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

astrazeneca pty ltd - dapagliflozin propanediol monohydrate, quantity: 12.3 mg (equivalent: dapagliflozin, qty 10 mg); saxagliptin, quantity: 5 mg - tablet - excipient ingredients: microcrystalline cellulose; magnesium stearate; lactose; croscarmellose sodium; silicon dioxide; titanium dioxide; purified talc; iron oxide yellow; iron oxide red; polyvinyl alcohol; macrogol 3350; propylene glycol; butan-1-ol; isopropyl alcohol; strong ammonia solution; indigo carmine aluminium lake; ethanol; shellac; sulfuric acid - qtern 5/10 is indicated as an adjunct to diet and exercise, in combination with metformin, to improve glycaemic control in adults with type 2 diabetes mellitus when treatment with both saxagliptin and dapagliflozin is appropriate.

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

astrazeneca pharmaceuticals lp - dapagliflozin (unii: 1ull0qj8uc) (dapagliflozin - unii:1ull0qj8uc), saxagliptin hydrochloride (unii: z8j84yix6l) (saxagliptin anhydrous - unii:8i7io46ivq), metformin hydrochloride (unii: 786z46389e) (metformin - unii:9100l32l2n) - qternmet xr (dapagliflozin, saxagliptin, and metformin hydrochloride) extended-release tablets is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use qternmet xr is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. qternmet xr initiation is intended only for patients currently taking metformin. qternmet xr is contraindicated in patients with: risk summary based on animal data showing adverse renal effects, from dapagliflozin, qternmet xr is not recommended during the second and third trimesters of pregnancy. the limited available data with qternmet xr or components (dapagliflozin and saxagliptin) in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or 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 moth

