Empagliflozin and Linagliptin

GLYXAMBI is a combination of empagliflozin and linagliptin indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Empagliflozin is indicated to reduce the risk of cardiovascular (CV) death in adults with type 2 diabetes mellitus and established CV disease. GLYXAMBI is a combination of empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor and linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, 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. It may increase the risk of diabetic ketoacidosis in these patients. Has not been studied in patients with a history of pancreatitis.

GLYXAMBI GLYXAMBI contains: empagliflozin, a SGLT2 inhibitor, and linagliptin, a DPP-4 inhibitor. Empagliflozin Empagliflozin is an inhibitor of SGLT2, the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Linagliptin Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation.

Assess renal function before initiating and as clinically indicated. Assess volume status and correct volume depletion before initiating. The recommended dosage of GLYXAMBI is 10 mg empagliflozin and 5 mg linagliptin once daily, taken in the morning, with or without food. Dosage may be increased to 25 mg empagliflozin and 5 mg linagliptin once daily. Withhold GLYXAMBI for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting.

GLYXAMBI is contraindicated in patients: with a hypersensitivity to empagliflozin, linagliptin, or any of the excipients in GLYXAMBI, reactions such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity have occurred. Hypersensitivity to empagliflozin, linagliptin, or any of the excipients in GLYXAMBI.

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients at risk of ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue GLYXAMBI if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. Pancreatitis: There have been reports of acute pancreatitis, including fatal pancreatitis. If pancreatitis is suspected, promptly discontinue GLYXAMBI. Volume Depletion: Before initiating GLYXAMBI, assess volume status and renal function in patients with impaired renal function, elderly patients, or patients on loop diuretics. Monitor for signs and symptoms during therapy.

The following important adverse reactions are described below and elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis Pancreatitis 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 and Insulin Secretagogues Lower Limb Amputation Hypersensitivity Reactions Severe and Disabling Arthralgia Bullous Pemphigoid Heart Failure Most common adverse reactions (5% or greater incidence) were urinary tract infections, nasopharyngitis, and upper respiratory tract infections

Table 3 describes clinically relevant interactions with GLYXAMBI. Table 3 Clinically Relevant Interactions with GLYXAMBI Diuretics Clinical Impact Coadministration of empagliflozin with diuretics resulted in increased urine volume and frequency of voids, which might enhance the potential for volume depletion. Intervention Before initiating GLYXAMBI, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating GLYXAMBI. Monitor for signs and symptoms of volume depletion, and renal function after initiating therapy. Insulin or Insulin Secretagogues Clinical Impact The risk of hypoglycemia is increased when GLYXAMBI is used in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).