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

takeda pharmaceuticals america, inc. - alogliptin benzoate (unii: een99869sc) (alogliptin - unii:jhc049lo86), pioglitazone hydrochloride (unii: jqt35npk6c) (pioglitazone - unii:x4ov71u42s) - alogliptin 12.5 mg - oseni is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use oseni should not be used in patients with type 1 diabetes mellitus. serious hypersensitivity reaction to alogliptin or pioglitazone or any of the excipients in oseni, such as anaphylaxis, angioedema and severe cutaneous adverse reactions have been reported [see warnings and precautions (5.3), adverse reactions (6.2)] . do not initiate in patients with nyha class iii or iv heart failure [see boxed warning] . risk summary limited data with oseni in pregnant women are not sufficient to inform a drug-associated risk for major birth defects or miscarriage. there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see clinical considerations]. in animal reproduction studies, no adverse developmental effects were observed when pioglitazone was administered to pregnant rats and rabbits during organogenesis at exposures up to 5 and 35 times the 45 mg clinical dose, respectively, based on body surface area. no adverse developmental effects were observed when alogliptin was administered to pregnant rats and rabbits during organogenesis at exposures 180 and 149 times the 25 mg clinical dose, respectively, based on plasma drug exposure (auc) [see data] . the estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a hba1c >7 and has been reported to be as high as 20-25% in women with a hba1c >10. the estimated background risk of miscarriage for the indicated population is 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 disease-associated maternal and/or embryo/fetal risk poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity. data animal data alogliptin and pioglitazone co-administration of 100 mg/kg alogliptin and 40 mg/kg pioglitazone (39 and 10 times the 25 mg and 45 mg clinical doses, respectively, based on body surface area) to pregnant rats during organogenesis slightly augmented pioglitazone-related fetal effects of delayed development and reduced fetal weights but did not result in embryofetal mortality or teratogenicity. alogliptin alogliptin administered to pregnant rabbits and rats during the period of organogenesis did not cause adverse developmental effects at doses of up to 200 mg/kg and 500 mg/kg, or 149 times and 180 times, the 25 mg clinical dose, respectively, based on plasma drug exposure (auc). placental transfer of alogliptin into the fetus was observed following oral dosing to pregnant rats. no adverse developmental outcomes were observed in offspring when alogliptin was administered to pregnant rats during gestation and lactation at doses up to 250 mg/kg (~95 times the 25 mg clinical dose, based on auc). pioglitazone pioglitazone administered to pregnant rats during organogenesis did not cause adverse developmental effects at a dose of 20 mg/kg (~5-times the 45 mg clinical dose), but delayed parturition and reduced embryofetal viability at 40 and 80 mg/kg, or ≥9-times the 45 mg clinical dose, by body surface area. in pregnant rabbits administered pioglitazone during organogenesis, no adverse developmental effects were observed at 80 mg/kg (~35-times the 45 mg clinical dose), but reduced embryofetal viability at 160 mg/kg, or ~69-times the 45 mg clinical dose, by body surface area. when pregnant rats received pioglitazone during late gestation and lactation, delayed postnatal development, attributed to decreased body weight, occurred in offspring at maternal doses of 10 mg/kg and above or ≥2 times the 45 mg clinical dose, by body surface area. risk summary there is no information regarding the presence of pioglitazone or alogliptin in human milk, the effects on the breastfed infant, or the effects on milk production. pioglitazone and alogliptin are present in rat milk; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for oseni and any potential adverse effects on the breastfed infant from oseni or from the underlying maternal condition. discuss the potential for unintended pregnancy with