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

astrazeneca pharmaceuticals lp - dapagliflozin (unii: 1ull0qj8uc) (dapagliflozin - unii:1ull0qj8uc), saxagliptin hydrochloride (unii: z8j84yix6l) (saxagliptin anhydrous - unii:8i7io46ivq) - dapagliflozin 10 mg - qtern is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use qtern is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see warnings and precautions (5.1) ] . qtern is contraindicated in patients with: risk summary based on animal data showing adverse renal effects from dapagliflozin, qtern is not recommended during the second and third trimesters of pregnancy. the limited available data with qtern or its components (dapagliflozin and saxagliptin) 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 in pregnancy (see clinical considerations) . in animal studies, adverse renal pelvic and tubular dilatations, that were not fully reversible, were observed in rats when dapagliflozin (a component of qtern) was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at all doses tested; the lowest of which provided an exposure 15-times the 10 mg clinical dose (see data) . no adverse developmental effects were observed when saxagliptin was administered to pregnant rats and rabbits (see data) . the estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with an hba1c greater than 7% and has been reported to be as high as 20 to 25% in women with an hba1c greater than 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 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryofetal risk poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery and delivery complications. poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. data animal data dapagliflozin dapagliflozin dosed directly to juvenile rats from postnatal day (pnd) 21 until pnd 90 at doses of 1, 15, or 75 mg/kg/day, increased kidney weights and increased the incidence of renal pelvic and tubular dilatations at all dose levels. exposure at the lowest dose was 15-times the 10 mg clinical dose (based on auc). the renal pelvic and tubular dilatations observed in juvenile animals did not fully reverse within a 1-month recovery period. in a prenatal and postnatal development study, dapagliflozin was administered to maternal rats from gestation day 6 through lactation day 21 at doses of 1, 15, or 75 mg/kg/day, and pups were indirectly exposed in utero and throughout lactation. increased incidence or severity of renal pelvic dilatation was observed in 21 day-old pup offspring of treated dams at 75 mg/kg/day (maternal and pup dapagliflozin exposures were 1415-times and 137-times, respectively, the human values at the 10 mg clinical dose, based on auc). dose-related reductions in pup body weights were observed at greater than or equal to 29-times the 10 mg clinical dose (based on auc). no adverse effects on developmental endpoints were noted at 1 mg/kg/day, (19-times the 10 mg clinical dose, based on auc). these outcomes occurred with drug exposure during periods of renal development in rats that corresponds to the late second and third trimester of human development. in embryofetal development studies in rats and rabbits, dapagliflozin was administered throughout organogenesis, corresponding to the first trimester of human pregnancy. in rats, dapagliflozin was neither embryolethal nor teratogenic at doses up to 75 mg/kg/day (1441-times the 10 mg clinical dose, based on auc). dose-related effects on the rat fetus (structural abnormalities and reduced body weight) occurred only at higher dosages, equal to or greater than 150 mg/kg (more than 2344-times the 10 mg clinical dose, based on auc), which were associated with maternal toxicity. no developmental toxicities were observed in rabbits at doses up to 180 mg/kg/day (1191-times the 10 mg clinical dose, based on auc). saxagliptin in embryofetal development studies, saxagliptin was administered to pregnant rats and rabbits during the period of organogenesis, corresponding to the first trimester of human pregnancy. no adverse developmental effects were observed in either species at exposures 1503- and 152-times the 5 mg clinical dose in rats and rabbits, respectively, based on auc. saxagliptin crosses the placenta into the fetus following dosing in pregnant rats. in a prenatal and postnatal development study, no adverse developmental effects were observed in maternal rats administered saxagliptin from gestation day 6 through lactation day 21 at exposures up to 470-times the 5 mg clinical dose, based on auc. risk summary there is no information regarding the presence of qtern or its components (dapagliflozin and saxagliptin) in human milk, the effects on the breastfed infant, or the effects on milk production. dapagliflozin and saxagliptin are present in the milk of lactating rats ( see data) . however, due to species-specific differences in lactation physiology, the clinical relevance of these data is not clear. since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney. because of the potential for serious adverse reactions in a breastfed infant, advise women that use of qtern is not recommended while breastfeeding. data dapagliflozin dapagliflozin was present at a milk/plasma ratio of 0.49, indicating that dapagliflozin and its metabolites are transferred into milk at a concentration that is approximately 50% of that in maternal plasma. juvenile rats directly exposed to dapagliflozin showed a risk to the developing kidney (renal pelvic and tubular dilatations) during maturation. saxagliptin saxagliptin is secreted in the milk of lactating rats at approximately a 1:1 ratio with plasma drug concentrations. safety and effectiveness of qtern in pediatric patients under 18 years of age have not been established. because elderly patients are more likely to have decreased renal function, care should be taken when using qtern in the elderly based on renal function [see dosage and administration (2.3) ] . dapagliflozin a total of 1424 (24%) of the 5936 dapagliflozin-treated patients were 65 years and older and 207 (3.5%) patients were 75 years and older in a pool of 21 double-blind, controlled, clinical studies assessing the efficacy of dapagliflozin in improving glycemic control. after controlling for level of renal function (egfr), in clinical studies with dapagliflozin, efficacy was similar for patients under age 65 years and those 65 years and older. in patients 65 years and older, a higher proportion of patients treated with dapagliflozin had adverse reactions of hypotension [see warnings and precautions (5.4) ] . saxagliptin in the seven double-blind, controlled clinical safety and efficacy trials of saxagliptin, a total of 4751 (42.0%) of the 11,301 patients randomized to saxagliptin were 65 years and over, and 1210 (10.7%) were 75 years and over. no overall differences in safety or effectiveness were observed between subjects ≥65 years old and younger subjects. while this clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out. qtern is contraindicated in patients with moderate to severe renal impairment (egfr less than 45 ml/min/1.73 m2 ), esrd, or on dialysis [see dosage and administration (2.3) , contraindications (4) and warnings and precautions (5.4) ]. dapagliflozin dapagliflozin was evaluated in two glycemic control studies that included patients with moderate renal impairment (an egfr of 45 to less than 60 ml/min/1.73 m2 , and an egfr of 30 to less than 60 ml/min/1.73 m2 ). patients with diabetes and renal impairment using dapagliflozin for glycemic control may be more likely to experience hypotension and may be at higher risk for acute kidney injury secondary to volume depletion. in the study of patients with an egfr 30 to less than 60 ml/min/1.73 m2 , 13 patients receiving dapagliflozin experienced bone fractures compared to none receiving placebo. qtern may be used in patients with hepatic impairment. however, the benefit-risk for the use of qtern in patients with severe hepatic impairment should be individually assessed since safety and efficacy have not been studied in this population [see clinical pharmacology (12.3) ].

