Dapagliflozin and Saxagliptin

Dapagliflozin and saxagliptin tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use Dapagliflozin and saxagliptin tablets are not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. Dapagliflozin and saxagliptin tablets is a combination of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor and saxagliptin a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus.

Dapagliflozin Sodium-glucose cotransporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Dapagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, dapagliflozin reduces reabsorption of filtered glucose and thereby promotes urinary glucose excretion. Saxagliptin Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production.

Assess renal function before initiation of therapy and periodically thereafter. Take orally, once daily in the morning with or without food. For patients not already taking dapagliflozin, the recommended starting dose of dapagliflozin and saxagliptin tablets is a 5 mg dapagliflozin/5 mg saxagliptin tablet once daily. In patients tolerating 5 mg dapagliflozin and 5 mg saxagliptin once daily who require additional glycemic control, the dapagliflozin and saxagliptin tablets dose can be increased to 10 mg dapagliflozin/5 mg saxagliptin tablet once daily. Swallow tablet whole. Do not crush, cut or chew. Withhold dapagliflozin and saxagliptin for at least 3 days, if possible, prior to major surgery or procedures associated with prolonged fasting.

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. Moderate to severe renal impairment (eGFR less than 45 mL/min/1.73 m 2 ), end-stage renal disease (ESRD), or patients on dialysis. History of a serious hypersensitivity reaction to dapagliflozin or to saxagliptin. Moderate to severe renal impairment (eGFR <45 mL/min/1.73 m 2 ), end-stage renal disease, or patients on dialysis.

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue dapagliflozin and saxagliptin if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. Pancreatitis: If pancreatitis is suspected, promptly discontinue dapagliflozin and saxagliptin. Heart Failure: Consider risks and benefits of dapagliflozin and saxagliptin in patients who have known risk factors for heart failure. Monitor patients for signs and symptoms. Volume Depletion: Before initiating dapagliflozin and saxagliptin, assess volume status and renal function in the elderly, patients with renal impairment or low systolic blood pressure, and in patients on diuretics.

The following important adverse reactions are described below or elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis Pancreatitis Heart Failure Volume Depletion Urosepsis and Pyelonephritis Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene) Hypersensitivity Reactions Genital Mycotic Infections Severe and Disabling Arthralgia Bullous Pemphigoid Adverse reactions reported in ≥5% of subjects treated with dapagliflozin and saxagliptin were: upper respiratory tract infection, urinary tract infection, and dyslipidemia.

Table 3: Clinically Relevant Interactions with Dapagliflozin and Saxagliptin Strong Inhibitors of CYP3A4/5 Enzymes Clinical Impact Ketoconazole significantly increased saxagliptin exposure. Similar significant increases in plasma concentrations of saxagliptin are anticipated with other strong CYP3A4/5 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin). Intervention Do not coadminister dapagliflozin and saxagliptin with strong cytochrome P450 3A4/5 inhibitors. Insulin or Insulin Secretagogues Clinical Impact The risk of hypoglycemia may be increased when dapagliflozin and saxagliptin is used concomitantly with insulin or insulin secretagogues (e.g., sulfonylurea). Intervention Concomitant use may require lower doses of insulin or the insulin secretagogue to reduce the risk of hypoglycemia.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).