danziten

Important safety information

Substitution with Other Nilotinib Products and Risk of Medication Errors : DANZITEN (nilotinib) tablets may not be substitutable with other nilotinib products, including other nilotinib tablets, on a milligram per milligram basis. Confirm that the intended nilotinib product is being prescribed and dispensed. ( 5.1 ) • Myelosuppression : Monitor complete blood count (CBC) during therapy and manage by treatment interruption or dose reduction. ( 5.2 ) • Cardiac and Arterial Vascular Occlusive Events : Evaluate cardiovascular status, monitor and manage cardiovascular risk factors during DANZITEN therapy. ( 5.5 ) • Pancreatitis and Elevated Serum Lipase : Monitor serum lipase; if elevations are accompanied by abdominal symptoms, interrupt doses and consider appropriate diagnostics to exclude pancreatitis. ( 5.6 ) • Hepatotoxicity : Monitor hepatic function tests monthly or as clinically indicated. ( 5.7 ) • Electrolyte Abnormalities : DANZITEN can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Correct electrolyte abnormalities prior to initiating DANZITEN and monitor periodically during therapy. ( 5.8 ) • Tumor Lysis Syndrome : Maintain adequate hydration and correct uric acid levels prior to initiating therapy with DANZITEN. ( 5.9 ) • Hemorrhage : Hemorrhage from any site may occur. Advise patients to report signs and symptoms of bleeding and medically manage as needed. ( 5.10 ) • Fluid Retention : Monitor patients for unexpected rapid weight gain, swelling, and shortness of breath. Manage medically. ( 5.13 ) • Effects on Growth and Development in Pediatric Patients : Growth retardation has been reported in pediatric patients treated with nilotinib. Monitor growth and development in pediatric patients. ( 5.14 ) • Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. ( 5.15 , 8.1 , 8.3 ) • Treatment Discontinuation : Patients must have typical BCR-ABL transcripts. An FDA-authorized test with a detection limit below MR4.5 must be used to determine eligibility for discontinuation. Patients must be frequently monitored by the FDA authorized test to detect possible loss of remission. ( 5.16 ) 5.1 Substitution with Other Nilotinib Products and Risk of Medication Errors Nilotinib is available in different formulations, recommended dosages, and tablet strengths, and for different indications. DANZITEN (nilotinib) tablets may not be substitutable with other nilotinib products, including other nilotinib tablets, on a milligram per milligram basis. When switching patients between other nilotinib products and DANZITEN (nilotinib) tablets, a dose conversion may be required [see Dosage and Administration ( 2.1 and 2.2 )] . Substitution of DANZITEN (nilotinib) tablets for another nilotinib product to achieve the same daily nilotinib dosage on a milligram per milligram basis may result in a clinically significant: • Increase in nilotinib exposure which may increase the risk of nilotinib-associated adverse reactions. • Decrease in nilotinib exposure which may reduce DANZITEN effectiveness. Confirm that the intended nilotinib product is being prescribed and dispensed. 5.2 Myelosuppression Treatment with DANZITEN can cause Grade 3/4 thrombocytopenia, neutropenia, and anemia. Perform CBCs every 2 weeks for the first 2 months and then monthly thereafter, or as clinically indicated. Myelosuppression was generally reversible and usually managed by withholding DANZITEN temporarily or dose reduction [ see Dosage and Administration ( 2.6 ) ]. 5.3 QT Prolongation Nilotinib has been shown to prolong cardiac ventricular repolarization as measured by the QT interval on the surface electrocardiogram (ECG) in a concentration-dependent manner [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.2 )] . Prolongation of the QT interval can result in a type of ventricular tachycardia called torsade de pointes, which may result in syncope, seizure, and/or death. Electrocardiograms should be performed at baseline, 7 days after initiation of DANZITEN, and periodically as clinically indicated and following dose adjustments [see Dosage and Administration ( 2.5 ) and Warnings and Precautions ( 5.12 )] . DANZITEN should not be used in patients who have hypokalemia, hypomagnesemia, or long QT syndrome. Before initiating DANZITEN and periodically, test electrolyte, calcium, and magnesium blood levels. Hypokalemia or hypomagnesemia must be corrected prior to initiating DANZITEN and these electrolytes should be monitored periodically during therapy [see Warnings and Precautions ( 5.12 )] . Significant prolongation of the QT interval may occur when DANZITEN is inappropriately taken with strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT. Therefore, avoid concomitant DANZITEN use with strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT [see Dosage and Administration ( 2.9 ), Drug Interactions ( 7.1 , 7.2 )] . The presence of hypokalemia and hypomagnesemia may further prolong the QT interval [see Warnings and Precautions ( 5.8 , 5.12 )] . 5.4 Sudden Deaths Sudden deaths have been reported in 0.3% of patients with CML treated with nilotinib in clinical studies of 5661 patients. The relative early occurrence of some of these deaths relative to the initiation of nilotinib suggests the possibility that ventricular repolarization abnormalities may have contributed to their occurrence. 5.5 Cardiac and Arterial Vascular Occlusive Events Cardiovascular events, including arterial vascular occlusive events, were reported in a randomized, clinical trial in newly diagnosed CML patients and observed in the postmarketing reports of patients receiving nilotinib therapy [see Adverse Reactions ( 6.1 )] . With a median time on therapy of 60 months in the clinical trial, cardiovascular events, including arterial vascular occlusive events, occurred in 9% and 15% of patients receiving nilotinib dosages equivalent to DANZITEN 142 mg and 190 mg twice daily, respectively, and in 3.2% in the imatinib arm. These included cases of cardiovascular events, including ischemic heart disease-related cardiac events (5% and 9% in the nilotinib dosages equivalent to DANZITEN 142 mg and 190 mg twice daily, respectively and 2.5% in the imatinib arm), peripheral arterial occlusive disease (3.6% and 2.9% in the nilotinib dosages equivalent to DANZITEN 142 mg and 190 mg twice daily, respectively and 0% in the imatinib arm), and ischemic cerebrovascular events (1.4% and 3.2% in the nilotinib dosages equivalent to DANZITEN 142 mg and 190 mg twice daily, respectively and 0.7% in the imatinib arm). If acute signs or symptoms of cardiovascular events occur, advise patients to seek immediate medical attention. The cardiovascular status of patients should be evaluated, and cardiovascular risk factors should be monitored and actively managed during DANZITEN therapy according to standard guidelines [see Dosage and Administration ( 2.5 )] . 5.6 Pancreatitis and Elevated Serum Lipase Nilotinib can cause increases in serum lipase [ see Adverse Reactions ( 6.1 ) ]. Patients with a previous history of pancreatitis may be at greater risk of elevated serum lipase. If lipase elevations are accompanied by abdominal symptoms, interrupt dosing and consider appropriate diagnostics to exclude pancreatitis [ see Dosage and Administration ( 2.7 ) ]. Test serum lipase levels monthly or as clinically indicated. 5.7 Hepatotoxicity Nilotinib may result in hepatotoxicity as measured by elevations in bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase. Grade 3-4 elevations of bilirubin, AST, and ALT were reported in adult patients. Grade 3-4 elevations of bilirubin, AST, and ALT were reported at a higher frequency in pediatric than in adult patients. Monitor hepatic function tests monthly or as clinically…