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

novartis pharmaceuticals corporation - canakinumab (unii: 37cq2c7x93) (canakinumab - unii:37cq2c7x93) - canakinumab 150 mg in 1 ml - ilaris® (canakinumab) is an interleukin-1β (il-1β) blocker indicated for the treatment of the following autoinflammatory periodic fever syndromes: cryopyrin-associated periodic syndromes (caps) ilaris is indicated for the treatment of cryopyrin-associated periodic syndromes (caps), in adults and pediatric patients 4 years of age and older, including: - familial cold autoinflammatory syndrome (fcas) - muckle-wells syndrome (mws) tumor necrosis factor receptor (tnf) associated periodic syndrome (traps) ilaris is indicated for the treatment of tumor necrosis factor (tnf) receptor associated periodic syndrome (traps) in adult and pediatric patients. hyperimmunoglobulin d syndrome (hids)/mevalonate kinase deficiency (mkd) ilaris is indicated for the treatment of hyperimmunoglobulin d (hyper-igd) syndrome (hids)/mevalonate kinase deficiency (mkd) in adult and pediatric patients. familial mediterranean fever (fmf) ilaris is indicated for the treatment of familial mediterranean fever (fmf) in adult and pediatric pat

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

novartis pharmaceuticals corporation - deferasirox (unii: v8g4mof2v9) (deferasirox - unii:v8g4mof2v9) - deferasirox 90 mg - jadenu is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older. jadenu is indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (ntdt) syndromes and with a liver iron concentration (lic) of at least 5 milligrams of iron per gram of liver dry weight (mg fe/g dw) and a serum ferritin greater than 300 mcg/l. the safety and efficacy of jadenu when administered with other iron chelation therapy have not been established. jadenu is contraindicated in patients with: - estimated gfr less than 40 ml/min/1.73 m2  [see dosage and administration (2.5), warnings and precautions (5.1)] ; - poor performance status [see warnings and precautions (5.1, 5.3)] ; - high-risk myelodysplastic syndromes (this patient population was not studied and is not expected to benefit from chelation therapy) ; - advanced malignancies [see warnings and precautions (5.1, 5.3)] ; - platelet counts less than 50 x 109 /l [see warnings and precautions (5.3, 5.4)] ; - known hypersensitivity to deferasirox or any component of jadenu [see warnings and precautions (5.7), adverse reactions (6.2)] . risk summary there are no studies with the use of jadenu in pregnant women to inform drug-associated risks. administration of deferasirox to rats during pregnancy resulted in decreased offspring viability and an increase in renal anomalies in male offspring at doses that were about or less than the recommended human dose on a mg/m2 basis. no fetal effects were noted in pregnant rabbits at doses equivalent to the human recommended dose on an mg/m2 basis. jadenu should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies had a background risk of birth defect, loss, or other adverse outcomes. however, the background risk in the u.s. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. data animal data in embryo-fetal developmental studies, pregnant rats and rabbits received oral deferasirox during the period of organogenesis at doses up to 100 mg/kg/day in rats and 50 mg/kg/day in rabbits (1.2 times the maximum recommended human dose (mrhd) on an mg/m2 basis). these doses resulted in maternal toxicity but no fetal harm was observed. in a prenatal and postnatal developmental study, pregnant rats received oral deferasirox daily from organogenesis through lactation day 20 at doses of 10, 30, and 90 mg/kg/day (0.1, 0.3, and 1.0 times the mrhd on a mg/m2 basis). maternal toxicity, loss of litters, and decreased offspring viability occurred at 90 mg/kg/day (1.0 times the mrhd on a mg/m2 basis), and increases in renal anomalies in male offspring occurred at 30 mg/kg/day (0.3 times the mrhd on a mg/m2 basis). risk summary no data are available regarding the presence of jadenu or its metabolites in human milk, the effects of the drug on the breastfed child, or the effects of the drug on milk production. deferasirox and its metabolites were excreted in rat milk. because many drugs are excreted in human milk and because of the potential for serious adverse reactions in a breastfeeding child from deferasirox and its metabolites, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother. contraception counsel patients to use non-hormonal method(s) of contraception since jadenu can render hormonal contraceptives ineffective [see drug interactions (7.2)] . transfusional iron overload the safety and effectiveness of jadenu have been established in pediatric patients 2 years of age and older for the treatment of transfusional iron overload [see dosage and administration (2.1)] . safety and effectiveness have not been established in pediatric patients less than 2 years of age for the treatment of transfusional iron overload. pediatric approval for treatment of transfusional iron overload was based on clinical studies of 292 pediatric patients 2 years to less than 16 years of age with various congenital and acquired anemias. seventy percent of these patients had beta-thalassemia [see indications and usage (1), dosage and administration (2.1), clinical studies (14)] . in those clinical studies, 173 children (ages 2 to < 12 years) and 119 adolescents (ages 12 to < 17 years) were exposed to deferasirox. a trial conducted in treatment naïve pediatric patients, 2 to < 18 years of age with transfusional iron overload (nct02435212) did not provide additional relevant information about the safety or effectiveness of the deferasirox granules dosage form (jadenu sprinkle) compared to the deferasirox oral tablets for suspension dosage form (exjade). iron overload in non-transfusion-dependent thalassemia syndromes the safety and effectiveness of jadenu have been established in patients 10 years of age and older for the treatment of chronic iron overload with non-transfusion-dependent thalassemia (ntdt) syndromes [see dosage and administration (2.2)] . safety and effectiveness have not been established in patients less than 10 years of age with chronic iron overload in ntdt syndromes. pediatric approval for treatment of ntdt syndromes with liver iron (fe) concentration (lic) of at least 5 mg fe per gram of dry weight and a serum ferritin greater than 300 mcg/l was based on 16 pediatric patients treated with deferasirox therapy (10 years to less than 16 years of age) with chronic iron overload and ntdt. use of jadenu in these age groups is supported by evidence from adequate and well-controlled studies of deferasirox in adult and pediatric patients [see indications and usage (1.2), dosage and administration (2.2), clinical studies (14)] . in general, risk factors for deferasirox-associated kidney injury include preexisting renal disease, volume depletion, overchelation, and concomitant use of other nephrotoxic drugs. acute kidney injury, and acute liver injury and failure has occurred in pediatric patients. in a pooled safety analysis, pediatric patients with higher deferasirox exposures had a greater probability of renal toxicity and decreased renal function, resulting in increased deferasirox exposure and progressive renal toxicity/kidney injury. higher rates of renal aes have been identified among pediatric patients receiving exjade doses greater than 25 mg/kg/day equivalent to 17.5 mg/kg/day jadenu when their serum ferritin values were less than 1,000 mcg/l [see dosage and administration (2.5), warnings and precautions (5.1, 5.6), adverse reactions (6.1, 6.2)] . monitoring recommendations for all pediatric patients with transfusional iron overload and ntdt it is recommended that serum ferritin be monitored every month to assess the patient’s response to therapy and to minimize the risk of overchelation [see warnings and precautions (5.6)] . monitor renal function by estimating gfr using an egfr prediction equation appropriate for pediatric patients and evaluate renal tubular function. monitor renal function more frequently in pediatric patients in the presence of renal toxicity risk factors, including episodes of dehydration, fever and acute illness that may result in volume depletion or decreased renal perfusion. use the minimum effective dose [see warnings and precautions (5.1)] . interrupt jadenu in pediatric patients with transfusional iron overload, and consider dose interruption in pediatric patients with non-transfusion-dependent iron overload, for acute illnesses, which can cause volume depletion, such as vomiting, diarrhea, or prolonged decreased oral intake, and monitor more frequently. resume therapy as appropriate, based on assessments of renal function, when oral intake and volume status are normal. evaluate the risk benefit profile of continued jadenu use in the setting of decreased renal function. avoid use of other nephrotoxic drugs [see dosage and administration (2.5), warnings and precautions (5.1)] . juvenile animal toxicity data renal toxicity was observed in adult mice, rats, and marmoset monkeys administered deferasirox at therapeutic doses. in a neonatal and juvenile toxicity study in rats, deferasirox was administered orally from postpartum day 7 through 70, which equates to a human age range of term neonate through adolescence. increased renal toxicity was identified in juvenile rats compared to adult rats at a dose based on mg/m2 approximately 0.4 times the recommended dose of 20 mg/kg/day. a higher frequency of renal abnormalities was noted when deferasirox was administered to non-iron overloaded animals compared to iron overloaded animals. four hundred thirty-one (431) patients greater than or equal to 65 years of age were studied in clinical trials of deferasirox in the transfusional iron overload setting. two hundred twenty-five (225) of these patients were between 65 and 75 years of age while 206 were greater than or equal to 75 years of age. the majority of these patients had myelodysplastic syndrome (mds) (n = 393). in these trials, elderly patients experienced a higher frequency of adverse reactions than younger patients. monitor elderly patients for early signs or symptoms of adverse reactions that may require a dose adjustment. elderly patients are at increased risk for toxicity due to the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range. in elderly patients, including those with mds, individualize the decision to remove accumulated iron based on clinical circumstances and the anticipated clinical benefit and risks of deferasirox tablets for oral suspension therapy. jadenu is contraindicated in patients with egfr less than 40 ml/min/1.73 m2  [see contraindications (4)] . for patients with renal impairment (egfr 40 to 60 ml/min/1.73 m2 ), reduce the starting dose by 50% [see dosage and administration (2.4), clinical pharmacology (12.3)]. exercise caution in pediatric patients with an egfr between 40 and 60 ml/min/1.73 m2  [see dosage and administration (2.4)]. if treatment is needed, use the minimum effective dose with enhanced monitoring of glomerular and renal tubular function. individualize dose titration based on improvement in renal injury [see dosage and administration (2.4, 2.5)] . jadenu can cause glomerular dysfunction, renal tubular toxicity, or both, and can result in acute renal failure. monitor all patients closely for changes in egfr and renal tubular dysfunction during jadenu treatment. if either develops, consider dose reduction, interruption or discontinuation of jadenu until glomerular or renal tubular function returns to baseline [see dosage and administration (2.4, 2.5), warnings and precautions (5.1)] . avoid use in patients with severe (child-pugh c) hepatic impairment. for patients with moderate (child-pugh b) hepatic impairment, reduce the starting dose by 50%. closely monitor patients with mild (child-pugh a) or moderate (child-pugh b) hepatic impairment for efficacy and adverse reactions that may require dose titration [see dosage and administration (2.4), warnings and precautions (5.2), clinical pharmacology (12.3)] .