premenopausal women as therapy with pioglitazone, like other thiazolidinediones, may result in ovulation in some anovulatory women. safety and effectiveness of oseni in pediatric patients have not been established. oseni is not recommended for use in pediatric patients based on adverse effects observed in adults, including fluid retention and congestive heart failure, fractures and urinary bladder tumors [see warnings and precautions (5.1, 5.5, 5.6, 5.7)] . alogliptin and pioglitazone of the total number of patients (n=1533) in clinical safety and efficacy studies treated with alogliptin and pioglitazone, 248 (16.2%) patients were 65 years and older and 15 (1%) patients were 75 years and older. no overall differences in safety or effectiveness were observed between these patients and younger patients. while this and other reported clinical experiences have not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be excluded. alogliptin of the total number of patients (n=9052) in clinical safety and efficacy studies treated with alogliptin, 2257 (24.9%) patients were ≥65 years old and 386 (4.3%) patients were ≥75 years old. no overall differences in safety or effectiveness were observed between patients ≥65 years old and younger patients. pioglitazone a total of 92 patients (15.2%) treated with pioglitazone in the three pooled, 16 to 26 week, double-blind, placebo-controlled, monotherapy trials were ≥65 years old and two patients (0.3%) were ≥75 years old. in the two pooled 16 to 24 week add-on to sulfonylurea trials, 201 patients (18.7%) treated with pioglitazone were ≥65 years old and 19 (1.8%) were ≥75 years old. in the two pooled 16 to 24 week add-on to metformin trials, 155 patients (15.5%) treated with pioglitazone were ≥65 years old and 19 (1.9%) were ≥75 years old. in the two pooled 16 to 24 week add-on to insulin trials, 272 patients (25.4%) treated with pioglitazone were ≥65 years old and 22 (2.1%) were ≥75 years old. in proactive, 1068 patients (41%) treated with pioglitazone were ≥65 years old and 42 (1.6%) were ≥75 years old. in pharmacokinetic studies with pioglitazone, no significant differences were observed in pharmacokinetic parameters between elderly and younger patients. these clinical experiences have not identified differences in effectiveness and safety between the elderly (≥65 years) and younger patients although small sample sizes for patients ≥75 years old limit conclusions [see clinical pharmacology (12.3)] . alogliptin a total of 602 patients with moderate renal impairment (egfr ≥30 and <60 ml/min/1.73 m2 ) and four patients with severe renal impairment/end-stage renal disease (egfr <30 ml/min/1.73 m2 or <15 ml/min/1.73 m2 , respectively) at baseline were treated with alogliptin in clinical trials in patients with type 2 diabetes. reductions in hba1c were generally similar in this subgroup of patients. the overall incidence of adverse reactions was generally balanced between alogliptin and placebo treatments in this subgroup of patients. in the examine trial of high cv risk type 2 diabetes patients, 694 patients had moderate renal impairment and 78 patients had severe renal impairment or end-stage renal disease at baseline. the overall incidences of adverse reactions, serious adverse reactions and adverse reactions leading to study drug discontinuation were generally similar between the treatment groups. alogliptin no dose adjustments are required in patients with mild to moderate hepatic impairment (child-pugh grade a and b) based on insignificant change in systemic exposures (e.g., auc) compared to subjects with normal hepatic function in a pharmacokinetic study. alogliptin has not been studied in patients with severe hepatic impairment (child-pugh grade c). use caution when administering alogliptin to patients with liver disease [see warnings and precautions (5.4)]. pioglitazone no dose adjustments are required in patients with hepatic impairment (child-pugh grade b and c) based on insignificant change in systemic exposures (e.g., auc) compared to subjects with normal hepatic function in a pharmacokinetic study. however, use with caution in patients with liver disease [see warnings and precautions (5.4)].

