Contraindications: STEGLUJAN is contraindicated in patients with severe renal impairment (<30 mL/min/1.73 m2), end-stage renal disease, or on dialysis, and/or hypersensitivity reaction, such as anaphylaxis or angioedema, to sitagliptin, ertugliflozin, or any excipient in STEGLUJAN.
Pancreatitis: Acute pancreatitis (including fatal and nonfatal hemorrhagic or necrotizing pancreatitis) has been reported in patients taking sitagliptin. Observe for signs and symptoms, and if suspected, discontinue STEGLUJAN and institute treatment. It is unknown whether patients with a history of pancreatitis are at increased risk for developing pancreatitis while using STEGLUJAN.
Ketoacidosis: Ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, has been identified in patients with type 1 and type 2 diabetes receiving sodium glucose co-transporter 2 (SGLT2) inhibitors, including ertugliflozin. Some cases were fatal. In placebo-controlled trials of patients with type 1 diabetes, the risk of ketoacidosis was increased in patients who received SGLT2 inhibitors compared to patients who received placebo. The risk of ketoacidosis may be greater with higher doses. Assess patients with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If ketoacidosis is suspected, discontinue STEGLUJAN, evaluate, treat promptly, and ensure risks for ketoacidosis are resolved prior to restarting. Before initiating, consider risk factors. Consider temporarily discontinuing STEGLUJAN for at least 4 days prior to scheduled surgery. Monitor patients and temporarily discontinue STEGLUJAN in clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or post-surgery). Educate patients on the signs and symptoms of ketoacidosis. Instruct patients to discontinue STEGLUJAN and seek medical attention immediately if signs and symptoms occur.
Lower Limb Amputations: In a long-term cardiovascular outcomes study, in patients with type 2 diabetes and established cardiovascular disease, the occurrence of non-traumatic lower limb amputations was higher with ertugliflozin compared to placebo. Amputation of the toe and foot were most frequent (81 out of 109 patients with lower limb amputations). Some patients had multiple amputations, some involving both lower limbs. Lower limb infections, gangrene, and diabetic foot ulcers were the most common precipitating medical events leading to the need for an amputation. Patients with amputations were more likely to be male, have higher A1C (%) at baseline, have a history of peripheral arterial disease, amputation or peripheral revascularization procedure, diabetic foot, and have been taking diuretics or insulin. Across seven Phase 3 clinical trials with STEGLUJAN, non-traumatic lower limb amputations were reported in 1 (0.1%) patient in the comparator group, 3 (0.2%) patients in the STEGLUJAN 5 mg group, and 8 (0.5%) patients in the STEGLUJAN 15 mg group. Before initiating STEGLUJAN, consider factors that may predispose patients to the need for amputations. Monitor patients and discontinue STEGLUJAN if complications occur. Counsel patients about the importance of routine preventative foot care.
Acute Renal Failure: There have been postmarketing reports of worsening renal function with sitagliptin, including acute renal failure, sometimes requiring dialysis.
Volume Depletion: STEGLUJAN can cause intravascular volume contraction which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including STEGLUJAN. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, patients with low systolic blood pressure, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating STEGLUJAN in these patients, assess volume status and renal function. Correct volume depletion before initiating STEGLUJAN. Monitor for signs and symptoms of volume depletion, and renal function after initiating therapy.
Urosepsis and Pyelonephritis: There have been postmarketing reports of serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization in patients receiving SGLT2 inhibitors. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated.
Heart Failure: Heart failure has been observed in cardiovascular outcomes trials for two other members of the dipeptidyl peptidase-4 inhibitor (DPP-4i) class. Consider risks and benefits of STEGLUJAN prior to initiating treatment in patients at risk for heart failure. Monitor for, and advise patients to immediately report, symptoms. If heart failure develops, consider discontinuation of STEGLUJAN.
Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Insulin and insulin secretagogues (e.g., sulfonylurea) are known to cause hypoglycemia. STEGLUJAN in combination with insulin or insulin secretagogues may increase the risk of hypoglycemia. A lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with STEGLUJAN.
Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): A rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention has been identified in postmarketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors, including ertugliflozin. Serious outcomes have included hospitalization, multiple surgeries, and death. Patients treated with STEGLUJAN 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 STEGLUJAN, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.
Genital Mycotic Infections: Ertugliflozin increases the risk of genital mycotic infections. Patients who have a history of genital mycotic infections or who are uncircumcised are more likely to develop genital mycotic infections. Monitor and treat appropriately.
Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions with sitagliptin, including anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. If suspected, discontinue STEGLUJAN, assess for potential causes, and institute other treatment for diabetes. Angioedema also has been reported with other DPP-4is. Use caution in patients with a history of angioedema with another DPP-4i because it is unknown whether such patients will be predisposed to angioedema with STEGLUJAN.
Severe and Disabling Arthralgia: There have been postmarketing reports of severe and disabling arthralgia with DPP-4is. Consider DPP-4is as a possible cause for severe joint pain and discontinue if appropriate.
Bullous Pemphigoid: Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4is. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue STEGLUJAN and consider referral to a dermatologist.
The most common adverse reactions associated with ertugliflozin (≥5%) were female genital mycotic infections.
The most common adverse reactions with sitagliptin (≥5%) were upper respiratory tract infection, nasopharyngitis, and headache.
Before prescribing STEGLUJAN® (ertugliflozin and sitagliptin), please read the accompanying Prescribing Information. The Medication Guide also is available.