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

novartis pharmaceuticals corporation - deferasirox (unii: v8g4mof2v9) (deferasirox - unii:v8g4mof2v9) - deferasirox 125 mg - exjade is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older. exjade is indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (ntdt) syndromes and with a liver iron concentration (lic) of at least 5 milligrams of iron per gram of liver dry weight (mg fe/g dw) and a serum ferritin greater than 300 mcg/l. the safety and efficacy of exjade when administered with other iron chelation therapy have not been established. exjade is contraindicated in patients with: - estimated gfr less than 40 ml/min/1.73 m2  [see dosage and administration (2.5), warnings and precautions (5.1)] ; - poor performance status; [see warnings and precautions (5.1, 5.3)] - high-risk myelodysplastic syndromes; (this patient population was not studied and is not expected to benefit from chelation therapy) - advanced malignancies. [see warnings and precautions (5.1, 5.3)]

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

novartis pharmaceuticals corporation - dexmethylphenidate hydrochloride (unii: 1678ok0e08) (dexmethylphenidate - unii:m32rh9mfgp) - dexmethylphenidate hydrochloride 30 mg - focalin xr is indicated for the treatment of attention deficit hyperactivity disorder (adhd) [see clinical studies (14)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adhd medications, including focalin xr, during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for adhd medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/. risk summary dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. there may be risks to the fetus associated with the use of cns stimulants during pregnancy (see clinical considerations) . embryo-fetal development studies in rats showed delayed fetal skeletal ossification at doses up to 5 times t

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

novartis pharmaceuticals corporation - methylphenidate hydrochloride (unii: 4b3sc438hi) (methylphenidate - unii:207zz9qz49) - methylphenidate hydrochloride 20 mg - ritalin la® is indicated for the treatment of attention deficit hyperactivity disorder (adhd), in pediatric patients 6 to 12 years of age [see clinical studies (14)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adhd medications, including ritalin la during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for adhd medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/. risk summary published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. there may be risks to the fetus associated with the use of cns stimulants use during pregnancy (see clinical considerations) . no effects on morphological development were observed in embryo-fetal development studies with oral administration of methylphenidate t

