factors for ASCVD (SAVOR trial), more patients randomized to saxagliptin (289/8280, 3.5%) were hospitalized for heart failure compared to patients randomized to placebo (228/8212, 2.8%). In a time-to-first-event analysis the risk of hospitalization for heart failure was higher in the saxagliptin group (estimated Hazard Ratio: 1.27; 95% CI: 1.07, 1.51). Subjects with a prior history of heart failure and subjects with renal impairment had a higher risk for hospitalization for heart failure, irrespective of treatment assignment.
Consider the risks and benefits of QTERN prior to initiating treatment in patients at a higher risk of heart failure. Observe patients for signs and symptoms of heart failure during therapy. Advise patients of the characteristic symptoms of heart failure and to immediately report such symptoms. If heart failure develops, eva luate and manage according to current standards of care and consider discontinuation of QTERN.
5.3 Hypotension
Dapagliflozin causes intravascular volume contraction. Symptomatic hypotension can occur after initiating QTERN [see Adverse Reactions (6.1)] particularly in patients with impaired renal function (eGFR <60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics. Before initiating QTERN volume status should be assessed and corrected. Do not initiate QTERN in patients with an eGFR <60 mL/min/1.73 m2. Monitor for signs and symptoms of hypotension after initiating therapy.
5.4 Ketoacidosis
Reports of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, have been identified in postmarketing surveillance in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose cotransporter-2 (SGLT-2) inhibitors, including dapagliflozin. Fatal cases of ketoacidosis have been reported in patients taking dapagliflozin. QTERN is not indicated for the treatment of patients with type 1 diabetes mellitus [see Indications and Usage (2)].
Patients treated with QTERN who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of presenting blood glucose levels as ketoacidosis associated with QTERN may be present even if blood glucose levels are less than 250 mg/dL. If ketoacidosis is suspected, QTERN should be discontinued, the patient should be eva luated and prompt treatment should be instituted. Treatment of ketoacidosis may require insulin, fluid and carbohydrate replacement.
In many of the postmarketing reports for dapagliflozin, and particularly in patients with type 1 diabetes, the presence of ketoacidosis was not immediately recognized and the institution of treatment was delayed because the presenting blood glucose levels were below those typically expected for diabetic ketoacidosis (often less than 250 mg/dL). Signs and symptoms at presentation were consistent with dehydration and severe metabolic acidosis and included nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. In some but not all cases, factors predisposing to ketoacidosis such as insulin dose reduction, acute febrile illness, reduced caloric intake due to illness or surgery, pancreatic disorders suggesting insulin deficiency (e.g., type 1 diabetes, history of pancreatitis or pancreatic surgery), and alcohol abuse were identified.
Before initiating QTERN, consider factors in the patient history that may predispose to ketoacidosis incl
