Canada - English - Health Canada

apotex inc - dapagliflozin; metformin hydrochloride - tablet - 5mg; 850mg - dapagliflozin 5mg; metformin hydrochloride 850mg

Canada - English - Health Canada

apotex inc - dapagliflozin; metformin hydrochloride - tablet - 5mg; 1000mg - dapagliflozin 5mg; metformin hydrochloride 1000mg

Canada - English - Health Canada

auro pharma inc - dapagliflozin; metformin hydrochloride - tablet - 5mg; 850mg - dapagliflozin 5mg; metformin hydrochloride 850mg

Canada - English - Health Canada

auro pharma inc - dapagliflozin; metformin hydrochloride - tablet - 5mg; 1000mg - dapagliflozin 5mg; metformin hydrochloride 1000mg

European Union - English - EMA (European Medicines Agency)

viatris limited - dapagliflozin - diabetes mellitus, type 2; heart failure, systolic; heart failure; renal insufficiency, chronic - drugs used in diabetes - type 2 diabetes mellitusdapagliflozin viatris is indicated in adults and children aged 10 years and above for the treatment of insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise- as monotherapy when metformin is considered inappropriate due to intolerance.- in addition to other medicinal products for the treatment of type 2 diabetes.for study results with respect to combination of therapies, effects on glycaemic control, cardiovascular and renal events, and the populations studied, see sections 4.4, 4.5 and 5.1.heart failuredapagliflozin viatris is indicated in adults for the treatment of symptomatic chronic heart failure with reduced ejection fraction.chronic kidney diseasedapagliflozin viatris is indicated in adults for the treatment of chronic kidney disease.

European Union - English - EMA (European Medicines Agency)

astrazeneca ab - dapagliflozin propanediol monohydrate, metformin hydrochloride - diabetes mellitus, type 2 - drugs used in diabetes - type 2 diabetes mellitusfor the treatment of insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise.as monotherapy when metformin is considered inappropriate due to intolerance.in addition to other medicinal products for the treatment of type 2 diabetes.for study results with respect to combination of therapies, effects on glycaemic control and cardiovascular events, and the populations studied, see sections 4.4, 4.5 and 5.1.type 1 diabetes mellitusedistride is indicated in adults for the treatment of insufficiently controlled type 1 diabetes mellitus as an adjunct to insulin in patients with bmi ≥ 27 kg/m2, when insulin alone does not provide adequate glycaemic control despite optimal insulin therapy.

European Union - English - 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.

Ireland - English - HPRA (Health Products Regulatory Authority)

krka, d.d., novo mesto - dapagliflozin - film-coated tablet - dapagliflozin

Ireland - English - HPRA (Health Products Regulatory Authority)

krka, d.d., novo mesto - dapagliflozin - film-coated tablet - dapagliflozin

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

prasco, llc - dapagliflozin propanediol (unii: 887k2391vh) (dapagliflozin - unii:1ull0qj8uc), metformin hydrochloride (unii: 786z46389e) (metformin - unii:9100l32l2n) - dapagliflozin and metformin hcl extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. dapagliflozin is indicated to reduce limitations of use dapagliflozin and metformin hcl extended-release tablets are contraindicated in patients with: risk summary based on animal data showing adverse renal effects, dapagliflozin and metformin hcl extended-release tablets are not recommended during the second and third trimesters of pregnancy. limited data with dapagliflozin and metformin hcl extended-release tablets or dapagliflozin in pregnant women are not sufficient to determine 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 mother and fetus associated with poorly controlled diabetes in pregnancy (see clinical considerations) . in animal studies, adverse renal pelvic and tubule dilatations, that were not fully reversible, were observed in rats when dapagliflozin 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) . the estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a hba1c greater than 7% and has been reported to be as high as 20 to 25% in women with 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 human data published data from post-marketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was 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 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 tested 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 pups 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 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). 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 2- and 6-times a 2000 mg clinical dose based on body surface area (mg/m2 ) for rats and rabbits, respectively. determination of fetal concentrations demonstrated a partial placental barrier to metformin. risk summary there is no information regarding the presence of dapagliflozin and metformin hcl extended-release tablets or dapagliflozin 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. dapagliflozin is 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 breastfed infants, advise women that use of dapagliflozin and metformin hcl extended-release tablets is not recommended while breastfeeding. data dapagliflozin dapagliflozin was present in rat milk 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 risk to the developing kidney (renal pelvic and tubular dilatations) during maturation. metformin hcl 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. discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some anovulatory women. safety and effectiveness of dapagliflozin and metformin hcl extended-release tablets in pediatric patients under 18 years of age have not been established. dapagliflozin and metformin hcl extended-release tablets no dapagliflozin and metformin hcl extended-release tablets dosage change is recommended based on age. more frequent assessment of renal function is recommended in elderly patients. 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), efficacy was similar for patients under age 65 years and those 65 years and older. in patients ≥65 years of age, a higher proportion of patients treated with dapagliflozin for glycemic control had adverse reactions of hypotension [see warnings and precautions (5.3) and adverse reactions (6.1)] . in both the dapa-hf and dapa-ckd studies, safety and efficacy were similar for patients age 65 years and younger and those older than 65 in both the overall population and the patients with type 2 diabetes mellitus. in the dapa-hf study, 2714 (57%) out of 4744 patients with heart failure with reduced ejection fraction (hfref) were older than 65 years. out of 2139 patients with hfref and type 2 diabetes mellitus, 1211 (57%) were older than 65 years. in the dapa-ckd study, 1818 (42%) out of 4304 patients with chronic kidney disease were older than 65 years. out of 2906 patients with chronic kidney disease and type 2 diabetes mellitus, 1399 (48%) were older than 65 years. metformin hcl controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently than 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 and the higher risk of lactic acidosis. assess renal function more frequently in elderly patients [see warnings and precautions (5.1)] . initiation of dapagliflozin and metformin hcl extended-release tablets is not recommended in patients with an egfr below 45 ml/min/1.73 m2 and is contraindicated in patients with severe renal impairment (egfr less than 30 ml/min/1.73 m2 ), end-stage renal disease or patients on dialysis [see dosage and administration (2.4), contraindications (4) and  warnings and precautions  (5.1, 5.3)] . dapagliflozin dapagliflozin 10 mg was evaluated in 4304 patients with chronic kidney disease (egfr 25 to 75 ml/min/1.73 m2 ) in the dapa-ckd study. dapagliflozin 10 mg was also evaluated in 1926 patients with an egfr of 30 to 60 ml/min/1.73 m2 in the dapa-hf study. the safety profile of dapagliflozin across egfr subgroups was consistent with the known safety profile [see adverse reactions (6.1) and clinical studies  (14.3 and 14.4)] . dapagliflozin 10 mg 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 ) [see clinical studies (14.1)] . patients with diabetes and renal impairment using dapagliflozin 10 mg are 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. use of dapagliflozin 10 mg for glycemic control in patients without established cv disease or cv risk factors is not recommended when egfr is less than 45 ml/min/1.73 m2  [see dosage and administration (2.4)] . metformin hcl metformin is substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment. dapagliflozin and metformin hcl extended-release tablets are contraindicated in severe renal impairment, patients with an estimated glomerular filtration rate (egfr) below 30 ml/min/1.73 m2 [see dosage and administration (2.4), 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. dapagliflozin and metformin hcl extended-release tablets are not recommended in patients with hepatic impairment [see warnings and precautions (5.1)] .