Dapagliflozin - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis : Consider ketone monitoring in patients with type 1 diabetes mellitus and consider ketone monitoring in others at risk for ketoacidosis, as indicated.

Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue dapagliflozin tablets if ketoacidosis is suspected.

Monitor patients for resolution of ketoacidosis before restarting.

Volume depletion : Before initiating dapagliflozin tablets, assess volume status and renal function in the elderly, patients with renal impairment or low systolic blood pressure, and in patients on diuretics.

Monitor for signs and symptoms during therapy.

Urosepsis and Pyelonephritis : Evaluate for signs and symptoms of urinary tract infections and treat promptly, if indicated.

Hypoglycemia : Consider a lower dose of insulin or the insulin secretagogue to reduce the risk of hypoglycemia when used in combination with dapagliflozin tablets.

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) : Serious, life- threatening cases have occurred in patients with diabetes, both females and males.

Assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise.

If suspected, institute prompt treatment.

Genital Mycotic Infections : Monitor and treat if indicated.

5.1 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, dapagliflozin tablets significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate.

In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium-glucose cotransporter 2 (SGLT2) inhibitors compared to patients who received placebo.

Dapagliflozin tablets are not indicated for glycemic control in patients with type 1 diabetes mellitus.

Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis.

There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors, including dapagliflozin tablets.

Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse.

Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath.

Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., less than 250 mg/dL).

Ketoacidosis and glucosuria may persist longer than typically expected.

Urinary glucose excretion persists for 3 days after discontinuing dapagliflozin tablets [see Clinical Pharmacology ] ; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors.

Consider ketone monitoring in patients with type 1 diabetes mellitus and consider ketone monitoring in others at risk for ketoacidosis if indicated by the clinical situation.

Assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis.

If ketoacidosis is suspected, discontinue dapagliflozin tablets, promptly evaluate, and treat ketoacidosis, if confirmed.

Monitor patients for resolution of ketoacidosis before restarting dapagliflozin tablets.