Združene države Amerike - angleščina - NLM (National Library of Medicine)

padagis israel pharmaceuticals ltd - alogliptin benzoate (unii: een99869sc) (alogliptin - unii:jhc049lo86), pioglitazone hydrochloride (unii: jqt35npk6c) (pioglitazone - unii:x4ov71u42s) - alogliptin 12.5 mg - alogliptin and pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use alogliptin and pioglitazone tablets should not be used in patients with type 1 diabetes mellitus. serious hypersensitivity reaction to alogliptin or pioglitazone or any of the excipients in alogliptin and pioglitazone tablets, 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 alogliptin and pioglitazone tablets 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 observ

Združene države Amerike - angleščina - NLM (National Library of Medicine)

padagis israel pharmaceuticals ltd - alogliptin benzoate (unii: een99869sc) (alogliptin - unii:jhc049lo86), metformin hydrochloride (unii: 786z46389e) (metformin - unii:9100l32l2n) - alogliptin 12.5 mg - alogliptin and metformin hcl tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use alogliptin and metformin hcl tablets should not recommended for use in patients with type 1 diabetes mellitus. alogliptin and metformin hcl tablets are 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, 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 alogliptin and metformin hcl tablets 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 [see data] . there are risks to the mother and fetus associated with poorly controlled diabetes mellitus in pregnancy [see clinical considerations]. concomitant administration of alogliptin and metformin in pregnant rats during the period of organogenesis did not cause adverse developmental effects in offspring at maternal exposures up to 28 times and two times the 25 mg and 2000 mg clinical doses, respectively [see data]. the estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes mellitus with a hba1c >7 and has been reported to be as high as 20-25% in women with 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 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 mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. poorly controlled diabetes mellitus increases the fetal risk for major malformations, still birth, and macrosomia related morbidity. data human data published data from postmarketing studies do not report a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin is used during pregnancy. however, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. animal data alogliptin and metformin concomitant administration of alogliptin and metformin in pregnant rats during the period of organogenesis did not cause adverse developmental effects in offspring at a dose of 100 mg/kg alogliptin and 150 mg/kg metformin, or approximately 28 and two times the clinical dose of alogliptin (25 mg) and metformin (2000 mg), respectively based on plasma drug exposure (auc). 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 (approximately 95 times the 25 mg clinical dose, based on auc). metformin hcl metformin hcl did not cause adverse developmental effects when administered to pregnant sprague dawley rats and rabbits up to 600 mg/kg/day during the period of organogenesis. this represents an exposure of about two to six times a clinical dose of 2000 mg based on body surface area (mg/m2 ) for rats and rabbits, respectively. risk summary there is no information regarding the presence of alogliptin and metformin or alogliptin in human milk, the effects on the breastfed infant, or the effects on milk production. alogliptin is present in rat milk. limited published studies report that metformin is present in human milk [see data]. however, there is insufficient information to determine the effects of metformin on the breastfed infant and no available information on the effects of metformin on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for alogliptin and metformin hcl tablets and any potential adverse effects on the breastfed infant from alogliptin and metformin hcl tablets or from the underlying maternal condition. data published clinical lactation studies report that metformin is present in human milk which resulted in infant doses approximately 0.11% to 1% of the maternal weight-adjusted dosage and a milk/plasma ratio (based on auc) ranging between 0.13 and 1. however, the studies were not designed to definitely establish the risk of use of metformin during lactation because of small sample size and limited adverse event data collected in infants. there is the potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some premenopausal anovulatory women. the safety and effectiveness of alogliptin and metformin hcl tablets have not been established in pediatric patients. effectiveness of alogliptin was not demonstrated in a 52 week, randomized, double-blind, placebo-controlled trial (nct02856113) in 151 pediatric patients aged 10 to 17 years with inadequately controlled type 2 diabetes mellitus. alogliptin and metformin hcl elderly patients are more likely to have decreased renal function. monitor renal function in the elderly more frequently [see warnings and precautions (5.1), clinical pharmacology (12.3)] . of the total number of patients (n = 2095) in clinical safety and efficacy studies, 343 (16.4%) patients were 65 years and older and 37 (1.8%) patients were 75 years and older. no overall differences in safety or effectiveness were observed between these patients and younger patients. alogliptin of the total number of patients (n=9052) in clinical safety and efficacy studies treated with alogliptin, 2,257 (24.9%) patients were 65 years and older and 386 (4.3%) patients were 75 years and older. no overall differences in safety or effectiveness were observed between patients 65 years and over and younger patients. metformin hcl controlled trials of metformin did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger patients. other reported clinical experience has 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 and cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. assess renal function more frequently in elderly patients [see contraindications (4), warnings and precautions (5.1), clinical pharmacology (12.3)]. metformin is substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment. alogliptin and metformin hcl tablets are contraindicated in severe renal impairment, patients with an egfr below 30 ml/min/1.73 m2 [see dosage and administration (2.2), contraindications (4), warnings and precautions (5.1), clinical pharmacology (12.3)] . use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis. alogliptin and metformin hcl tablets are not recommended in patients with hepatic impairment [see warnings and precautions (5.1)] .

