GLIPITA 50

For the Management of Type 2 Diabetes

Antidiabetic

Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes 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. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, Sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.

The recommended dose is 100 mg once daily. It can be taken with or without food. For patients with mild renal insufficiency (creatinine clearance [CrCl] ?50 mL/min) no dosage adjustment for it is required. For patients with moderate renal insufficiency (CrCl ?30 to <50 mL/min), the dose of It is 50 mg once daily. For patients with severe renal insufficiency (CrCl <30 mL/min) or with end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis, the dose is 25 mg once daily. It may be administered without regard to the timing of hemodialysis.

Effects of sitagliptin on other Drugs: Sitagliptin did not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptive. Digoxin: Sitagliptin slightly increases the mean of Digoxin concentration. However, no dose adjustment of either drug is required.

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

The most common adverse reactions are; upper respiratory tract infection, nasopharyngitis & headache. Hypoglycemia may occur in patients treated with the combination of Sitagliptin & sulfonylurea & add-on to insulin.

Pregnancy Category B Safety of Sitagliptin in pregnant women has not been established. Sitagliptin should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. Nursing Mothers: It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Sitagliptin is administered to a nursing woman.

During controlled clinical trials in healthy subjects, single doses of up to 800 mg Sitagliptin were administered. Maximal mean increases in QTc of 8.0 msec were observed in one study at a dose of 800 mg Sitagliptin, a mean effect that is not considered clinically important. There is no experience with doses above 800 mg in clinical studies. In Phase I multiple-dose studies, there were no dose-related clinical adverse reactions observed with Sitagliptin with doses of up to 600 mg per day for periods of up to 10 days and 400 mg per day for up to 28 days. In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy as dictated by the patient's clinical status. Sitagliptin is modestly dialyzable. In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour hemodialysis session. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

Store below 25°C in a dry place away from light. Keep the medicines in a safe place, out of the reach of children. Do not use later than the date of expiry. To be dispensed only on the prescription of a registered physician