5.5 Acute Kidney Injury and Impairment in Renal Function

Dapagliflozin causes intravascular volume contraction [see Warning and Precautions (5.3)], and can cause renal impairment [see Adverse Reactions (6.1)]. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving dapagliflozin; some reports involved patients younger than 65 years of age.

Before initiating QTERN, consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure, and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs). Consider temporarily discontinuing QTERN in any setting of reduced oral intake (such as acute illness or fasting) or fluid losses (gastrointestinal illness or excessive heat exposure); monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue QTERN promptly and institute treatment.

Dapagliflozin increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Adverse reactions related to renal function can occur after initiating QTERN [see Adverse Reactions (6.1)]. Discontinue QTERN in patients if eGFR falls persistently below 60 mL/min/1.73 m2. QTERN is contraindicated in patients with an eGFR less than 45 mL/min/1.73 m2 [see Dosage and Administration (3.2), Contraindications (4), and Use in Specific Populations (8.6)].

5.6 Urosepsis and Pyelonephritis

There have been postmarketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT-2 inhibitors, including dapagliflozin. Treatment with SGLT-2 inhibitors increases the risk for urinary tract infections. eva luate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated [see Adverse Reactions (6.2)].

5.7 Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues

Insulin and insulin secretagogues, such as sulfonylureas, are known to cause hypoglycemia. Both saxagliptin and dapagliflozin can individually increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue. Therefore, a lower dose of insulin or insulin secretagogue may be required to reduce the risk of hypoglycemia when these agents are used in combination with QTERN [see Adverse Reactions (6.1)].

5.8 Hypersensitivity Reactions

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with saxagliptin. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with saxagliptin, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue QTERN, treat per standard of care, and monitor until signs and symptoms are resolved. Assess for other potential causes for the event. Institute a