United States - English - NLM (National Library of Medicine)

novartis pharmaceuticals corporation - nilotinib (unii: f41401512x) (nilotinib - unii:f41401512x) - nilotinib 200 mg - 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)] .

European Union - English - EMA (European Medicines Agency)

novartis europharm limited - nilotinib - leukemia, myelogenous, chronic, bcr-abl positive - antineoplastic agents - tasigna is indicated for the treatment of:adult and paediatric patients with newly diagnosed philadelphia chromosome positive chronic myelogenous leukaemia (cml) in the chronic phase,paediatric patients with philadelphia chromosome positive cml in chronic phase with resistance or intolerance to prior therapy including imatinib.tasigna is indicated for the treatment of:adult and paediatric patients with newly diagnosed philadelphia chromosome positive chronic myelogenous leukaemia (cml) in the chronic phase,adult patients with chronic phase and accelerated phase philadelphia chromosome positive cml with resistance or intolerance to prior therapy including imatinib. efficacy data in patients with cml in blast crisis are not available,paediatric patients with chronic phase philadelphia chromosome positive cml with resistance or intolerance to prior therapy including imatinib.

Israel - English - Ministry of Health

novartis israel ltd - nilotinib as monohydrate - capsules - nilotinib as monohydrate 200 mg - nilotinib - nilotinib - treatment of philadelphia chromosome positive chronic myeloid leukaemia (ph+ cml) in chronic or accelerated phase in patients resistant to or experiencing significant toxicity during treatment with imatinib.treatment of adult patients with newly diagnosed philadelphia chromosome positive chronic myelogenous leukemia in chronic phase.

Israel - English - Ministry of Health

novartis israel ltd - nilotinib as hydrochloride monohydrate - capsules - nilotinib as hydrochloride monohydrate 150 mg - nilotinib - nilotinib - treatment of adult patients with newly diagnosed philadelphia chromosome positive chronic myelogenous leukemia in chronic phase.

New Zealand - English - Medsafe (Medicines Safety Authority)

novartis new zealand ltd - nilotinib hydrochloride monohydrate 165.45mg equivalent to 150 mg nilotinib anhydrous free base;  ;   - capsule - 150 mg - active: nilotinib hydrochloride monohydrate 165.45mg equivalent to 150 mg nilotinib anhydrous free base     excipient: colloidal silicon dioxide crospovidone gelatin iron oxide red iron oxide yellow lactose monohydrate magnesium stearate opacode ink black s-1-277002 poloxamer 188 titanium dioxide - tasigna is indicated for the: · treatment of adult patients with newly diagnosed philadelphia chromosome positive chronic myeloid leukemia (ph+ cml) in chronic phase, · treatment of chronic phase and accelerated phase philadelphia chromosome positive chronic myelogenous leukaemia (cml) in adult patients resistant to or intolerant to at least one prior therapy including imatinib.

New Zealand - English - Medsafe (Medicines Safety Authority)

novartis new zealand ltd - nilotinib hydrochloride monohydrate 220.6mg equivalent to 200 mg nilotinib anhydrous free base;   - capsule - 200 mg - active: nilotinib hydrochloride monohydrate 220.6mg equivalent to 200 mg nilotinib anhydrous free base   excipient: colloidal silicon dioxide crospovidone gelatin iron oxide yellow lactose monohydrate magnesium stearate poloxamer 188 tekprint red sw-1102 titanium dioxide - tasigna is indicated for the: · treatment of adult patients with newly diagnosed philadelphia chromosome positive chronic myeloid leukaemia (ph+ cml) in chronic phase, · treatment of chronic phase and accelerated phase philadelphia chromosome positive chronic myelogenous leukaemia (cml) in adult patients resistant to or intolerant to at least one prior therapy including imatinib.

Australia - English - Department of Health (Therapeutic Goods Administration)

novartis pharmaceuticals australia pty ltd - nilotinib hydrochloride monohydrate, quantity: 165.45 mg (equivalent: nilotinib, qty 150 mg) - capsule, hard - excipient ingredients: magnesium stearate; gelatin; titanium dioxide; lactose monohydrate; colloidal anhydrous silica; poloxamer; iron oxide yellow; crospovidone; iron oxide red; propylene glycol; butan-1-ol; isopropyl alcohol; purified water; strong ammonia solution; ethanol absolute; iron oxide black; ethanol; shellac; sulfuric acid; industrial methylated spirit; ammonia - tasigna is indicated for the:,? treatment of adult patients with newly diagnosed philadelphia chromosome positive chronic myeloid leukaemia (cml) in chronic phase. ? treatment of adults with chronic phase and accelerated phase philadelphia chromosome positive chronic myeloid leukaemia (cml) resistant to or intolerant of prior therapy including imatinib.

Australia - English - Department of Health (Therapeutic Goods Administration)

novartis pharmaceuticals australia pty ltd - nilotinib hydrochloride monohydrate, quantity: 220.6 mg (equivalent: nilotinib, qty 200 mg) - capsule, hard - excipient ingredients: magnesium stearate; crospovidone; titanium dioxide; iron oxide yellow; poloxamer; gelatin; lactose monohydrate; colloidal anhydrous silica; propylene glycol; butan-1-ol; isopropyl alcohol; purified water; shellac; iron oxide red; ethanol absolute; potassium hydroxide; ammonia; industrial methylated spirit; iron oxide black; sulfuric acid; lecithin; xanthan gum; benzoic acid; sorbic acid; methylcellulose; polyethylene glycol; silica dimethicone silylate; dimeticone - tasigna is indicated for the:,? treatment of adult patients with newly diagnosed philadelphia chromosome positive chronic myeloid leukaemia (cml) in chronic phase. ? treatment of adults with chronic phase and accelerated phase philadelphia chromosome positive chronic myeloid leukaemia (cml) resistant to or intolerant of prior therapy including imatinib.

Singapore - English - HSA (Health Sciences Authority)

novartis (singapore) pte ltd - nilotinib hydrochloride monohydrate 220.6 mg eqv nilotinib anhydrous - capsule - 200mg - nilotinib hydrochloride monohydrate 220.6 mg eqv nilotinib anhydrous 200mg

Singapore - English - HSA (Health Sciences Authority)

novartis (singapore) pte ltd - nilotinib hcl monohydrate 165.45mg eqv nilotinib - capsule - 150mg - nilotinib hcl monohydrate 165.45mg eqv nilotinib 150mg