Združene države Amerike - angleščina - NLM (National Library of Medicine)

padagis israel pharmaceuticals ltd - alogliptin benzoate (unii: een99869sc) (alogliptin - unii:jhc049lo86) - alogliptin 6.25 mg - alogliptin tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use alogliptin tablet is not recommended for use in patients with type 1 diabetes mellitus. alogliptin tablets is contraindicated in patients with a history of serious hypersensitivity to alogliptin or any of the excipients in alogliptin tablets. reactions such as anaphylaxis, angioedema and severe cutaneous adverse reactions have been reported [see warnings and precautions (5.3), adverse reactions (6.2)] . risk summary limited data with alogliptin in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. there are risks to the mother and fetus associated with poorly controlled diabetes mellitus in pregnancy [see clinical considerations]. 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 mellitus with a hba1c >7 and has been reported to be as high as 20-25% in women with 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 mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery and delivery complications. poorly controlled diabetes mellitus increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity. data animal data 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). risk summary there is no information regarding the presence of alogliptin in human milk, the effects on the breastfed infant, or the effects on milk production. alogliptin is present in rat milk: however, due to species specific differences in lactation physiology, animal lactation data may not reliably predict levels in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for alogliptin tablets and any potential adverse effects on the breastfed infant from alogliptin tablets or from the underlying maternal condition. the safety and effectiveness of alogliptin tablets have not been established in pediatric patients. effectiveness of alogliptin tablets was not demonstrated in a 52 week, randomized, double-blind, placebo-controlled trial (nct02856113) in 151 pediatric patients aged 10 to 17 years with inadequately controlled type 2 diabetes mellitus. of the total number of patients (n=9052) in clinical safety and efficacy trials treated with alogliptin tablets, 2,257 (24.9%) patients were 65 years and older and 386 (4.3%) patients were 75 years and older. no overall differences in safety or effectiveness were observed between patients 65 years and over and younger patients. a total of 602 adult patients with moderate renal impairment (egfr ≥30 and <60 ml/min/1.73 m2 ) and 4 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 tablets in clinical trials in patients with type 2 diabetes mellitus. in the examine trial of high cv risk type 2 diabetes mellitus patients, 694 patients had moderate renal impairment and 78 patients had severe renal impairment or end-stage renal disease at baseline. the recommended dose is 12.5 mg once daily in patients with moderate renal impairment and 6.25 mg once daily in patients with severe renal impairment, as well as in patients with esrd requiring dialysis. alogliptin tablets may be administered without regard to the timing of the dialysis. no dose adjustments are required in patients with mild to moderate hepatic impairment (child-pugh grade a and b) [see clinical pharmacology (12.3)] . alogliptin tablets have not been studied in patients with severe hepatic impairment (child-pugh grade c). use caution when administering alogliptin tablets to patients with liver disease [see warnings and precautions (5.4)] .

Združene države Amerike - angleščina - NLM (National Library of Medicine)

a-s medication solutions - alogliptin benzoate (unii: een99869sc) (alogliptin - unii:jhc049lo86), metformin hydrochloride (unii: 786z46389e) (metformin - unii:9100l32l2n) - alogliptin and metformin hcl tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use alogliptin and metformin hcl tablets should not be used in patients with type 1 diabetes mellitus. alogliptin and metformin hcl tablets are 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. - serious hypersensitivity reaction to alogliptin or metformin or any of the exciptients, 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 alogliptin and metformin hcl tablets 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 pregnan

Združene države Amerike - angleščina - 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)].

Avstralija - angleščina - Department of Health (Therapeutic Goods Administration)

takeda pharmaceuticals australia pty ltd - alogliptin benzoate,pioglitazone hydrochloride -

Avstralija - angleščina - Department of Health (Therapeutic Goods Administration)

takeda pharmaceuticals australia pty ltd - alogliptin benzoate,pioglitazone hydrochloride -

Avstralija - angleščina - Department of Health (Therapeutic Goods Administration)

takeda pharmaceuticals australia pty ltd - alogliptin benzoate,pioglitazone hydrochloride -

Avstralija - angleščina - Department of Health (Therapeutic Goods Administration)

takeda pharmaceuticals australia pty ltd - alogliptin benzoate,pioglitazone hydrochloride -

Kanada - angleščina - Health Canada

takeda canada inc - alogliptin (alogliptin benzoate); pioglitazone (pioglitazone hydrochloride) - tablet - 12.5mg; 15mg - alogliptin (alogliptin benzoate) 12.5mg; pioglitazone (pioglitazone hydrochloride) 15mg - dipeptidyl peptidase-4 (dpp-4) inhibitors