Spojené státy - angličtina - NLM (National Library of Medicine)

alembic pharmaceuticals limited - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole 2 mg - aripiprazole is indicated for the treatment of: •schizophrenia [see clinical studies (14.1)] additional pediatric use information is approved for otsuka america pharmaceutical, inc.’s abilify® (aripiprazole) product. however, due to otsuka america pharmaceutical, inc.’s marketing exclusivity rights, this drug product is not labeled with that information. aripiprazole is contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. reactions have ranged from pruritus/urticaria to anaphylaxis [see adverse reactions (6.2)]. teratogenic effects pregnancy category c: pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aripiprazole during pregnancy. for more information contact the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. risk summary neonates exposed to antipsychotic drugs (includi

Spojené státy - angličtina - NLM (National Library of Medicine)

alembic pharmaceuticals limited - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole 10 mg - aripiprazole orally disintegrating tablets are indicated for the treatment of: •schizophrenia [see clinical studies (14.1)] additional pediatric use information is approved for otsuka america pharmaceutical, inc.’s abilify® (aripiprazole) product. however, due to otsuka america pharmaceutical, inc.’s marketing exclusivity rights, this drug product is not labeled with that information.  aripiprazole is contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. reactions have ranged from pruritus/urticaria to anaphylaxis [see adverse reactions (6.2)]. teratogenic effects pregnancy category c: pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aripiprazole during pregnancy. for more information contact the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . risk summary   neonates exposed to an

Spojené státy - angličtina - NLM (National Library of Medicine)

trigen laboratories, llc - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole 2 mg - aripiprazole is indicated for the treatment of: •schizophrenia [see clinical studies (14.1)] additional pediatric use information is approved for otsuka america pharmaceutical, inc.’s abilify® (aripiprazole) product. however, due to otsuka america pharmaceutical, inc.’s marketing exclusivity rights, this drug product is not labeled with that information. aripiprazole is contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. reactions have ranged from pruritus/urticaria to anaphylaxis [see adverse reactions (6.2)]. teratogenic effects pregnancy category c: pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aripiprazole during pregnancy. for more information contact the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. risk summary neonates exposed to antipsychotic drugs (includi

Spojené státy - angličtina - NLM (National Library of Medicine)

