TASIGNA CAPSULE 200MG [SIN13498P]

Product Info

TASIGNA CAPSULE 200MG

[SIN13498P]

INDICATIONS

Tasigna hard capsules are indicated for the:

• treatment of adult and paediatric patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. The effectiveness of Tasigna is based on major molecular response and cytogenetic response rates.

• treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) in adult patients resistant to or intolerant to at least one prior therapy including imatinib. The effectiveness of Tasigna is based on hematologic and cytogenetic response rates.

• treatment of paediatric patients with chronic phase Philadelphia chromosome positive CML with resistance or intolerance to prior therapy including imatinib.

DOSAGE REGIMEN AND ADMINISTRATION

Tasigna is available in three dosage strengths (50 mg, 150 mg and 200 mg).

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 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 section CLINICAL STUDIES – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Treatment should be continued as long as the patient continues to benefit.

Dosage for Philadelphia chromosome positive CML paediatric patients

Dosing in paediatric patients is individualised and is based on body surface area (mg/m²). The recommended dose of nilotinib is 230 mg/m² twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg) (see Table 1-1). Different strengths of Tasigna hard capsules can be combined to attain the desired dose.

There is no experience with treatment of paediatric patients below 2 years of age. There are no data in newly diagnosed paediatric patients below 10 years of age and limited data in imatinib-resistant or intolerant paediatric patients below 6 years of age.

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 section CLINICAL STUDIES – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Treatment should be continued as long as the patient continues to benefit.

Monitoring recommendations and dose adjustments

A baseline 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 section WARNINGS AND PRECAUTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

QT interval prolongation

Increases in total serum cholesterol levels have been reported with Tasigna therapy (see Section WARNINGS AND PRECAUTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). 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 section WARNINGS AND PRECAUTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). 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 section ADVERSE DRUG REACTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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 2).

If clinically significant moderate or severe non-hematologic toxicity develops, dosing should be interrupted, and patients should be monitored and treated accordingly. If the prior dose was 300 mg twice daily in adult newly diagnosed patients with CML-CP or 400 mg twice daily in adult patients with resistant or intolerant CML-CP and CML-AP or 230 mg/m² twice daily in paediatric patients, dosing may be resumed at 400 mg once daily once the toxicity has resolved. If the prior dose was 400 mg once daily in adult patients or 230 mg/m² once daily in paediatric patients, treatment should be discontinued. If clinically appropriate, re-escalation of the dose in adult patients to 300 mg (newly diagnosed Ph+ CML-CP) or 400 mg (resistant or intolerant Ph+ CML-CP and CML-AP) twice daily or 230 mg/m² twice daily in paediatric patients should be attempted.

Elevated serum lipase: For Grade 3 to 4 lipase elevations, doses in adult patients should be reduced to 400 mg once daily or interrupted. In paediatric patients, treatment must be interrupted until the event returns to Grade ≤1. Thereafter, if the prior dose was 230 mg/m² once daily treatment can be resumed at 230 mg/m² once daily. If the prior dose was 230 mg/m² once daily, and recovery to Grade ≤1 takes longer than 28 days, treatment should be discontinued. Serum lipase levels should be tested monthly or as clinically indicated (see sections WARNINGS AND PRECAUTIONS and ADVERSE DRUG REACTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Elevated bilirubin and hepatic transaminases: For Grade 3 to 4 bilirubin or hepatic transaminase elevations, 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 section ADVERSE DRUG REACTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Special populations

Paediatric patients (below 18 years)

The safety and efficacy of Tasigna in paediatric patients with Philadelphia chromosome positive CML in chronic phase from 2 to less than 18 years of age have been established. There is no experience in paediatric patients below 2 years of age or in paediatric patients with Philadelphia chromosome positive CML in accelerated phase or blast crisis. There are no data in newly diagnosed paediatric patients below 10 years of age and limited data in imatinib-resistant or intolerant paediatric patients below 6 years of age.

Geriatric patients (65 years 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.

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 section WARNINGS AND PRECAUTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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 section WARNINGS AND PRECAUTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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 section WARNINGS AND PRECAUTIONS and section INTERACTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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 section CLINICAL PHARMACOLOGY – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

If a dose is missed the patient should not take an additional dose, but take the usual prescribed next dose.

CONTRAINDICATIONS

Tasigna is contraindicated in patients with known hypersensitivity to nilotinib or to any of the excipients.