Each film coated tablet contains:
Sitagliptin Phosphate Monohydrate
Equivalent to Sitagliptin 50 mg
Colour: Approved colours and Titanium Dioxide BP
CHEMISTRY: 7-[(3R)-3-Amino-1-oxo-4-(2,4,5-trifluorophenyl)Butyl]-5,6,7,8-tetrahydro-3 (trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazinephosphatemonohydrate.
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. By inhibiting the DPP-4 enzyme, sitagliptin increases the levels of two known active incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent
insulinotropic polypeptide (GIP). 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. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production.
When blood glucose levels are low, insulin release is not enhanced and glucagon secretion is not suppressed.
The absolute bioavailability of sitagliptin is approximately 87%. Sitagliptin tablet may be administered with or without food.
The mean volume of distribution at steady state following a single 100 mg intravenous dose of sitagliptin to healthy subjects is approximately 198 liters. The fraction of sitagliptin reversibly bound to plasma proteins is low (38%).
Sitagliptin is primarily eliminated unchanged in urine, and metabolism is a minor pathway. Approximately 79 % of sitagliptin is excreted unchanged in the urine.
Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion.
Monotherapy and Combination Therapy
Sitagliptin tablet is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Important Limitations of Use
Sitagliptin tablet should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.
Sitagliptin tablet 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 sitagliptin tablet.
DOSAGE AND ADMINISTRATION:
The recommended dose of sitagliptin tablet is 100 mg once daily. Sitagliptin tablet can be taken with or without food.
For patients with mild renal insufficiency no dosage adjustment for sitagliptin tablet is required.
For patients with severe renal insufficiency or with end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis, the dose of sitagliptin tablet is 25 mg once daily. Sitagliptin tablet may be administered without regard to the timing of dialysis.
Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin
When sitagliptin tablet is used in combination with an insulin secretagogue (e.g., sulfonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia.
History of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema.
WARNINGS AND PRECAUTIONS:
There have been post marketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients taking sitagliptin tablet. After initiation of sitagliptin tablet, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, sitagliptin tablet should promptly be discontinued and appropriate management should be initiated.
Assessment of renal function is recommended prior to initiating sitagliptin tablet and periodically thereafter.
Use with Medications Known to Cause Hypoglycemia
When sitagliptin tablet was used in combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia. Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia
Serious hypersensitivity reactions in patients treated with Sitagliptin tablet have been reported. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome.
Patients receiving digoxin should be monitored appropriately. No dosage adjustment of digoxin or Sitagliptin tablet is recommended.
PREGNANCY AND LACTATION:
Pregnancy Category B:
There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed.
Sitagliptin is secreted in the milk of lactating rats at milk to plasma ratio of 4:1. 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 tablet is administered to a nursing woman.
Safety and effectiveness of Sitagliptin tablet in pediatric patients under 18 years of age have not been established.
This drug is known to be substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly, and it may be useful to assess renal function in these patients prior to initiating dosing and periodically thereafter.
Effect to Drive & Use the Machine:
Sitagliptin tablet has no known influence on the ability to drive and use machines. However, when driving or using machines, it should be taken into account that dizziness and somnolence has been reported with sitagliptin.
ADVERSE DRUG REACTIONS:
Serious adverse reactions including pancreatitis and hypersensitivity reactions have been reported. Hypoglycemia has been reported in combination with sulphonylurea and insulin.
In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, and employ clinical monitoring (including obtaining an electrocardiogram). Sitagliptin is modestly dialyzable. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.
PRESENTATION: Blister of 10 tablets
STORAGE: Store in cool and dry place below 30o C.