otsuka america pharmaceutical, inc. - decitabine (unii: 776b62cq27) (decitabine - unii:776b62cq27) - decitabine 50 mg in 20 ml - dacogen is indicated for treatment of adult patients with myelodysplastic syndromes (mds) including previously treated and untreated, de novo and secondary mds of all french-american-british subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk international prognostic scoring system groups. none. risk summary based on findings from human data, animal studies, and the mechanism of action, dacogen can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1) and nonclinical toxicology (13.1)] . limited published data on dacogen use throughout the first trimester during pregnancy describe adverse developmental outcomes including major birth defects (structural abnormalities). in animal reproduction studies, administration of decitabine to pregnant mice and rats during organogenesis caused adverse developmental outcomes including malformations and embryo-fetal lethality starting at doses approximately 7% of the recommended human dose on a mg/m2 basis (see data) . advise pregnant women of the potential risk to a fetus. the estimated 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. the estimated background risk of major birth defects and miscarriage in the u.s. general population is 2% to 4% and 15% to 20% of clinically recognized pregnancies, respectively. data human data a single published case report of decitabine pregnancy exposure in a 39-year old woman with a hematologic malignancy described multiple structural abnormalities after 6 cycles of therapy in the 18th week of gestation. these abnormalities included holoprosencephaly, absence of nasal bone, mid-facial deformity, cleft lip and palate, polydactyly and rocker-bottom feet. the pregnancy was terminated. animal data in utero exposure to decitabine causes temporal related defects in the rat and/or mouse, which include growth suppression, exencephaly, defective skull bones, rib/sternabrae defects, phocomelia, digit defects, micrognathia, gastroschisis, micromelia. decitabine inhibits proliferation and increases apoptosis of neural progenitor cells of the fetal cns and induces palatal clefting in the developing murine fetus. studies in mice have also shown that decitabine administration during osteoblastogenesis (day 10 of gestation) induces bone loss in offspring. in mice exposed to single ip (intraperitoneal) injections (0, 0.9 and 3.0 mg/m2 , approximately 2% and 7% of the recommended daily clinical dose, respectively) over gestation days 8, 9, 10 or 11, no maternal toxicity was observed but reduced fetal survival was observed after treatment at 3 mg/m2 and decreased fetal weight was observed at both dose levels. the 3 mg/m2 dose elicited characteristic fetal defects for each treatment day, including supernumerary ribs (both dose levels), fused vertebrae and ribs, cleft palate, vertebral defects, hind-limb defects and digital defects of fore- and hind-limbs. in rats given a single ip injection of 2.4, 3.6 or 6 mg/m2 (approximately 5%, 8%, or 13% the daily recommended clinical dose, respectively) on gestation days 9-12, no maternal toxicity was observed. no live fetuses were seen at any dose when decitabine was injected on gestation day 9. a significant decrease in fetal survival and reduced fetal weight at doses greater than 3.6 mg/m2 was seen when decitabine was given on gestation day 10. increased incidences of vertebral and rib anomalies were seen at all dose levels, and induction of exophthalmia, exencephaly, and cleft palate were observed at 6.0 mg/m2 . increased incidence of foredigit defects was seen in fetuses at doses greater than 3.6 mg/m2 . reduced size and ossification of long bones of the fore-limb and hind-limb were noted at 6.0 mg/m2 . the effect of decitabine on postnatal development and reproductive capacity was evaluated in mice administered a single 3 mg/m2 ip injection (approximately 7% the recommended daily clinical dose) on day 10 of gestation. body weights of males and females exposed in utero to decitabine were significantly reduced relative to controls at all postnatal time points. no consistent effect on fertility was seen when female mice exposed in utero were mated to untreated males. untreated females mated to males exposed in utero showed decreased fertility at 3 and 5 months of age (36% and 0% pregnancy rate, respectively). follow up studies indicated that treatment of pregnant mice with decitabine on gestation day 10 was associated with a reduced pregnancy rate resulting from effects on sperm production in the f1-generation. risk summary there are no data on the presence of decitabine or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. because of the potential for serious adverse reactions from dacogen in a breastfed child, advise women not to breastfeed while receiving dacogen and for at least 2 weeks after the last dose. pregnancy testing conduct pregnancy testing of females of reproductive potential prior to initiating dacogen. contraception females dacogen can cause fetal harm when administered to pregnant women [see use in specific populations (8.1)]. advise females of reproductive potential to use effective contraception while receiving dacogen and for 6 months following the last dose. males advise males with female partners of reproductive potential to use effective contraception while receiving treatment with dacogen and for 3 months following the last dose [see nonclinical toxicology (13.1)] . infertility based on findings of decitabine in animals, male fertility may be compromised by treatment with dacogen. the reversibility of the effect on fertility is unknown [see nonclinical toxicology (13.1)]. the safety and effectiveness of dacogen in pediatric patients have not been established. of the total number of patients exposed to dacogen in the controlled clinical trial, 61 of 83 patients were age 65 years and over, while 21 of 83 patients were age 75 years and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Spojené státy - angličtina - NLM (National Library of Medicine)

