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Treatment with Tasigna should be initiated by a physician experienced in the treatment of patients with CML.
Tasigna may be given in combination with hematopoietic growth factors such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) if clinically indicated. Tasigna may be given with hydroxyurea or anagrelide if clinically indicated.
Monitoring of response to Tasigna therapy in Ph+ CML patients should be performed both routinely and when therapy is modified, to identify suboptimal response, loss of response to therapy, poor patient compliance, or possible drug-drug interaction. Results of monitoring should guide appropriate CML management.
General target population: Dosage in adult patients with newly diagnosed Ph+ CML- Chronic Phase (CP): The recommended dose of Tasigna is 300 mg twice daily (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). Treatment should be continued as long as clinical benefit is observed or until unacceptable toxicity occurs.
Dosage in newly diagnosed Ph+ CML-CP adult patients who have achieved a sustained deep molecular response (MR4.5): Discontinuation of treatment may be considered in eligible Ph+ CML-CP patients who have been treated with Tasigna at 300 mg twice daily for a minimum of 3 years if a deep molecular response is sustained for a minimum of one year immediately prior to discontinuation of therapy. Discontinuation of Tasigna should be initiated by a physician experienced in the treatment of patients with CML (see Precautions and Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Patients who are eligible to discontinue Tasigna therapy must have their BCR-ABL transcript levels and complete blood count with differential monitored monthly for one year, then every 6 weeks for the second year, and every 12 weeks thereafter. Monitoring of BCR-ABL transcript levels must be performed with a quantitative diagnostic test validated to measure molecular response levels on the International Scale (IS) with a sensitivity of at least molecular response 4.5 (MR4.5).
For patients who lose MR4.0 but not major molecular response (MMR) during the treatment-free phase, BCR-ABL transcript levels should be monitored every 2 weeks until BCR-ABL levels return to a range between MR4.0 and MR4.5. Patients who maintain BCR-ABL levels between MMR and MR4.0 for a minimum of 4 consecutive measurements can return to the original monitoring schedule.
Patients who lose MMR must re-initiate treatment within 4 weeks of when loss of remission is known to have occurred. Tasigna therapy should be re-initiated at 300 mg twice daily or at a reduced dose level of 400 mg once daily if the patient had a dose reduction prior to discontinuation of therapy. Patients who re-initiate Tasigna therapy should have their BCR-ABL transcript levels monitored monthly until MMR is re-established (see Precautions and Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Dosage in adult patients with Ph+ CML-CP and CML- Accelerated Phase (AP) resistant to or intolerant to at least one prior therapy including imatinib: The recommended dose of Tasigna is 400 mg twice daily (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). Treatment should be continued as long as clinical benefit is observed or until unacceptable toxicity occurs.
Dosage in Ph+ CML-CP adult patients who have achieved a sustained deep molecular response (MR4.5) on Tasigna following prior imatinib therapy: Discontinuation of treatment may be considered in eligible Ph+ CML-CP patients who have been treated with Tasigna for a minimum of 3 years if a deep molecular response is sustained for a minimum of one year immediately prior to discontinuation of therapy. Discontinuation of Tasigna should be initiated by a physician experienced in the treatment of patients with CML (see Precautions and Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Patients who are eligible to discontinue Tasigna therapy must have their BCR-ABL transcript levels and complete blood count with differential monitored monthly for one year, then every 6 weeks for the second year, and every 12 weeks thereafter. Monitoring of BCR-ABL transcript levels must be performed with a quantitative diagnostic test validated to measure molecular response levels on the International Scale (IS) with a sensitivity of at least MR4.5.
Patients with confirmed loss of MR4.0 (two consecutive measures separated by at least 4 weeks showing loss of MR4.0) or loss of MMR must re-initiate treatment within 4 weeks of when loss of remission is known to have occurred. Tasigna therapy should be re-initiated at either 300 mg or 400 mg twice daily. Patients who re-initiate Tasigna therapy should have their BCR-ABL transcript levels monitored monthly until previous MMR or MR4.0 is re-established (see Precautions and Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Monitoring recommendations and dose adjustments: A baseline electrocardiogram (ECG) is recommended prior to initiating therapy with Tasigna and should be repeated after 7 days and as clinically indicated. Hypokalemia or hypomagnesemia must be corrected prior to Tasigna administration and potassium and magnesium blood levels should be monitored periodically during therapy, particularly in patients at risk for these electrolyte abnormalities (see Precautions).