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

novartis pharmaceuticals corporation - fingolimod hydrochloride (unii: g926ec510t) (fingolimod - unii:3qn8byn5qf) - fingolimod 0.5 mg - gilenya is indicated for the treatment of relapsing forms of multiple sclerosis (ms), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in patients 10 years of age and older. gilenya is contraindicated in patients who have: - in the last 6 months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (tia), decompensated heart failure requiring hospitalization or class iii/iv heart failure - a history or presence of mobitz type ii second-degree or third-degree av block or sick sinus syndrome, unless patient has a functioning pacemaker [see warnings and precautions (5.1)] - a baseline qtc interval ≥ 500 msec - cardiac arrhythmias requiring anti-arrhythmic treatment with class ia or class iii anti-arrhythmic drugs - had a hypersensitivity reaction to fingolimod or any of the excipients in gilenya. observed reactions include rash, urticaria and angioedema upon treatment initiation [see warnings and precautions (5.14)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to gilenya during pregnancy. physicians are encouraged to enroll pregnant patients, or pregnant women may register themselves in the gilenya pregnancy registry by calling 1-877-598-7237, sending an email to gpr@quintiles.com, or visiting www.gilenyapregnancyregistry.com. risk summary based on findings from animal studies, gilenya may cause fetal harm when administered to a pregnant woman. data from prospective reports to the gilenya pregnancy registry (gpr) are currently not sufficient to allow for an adequate assessment of the drug-associated risk for birth defects and miscarriage in humans. in oral studies conducted in rats and rabbits, fingolimod demonstrated developmental toxicity, including an increase in malformations (rats) and embryolethality, when given to pregnant animals. in rats, the highest no-effect dose was less than the recommended human dose of 0.5 mg/day on a body surface area (mg/m2 ) basis. the most common fetal visceral malformations in rats were persistent truncus arteriosus and ventricular septal defect. the receptor affected by fingolimod (sphingosine 1-phosphate receptor) is known to be involved in vascular formation during embryogenesis (see data ). advise pregnant women of the potential risk to a fetus. in the us general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. the background risk of major birth defects and miscarriage for the indicated population is unknown. clinical considerations in females planning to become pregnant, gilenya should be stopped 2 months before planned conception. the possibility of severe increase in disability should be considered in women who discontinue or are considering discontinuation of gilenya because of pregnancy or planned pregnancy. in many of the cases in which increase in disability was reported after stopping gilenya, patients had stopped gilenya because of pregnancy or planned pregnancy [see warnings and precautions (5.9)] . data animal data when fingolimod was orally administered to pregnant rats during the period of organogenesis (0, 0.03, 0.1, and 0.3 mg/kg/day or 0, 1, 3, and 10 mg/kg/day), increased incidences of fetal malformations and embryofetal deaths were observed at all but the lowest dose tested (0.03 mg/kg/day), which is less than the recommended human dose (rhd) on a mg/m2 basis. oral administration to pregnant rabbits during organogenesis (0, 0.5, 1.5, and 5 mg/kg/day) resulted in increased incidences of embryofetal mortality and fetal growth retardation at the mid and high doses. the no-effect dose for these effects in rabbits (0.5 mg/kg/day) is approximately 20 times the rhd on a mg/m2 basis. when fingolimod was orally administered to female rats during pregnancy and lactation (0, 0.05, 0.15, and 0.5 mg/kg/day), pup survival was decreased at all doses and a neurobehavioral (learning) deficit was seen in offspring at the high dose. the low-effect dose of 0.05 mg/kg/day is similar to the rhd on a mg/m2 basis. risk summary there are no data on the presence of fingolimod in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. fingolimod is excreted in the milk of treated rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for gilenya and any potential adverse effects on the breastfed infant from gilenya or from the underlying maternal condition. pregnancy testing the pregnancy status of females of reproductive potential should be verified prior to starting treatment with gilenya [see use in specific populations (8.1)] . contraception before initiation of gilenya treatment, females of reproductive potential should be counseled on the potential for a serious risk to the fetus and the need for effective contraception during treatment with gilenya [see warnings and precautions (5.8) and use in specific populations (8.1)] . since it takes approximately 2 months to eliminate the compound from the body after stopping treatment, the potential risk to the fetus may persist and women should use effective contraception during this period [see warnings and precautions (5.8, 5.13)] . safety and effectiveness of gilenya for the treatment of relapsing forms of multiple sclerosis in pediatric patients 10 to less than 18 years of age were established in one randomized, double-blind clinical study in 215 patients (gilenya n = 107; intramuscular interferon (ifn) beta-1a n = 108) [see clinical studies (14.2)] . in the controlled pediatric study, the safety profile in pediatric patients (10 to less than 18 years of age) receiving gilenya 0.25 mg or 0.5 mg daily was similar to that seen in adult patients. in the pediatric study, cases of seizures were reported in 5.6% of gilenya-treated patients and 0.9% of interferon beta-1a-treated patients. it is recommended that pediatric patients, if possible, complete all immunizations in accordance with current immunization guidelines prior to initiating gilenya therapy. safety and effectiveness of gilenya in pediatric patients below the age of 10 years have not been established. juvenile animal toxicity data in a study in which fingolimod (0.3, 1.5, or 7.5 mg/kg/day) was orally administered to young rats from weaning through sexual maturity, changes in bone mineral density and persistent neurobehavioral impairment (altered auditory startle) were observed at all doses. delayed sexual maturation was noted in females at the highest dose tested and in males at all doses. the bone changes observed in fingolimod-treated juvenile rats are consistent with a reported role of s1p in the regulation of bone mineral homeostasis. when fingolimod (0.5 or 5 mg/kg/day) was orally administered to rats from the neonatal period through sexual maturity, a marked decrease in t-cell dependent antibody response was observed at both doses. this effect had not fully recovered by 6-8 weeks after the end of treatment. overall, a no-effect dose for adverse developmental effects in juvenile animals was not identified. clinical ms studies of gilenya did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently than younger patients. gilenya should be used with caution in patients aged 65 years and over, reflecting the greater frequency of decreased hepatic, or renal, function and of concomitant disease or other drug therapy. because fingolimod, but not fingolimod-phosphate, exposure is doubled in patients with severe hepatic impairment, patients with severe hepatic impairment should be closely monitored, as the risk of adverse reactions may be greater [see warnings and precautions (5.5), clinical pharmacology (12.3)] . no dose adjustment is needed in patients with mild or moderate hepatic impairment. the blood level of some gilenya metabolites is increased (up to 13-fold) in patients with severe renal impairment [see clinical pharmacology (12.3)] . the toxicity of these metabolites has not been fully explored. the blood level of these metabolites has not been assessed in patients with mild or moderate renal impairment.

