Ertugliflozin pidolate and Metformin

SEGLUROMET ® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. SEGLUROMET is a combination of ertugliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, and metformin, a biguanide, 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.

SEGLUROMET SEGLUROMET 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 metformin hydrochloride, a member of the biguanide class. 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. Metformin HCl Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose.

Assess renal function prior to initiation and as clinically indicated. Correct volume depletion before initiation. Individualize the starting dosage based on the patient's current regimen. Maximum recommended dosage is 7.5 mg ertugliflozin/1,000 mg metformin orally twice daily. Take orally twice daily with meals, with gradual dose escalation. Do not use in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m 2. Use is not recommended in patients with an eGFR less than 45 mL/min/1.73 m 2. Use 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. SEGLUROMET may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures. Withhold SEGLUROMET for at least 4 days, if possible, prior to surgery or procedures associated with prolonged fasting.

SEGLUROMET is contraindicated in patients with: Hypersensitivity to ertugliflozin, metformin, or any excipient in SEGLUROMET. Reactions such as angioedema or anaphylaxis have occurred. Severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end stage-renal disease (ESRD), or on dialysis. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end stage-renal disease, or patients on dialysis. Metabolic acidosis, including diabetic ketoacidosis. Hypersensitivity to ertugliflozin, metformin or any excipient.

Boxed warning (lactic acidosis): Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. 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 SEGLUROMET if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. Lower Limb Amputation: Monitor patients for infections or ulcers of lower limbs, and institute appropriate treatment. Volume Depletion: May result in acute kidney injury.

The following important adverse reactions are described elsewhere in the labeling: Lactic Acidosis Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis Lower Limb Amputation 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 or Insulin Secretagogues Vitamin B 12 Deficiency Most common adverse reactions associated with ertugliflozin (incidence ≥5%) were female genital mycotic infections. Most common adverse reactions associated with metformin (incidence ≥5%) were diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.

Table 3: Clinically Significant Drug Interactions with SEGLUROMET Carbonic Anhydrase Inhibitors Clinical Impact: The risk of lactic acidosis may increase due to concomitant use of Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) with metformin. These drugs frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Intervention: more frequent monitoring of these patients.

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.