otsuka america pharmaceutical, inc. - busulfan (unii: g1ln9045dk) (busulfan - unii:g1ln9045dk) - busulfex is indicated for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia. busulfex is contraindicated in patients with a history of hypersensitivity to any of its components. risk summary busulfex can cause fetal harm when administered to a pregnant woman based on animal data. busulfan was teratogenic in mice, rats, and rabbits following administration during organogenesis. the solvent, dma, may also cause fetal harm when administered to a pregnant woman. in rats, dma doses of approximately 40% of the daily dose of dma in the busulfex dose on a mg/m2 basis given during organogenesis caused significant developmental anomalies (see data ). there are no available human data informing the drug-associated risk. advise pregnant women of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated populations are unknown. however, the background risk in the u.s. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. animal data following administration during organogenesis in animals, busulfan caused malformations and anomalies, including significant alterations in the musculoskeletal system, body weight gain, and size. in pregnant rats, busulfan produced sterility in both male and female offspring due to the absence of germinal cells in the testes and ovaries. the solvent, n,n-dimethylacetamide (dma), administered to rats at doses of 400 mg/kg/day (about 40% of the daily dose of dma in the busulfex dose on a mg/m2 basis) during organogenesis caused significant developmental anomalies. the most striking abnormalities included anasarca, cleft palate, vertebral anomalies, rib anomalies, and serious anomalies of the vessels of the heart. risk summary it is not known whether busulfex is present in human milk. because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for busulfan in human and animal studies, discontinue breastfeeding during treatment with busulfex. contraception females busulfex can cause fetal harm when administered to a pregnant woman [ see use in specific populations (8.1)] . advise females of reproductive potential to use effective contraception during treatment with busulfex and for 6 months following cessation of therapy. males busulfex may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities. males with female sexual partners of reproductive potential should use effective contraception during treatment with busulfex and for 3 months after cessation of therapy [ see nonclinical toxicology (13.1)]. infertility females ovarian suppression and amenorrhea commonly occur in premenopausal women undergoing chronic, low-dose busulfan therapy for chronic myelogenous leukemia. busulfex may cause temporary or permanent infertility in prepubertal girls or in females of child-bearing potential treated with high-dose busulfex in the conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation. males sterility, azoospermia, and testicular atrophy have been reported in male patients. the effectiveness of busulfex in the treatment of cml has not been specifically studied in pediatric patients. an open-label, uncontrolled study evaluated the pharmacokinetics of busulfex in 24 pediatric patients receiving busulfex as part of a conditioning regimen administered prior to hematopoietic progenitor cell transplantation for a variety of malignant hematologic (n=15) or non-malignant diseases (n=9). patients ranged in age from 5 months to 16 years (median 3 years). busulfex dosing was targeted to achieve an area under the plasma concentration curve (auc) of 900-1350 µm∙min with an initial dose of 0.8 mg per kg or 1.0 mg per kg (based on actual body weight (abw)) if the patient was greater than 4 or less than or equal to 4 years, respectively. the dose was adjusted based on plasma concentration after completion of dose 1. patients received busulfex doses every six hours as a two‑hour infusion over four days for a total of 16 doses, followed by cyclophosphamide 50 mg per kg once daily for four days. after one rest day, hematopoietic progenitor cells were infused. all patients received phenytoin as seizure prophylaxis. the target auc (900-1350±5% µm∙min) for busulfex was achieved at dose 1 in 71% (17/24) of patients. steady state pharmacokinetic testing was performed at dose 9 and 13. busulfex levels were within the target range for 21 of 23 evaluable patients. all 24 patients experienced neutropenia (absolute neutrophil count (anc) less than 0.5×109 /l) and thrombocytopenia (platelet transfusions or platelet count less than 20,000/mm3 ). seventy-nine percent (19/24) of patients experienced lymphopenia (absolute lymphocyte count less than 0.1×109 ). in 23 patients, the anc recovered to greater than 0.5×109 /l (median time to recovery = bmt day +13; range = bmt day +9 to +22). one patient who died on day +20 had not recovered to an anc >0.5×109 /l. four (17%) patients died during the study. two patients died within 28 days of transplant; one with pneumonia and capillary leak syndrome, and the other with pneumonia and veno-occlusive disease. two patients died prior to day 100; one due to progressive disease and one due to multi-organ failure. adverse reactions were reported in all 24-patients during the study period (bmt day -10 through bmt day +28) or post-study surveillance period (day +29 through +100). these included vomiting (100%), nausea (83%), stomatitis (79%), hvod (21%), graft-versus host disease (gvhd) (25%), and pneumonia (21%). based on the results of this 24‑patient clinical trial, a suggested dosing regimen of busulfex in pediatric patients is shown in the following dosing nomogram: simulations based on a pediatric population pharmacokinetic model indicate that approximately 60% of pediatric patients will achieve a target busulfex exposure (auc) between 900 to 1350 µm∙min with the first dose of busulfex using this dosing nomogram. therapeutic drug monitoring and dose adjustment following the first dose of busulfex is recommended. dose adjustment based on therapeutic drug monitoring instructions for measuring the auc of busulfan at dose 1 (see blood sample collection for auc determination ) and the formula for adjustment of subsequent doses to achieve the desired target auc (1125 µm∙min), are provided below. for example, if a patient received a dose of 11 mg busulfan and if the corresponding auc measured was 800 µm∙min, for a target auc of 1125 µm∙min, the target mg dose would be: busulfex dose adjustment may be made using this formula and instructions below. blood sample collection for auc determination calculate the auc (µm∙min) based on blood samples collected at the following time points: for dose 1:2 hr (end of infusion), 4 hr and 6 hr (immediately prior to the next scheduled busulfex administration). actual sampling times should be recorded. for doses other than dose 1: pre-infusion (baseline), 2 hr (end of infusion), 4 hr and 6 hr (immediately prior to the next scheduled busulfex administration). auc calculations based on fewer than the three specified samples may result in inaccurate auc determinations. for each scheduled blood sample, collect one to three ml of blood into heparinized (na or li heparin) vacutainer® tubes. the blood samples should be placed on wet ice immediately after collection and should be centrifuged (at 4°c) within one hour. the plasma, harvested into appropriate cryovial storage tubes, is to be frozen immediately at -20°c. all plasma samples are to be sent in a frozen state (i.e., on dry ice) to the assay laboratory for the determination of plasma busulfan concentrations. calculation of auc busulfex auc calculations may be made using the following instructions and appropriate standard pharmacokinetic formula: if the auc is assessed subsequent to dose 1, steady-state aucss (auc0-6hr ) is to be estimated from the trough, 2 hr, 4 hr and 6 hr concentrations using the linear trapezoidal rule. instructions for drug administration and blood sample collection for therapeutic drug monitoring use an administration set with minimal residual hold up (priming) volume (1 to 3 ml) for drug infusion to ensure accurate delivery of the entire prescribed dose and to ensure accurate collection of blood samples for therapeutic drug monitoring and dose adjustment. prime the administration set tubing with drug solution to allow accurate documentation of the start time of busulfex infusion. collect the blood sample from a peripheral iv line to avoid contamination with infusing drug. if the blood sample is taken directly from the existing central venous catheter (cvc), do not collect the blood sample while the drug is infusing to ensure that the end of infusion sample is not contaminated with any residual drug. at the end of infusion (2 hr), disconnect the administration tubing and flush the cvc line with 5 ml of normal saline prior to the collection of the end of infusion sample from the cvc port. collect the blood samples from a different port than that used for the busulfex infusion. when recording the busulfex infusion stop time, do not include the time required to flush the indwelling catheter line. discard the administration tubing at the end of the two‑hour infusion [see dosage and administration (2.3)]. clinical studies of busulfex did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Spojené státy - angličtina - NLM (National Library of Medicine)