Unia Europejska - angielski - EMA (European Medicines Agency)

astra zeneca ab - saxagliptin, dapagliflozin propanediol monohydrate - diabetes mellitus, type 2; diabetes mellitus; nutritional and metabolic diseases; metabolic diseases; glucose metabolism disorders - drugs used in diabetes - qtern, fixed dose combination of saxagliptin and dapagliflozin, is indicated in adults aged 18 years and older with type 2 diabetes mellitus:to improve glycaemic control when metformin and/or sulphonylurea (su) and one of the monocomponents of qtern do not provide adequate glycaemic control,when already being treated with the free combination of dapagliflozin and saxagliptin.(see sections 4.2, 4.4, 4.5 and 5.1 for available data on combinations studied.)

Unia Europejska - angielski - EMA (European Medicines Agency)

astrazeneca ab - metformin hydrochloride, saxagliptin, dapagliflozin - diabetes mellitus, type 2 - drugs used in diabetes - qtrilmet is indicated in adults aged 18 years and older with type 2 diabetes mellitus:to improve glycaemic control when metformin with or without sulphonylurea (su) and either saxagliptin or dapagliflozin does not provide adequate glycaemic control.when already being treated with metformin and saxagliptin and dapagliflozin.

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

aurobindo pharma limited - saxagliptin hydrochloride (unii: z8j84yix6l) (saxagliptin anhydrous - unii:8i7io46ivq) - saxagliptin tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus [see clinical studies (14) ]. saxagliptin tablets are not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, as it would not be effective in these settings. saxagliptin is contraindicated in patients with a history of a serious hypersensitivity reaction to saxagliptin tablets, such as anaphylaxis, angioedema, or exfoliative skin conditions [see  warnings and precautions (5.4) and adverse reactions (6.2) ]. risk summary limited data with saxagliptin in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriages. there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see clinical considerations] . no adverse developmental effects independent of maternal toxicity were observed when saxagliptin was administered to pregnant rats and rabbits during the period of organogenesis and in pregnant and lactating rats during the pre- and postnatal period [see data] . the estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with an hba1c greater than 7 and has been reported to be as high as 20 to 25% in women with an hba1c greater than 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 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications. poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. data animal data in embryo-fetal development studies, saxagliptin was administered to pregnant rats and rabbits during the period of organogenesis, corresponding to the first trimester of human pregnancy. no adverse developmental effects were observed in either species at exposures 1503- and 152-times the 5 mg clinical dose in rats and rabbits, respectively, based on auc. saxagliptin crosses the placenta into the fetus following dosing in pregnant rats. in a prenatal and postnatal development study, no adverse developmental effects were observed in maternal rats administered saxagliptin from gestation day 6 through lactation day 21 at exposures up to 470-times the 5 mg clinical dose, based on auc. risk summary there is no information regarding the presence of saxagliptin in human milk, the effects on the breastfed infant, or the effects on milk production. saxagliptin is present in the milk of lactating rats [see data] . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for saxagliptin and any potential adverse effects on the breastfed infant from saxagliptin or from the underlying maternal condition. data saxagliptin is secreted in the milk of lactating rats at approximately a 1:1 ratio with plasma drug concentrations. safety and effectiveness of saxagliptin in pediatric patients under 18 years of age have not been established. additionally, studies characterizing the pharmacokinetics of saxagliptin in pediatric patients have not been performed. in the seven, double-blind, controlled clinical safety and efficacy trials of saxagliptin, a total of 4751 (42.0%) of the 11301 patients randomized to saxagliptin were 65 years and over, and 1210 (10.7%) were 75 years and over. no overall differences in safety or effectiveness were observed between subjects ≥65 years old and younger subjects. while this clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out. saxagliptin and its active metabolite are eliminated in part by the kidney. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly based on renal function [see dosage and administration (2.2)   and  clinical pharmacology (12.3) ]. in a 12-week randomized placebo-controlled trial, saxagliptin 2.5 mg was administered to 85 subjects with moderate (n=48) or severe (n=18) renal impairment or end-stage renal disease (esrd) (n=19) [see clinical studies (14) ]. the incidence of adverse events, including serious adverse events and discontinuations due to adverse events, was similar between saxagliptin and placebo. the overall incidence of reported hypoglycemia was 20% among subjects treated with saxagliptin 2.5 mg and 22% among subjects treated with placebo. four saxagliptin-treated subjects (4.7%) and three placebo-treated subjects (3.5%) reported at least one episode of confirmed symptomatic hypoglycemia (accompanying fingerstick glucose ≤50 mg/dl).

