Linagliptin

TRADJENTA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. TRADJENTA is 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 in patients with type 1 diabetes mellitus as it would not be effective. Has not been studied in patients with a history of pancreatitis. Limitations of Use TRADJENTA is not recommended in patients with type 1 diabetes mellitus as it would not be effective. TRADJENTA has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using TRADJENTA.

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. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha-cells, resulting in a reduction in hepatic glucose output.

The recommended dosage of TRADJENTA is 5 mg orally once daily. TRADJENTA can be taken with or without food Recommended Dosage and Administration The recommended dosage of TRADJENTA is 5 mg taken orally once daily, with or without food.

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

Pancreatitis: There have been reports of acute pancreatitis, including fatal pancreatitis. If pancreatitis is suspected, promptly discontinue TRADJENTA. Hypoglycemia: Consider lowering the dosage of insulin secretagogue or insulin to reduce the risk of hypoglycemia when initiating TRADJENTA. Hypersensitivity reactions: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema, and exfoliative skin conditions) have occurred with TRADJENTA. If hypersensitivity reactions occur, discontinue TRADJENTA, treat promptly, and monitor until signs and symptoms resolve. Arthralgia: Severe and disabling arthralgia has been reported in patients taking TRADJENTA. Consider as a possible cause for severe joint pain and discontinue drug if appropriate. Bullous pemphigoid: There have been reports of bullous pemphigoid requiring hospitalization.

The following serious adverse reactions are described below or elsewhere in the prescribing information: Pancreatitis Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Hypersensitivity Reactions Severe and Disabling Arthralgia Bullous Pemphigoid Heart Failure Most common adverse reaction (incidence ≥5% and more often than placebo) was nasopharyngitis

Strong P-glycoprotein/CYP3A4 inducer: The efficacy of TRADJENTA may be reduced when administered in combination (e.g., with rifampin). Use of alternative treatments is strongly recommended.

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).