zydus pharmaceuticals usa inc. - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole tablets are indicated for the treatment of - schizophrenia - irritability associated with autistic disorder - treatment of tourette's disorder aripiprazole is contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. reactions have ranged from pruritus/urticaria to anaphylaxis [see adverse reactions (6.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including aripiprazole, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit  http://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/. risk summary neonates exposed to antipsychotic drugs, including aripiprazole, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see clinical considerations) . overall availabl

Malajsie - angličtina - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

luen wah medical co. sdn. bhd. - dextrose monohydrate/dextrose/glucose; sodium chloride (salt) -

Spojené státy - angličtina - NLM (National Library of Medicine)

otsuka america pharmaceutical, inc. - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole 300 mg in 1.5 ml - abilify maintena (aripiprazole) is indicated for: - treatment of schizophrenia in adults [see clinical studies (14.1)] - maintenance monotherapy treatment of bipolar i disorder in adults [see clinical studies (14.2)] abilify maintena is contraindicated in patients with a known hypersensitivity to aripiprazole. hypersensitivity reactions ranging from pruritus/urticaria to anaphylaxis have been reported in patients receiving aripiprazole [see adverse reactions (6.1 and 6.2)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to abilify during pregnancy. for more information contact the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. risk summary neonates exposed to antipsychotic drugs, including abilify maintena, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. there are insufficient data with abilify maintena use in pregnant women to inform a drug-associated risk. in animal reproduction studies, oral and intravenous aripiprazole administration during organogenesis in rats and/or rabbits at doses 10 and 11 times, respectively, the maximum recommended human dose (mrhd) produced fetal death, decreased fetal weight, undescended testicles, delayed skeletal ossification, skeletal abnormalities, and diaphragmatic hernia. oral and intravenous aripiprazole administration during the pre- and post-natal period in rats at doses 10 times the mrhd produced prolonged gestation, stillbirths, decreased pup weight, and decreased pup survival. consider the benefits and risks of abilify maintena and possible risks to the fetus when prescribing abilify maintena to a pregnant woman. advise pregnant women of potential fetal risk. the background risk of major birth defects and miscarriage for the indicated population are unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations fetal/neonatal adverse reactions extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs (including oral aripiprazole) during the third trimester of pregnancy. these symptoms have varied in severity. some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. monitor neonates exhibiting extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. animal data in animal studies, aripiprazole demonstrated developmental toxicity, including possible teratogenic effects in rats and rabbits. pregnant rats were treated with oral doses of 3, 10, and 30 mg/kg/day which are approximately 1 to 10 times the mrhd of 30 mg/day on mg/m2 basis of aripiprazole during the period of organogenesis. treatment at the highest dose caused a slight prolongation of gestation and delay in fetal development, as evidenced by decreased fetal weight and undescended testes. delayed skeletal ossification was observed at 3 and 10 times the oral mrhd on mg/m2 basis. at 3 and 10 times the oral mrhd on mg/m2 basis, delivered offspring had decreased body weights. increased incidences of hepatodiaphragmatic nodules and diaphragmatic hernia were observed in offspring from the highest dose group (the other dose groups were not examined for these findings). postnatally, delayed vaginal opening was seen at 3 and 10 times the oral mrhd on mg/m2 basis and impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-implantation loss, likely mediated through effects on female offspring) along with some maternal toxicity were seen at the highest dose; however, there was no evidence to suggest that these developmental effects were secondary to maternal toxicity. in pregnant rats treated with aripiprazole intravenously at doses of 3, 9, and 27 mg/kg/day, which are 1 to 9 times the oral mrhd on mg/m2 basis, during the period of organogenesis, decreased fetal weight and delayed skeletal ossification were seen at the highest dose which also caused maternal toxicity. in pregnant rabbits treated with oral doses of 10, 30, and 100 mg/kg/day which are 2 to 11 times human exposure at the oral mrhd based on auc and 6 to 65 times the oral mrhd of aripiprazole on mg/m2 basis during the period of organogenesis, decreased maternal food consumption and increased abortions were seen at the highest dose as well as increased fetal mortality. decreased fetal weight and increased incidence of fused sternebrae were observed at 3 and 11 times the mrhd based on auc. in pregnant rabbits receiving aripiprazole injection intravenously at doses of 3, 10, and 30 mg/kg/day, which are 2 to 19 times the oral mrhd on mg/m2 basis during the period of organogenesis, the highest dose caused