-ABL kinase mutations, in 32 out of 33 mutations tested. Nilotinib inhibited the autophosphorylation of the following kinases at IC50 values as indicated: BCR-ABL (20 to 60 nM), PDGFR (69 nM), c-KIT (210 nM), CSF-1R (125 to 250 nM), and DDR1 (3.7 nM).

Recommended Adult Dose: Newly diagnosed Ph+ CML-CP: 300 mg orally twice daily. Resistant or intolerant Ph+ CML-CP and CML-AP: 400 mg orally twice daily. Recommended Pediatric Dose: Newly Diagnosed Ph+ CML-CP or Ph+ CML-CP and CML-AP resistant or intolerant to prior TKI therapy: 230 mg/m 2 orally twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg). See Dosage and Administration for full dosing instructions and dose-reduction instructions for toxicity. Reduce starting dose in patients with baseline hepatic impairment.

Tasigna is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome.

Boxed warning (qt prolongation and sudden deaths): Tasigna prolongs the QT interval. Prior to Tasigna administration and periodically, monitor for hypokalemia or hypomagnesemia and correct deficiencies. Obtain ECGs to monitor the QTc at baseline, seven days after initiation, and periodically thereafter, and following any dose adjustments. Sudden deaths have been reported in patients receiving Tasigna. Myelosuppression: Monitor complete blood count (CBC) during therapy and manage by treatment interruption or dose reduction. Cardiac and Arterial Vascular Occlusive Events: Evaluate cardiovascular status, monitor and manage cardiovascular risk factors during Tasigna therapy. Pancreatitis and Elevated Serum Lipase: Monitor serum lipase, if elevations are accompanied by abdominal symptoms, interrupt doses and consider appropriate diagnostics to exclude pancreatitis.

The following clinically significant adverse reactions can occur with Tasigna and are discussed in greater detail in other sections of labeling: Myelosuppression QT Prolongation Sudden Deaths Cardiac and Arterial Vascular Occlusive Events Pancreatitis and Elevated Serum Lipase Hepatotoxicity Electrolyte Abnormalities Hemorrhage Fluid Retention The most commonly reported non-hematologic adverse reactions (≥ 20%) in adult and pediatric patients were nausea, rash, headache, fatigue, pruritus, vomiting, diarrhea, cough, constipation, arthralgia, nasopharyngitis, pyrexia, and night sweats. Hematologic adverse drug reactions include myelosuppression: thrombocytopenia, neutropenia, and anemia.

Tumor Lysis Syndrome Tumor lysis syndrome (TLS) cases have been reported in Tasigna treated patients with resistant or intolerant CML. Malignant disease progression, high white blood cell (WBC) counts and/or dehydration were present in the majority of these cases. Due to potential for TLS, maintain adequate hydration and correct uric acid levels prior to initiating therapy with Tasigna. 7 DRUG INTERACTIONS Strong CYP3A Inhibitors: Avoid concomitant use with Tasigna, or reduce Tasigna dose if coadministration cannot be avoided. Strong CYP3A Inducers: Avoid concomitant use with Tasigna. Proton Pump Inhibitors: Use short-acting antacids or H2 blockers as an alternative to proton pump inhibitors.

Tasigna (nilotinib) 50 mg capsules are red opaque cap and light yellow opaque body hard gelatin capsules, size 4 with black radial imprint “NVR/ABL.” Tasigna (nilotinib) 150 mg capsules are red opaque hard gelatin capsules, size 1 with black axial imprint “NVR/BCR.” Tasigna (nilotinib) 200 mg capsules are light yellow opaque hard gelatin capsules, size 0 with the red axial imprint “NVR/TKI.” Tasigna 50 mg capsules are supplied in bottles and Tasigna 150 mg and 200 mg capsules are supplied in blister packs. 50 mg Bottle of 120 capsules………………………………………………………………NDC 0078-0951-66 150 mg Carton of 4 blister packs of (4x28)…………………………………………………NDC 0078-0592-87 Blisters of 28…