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

takeda pharmaceuticals america, inc. - colchicine (unii: sml2y3j35t) (colchicine - unii:sml2y3j35t) - colchicine 0.6 mg - colcrys (colchicine, usp) tablets are indicated for prophylaxis and the treatment of acute gout flares. - prophylaxis of gout flares: colcrys is indicated for prophylaxis of gout flares. - treatment of gout flares: colcrys tablets are indicated for treatment of acute gout flares when taken at the first sign of a flare. colcrys (colchicine, usp) tablets are indicated in adults and children four years or older for treatment of familial mediterranean fever (fmf). patients with renal or hepatic impairment should not be given colcrys in conjunction with p-gp or strong cyp3a4 inhibitors (this includes all protease inhibitors except fosamprenavir). in these patients, life-threatening and fatal colchicine toxicity has been reported with colchicine taken in therapeutic doses. risk summary available data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see data). colchicine crosses the human placenta. although animal reproductive and developmental studies were not conducted with colcrys (colchicine), published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity, teratogenicity and altered postnatal development at exposures within or above the clinical therapeutic range. 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. in the u.s. 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. data human data available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects or miscarriage in pregnant women with rheumatic diseases (such as rheumatoid arthritis, behcet's disease, or familial mediterranean fever (fmf) treated with colchicine at therapeutic doses during pregnancy. limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications. risk summary colchicine is present in human milk (see data) . adverse events in breastfed infants have not been reported in the published literature after administration of colchicine to lactating women. there are no data on the effects of colchicine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for colcrys and any potential adverse effects on the breastfed child from colcrys or from the underlying maternal condition. data limited published data from case reports and a small lactation study demonstrate that colchicine is present in breastmilk. a systematic review of literature reported no adverse effects in 149 breastfed children. in a prospective observational cohort study, no gastrointestinal or other symptoms were reported in 38 colchicine-exposed breastfed infants. infertility case reports and epidemiology studies in human male subjects on colchicine therapy indicated that infertility from colchicine is rare and may be reversible. a case report indicated that azoospermia was reversed when therapy was stopped. case reports and epidemiology studies in female subjects on colchicine therapy have not established a clear relationship between colchicine use and female infertility. however, since the progression of fmf without treatment may result in infertility, the use of colchicine needs to be weighed against the potential risks [see nonclinical toxicology (13.1)] . the safety and efficacy of colchicine in children of all ages with fmf has been evaluated in uncontrolled studies. there does not appear to be an adverse effect on growth in children with fmf treated long-term with colchicine. safety and effectiveness of colchicine in pediatric patients with gout has not been established. clinical studies with colchicine for prophylaxis and treatment of gout flares and for treatment of fmf did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. in general, dose selection for an elderly patient with gout should be cautious, reflecting the greater frequency of decreased renal function, concomitant disease or other drug therapy [see dosage and administration (2.4), clinical pharmacology (12.3)] . colchicine is significantly excreted in urine in healthy subjects. clearance of colchicine is decreased in patients with impaired renal function. total body clearance of colchicine was reduced by 75% in patients with end-stage renal disease undergoing dialysis. prophylaxis of gout flares for prophylaxis of gout flares in patients with mild (estimated creatinine clearance clcr 50 to 80 ml/min) to moderate (clcr 30 to 50 ml/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. however, in patients with severe impairment, the starting dose should be 0.3 mg per day and any increase in dose should be done with close monitoring. for the prophylaxis of gout flares in patients undergoing dialysis, the starting doses should be 0.3 mg given twice a week with close monitoring [see dosage and administration (2.5)] . treatment of gout flares for treatment of gout flares in patients with mild (clcr 50 to 80 ml/min) to moderate (clcr 30 to 50 ml/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colcrys. however, in patients with severe impairment, while the dose does not need to be adjusted for the treatment of gout flares, a treatment course should be repeated no more than once every two weeks. for patients with gout flares requiring repeated courses, consideration should be given to alternate therapy. for patients undergoing dialysis, the total recommended dose for the treatment of gout flares should be reduced to a single dose of 0.6 mg (one tablet). for these patients, the treatment course should not be repeated more than once every two weeks [see dosage and administration (2.5)] . fmf although pharmacokinetics of colchicine in patients with mild (clcr 50 to 80 ml/min) and moderate (clcr 30 to 50 ml/min) renal impairment is not known, these patients should be monitored closely for adverse effects of colchicine. dose reduction may be necessary. in patients with severe renal failure (clcr less than 30 ml/min) and end-stage renal disease requiring dialysis, colcrys may be started at the dose of 0.3 mg/day. any increase in dose should be done with adequate monitoring of the patient for adverse effects of colcrys [see clinical pharmacology (12.3), dosage and administration (2.5)] . the clearance of colchicine may be significantly reduced and plasma half-life prolonged in patients with chronic hepatic impairment compared to healthy subjects [see clinical pharmacology (12.3)] . prophylaxis of gout flares for prophylaxis of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. dose reduction should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment [see dosage and administration (2.6)] . treatment of gout flares for treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended colcrys dose is not required, but patients should be monitored closely for adverse effects of colcrys. however, for the treatment of gout flares in patients with severe impairment, while the dose does not need to be adjusted, the treatment course should be repeated no more than once every two weeks. for these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see dosage and administration (2.6)] . fmf in patients with severe hepatic disease, dose reduction should be considered with careful monitoring [see clinical pharmacology (12.3), dosage and administration (2.6)] . tolerance, abuse or dependence with colchicine has not been reported.