pronounced maternal toxicity that resulted in decreased fetal weight, increased fetal abnormalities (primarily skeletal), and decreased fetal skeletal ossification. the fetal no-effect dose was 5 times the human exposure at the oral mrhd based on auc and is 6 times the oral mrhd on mg/m2 basis. in rats treated with oral doses of 3, 10, and 30 mg/kg/day, which are 1 to 10 times the oral mrhd of aripiprazole on a mg/m2 basis, peri- and post-natally (from day 17 of gestation through day 21 postpartum), slight maternal toxicity and slightly prolonged gestation were seen at the highest dose. an increase in stillbirths and decreases in pup weight (persisting into adulthood) and survival were also seen at this dose. in rats treated with aripiprazole intravenously at doses of 3, 8, and 20 mg/kg/day which are 1 to 6 times the oral mrhd on mg/m2 basis from day 6 of gestation through day 20 postpartum, increased stillbirths were seen at 3 and 6 times the mrhd on mg/m2 basis, and decreases in early postnatal pup weight and survival were seen at the highest dose; these doses produced some maternal toxicity. there were no effects on postnatal behavioral and reproductive development. risk summary aripiprazole is present in human breast milk; however, there are insufficient data to assess the amount in human milk, the effects on the breastfed infant, or the effects on milk production. the development and health benefits of breastfeeding should be considered along with the mother's clinical need for abilify maintena and any potential adverse effects on the breastfed infant from abilify maintena or from the underlying maternal condition. abilify maintena has not been studied in children 18 years of age or younger. however, juvenile animal studies have been conducted in rats and dogs. juvenile animal studies aripiprazole in juvenile rats caused mortality, cns clinical signs, impaired memory and learning, and delayed sexual maturation when administered at oral doses of 10, 20, 40 mg/kg/day from weaning (21 days old) through maturity (80 days old). at 40 mg/kg/day, mortality, decreased activity, splayed hind limbs, hunched posture, ataxia, tremors and other cns signs were observed in both genders. in addition, delayed sexual maturation was observed in males. at all doses and in a dose-dependent manner, impaired memory and learning, increased motor activity, and histopathology changes in the pituitary (atrophy), adrenals (adrenocortical hypertrophy), mammary glands (hyperplasia and increased secretion), and female reproductive organs (vaginal mucification, endometrial atrophy, decrease in ovarian corpora lutea) were observed. the changes in female reproductive organs were considered secondary to the increase in prolactin serum levels. a no observed adverse effect level (noael) could not be determined and, at the lowest tested dose of 10 mg/kg/day, there is no safety margin relative to the systemic exposures (auc0-24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. all drug-related effects were reversible after a 2-month recovery period, and most of the drug effects in juvenile rats were also observed in adult rats from previously conducted studies. aripiprazole in juvenile dogs (2 months old) caused cns clinical signs of tremors, hypoactivity, ataxia, recumbency and limited use of hind limbs when administered orally for 6 months at 3, 10, 30 mg/kg/day. mean body weight and weight gain were decreased up to 18% in females in all drug groups relative to control values. a noael could not be determined and, at the lowest tested dose of 3 mg/kg/day, there is no safety margin relative to the systemic exposures (auc0-24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. all drug-related effects were reversible after a 2-month recovery period. clinical studies of oral aripiprazole did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. other reported clinical experience and pharmacokinetic data [see clinical pharmacology (12.3)] have not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. in single-dose and multiple-dose pharmacokinetic studies, there was no detectable age effect in the population pharmacokinetic analysis of oral aripiprazole in schizophrenia patients [see clinical pharmacology (12.3)] . no dosage adjustments are recommended based on age alone. abilify maintena is not approved for the treatment of patients with dementia-related psychosis [see also boxed warning and warnings and precautions (5.1)]. dosage adjustment is recommended in known cyp2d6 poor metabolizers due to high aripiprazole concentrations. approximately 8% of caucasians and 3% to 8% of black/african americans cannot metabolize cyp2d6 substrates and are classified as poor metabolizers (pm) [see dosage and administration (2.3) and clinical pharmacology (12.3)] . no dosage adjustment for abilify maintena is required on the basis of a patient's hepatic function (mild to severe hepatic impairment, child-pugh score between 5 and 15), or renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 ml/minute) [see clinical pharmacology (12.3)] . no dosage adjustment for abilify maintena is required on the basis of a patient's sex, race, or smoking status [see clinical pharmacology (12.3)] .

Japonsko - angličtina - すりの適正使用協議会 RAD-AR Council, Japan

otsuka pharmaceutical factory, inc. - water for injection - injection

Japonsko - angličtina - すりの適正使用協議会 RAD-AR Council, Japan

otsuka pharmaceutical factory, inc. - sodium chloride - colorless and limpid solution (500ml, narrow‐mouthed/wide‐mouthed opening container )