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

astrazeneca pty ltd - saxagliptin, quantity: 2.5 mg - tablet, film coated - excipient ingredients: microcrystalline cellulose; croscarmellose sodium; magnesium stearate; lactose monohydrate; propylene glycol; butan-1-ol; isopropyl alcohol; strong ammonia solution; indigo carmine aluminium lake; ethanol; shellac; sulfuric acid; titanium dioxide; purified talc; polyvinyl alcohol; macrogol 3350 - add-on combination: onglyza is indicated in patients with type 2 diabetes mellitus to improve glycaemic control in combination with other glucose lowering medicines, when these together with diet and exercise, do not provide adequate glycaemic control (see clinical trials and precautions for available data on different add-on combination therapies).,initial combination: onglyza is indicated for use as initial combination therapy with metformin, in patients with type 2 diabetes mellitus, to improve glycaemic control as an adjunct to diet and exercise, when dual saxagliptin and metformin therapy is appropriate (i.e. high initial hba1c levels and poor prospects for response to monotherapy).

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

astrazeneca pty ltd - saxagliptin, quantity: 5 mg - tablet, film coated - excipient ingredients: lactose monohydrate; microcrystalline cellulose; croscarmellose sodium; magnesium stearate; propylene glycol; butan-1-ol; isopropyl alcohol; strong ammonia solution; indigo carmine aluminium lake; ethanol; shellac; sulfuric acid; titanium dioxide; purified talc; polyvinyl alcohol; macrogol 3350; iron oxide red - add-on combination: onglyza is indicated in patients with type 2 diabetes mellitus to improve glycaemic control in combination with other glucose lowering medicines, when these together with diet and exercise, do not provide adequate glycaemic control (see clinical trials and precautions for available data on different add-on combination therapies).,initial combination: onglyza is indicated for use as initial combination therapy with metformin, in patients with type 2 diabetes mellitus, to improve glycaemic control as an adjunct to diet and exercise, when dual saxagliptin and metformin therapy is appropriate (i.e. high initial hba1c levels and poor prospects for response to monotherapy).

