Dapagliflozin propanediol

FARXIGA (dapagliflozin) is indicated: • To reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular (CV) death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression. • To reduce the risk of CV death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure. • To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established CV disease or multiple CV risk factors. • As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. Limitations of Use • FARXIGA is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus.

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. Dapagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, lowering both pre- and afterload of the heart and downregulation of sympathetic activity, and decreased intraglomerular pressure which is believed to be mediated by increased tubuloglomerular feedback.

• Assess renal function prior to initiation and then as clinically indicated. Assess volume status and correct volume depletion before initiating. • To improve glycemic control, the recommended starting dosage is 5 mg orally once daily. Dosage can be increased to 10 mg orally once daily for additional glycemic control. • For all other indications, the recommended dosage is 10 mg orally once daily. • See full prescribing information for dosage recommendations in patients with renal impairment. • Withhold FARXIGA for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting.

FARXIGA is contraindicated in patients with a history of a serious hypersensitivity reaction to dapagliflozin or any of the excipients in FARXIGA. Serious hypersensitivity reactions, including anaphylaxis and angioedema have been reported with FARXIGA. • History of serious hypersensitivity reaction to dapagliflozin or any of the excipients in FARXIGA.

• 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 FARXIGA if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. • Volume depletion: Before initiating FARXIGA, 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.

The following important adverse reactions are described below and elsewhere in the labeling: • Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis • Volume Depletion • Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections • Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues • Most common adverse reactions (5% or greater incidence) were female genital mycotic infections, nasopharyngitis, and urinary tract infections.

Table 4: Clinically Relevant Interactions with FARXIGA Insulin or Insulin Secretagogues Clinical Impact The risk of hypoglycemia may be increased when FARXIGA 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. Lithium Clinical Impact Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Intervention Monitor serum lithium concentration more frequently during FARXIGA initiation and dosage changes. Positive Urine Glucose Test Clinical Impact SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Intervention Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors.

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