TASIGNA- nilotinib capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

NILOTINIB (UNII: F41401512X) (NILOTINIB - UNII:F41401512X)

Available from:

Novartis Pharmaceuticals Corporation

INN (International Name):

NILOTINIB

Composition:

NILOTINIB 200 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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. 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. Tasigna is indicated for the treatment of pediatric patients greater than or equal to 1 year of age with chronic phase and accelerated phase Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) with resistance or intolerance to prior tyrosine-kinase inhibitor (TKI) therapy. Tasigna is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome [see Boxed Warning]. Risk Summary Based on findings from animal studies and the mechanism of action, Tasigna can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of nilotinib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes, including embryo-fetal lethality, fetal effects, and fetal variations in rats and rabbits at maternal exposures (AUC) approximately 2 and 0.5 times, respectively, the exposures in patients at the recommended dose (see Data ). Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of nilotinib up to 100 mg/kg/day and 300 mg/kg/day, respectively, during the period of organogenesis. In rats, oral administration of nilotinib produced embryo-lethality/fetal effects at doses ≥ 30 mg/kg/day. At ≥ 30 mg/kg/day, skeletal variations of incomplete ossification of the frontals and misshapen sternebra were noted, and there was an increased incidence of small renal papilla and fetal edema. At 100 mg/kg/day, nilotinib was associated with maternal toxicity (decreased gestation weight, gravid uterine weight, net weight gain, and food consumption) and resulted in a single incidence of cleft palate and two incidences of pale skin were noted in the fetuses. A single incidence of dilated ureters was noted in a fetus also displaying small renal papilla at 100 mg/kg/day. Additional variations of forepaw and hindpaw phalanx unossified, fused sternebra, bipartite sternebra ossification, and incomplete ossification of the cervical vertebra were noted at 100 mg/kg/day. In rabbits, oral administration of nilotinib resulted in the early sacrifice of two females, maternal toxicity and increased resorption of fetuses at 300 mg/kg/day. Fetal skeletal variations (incomplete ossification of the hyoid, bent hyoid, supernumerary short detached ribs and the presence of additional ossification sites near the nasals, frontals and in the sternebral column) were also increased at this dose in the presence of maternal toxicity. Slight maternal toxicity was evident at 100 mg/kg/day but there were no reproductive or embryo-fetal effects at this dose. At 30 mg/kg/day in rats and 300 mg/kg/day in rabbits, the maternal systemic exposure (AUC) were 72700 ng*hr/mL and 17100 ng*hr/mL, respectively, representing approximately 2 and 0.5 times the exposure in humans at the highest recommended dose 400 mg twice daily. When pregnant rats were dosed with nilotinib during organogenesis and through lactation, the adverse effects included a longer gestational period, lower pup body weights until weaning and decreased fertility indices in the pups when they reached maturity, all at a maternal dose of 60 mg/kg (i.e., 360 mg/m2 , approximately 0.7 times the clinical dose of 400 mg twice daily based on body surface area). At doses up to 20 mg/kg (i.e., 120 mg/m2 , approximately 0.25 times the clinical dose of 400 mg twice daily based on body surface area) no adverse effects were seen in the maternal animals or the pups. Risk Summary There are no data on the presence of nilotinib or its metabolites in human milk or its effects on a breastfed child or on milk production. However, nilotinib is present in the milk of lactating rats. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with Tasigna and for 14 days after the last dose. Animal Data After a single 20 mg/kg of [14 C] nilotinib dose to lactating rats, the transfer of parent drug and its metabolites into milk was observed. The overall milk-to-plasma exposure ratio of total radioactivity was approximately 2, based on the AUC0-24h or AUC0-INF values. No rat metabolites of nilotinib were detected that were unique to milk. Based on animal studies, Tasigna can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Pregnancy Testing Females of reproductive potential should have a pregnancy test prior to starting treatment with Tasigna. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Tasigna and for 14 days after the last dose. Infertility The risk of infertility in females or males of reproductive potential has not been studied in humans. In studies in rats and rabbits, the fertility in males and females was not affected [see Nonclinical Toxicology (13.1)] . The safety and effectiveness of Tasigna have been established in pediatric patients greater than or equal to 1 year of age with newly diagnosed and resistant or intolerant Ph+ CML in chronic phase [see Clinical Studies (14.5)] . There are no data for pediatric patients under 2 years of age. Use of Tasigna in pediatric patients 1 year to less than 2 years of age with newly diagnosed or resistant or intolerant Ph+ CML in chronic phase is supported by efficacy in pediatric patients 2 to 6 years of age for these indications. The safety and effectiveness of Tasigna have been established in pediatric patients greater than or equal to 1 year of age with resistant or intolerant Ph+ CML in accelerated phase based on evidence of effectiveness from an adequate and well-controlled single-arm study in adults [see Clinical Studies (14.2)] with safety data from two pediatric studies as described in the next paragraph. Use of Tasigna in pediatric patients 1 to less than 18 years of age is supported by evidence from two clinical trials [see Clinical Studies (14.5)] . The 25 patients with newly diagnosed Ph+ CML-CP were in the following age groups: 6 children (age 2 to less than 12 years) and 19 adolescents (age 12 to less than 18 years). The 44 patients with resistant or intolerant Ph+ CML-CP included 18 children (age 2 to less than 12 years) and 26 adolescents (age 12 to less than 18 years). All pediatric patients received Tasigna treatment at a dose of 230 mg/m2 twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg). No differences in efficacy or safety were observed between the different age subgroups in the two trials. The frequency, type, and severity of adverse reactions observed were generally consistent with those observed in adults, with the exception of the laboratory abnormalities of hyperbilirubinemia (Grade 3/4: 16%) and transaminase elevation (AST Grade 3/4: 2.9%, ALT Grade 3/4: 10%), which were reported at a higher frequency in pediatric patients than in adults [see Adverse Reactions (6.1)] . For pediatric growth and development, growth retardation has been reported in pediatric patients with Ph+ CML-CP treated with Tasigna [see Warnings and Precautions (5.14), Adverse Reactions (6.1)] . The safety and effectiveness of Tasigna in pediatric patients below the age of 1 year with newly diagnosed, or resistant or intolerant Ph+ CML in chronic phase and accelerated phase, have not been established. In the clinical trials of Tasigna (patients with newly diagnosed Ph+ CML-CP and resistant or intolerant Ph+ CML-CP and CML-AP), approximately 12% and 30% of patients were 65 years or over, respectively. - Patients with newly diagnosed Ph+ CML-CP: There was no difference in major molecular response between patients aged less than 65 years and those greater than or equal to 65 years. - Patients with resistant or intolerant CML-CP: There was no difference in major cytogenetic response rate between patients aged less than 65 years and those greater than or equal to 65 years. - Patients with resistant or intolerant CML-AP: The hematologic response rate was 44% in patients less than 65 years of age and 29% in patients greater than or equal to 65 years. No major differences for safety were observed in patients greater than or equal to 65 years of age as compared to patients less than 65 years. In the clinical trials, patients with a history of uncontrolled or significant cardiovascular 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 Boxed Warning, Warnings and Precautions (5.2)]. Reduce the Tasigna dosage in patients with hepatic impairment and monitor the QT interval closely in these patients [see Dosage and Administration (2.7), Clinical Pharmacology (12.3)] .

