Ertugliflozin pidolate and Sitagliptin

STEGLUJAN ® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. Has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using STEGLUJAN. STEGLUJAN is a combination of ertugliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, and sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

STEGLUJAN STEGLUJAN combines two antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus: ertugliflozin, a SGLT2 inhibitor, and sitagliptin, a DPP-4 inhibitor. Ertugliflozin SGLT2 is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. Ertugliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, ertugliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Sitagliptin Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes mellitus by slowing the inactivation of incretin hormones.

Assess renal function before initiating and as clinically indicated. Correct volume depletion before initiating. Recommended starting dosage is 5 mg ertugliflozin/100 mg sitagliptin orally once daily, taken in the morning, with or without food. Increase dosage to 15 mg ertugliflozin/100 mg sitagliptin orally once daily in those tolerating STEGLUJAN and needing additional glycemic control. Use is not recommended in patients with an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m 2. Withhold STEGLUJAN for at least 4 days, if possible, prior to surgery or procedures associated with prolonged fasting.

STEGLUJAN is contraindicated in patients with: Severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end-stage renal disease (ESRD), or on dialysis. Hypersensitivity to sitagliptin, ertugliflozin, or any excipient, in STEGLUJAN. Reactions such as anaphylaxis or angioedema have occurred. Severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end-stage renal disease, or dialysis.

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue STEGLUJAN if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. Pancreatitis: There have been postmarketing reports of acute pancreatitis in patients taking sitagliptin, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue. Lower Limb Amputation: Monitor patients for infections or ulcers of lower limbs, and institute appropriate treatment. Acute Renal Failure: There have been postmarketing reports of acute renal failure in patients taking sitagliptin, sometimes requiring dialysis. Monitor renal function.

The following important adverse reactions are described elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis Pancreatitis Lower Limb Amputation Acute Renal Failure Volume Depletion Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections Heart Failure Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues Hypersensitivity Reactions Severe and Disabling Arthralgia Bullous Pemphigoid Most common adverse reactions associated with ertugliflozin (incidence ≥5%): female genital mycotic infections. Most common adverse reactions associated with sitagliptin (incidence ≥5%): upper respiratory tract infection, nasopharyngitis and headache.

Table 3: Clinically Significant Drug Interactions with STEGLUJAN Insulin or Insulin Secretagogues Clinical Impact: The risk of hypoglycemia is increased when STEGLUJAN is used in combination with insulin or an insulin secretagogue. Intervention: A lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with STEGLUJAN. Lithium Clinical Impact: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Intervention: Monitor serum lithium concentration more frequently during STEGLUJAN 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-25°C (68°F-77°F), excursions permitted between 15°C-30°C (between 59°F-86°F). Protect from moisture. Store in a dry place.