dium glucose co-transporter-2 (SGLT2) inhibitors and cases have been reported in ertugliflozin-treated patients in clinical trials. Across the clinical program, ketoacidosis was identified in 3 of 3,409 (0.1%) of ertugliflozin-treated patients and 0% of comparator-treated patients. Fatal cases of ketoacidosis have been reported in patients taking medicines containing SGLT2 inhibitors. STEGLUJAN is not indicated for the treatment of patients with type 1 diabetes mellitus [see Indications and Usage (1)].
treatment should be instituted. Treatment of ketoacidosis may require insulin, fluid, and carbohydrate replacement.
In many of the reported cases, and particularly in patients with type 1 diabetes, the presence of ketoacidosis was not immediately recognized and institution of treatment was delayed because 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 STEGLUJAN, consider factors in the patient history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse. In patients treated with STEGLUJAN consider monitoring for ketoacidosis and temporarily discontinuing STEGLUJAN in clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or surgery).
5.4 Acute Kidney Injury and Impairment in Renal Function
STEGLUJAN causes intravascular volume contraction 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 SGLT2 inhibitors.
Before initiating STEGLUJAN, 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 STEGLUJAN in any setting of reduced oral intake (such as acute illness or fasting) or fluid losses (such as gastrointestinal illness or excessive heat exposure); monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue STEGLUJAN promptly and institute treatment.
Ertugliflozin, a component of STEGLUJAN, increases serum creatinine and decreases eGFR. Patients with moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2) may be more susceptible to these changes. Renal function abnormalities can occur after initiating STEGLUJAN [see Adverse Reactions (6.1)]. Renal function should be eva luated prior to initiating STEGLUJAN and periodically thereafter. Use of STEGLUJAN is not recommended when eGFR is persistently between 30 and less than 60 mL/min/1.73 m2 and is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2 [see Dosage and Administration (2.2), Contraind
