Sitagliptin

JANUVIA ® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. JANUVIA 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: JANUVIA should not be used in patients with type 1 diabetes. JANUVIA has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using JANUVIA.

Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes mellitus by slowing the inactivation of incretin hormones. Concentrations of the active intact hormones are increased by sitagliptin, thereby increasing and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP.

The recommended dose of JANUVIA is 100 mg once daily. JANUVIA can be taken with or without food. Dosage adjustment is recommended for patients with eGFR less than 45 mL/min/1.73 m 2. Dosage Adjustment in Patients with Renal Impairment eGFR greater than or equal to 30 mL/min/1.73 m 2 to less than 45 mL/min/1.73 m 2 eGFR less than 30 mL/min/1.73 m 2 (including patients with end stage renal disease [ESRD] on dialysis) 50 mg once daily 25 mg once daily

History of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema.

Pancreatitis: There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue JANUVIA. Heart failure: Heart failure has been observed with two other members of the DPP-4 inhibitor class. Consider risks and benefits of JANUVIA in patients who have known risk factors for heart failure. Monitor patients for signs and symptoms. Acute Renal Failure: Has been reported postmarketing, sometimes requiring dialysis. Assessment of renal function is recommended prior to initiating JANUVIA and periodically thereafter. Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues: Increased risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. Lower dose of insulin or insulin secretagogue may be required.

The following adverse reactions are also discussed elsewhere in the labeling: Pancreatitis Heart Failure Acute Renal Failure Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues Hypersensitivity Reactions Severe and Disabling Arthralgia Bullous Pemphigoid Adverse reactions reported in ≥5% of patients treated with JANUVIA and more commonly than in patients treated with placebo are: upper respiratory tract infection, nasopharyngitis and headache. In the add-on to sulfonylurea and add-on to insulin studies, hypoglycemia was also more commonly reported in patients treated with JANUVIA compared to placebo.

Insulin Secretagogues or Insulin Coadministration of JANUVIA with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.

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