Product summary:

Tasigna (nilotinib) 50 mg capsules are red opaque cap and light yellow opaque body hard gelatin capsules, size 4 with black radial imprint “NVR/ABL.” Tasigna (nilotinib) 150 mg capsules are red opaque hard gelatin capsules, size 1 with black axial imprint “NVR/BCR.” Tasigna (nilotinib) 200 mg capsules are light yellow opaque hard gelatin capsules, size 0 with the red axial imprint “NVR/TKI.” Tasigna 50 mg capsules are supplied in bottles and Tasigna 150 mg and 200 mg capsules are supplied in blister packs. 50 mg Bottle of 120 capsules………………………………………………………………NDC 0078-0951-66 150 mg Carton of 4 blister packs of (4x28)…………………………………………………NDC 0078-0592-87 Blisters of 28 capsules………………………………………………………………NDC 0078-0592-51 200 mg Carton of 4 blister packs of (4x28)…………………………………………………NDC 0078-0526-87 Blisters of 28 capsules………………………………………………………………NDC 0078-0526-51 Tasigna (nilotinib) capsules should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

Authorization status:

New Drug Application

Patient Information leaflet

Novartis Pharmaceuticals Corporation
----------
This Medication Guide has been approved by the U.S. Food and
Drug Administration.
Revised: September 2021
Medication Guide
TASIGNA® (ta-sig-na)
(nilotinib)
capsules
What is the most important information I should know about Tasigna?
Tasigna can cause a possible life-threatening heart problem called QTc
prolongation. QTc prolongation
causes an irregular heartbeat, which may lead to sudden death.
Your healthcare provider should check the electrical activity of your
heart with a test called an
electrocardiogram (ECG):
• before starting Tasigna
• 7 days after starting Tasigna
• with any dose changes
• regularly during Tasigna treatment
You may lower your chances for having QTc prolongation with Tasigna if
you:
•
Take Tasigna on an empty stomach:
•
Avoid eating food for at least 2 hours before the dose is taken, and
•
Avoid eating food for at least 1 hour after the dose is taken.
•
Avoid grapefruit, grapefruit juice, and any supplement containing
grapefruit extract during treatment
with Tasigna. Food and grapefruit products increase the amount of
Tasigna in your body.
•
Avoid taking other medicines or supplements with Tasigna that can also
cause QTc prolongation.
•
Tasigna can interact with many medicines and supplements and increase
your chance for serious and
life-threatening side effects.
•
Do not take any other medicine during treatment with Tasigna unless
your healthcare provider tells
you it is okay to do so.
•
If you cannot swallow Tasigna capsules whole, you may open the Tasigna
capsule and sprinkle the
contents of each capsule in 1 teaspoon of applesauce (puréed apple).
Swallow the mixture right away
(within 15 minutes). For more information, see “How should I take
Tasigna?”
Call your healthcare provider right away if you feel lightheaded,
faint, or have an irregular heartbeat during
treatment with Tasigna. These can be symptoms of QTc prolongation.
What is Tasigna?
Tasigna is a prescription medicine used to treat:
•
adults and ch

Summary of Product characteristics

TASIGNA- NILOTINIB CAPSULE
NOVARTIS PHARMACEUTICALS CORPORATION
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TASIGNA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR TASIGNA.
TASIGNA (NILOTINIB) CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2007
WARNING: QT PROLONGATION AND SUDDEN DEATHS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
TASIGNA PROLONGS THE QT INTERVAL. PRIOR TO TASIGNA ADMINISTRATION AND
PERIODICALLY,
MONITOR FOR HYPOKALEMIA OR HYPOMAGNESEMIA AND CORRECT DEFICIENCIES.
(5.2) OBTAIN
ECGS TO MONITOR THE QTC AT BASELINE, SEVEN DAYS AFTER INITIATION, AND
PERIODICALLY
THEREAFTER, AND FOLLOWING ANY DOSE ADJUSTMENTS. (5.2, 5.3, 5.7, 5.12)
SUDDEN DEATHS HAVE BEEN REPORTED IN PATIENTS RECEIVING TASIGNA. (5.3)
DO NOT
ADMINISTER TASIGNA TO PATIENTS WITH HYPOKALEMIA, HYPOMAGNESEMIA, OR
LONG QT
SYNDROME. (4, 5.2)
AVOID USE OF CONCOMITANT DRUGS KNOWN TO PROLONG THE QT INTERVAL AND
STRONG
CYP3A4 INHIBITORS. (7.1, 7.2)
AVOID FOOD 2 HOURS BEFORE AND 1 HOUR AFTER TAKING THE DOSE. (2.1)
INDICATIONS AND USAGE
Tasigna is a kinase inhibitor 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. (1.1)
Adult patients with chronic phase (CP) and accelerated phase (AP) Ph+
CML resistant to or intolerant to
prior therapy that included imatinib. (1.2)
Pediatric patients greater than or equal to 1 year of age with Ph+
CML-CP and CML-AP resistant or
intolerant to prior tyrosine-kinase inhibitor (TKI) therapy. (1.3)
DOSAGE AND ADMINISTRATION
Recommended Adult Dose: Newly diagnosed Ph+ CML-CP: 300 mg orally
twice daily. Resistant or
intolerant Ph+ CML-CP and CML-AP: 400 mg orally twice daily. (2.1)
Recommended Pediatric Dose: Newly Diagnosed Ph+ CML-CP or Ph+ CML-CP
and CML-AP resistant or
intolerant to prior TKI therapy: 230 mg/m orally twice daily, rounded
to the nearest 50 mg dose (