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

takeda pharmaceuticals america, inc. - alogliptin benzoate (unii: een99869sc) (alogliptin - unii:jhc049lo86), metformin hydrochloride (unii: 786z46389e) (metformin - unii:9100l32l2n) - alogliptin 12.5 mg - kazano is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use kazano is not recommended for use in patients with type 1 diabetes mellitus. kazano is contraindicated in patients with: - severe renal impairment (egfr below 30 ml/min/1.73 m2 ) [see warnings and precautions (5.1)] . - acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma. - history of serious hypersensitivity reaction to alogliptin or metformin or any of the excipients in kazano, such as anaphylaxis, angioedema and severe cutaneous adverse reactions [see warnings and precautions (5.4), adverse reactions (6.2)]. risk summary limited available data with kazano or alogliptin in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [se

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

takeda pharmaceuticals america, inc. - ramelteon (unii: 901as54i69) (ramelteon - unii:901as54i69) - ramelteon 8 mg - rozerem is indicated for the treatment of insomnia characterized by difficulty with sleep onset. the clinical trials performed in support of efficacy were up to six months in duration. the final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly) [see clinical studies (14)] . patients who develop angioedema after treatment with rozerem should not be rechallenged with the drug. patients should not take rozerem in conjunction with fluvoxamine [see drug interactions (7)] . risk summary available data from postmarketing reports with rozerem use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic effects, in rats at doses greater than 36 times the rec

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

takeda pharmaceuticals america, inc. - vortioxetine hydrobromide (unii: tks641koay) (vortioxetine - unii:3o2k1s3wqv) - vortioxetine 5 mg - trintellix is indicated for the treatment of major depressive disorder (mdd) in adults. - hypersensitivity to vortioxetine or any component of the formulation. hypersensitivity reactions including anaphylaxis, angioedema, and urticaria have been reported in patients treated with trintellix [see adverse reactions (6.2)] . - the use of maois intended to treat psychiatric disorders with trintellix or within 21 days of stopping treatment with trintellix is contraindicated because of an increased risk of serotonin syndrome. the use of trintellix within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration (2.4), warnings and precautions (5.2)] . starting trintellix in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see warnings and precautions (5.2)] . pregnancy exposure registry there is a pregnancy exposure registry that monit

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

takeda pharmaceuticals america, inc. - dexlansoprazole (unii: uye4t5i70x) (dexlansoprazole - unii:uye4t5i70x) - dexlansoprazole 30 mg - dexilant is indicated in patients 12 years of age and older for healing of all grades of erosive esophagitis (ee) for up to eight weeks. dexilant is indicated in patients 12 years of age and older to maintain healing of ee and relief of heartburn for up to six months in adults and 16 weeks in patients 12 to 17 years of age. dexilant is indicated in patients 12 years of age and older for the treatment of heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (gerd) for four weeks. - dexilant is contraindicated in patients with known hypersensitivity to any component of the formulation [see description (11)] . hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis and urticaria [see warnings and precautions (5.2), adverse reactions (6)] . - ppis, including dexilant, are contraindicated with rilpivirine-containing products [see drug interactions (7)] . risk summary there are no studies with dexlansoprazole us

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

takeda pharmaceuticals america, inc. - ponatinib hydrochloride (unii: 96r6pu3d8j) (ponatinib - unii:4340891kfs) - ponatinib 15 mg - iclusig is indicated for the treatment of adult patients with: - chronic phase (cp) chronic myeloid leukemia (cml) with resistance or intolerance to at least two prior kinase inhibitors. - accelerated phase (ap) or blast phase (bp) cml or philadelphia chromosome positive acute lymphoblastic leukemia (ph+ all) for whom no other kinase inhibitors are indicated. - t315i-positive cml (chronic phase, accelerated phase, or blast phase) or t315i-positive ph+ all. limitations of use : iclusig is not indicated and is not recommended for the treatment of patients with newly diagnosed cp-cml [see warnings and precautions (5.7)] . none. risk summary based on findings in animals and its mechanism of action [see clinical pharmacology (12.1)] , iclusig can cause fetal harm when administered to a pregnant woman. there are no available data on iclusig use in pregnant women. in animal reproduction studies, oral administration of ponatinib to pregnant rats during organogenesis caused adverse developmental effects at doses lower

Israel - English - Ministry of Health

takeda israel ltd - ixazomib as citrate - capsules - ixazomib as citrate 2.3 mg - ixazomib - ninlaro is indicated, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Israel - English - Ministry of Health

takeda israel ltd - ixazomib as citrate - capsules - ixazomib as citrate 2.3 mg - ixazomib - ninlaro is indicated, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Israel - English - Ministry of Health

takeda israel ltd - ixazomib as citrate - capsules - ixazomib as citrate 3 mg - ixazomib - ninlaro is indicated, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.