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

astrazeneca pharmaceuticals lp - saxagliptin hydrochloride (unii: z8j84yix6l) (saxagliptin anhydrous - unii:8i7io46ivq), metformin hydrochloride (unii: 786z46389e) (metformin - unii:9100l32l2n) - saxagliptin anhydrous 2.5 mg - kombiglyze xr is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both saxagliptin and metformin is appropriate [see clinical studies (14) ]. kombiglyze xr is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. kombiglyze xr is contraindicated in patients with: limited available data with kombiglyze xr or saxagliptin in pregnant women are not sufficient to determine 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 ]. no adverse developmental effects independent of maternal toxicity were observed when saxagliptin and metformin were administered separately or in combination to pregnant rats and rabbits during the period of organogenesis [see data ]. the estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with an hba1c greater than 7 and has been reported to be as high as 20 to 25% in women with an hba1c greater than 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 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications. poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. data animal data saxagliptin in embryo-fetal development studies, saxagliptin was administered to pregnant rats and rabbits during the period of organogenesis, corresponding to the first trimester of human pregnancy. no adverse developmental effects were observed in either species at exposures 1503- and 152-times the 5 mg clinical dose in rats and rabbits, respectively, based on auc. saxagliptin crosses the placenta into the fetus following dosing in pregnant rats. in a prenatal and postnatal development study, no adverse developmental effects were observed in maternal rats administered saxagliptin from gestation day 6 through lactation day 21 at exposures up to 470-times the 5 mg clinical dose, based on auc. metformin hydrochloride metformin hydrochloride did not cause adverse developmental effect 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 2- and 6-times a 2000 mg clinical dose based on body surface area (mg/m2 ) for rats and rabbits, respectively. saxagliptin and metformin saxagliptin and metformin coadministered to pregnant rats and rabbits during the period of organogenesis did not result in adverse developmental effects considered clinically relevant in either species. doses tested in rats provided exposure up to 100- and 10-times clinical exposure, and doses tested in rabbits provided exposure up to 249- and 1-times clinical exposure relative to the clinical dose of 5 mg saxagliptin and 2000 mg metformin. minor skeletal abnormalities associated with maternal toxicity were observed in rats. in rabbits, coadministration was poorly tolerated in a subset of mothers (12 of 30), resulting in death, moribundity, or abortion. however, among surviving mothers with evaluable litters, maternal toxicity was limited to marginal reductions in body weight over the course of gestation days 21 to 29, associated with fetal body weight decrements of 7%, and a low incidence of delayed ossification of the fetal hyoid bone. risk summar y there is no information regarding the presence of kombiglyze xr or saxagliptin in human milk, the effects on the breastfed infant, or the effects on milk production. limited published studies report that metformin is present in human milk [see data ]. however, there is insufficient information on the effects of metformin on the breastfed infant and no available information on the effects of metformin on milk production. saxagliptin is present in the milk of lactating rats [see data ]. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for kombiglyze xr and any potential adverse effects on the breastfed child from kombiglyze xr or from the underlying maternal condition. data human 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 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. animals no studies in lactating animals have been conducted with the combined components of kombiglyze xr. in studies performed with the individual components, both saxagliptin and metformin are secreted in the milk of lactating rats. saxagliptin is secreted in the milk of lactating rats at approximately a 1:1 ratio with plasma drug concentrations. safety and effectiveness of kombiglyze xr in pediatric patients under 18 years of age have not been established. additionally, studies characterizing the pharmacokinetics of kombiglyze xr in pediatric patients have not been performed. kombiglyze xr elderly patients are more likely to have decreased renal function. assess renal function more frequently in the elderly [see warnings and precautions (5.1) and clinical pharmacology (12.3) ]. saxagliptin in the seven, double-blind, controlled clinical safety and efficacy trials of saxagliptin, a total of 4751 (42.0%) of the 11301 patients randomized to saxagliptin were 65 years and over, and 1210 (10.7%) were 75 years and over. no overall differences in safety or effectiveness were observed between subjects ≥65 years old and younger subjects. while this clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out. metformin hydrochloride controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and young patients. metformin is known to be substantially excreted by the kidney. 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 and the higher risk of lactic acidosis. assess renal function more frequently in elderly patients [see contraindications (4), warnings and precautions (5.1), and clinical pharmacology (12.3) ]. saxagliptin in a 12-week randomized placebo-controlled trial, saxagliptin 2.5 mg was administered to 85 subjects with moderate (n=48) or severe (n=18) renal impairment or end-stage renal disease (esrd) (n=19) [see clinical studies (14) ]. the incidence of adverse events, including serious adverse events and discontinuations due to adverse events, was similar between saxagliptin and placebo. the overall incidence of reported hypoglycemia was 20% among subjects treated with saxagliptin 2.5 mg and 22% among subjects treated with placebo. four saxagliptin-treated subjects (4.7%) and three placebo-treated subjects (3.5%) reported at least one episode of confirmed symptomatic hypoglycemia (accompanying fingerstick glucose ≤50 mg/dl). metformin hydrochloride metformin is substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment. kombiglyze xr is contraindicated in severe renal impairment, patients with an estimated glomerular filtration rate (egfr) below 30 ml/min/1.73 m2 [see dosage and administration (2.3), contraindications (4), warnings and precautions (5.1) and clinical pharmacology (12.3) ]. use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis. kombiglyze xr is not recommended in patients with hepatic impairment [see warnings and precautions (5.1) ].

