Dapagliflozin And Saxagliptin

Contraindications

4 CONTRAINDICATIONS Dapagliflozin and saxagliptin is contraindicated in patients with: History of a serious hypersensitivity reactions to dapagliflozin or to saxagliptin, including anaphylactic reaction, angioedema or exfoliative skin conditions [ see WARNINGS AND PRECAUTIONS (5.8) and ADVERSE REACTIONS (6.2)]. Moderate to severe renal impairment (eGFR less than 45 mL/min/1.73 m 2 ), end-stage renal disease (ESRD), or patients on dialysis [ see USE IN SPECIFIC POPULATIONS (8.6)]. History of a serious hypersensitivity reaction to dapagliflozin or to saxagliptin. ( 4 ) Moderate to severe renal impairment (eGFR <45 mL/min/1.73 m 2 ), end-stage renal disease, or patients on dialysis. ( 4 )

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Based on animal data showing adverse renal effects from dapagliflozin, dapagliflozin and saxagliptin is not recommended during the second and third trimesters of pregnancy. The limited available data with dapagliflozin and saxagliptin 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 dapagliflozin and saxagliptin) 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 embryo-fetal 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 Dapaglifl