TASIGNA prolongs the QT Interval and may cause sudden death. Monitor/correct electrolytes and ECGs prior to and during treatment. Avoid strong CYP3A4 inhibitors. Take TASIGNA on an empty stomach.
IMPORTANT SAFETY INFORMATION FOR TASIGNA® (nilotinib) Capsules
Do not use in patients with hypokalemia, hypomagnesemia, or long QT syndrome.
WARNINGS AND PRECAUTIONS
Treatment with TASIGNA can cause Grade 3/4 thrombocytopenia, neutropenia, and anemia. Perform complete blood counts 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 TASIGNA temporarily or dose reduction.
TASIGNA prolongs the QT interval. ECGs should be performed at baseline, 7 days after initiation, periodically as clinically indicated, and following dose adjustments. Correct hypokalemia or hypomagnesemia prior to administration and monitor periodically.
Significant prolongation of the QT interval may occur when TASIGNA is inappropriately taken with food and/or strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT. Therefore, co-administration with food must be avoided and concomitant use with strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT should be avoided. The presence of hypokalemia and hypomagnesemia may further enhance this effect.
Sudden deaths have been reported in patients with resistant or intolerant Ph+ CML receiving nilotinib. 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.
Cardiac and Arterial Vascular Occlusive Events
Cardiovascular events, including arterial vascular occlusive events, were reported in a randomized, clinical trial in newly diagnosed Ph+ CML patients and observed in the post-marketing reports of patients receiving nilotinib therapy. Cases of cardiovascular events included ischemic heart disease-related events, peripheral arterial occlusive disease, and ischemic cerebrovascular events.
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 TASIGNA therapy according to standard guidelines.
Pancreatitis and Elevated Serum Lipase
TASIGNA can cause increases in serum lipase. 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. Test serum lipase levels monthly or as clinically indicated.
TASIGNA may result in hepatotoxicity as measured by elevations in bilirubin, AST/ALT, and alkaline phosphatase. Monitor hepatic function tests monthly or as clinically indicated.
The use of TASIGNA can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Electrolyte abnormalities must be corrected prior to initiating TASIGNA and these electrolytes should be monitored periodically during therapy.
Avoid administration of TASIGNA with agents that may increase nilotinib exposure (eg, strong CYP3A4 inhibitors) or anti-arrhythmic drugs (including, but not limited to amiodarone, disopyramide, procainamide, quinidine and sotalol) and other drugs that may prolong QT interval (including, but not limited to chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin and pimozide). Should treatment with any of these agents be required, interrupt therapy with TASIGNA. If interruption of treatment with TASIGNA is not possible, patients who require treatment with a drug that prolongs QT or strongly inhibits CYP3A4 should be closely monitored for prolongation of the QT interval.
The concomitant use of QT-prolonging drugs and strong inhibitors or inducers of CYP3A4 should be avoided as they may affect serum concentration of TASIGNA.
Drugs that affect gastric pH
Nilotinib has pH-dependent solubility, with decreased solubility and reduced bioavailability at higher pH. Since proton pump inhibitors affect pH of the upper GI tract for an extended period, separation of doses may not eliminate the interaction. The concomitant use of proton pump inhibitors with TASIGNA is not recommended.
When the concurrent use of a H2 blocker is necessary, it may be administered approximately 10 hours before and approximately 2 hours after the dose of TASIGNA. If necessary, an antacid may be administered approximately 2 hours before or approximately 2 hours after the dose of TASIGNA.
The bioavailability of nilotinib is increased with food, thus TASIGNA must not be taken with food. No food should be consumed for at least 2 hours before and for at least 1 hour after the dose is taken. Also avoid grapefruit products and other foods that are known to inhibit CYP3A4.
Nilotinib exposure is increased in patients with impaired hepatic function. Use a lower starting dose for patients with mild to severe hepatic impairment (at baseline) and monitor the QT interval frequently.
Tumor Lysis Syndrome
Tumor lysis syndrome cases have been reported in TASIGNA-treated patients with resistant or intolerant Ph+ CML. Malignant disease progression, high WBC counts and/or dehydration were present in the majority of these cases. Due to potential for tumor lysis syndrome, maintain adequate hydration and correct uric acid levels prior to initiating therapy with TASIGNA.
Grade 3/4 hemorrhage from various sites including GI were reported in patients with newly diagnosed Ph+ CML and observed in the postmarketing reports of patients receiving TASIGNA. Monitor patients for signs of hemorrhage and evaluate etiology during therapy with TASIGNA.
Since the exposure of nilotinib is reduced in patients with total gastrectomy, perform more frequent monitoring of these patients. Consider dose increase or alternative therapy in patients with total gastrectomy.
Since the capsules contain lactose, TASIGNA is not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency with a severe degree of intolerance to lactose-containing products, or of glucose-galactose malabsorption.
Monitoring Laboratory Tests
Complete blood counts should be performed every 2 weeks for the first 2 months and then monthly thereafter. Chemistry panels, including electrolytes, calcium, magnesium, liver enzymes, lipid profile, and glucose should be checked prior to therapy and periodically. ECGs should be obtained at baseline, 7 days after initiation and periodically thereafter, as well as following dose adjustments.
Monitor lipid profiles and glucose periodically during the first year of TASIGNA therapy and at least yearly during chronic therapy. Assess glucose levels before initiating treatment with TASIGNA and monitor during treatment as clinically indicated. If test results warrant therapy, physicians should follow their local standards of practice and treatment guidelines.
Advise patients that the use of TASIGNA during pregnancy may cause harm to the fetus and that TASIGNA should not be taken during pregnancy unless necessary. Sexually active female patients taking TASIGNA should use adequate contraception to avoid pregnancy.
Grade 3/4 fluid retention including pleural effusion, pericardial effusion, ascites and pulmonary edema have been reported in patients with newly diagnosed Ph+ CML receiving TASIGNA and observed in the postmarketing reports of patients receiving TASIGNA. Monitor patients for signs of severe fluid retention (eg, unexpected rapid weight gain or swelling) and for symptoms of respiratory or cardiac compromise (eg, shortness of breath); evaluate etiology and treat patients accordingly.
The most commonly reported non-hematologic adverse reactions (≥20% in patients with newly diagnosed Ph+ CML-CP, resistant or intolerant Ph+ CML-CP, or resistant or intolerant Ph+ CML-AP) were nausea, rash, headache, fatigue, pruritus, vomiting, diarrhea, cough, constipation, arthralgia, nasopharyngitis, pyrexia, and night sweats.
Hematologic adverse drug reactions (all grades) include myelosuppression: thrombocytopenia, neutropenia, and anemia.
DOSE ADJUSTMENTS OR MODIFICATIONS
TASIGNA may need to be temporarily withheld and/or dose reduced for QT prolongation, hematologic toxicities that are not related to underlying leukemia, clinically significant moderate or severe non-hematologic toxicities, laboratory abnormalities (lipase, bilirubin, or hepatic transaminase elevations) or concomitant use of strong CYP3A4 inhibitors.
Please see full Prescribing Information, including Boxed WARNING, by clicking the link at the top of this page.