SEGLUROMET^™

(ertugliflozin and metformin HCI) 2.5 mg/500 mg, 2.5 mg/1000 mg, 7.5 mg/500 mg, 7.5 mg/1000 mg tablets)

SEGLUROMET^™(ertugliflozin and metformin HCI) 2.5 mg/500 mg, 2.5 mg/1000 mg, 7.5 mg/500 mg, 7.5 mg/1000 mg tablets)

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Indication

SEGLUROMET^™ (ertugliflozin and metformin HCl) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled on a regimen containing ertugliflozin or metformin, or in patients who are already treated with both ertugliflozin and metformin. SEGLUROMET is not recommended in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Selected Safety Information

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. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio, and metformin plasma levels generally >5 mcg/mL.

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

If metformin-associated lactic acidosis is suspected, immediately discontinue SEGLUROMET and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

Contraindications: Severe renal impairment, end-stage renal disease, or dialysis. Acute or chronic metabolic acidosis, including ketoacidosis with or without coma. A history of a serious hypersensitivity reaction to SEGLUROMET, ertugliflozin, or metformin hydrochloride.

Lactic Acidosis: Educate patients and their families about the symptoms of lactic acidosis and, if these symptoms occur, instruct them to discontinue SEGLUROMET and promptly notify their health care provider.

Recommendations to reduce the risk include:
Renal Impairment: Obtain an estimated glomerular filtration rate (eGFR) prior to initiating therapy and annually or more frequently in patients at increased risk of developing renal impairment.
Drug Interactions: More frequent monitoring is recommended when administered with drugs that impair renal function, result in hemodynamic change, interfere with acid-base balance, or increase metformin accumulation.
Age 65 or Greater: Assess renal function more frequently.
Radiological Studies With Contrast: Stop SEGLUROMET at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR of less than 60 mL/min/1.73 m²; in patients with a history of hepatic impairment, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the procedure and restart SEGLUROMET if renal function is stable.
Surgery and Other Procedures: Discontinue while patients have restricted food and fluid intake.
Hypoxic States: Discontinue in conditions associated with hypoxemia.
Excessive Alcohol Intake: Warn patients against excessive alcohol intake.
Hepatic Impairment: Avoid use in patients with evidence of hepatic disease.

Hypotension: Ertugliflozin causes intravascular volume contraction and symptomatic hypotension may occur after initiating SEGLUROMET, particularly in patients with impaired renal function (eGFR less than 60 mL/min/1.73 m²), elderly patients (≥65 years), in patients with low systolic blood pressure, or patients on diuretics. Before initiating SEGLUROMET, assess and correct volume status. Monitor for hypotension.

Ketoacidosis: Ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, has been reported in patients with type 1 and type 2 diabetes receiving sodium glucose co-transporter 2 inhibitors (SGLT2is), including ertugliflozin. Some cases were fatal. Assess patients with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If ketoacidosis is suspected, discontinue SEGLUROMET, evaluate, treat promptly, and ensure risks for ketoacidosis are resolved prior to restarting. Before initiating, consider risk factors. Consider temporarily discontinuing SEGLUROMET for at least 4 days prior to scheduled surgery. Monitor patients and temporarily discontinue SEGLUROMET in clinical situations known to predispose to ketoacidosis (eg, prolonged fasting due to acute illness or post-surgery). Educate patients on the signs and symptoms of ketoacidosis. Instruct patients to discontinue SEGLUROMET and seek medical attention immediately if signs and symptoms occur.

Acute Kidney Injury and Impairment in Renal Function: SEGLUROMET causes intravascular volume contraction and can cause renal impairment. There have been reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving SGLT2 inhibitors. Before initiating SEGLUROMET, consider factors that may predispose patients to acute kidney injury. Consider temporarily discontinuing SEGLUROMET in any setting of reduced oral intake or fluid losses; monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue SEGLUROMET promptly and institute treatment.

SEGLUROMET 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 SEGLUROMET. Renal function should be evaluated prior to initiating SEGLUROMET and periodically thereafter. Use of SEGLUROMET 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.

Urosepsis and Pyelonephritis: There have been postmarketing reports of serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization in patients receiving SGLT2 inhibitors. Cases of pyelonephritis also have been reported in ertugliflozin-treated patients in clinical trials. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate for urinary tract infections and treat promptly.

Lower Limb Amputations: An increased risk for lower limb amputation has been observed in clinical studies with another SGLT2 inhibitor. Across seven Phase 3 clinical trials with ertugliflozin, nontraumatic lower limb amputations were reported in 1 (0.1%) patient in the comparator group, 3 (0.2%) patients in the ertugliflozin 5-mg group, and 8 (0.5%) patients in the ertugliflozin 15-mg group. A causal association between ertugliflozin and lower limb amputation has not been definitively established. Before initiating SEGLUROMET, consider factors that may predispose patients to the need for amputations. Monitor patients and discontinue SEGLUROMET if complications occur. Counsel patients about the importance of routine preventative foot care.

Hypoglycemia With Concomitant Use With Insulin and Insulin Secretagogues: Ertugliflozin may increase the risk of hypoglycemia when combined with insulin and/or an insulin secretagogue. Consider lowering the dose of these agents when coadministered with SEGLUROMET. Hypoglycemia could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation or during concomitant use with other glucose-lowering agents or with the use of ethanol.

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): A rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention has been reported in post-marketing surveillance in females and males with diabetes mellitus receiving SGLT2 inhibitors. Serious outcomes have included hospitalization, multiple surgeries, and death. Patients treated with SEGLUROMET presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, should be assessed for necrotizing fasciitis. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue SEGLUROMET, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.

Genital Mycotic Infections: Ertugliflozin increases the risk of genital mycotic infections, particularly in patients with a history of these infections or who are uncircumcised. Monitor and treat appropriately.

Increases in Low-Density Lipoprotein Cholesterol (LDL-C): Dose-related increases in LDL-C can occur with SEGLUROMET. Monitor and treat as appropriate.

Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with SEGLUROMET.

The most common adverse reactions associated with ertugliflozin (≥5%) were female genital mycotic infections. The most common adverse reactions associated with metformin (≥5%) were diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.

Before prescribing SEGLUROMET, please read the accompanying Prescribing Information, including the Boxed Warning about lactic acidosis. The Medication Guide also is available.