Increases in total serum cholesterol levels have been reported with Tasigna therapy (see Precautions). Lipid profiles should be determined prior to initiating Tasigna therapy, assessed at month 3 and 6 after initiating therapy, and at least yearly during chronic therapy.
Increases in blood glucose levels have been reported with Tasigna therapy (see Precautions). Blood glucose levels should be assessed prior to initiating Tasigna therapy and monitored during treatment.
Due to possible occurrence of Tumor Lysis Syndrome (TLS) correction of clinically significant dehydration and treatment of high uric acid levels are recommended prior to initiating therapy with Tasigna (see Adverse Reactions).
Tasigna may need to be temporarily withheld and/or dose reduced for hematological toxicities (neutropenia, thrombocytopenia) that are not related to underlying leukemia (see Table 9).
Click on icon to see table/diagram/imageIf clinically significant moderate or severe non-hematologic toxicity develops, dosing should be interrupted, and may be resumed at 400 mg once daily once the toxicity has resolved. If clinically appropriate, re-escalation of the dose to 300 mg (newly diagnosed Ph+ CML-CP) or 400 mg (resistant or intolerant Ph+ CML-CP and CML-AP) twice daily should be attempted.
Elevated serum lipase: Asymptomatic serum lipase elevations were observed. Few of these elevations were associated with clinical symptoms such as abdominal pain or a diagnosis of pancreatitis. Overall, this finding was clinically manageable in the majority of patients without requirement for dose reduction or interruption. For Grade 3 to 4 lipase elevations, doses in adult patients should be reduced to 400 mg once daily or interrupted. Serum lipase levels should be tested monthly or as clinically indicated (see Precautions and Adverse Reactions).
Elevated bilirubin and hepatic transaminases: In clinical studies, the majority of bilirubin and hepatic transaminase laboratory abnormalities in patients were of low grade toxicity which did not require dose interruption or reduction. For Grade 3 to 4 bilirubin or hepatic transaminase elevations in adult patients, doses should be reduced to 400 mg once daily or interrupted. Bilirubin and hepatic transaminases levels should be tested monthly or as clinically indicated (see Adverse Reactions).
Special populations: Renal impairment: Clinical studies have not been performed in patients with impaired renal function. Clinical studies have excluded patients with serum creatinine concentration >1.5 times the upper limit of the normal range.
Since nilotinib and its metabolites are not renally excreted, a decrease in total body clearance is not anticipated in patients with renal impairment.
Hepatic impairment: Hepatic impairment has a modest effect on the pharmacokinetics of nilotinib. Dose adjustment is not considered necessary in hepatically impaired patients. Patients with hepatic impairment should be treated with caution (see Precautions).
Cardiac disorders: Tasigna has not been investigated in patients with cardiac disorders. In clinical studies, patients with uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina, or clinically significant bradycardia were excluded.
Caution should be exercised in patients with relevant cardiac disorders (see Precautions).
Pediatric patients (below 18 years): Safety and efficacy in children and adolescents below the age of 18 has not been established.
Geriatric patients (65 years of age or above): Approximately 12% and 30% of subjects in the clinical studies (newly diagnosed Ph+ CML-CP and resistant or intolerant Ph+ CML-CP and CML-AP) were 65 years of age or older. No major differences were observed for safety and efficacy in patients ≥65 years of age as compared to adults 18 to 65 years of age.
Method of administration: Tasigna should be taken twice daily, at approximately 12 hour intervals, and must not be taken with food. The capsules should be swallowed whole with water. No food should be consumed for at least two hours before the dose is taken and no additional food should be consumed for at least one hour after the dose is taken (see Precautions and Interactions).
For patients who are unable to swallow capsules, the content of each capsule may be dispersed in one teaspoon of applesauce (pureed apple) and should be taken immediately. Not more than one teaspoon of applesauce and no food other than applesauce must be used (see Pharmacology under Actions).
If a dose is missed the patient should not take an additional dose, but take the usual prescribed next dose.