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

astrazeneca pharmaceuticals lp - saxagliptin hydrochloride (unii: z8j84yix6l) (saxagliptin anhydrous - unii:8i7io46ivq) - saxagliptin anhydrous 5 mg - onglyza is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus [see clinical studies (14) ]. onglyza is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, as it would not be effective in these settings. onglyza is contraindicated in patients with a history of a serious hypersensitivity reaction to onglyza, such as anaphylaxis, angioedema, or exfoliative skin conditions [see warnings and precautions (5.4) and adverse reactions (6.2) ]. limited data with onglyza in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriages. there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see clinical considerations ]. no adverse developmental effects independent of maternal toxicity were observed when saxagliptin was administered to pregnant rats and rabbits during the period of organogenesis and in pregnant and lactating rats during the pre- and postnatal period [see data ]. the estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with an hba1c greater than 7 and has been reported to be as high as 20 to 25% in women with an hba1c greater than 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 to 4% and 15 to 20%, respectively. disease-associated maternal and/or embryo/fetal risk poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications. poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. animal data in embryo-fetal development studies, saxagliptin was administered to pregnant rats and rabbits during the period of organogenesis, corresponding to the first trimester of human pregnancy. no adverse developmental effects were observed in either species at exposures 1503- and 152-times the 5 mg clinical dose in rats and rabbits, respectively, based on auc. saxagliptin crosses the placenta into the fetus following dosing in pregnant rats. in a prenatal and postnatal development study, no adverse developmental effects were observed in maternal rats administered saxagliptin from gestation day 6 through lactation day 21 at exposures up to 470-times the 5 mg clinical dose, based on auc. there is no information regarding the presence of onglyza in human milk, the effects on the breastfed infant, or the effects on milk production. saxagliptin is present in the milk of lactating rats [see data ]. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for onglyza and any potential adverse effects on the breastfed infant from onglyza or from the underlying maternal condition. saxagliptin is secreted in the milk of lactating rats at approximately a 1:1 ratio with plasma drug concentrations. safety and effectiveness of onglyza in pediatric patients under 18 years of age have not been established. additionally, studies characterizing the pharmacokinetics of onglyza in pediatric patients have not been performed. in the seven, double-blind, controlled clinical safety and efficacy trials of onglyza, a total of 4751 (42.0%) of the 11301 patients randomized to onglyza were 65 years and over, and 1210 (10.7%) were 75 years and over. no overall differences in safety or effectiveness were observed between subjects ≥65 years old and younger subjects. while this clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out. saxagliptin and its active metabolite are eliminated in part by the kidney. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly based on renal function [see dosage and administration (2.2) and clinical pharmacology (12.3) ]. in a 12-week randomized placebo-controlled trial, onglyza 2.5 mg was administered to 85 subjects with moderate (n=48) or severe (n=18) renal impairment or end-stage renal disease (esrd) (n=19) [see clinical studies (14) ]. the incidence of adverse events, including serious adverse events and discontinuations due to adverse events, was similar between onglyza and placebo. the overall incidence of reported hypoglycemia was 20% among subjects treated with onglyza 2.5 mg and 22% among subjects treated with placebo. four onglyza-treated subjects (4.7%) and three placebo-treated subjects (3.5%) reported at least one episode of confirmed symptomatic hypoglycemia (accompanying fingerstick glucose ≤50 mg/dl).