Tasigna

TASIGNA- nilotinib capsule
Novartis Pharmaceuticals Corporation

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 [see Warnings and Precautions (5.2)]. Obtain ECGs to monitor the QTc at baseline, seven days after initiation, and periodically thereafter, and following any dose adjustments [see Warnings and Precautions (5.2, 5.3, 5.7, 5.12)].
  • Sudden deaths have been reported in patients receiving Tasigna [see Warnings and Precautions (5.3)]. Do not administer Tasigna to patients with hypokalemia, hypomagnesemia, or long QT syndrome [see Contraindications (4), Warnings and Precautions (5.2)].
  • Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors [see Drug Interactions (7.1, 7.2)].
  • Avoid food 2 hours before and 1 hour after taking the dose [see Dosage and Administration (2.1)].

1 INDICATIONS AND USAGE

1.1 Adult and Pediatric Patients With Newly Diagnosed Ph+ CML-CP

Tasigna is 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.

1.2 Adult Patients With Resistant or Intolerant Ph+ CML-CP and CML-AP

Tasigna is indicated for the treatment of adult patients with chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) resistant or intolerant to prior therapy that included imatinib.

1.3 Pediatric Patients With Resistant or Intolerant Ph+ CML-CP

Tasigna is indicated for the treatment of pediatric patients greater than or equal to 1 year of age with chronic phase Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) with resistance or intolerance to prior tyrosine-kinase inhibitor (TKI) therapy.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

Dose Tasigna twice daily at approximately 12-hour intervals on an empty stomach. No food should be consumed for at least 2 hours before the dose is taken and for at least 1 hour after the dose is taken. Advise patients to swallow the capsules whole with water [see Boxed Warning, Clinical Pharmacology (12.3)].

For patients who are unable to swallow capsules, the contents of each capsule may be dispersed in 1 teaspoon of applesauce (puréed apple). The mixture should be taken immediately (within 15 minutes) and should not be stored for future use [see Clinical Pharmacology (12.3)].

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.

Dosage in Adult Patients with Newly Diagnosed Ph+ CML-CP

The recommended dosage of Tasigna is 300 mg orally twice daily.

Dosage in Adult Patients with Resistant or Intolerant Ph+ CML-CP and CML-AP

The recommended dosage of Tasigna is 400 mg orally twice daily.

Dosage in Pediatric Patients with Newly Diagnosed Ph+ CML-CP or Resistant or Intolerant Ph+ CML-CP

The recommended dosage of Tasigna for pediatric patients is 230 mg/m2 orally twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg) (see Table 1). If needed, attain the desired dose by combining different strengths of Tasigna capsules. Continue treatment as long as clinical benefit is observed or until unacceptable toxicity occurs.

Table 1: Pediatric Dosing of Tasigna (230 mg/m2 twice daily, maximum single dose of 400 mg)
Body Surface Area Single Dose Total Daily Dose
Up to 0.32 m2 50 mg 100 mg
0.33–0.54 m2 100 mg 200 mg
0.55–0.76 m2 150 mg 300 mg
0.77–0.97 m2 200 mg 400 mg
0.98–1.19 m2 250 mg 500 mg
1.20–1.41 m2 300 mg 600 mg
1.42–1.63 m2 350 mg 700 mg
≥ 1.64 m2 400 mg 800 mg

2.2 Discontinuation of Treatment After a Sustained Molecular Response (MR4.5) on Tasigna

Patient Selection

Eligibility for Discontinuation of Treatment

Ph+ CML-CP patients with typical BCR-ABL transcripts, who have been taking Tasigna for a minimum of 3 years and have achieved a sustained molecular response (MR4.5, corresponding to = BCR-ABL/ABL ≤ 0.0032% IS), may be eligible for treatment discontinuation [see Clinical Studies (14.3, 14.4)]. Information on FDA authorized tests for the detection and quantitation of BCR-ABL transcripts to determine eligibility for treatment discontinuation is available at http://www.fda.gov/CompanionDiagnostics.

Patients with typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2), who achieve the sustained MR4.5 criteria, are eligible for discontinuation of Tasigna. Patients must continue to be monitored for possible loss of molecular remission after treatment discontinuation. Use the same FDA-authorized test to consistently monitor molecular response levels while on and off treatment.

Consider discontinuation in patients with newly diagnosed Ph+ CML-CP who have:

● been treated with Tasigna for at least 3 years

● maintained a molecular response of at least MR4.0 (corresponding to = BCR-ABL/ABL ≤ 0.01% IS) for one year prior to discontinuation of therapy

● achieved an MR4.5 for the last assessment taken immediately prior to discontinuation of therapy

● been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2)

● no history of accelerated phase or blast crisis

● no history of prior attempts of treatment-free remission discontinuation that resulted in relapse.

Consider discontinuation in patients with Ph+ CML-CP that are resistant or intolerant to imatinib who have achieved a sustained molecular response (MR4.5) on Tasigna who have:

● been treated with Tasigna for a minimum of 3 years

● been treated with imatinib only prior to treatment with Tasigna

● achieved a molecular response of MR4.5 (corresponding to = BCR-ABL/ABL ≤ 0.0032% IS)

● sustained an MR4.5 for a minimum of one year immediately prior to discontinuation of therapy

● been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2)

● no history of accelerated phase or blast crisis

● no history of prior attempts of treatment-free remission discontinuation that resulted in relapse.

Monitor BCR-ABL transcript levels and complete blood count (CBC) with differential in patients who have discontinued Tasigna therapy monthly for one year, then every 6 weeks for the second year, and every 12 weeks thereafter [see Warnings and Precautions (5.16)].

Upon the loss of MR4.0 (corresponding to = BCR-ABL/ABL ≤ 0.01% IS) during the treatment-free phase, monitor BCR-ABL transcript levels every 2 weeks until BCR-ABL levels remain lower than major molecular response [(MMR), corresponding to MR3.0 or = BCR-ABL/ABL ≤ 0.1% IS] for 4 consecutive measurements. The patient can then proceed to the original monitoring schedule.

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