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

novartis pharmaceuticals corporation - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid anhydrous 5 mg in 100 ml - reclast is indicated for treatment of osteoporosis in postmenopausal women. in postmenopausal women with osteoporosis, diagnosed by bone mineral density (bmd) or prevalent vertebral fracture, reclast reduces the incidence of fractures (hip, vertebral, and non-vertebral osteoporosis-related fractures). in patients at high risk of fracture, defined as a recent low-trauma hip fracture, reclast reduces the incidence of new clinical fractures [see clinical studies (14.1) ]. reclast is indicated for prevention of osteoporosis in postmenopausal women [see clinical studies (14.2) ]. reclast is indicated for treatment to increase bone mass in men with osteoporosis [see clinical studies (14.3 ) ]. reclast is indicated for the treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who are expected to remain on glucocorticoids for at least 12 months [s ee clinical

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

novartis pharmaceuticals corporation - panobinostat lactate (unii: hn0t99oo4v) (panobinostat - unii:9647fm7y3z) - panobinostat 10 mg - farydak, a histone deacetylase inhibitor, in combination with bortezomib and dexamethasone, is indicated for the treatment of patients with multiple myeloma who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent. this indication is approved under accelerated approval based on progression free survival [see clinical studies (14.1)] . continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. none risk summary farydak can cause fetal harm when administered to a pregnant woman. panobinostat was teratogenic in rats and rabbits. if farydak is used during pregnancy or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus. data animal data in embryofetal development studies, panobinostat was administered orally 3 times per week during the period of organogenesis to pregnant rats (30, 100, and 300 mg/kg) and rabbits (10, 40, and 80 mg/kg). i

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)] .

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

novartis pharmaceuticals corporation - hydralazine hydrochloride (unii: fd171b778y) (hydralazine - unii:26nak24ls8), hydrochlorothiazide (unii: 0j48lph2th) (hydrochlorothiazide - unii:0j48lph2th), reserpine (unii: 8b1qwr724a) (reserpine - unii:8b1qwr724a) - tablet, coated - 25 mg - hypertension (see boxed warning). hypersensitivity to reserpine; mental depression or history of mental depression (especially with suicidal tendencies); active peptic ulcer, ulcerative colitis; patients receiving electroconvulsive therapy. hypersensitivity to hydralazine; coronary artery disease; mitral valvular rheumatic heart disease. anuria; hypersensitivity to this or other sulfonamide-derived drugs.