DAPAGLIFLOZIN-SAXAGLIPTIN (dapagliflozin/saxagliptin hcl)

There are 1 contraindications. Absolute contraindication.

Contraindication List
Acute pancreatitis

There are 10 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Chronic heart failure
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Hypoglycemic disorder
Hypovolemia
Invasive surgical procedure
Necrotizing fasciitis of perineum or genital area
Pregnancy
Type 1 diabetes mellitus

There are 2 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Hypoglycemic disorder
Lymphopenia

There are 30 severe adverse reactions.

More Frequent	Less Frequent
Urinary tract infection	Dehydration Heart failure Hypotension

Rare/Very Rare

Acquired phimosis Acute kidney injury Acute pancreatitis Anaphylaxis Angioedema Arthralgia Bacterial sepsis Bullous pemphigoid Diabetic ketoacidosis Exfoliative dermatitis Fracture Hypersensitivity drug reaction Hypoglycemic disorder Infection Ketoacidosis Kidney disease with reduction in glomerular filtration rate (GFr) Lymphopenia Malignant tumor of urinary bladder Metabolic acidosis Necrotizing fasciitis of perineum or genital area Pancreatitis Pyelonephritis Rhabdomyolysis Skin rash Urosepsis Urticaria

There are 28 less severe adverse reactions.

More Frequent	Less Frequent
Headache disorder Pharyngitis Upper respiratory infection Urinary tract infection Vulvovaginal candidiasis	Back pain Candidal balanitis Constipation Dysuria Gastroenteritis Genital organ pruritus Genitourinary tract infections Hypercholesterolemia Hyperphosphatemia Hypoglycemic disorder Hypovolemia Increased hemoglobin Increased urinary frequency Influenza Nausea Orthostatic hypotension Peripheral edema Pharyngitis Sinusitis Vomiting

Rare/Very Rare
Facial edema Skin rash Urticaria

Data on the use of saxagliptin in pregnant women are insufficient to determine a drug-associated risk for major birth defects or miscarriage. Poorly controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications. In addition, poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.

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 prenatal and postnatal period. There is insufficient evidence with dapagliflozin in pregnant women to evaluate a drug-associated risk of major birth defects or miscarriage. Based on the results of reproductive and developmental toxicity studies in animals, dapagliflozin use during pregnancy may affect renal development and maturation.

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 dosage. Poorly controlled diabetes mellitus and untreated heart failure also are associated with risks to the mother and fetus, including DKA, preeclampsia, spontaneous abortions, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia-related morbidity. The manufacturer states that dapagliflozin therapy is not recommended in pregnant women during the second and third trimesters of pregnancy.

Saxagliptin is distributed into milk in rats at a milk-to-plasma ratio of approximately 1:1. Data are lacking regarding the presence of saxagliptin in human milk and on the effects of the drug on the breast-fed infant or on milk production. 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 breast-fed infant from the drug or the underlying maternal condition.

There are no data on the presence of dapagliflozin in human milk, the effects on the breast-fed child, or the effects on milk production. Dapagliflozin is distributed into milk in rats. 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. Use of dapagliflozin in women who are breast-feeding is not recommended.

Of the 11,301 patients enrolled in clinical trials with saxagliptin, 4751 (42%) were >=65 years of age and 1210 (10.7%) were >=75 years of age. No substantial differences in safety and efficacy in patients >=65 years of age relative to younger adults have been observed, but increased sensitivity cannot be ruled out. Saxagliptin and its active metabolite are eliminated in part by the kidneys; renal function should be assessed periodically since geriatric patients are more likely to have decreased renal function.

Among patients with type 2 diabetes mellitus in 21 clinical trials, 1424 (24%) were 65 years of age or older and 207 (3.5%) were 75 years of age or older. Efficacy of dapagliflozin was similar for patients younger than 65 years of age and those 65 years of age or older after controlling for renal function (eGFR). Geriatric patients receiving dapagliflozin for glycemic control were more likely to experience hypotension compared with patients treated with placebo.

In the DAPA-CKD, DAPA-HF, and DELIVER trials, safety and efficacy were similar for patients aged 65 years and younger and those older than 65 years of age. In the DAPA-CKD study, 42% of patients were older than 65 years of age. In the DAPA-HF study, 57% of patients were older than 65 years. In the DELIVER study, 76% of patients were older than 65 years.