Each film coated tablet of Sitagliptin Domina contains 128.5 mg sitagliptin phosphate monohydrate, equivalent to 100mg sitagliptin base.
Calcium hydrogen phosphate, Magnesium Stearate, Cellulose.
Mechanism of action :
Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones.
After oral administration of a dose to healthy subjects, sitagliptin was rapidly absorbed, with peak plasma concentrations (median Tmax) occurring 1 to 4 hours postdose. Plasma AUC of sitagliptin increased in a dose-proportional manner.
Absorption: The absolute bioavailability of sitagliptin is approximately 87%. Sitagliptin may be administered with or without food.
Distribution :The fraction of sitagliptin reversibly bound to plasma proteins is low (38%).
Metabolism : Approximately 79% of sitagliptin is excreted unchanged in the urine with metabolism being a minor pathway of elimination. Metabolism by CYP3A4 and, to a lesser degree, CYP2C8.
Excretion : Approximately 100% of the administered dose is eliminated in feces (13%) or urine (87%) within one week of dosing. The apparent terminal t½ following a 100 mg oral dose of sitagliptin was approximately 12.4 hours and renal clearance was approximately 350 mL/min. Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion.
Special populations :
Renal insufficiency :Plasma AUC levels of Sitagliptin are increased approximately 2 and 4 folds in patients with moderate and sever renal impairment, including patients on haemodialysis. Lower doses are recommended in patients with moderate and sever renal insufficiency, as well as patients on haemodialysis.
Sitagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, as monotherapy or as combination therapy.
Important Limitations of Use:
Sitagliptin 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 is contraindicated in patients with history of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema.
Warnings & Precautions:
Pancreatitis: There have been reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients taking Sitagliptin. After initiation of Sitagliptin, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, Sitagliptin should promptly be discontinued and appropriate management should be initiated.
Renal Impairment: Assessment of renal function is recommended prior to initiating Sitagliptin and periodically thereafter. A dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with ESRD requiring hemodialysis or peritoneal dialysis.
Use with Medications Known to Cause Hypoglycemia: When Sitagliptin was used in combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the incidence of hypoglycemia was increased
Hypersensitivity Reactions: These reactions include: anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Onset of these reactions occurred within the first 3 months after initiation of treatment with Sitagliptin, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue Sitagliptin
Blood glucose and HbA 1c should be monitored periodically. Renal function prior to initiation of therapy and periodically thereafter should be assessed. Patients should be observed carefully for signs and symptoms of pancreatitis.
Pregnancy Category B:
This drug should be used during pregnancy only if clearly needed.
Nursing Mothers:Because many drugs are excreted in human milk, caution should be exercised when Sitagliptin is administered to a nursing woman.
Safety and effectiveness of Sitagliptin 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.
Digoxin: There was a slight increase in the area under the curve (AUC, 11%) and mean peak drug concentration (Cmax, 18%) of digoxin with the co-administration of 100 mg sitagliptin for 10 days. Patients receiving digoxin should be monitored appropriately. No dosage adjustment of digoxin or Sitagliptin is recommended.
Insulin, Sulfonureas: A lower dose of insulin or sulfonylurea may be needed to reduce the risk of hypoglycemia.
The most common side effects include: diarrhea, abdominal pain, nausea, acute pancreatitis, constipation, hepatic enzyme elevation, vomiting, hypersensitivity reactions, rash, urticaria, nasopharyngitis, upper repiratory tract infection, headache, hypoglycemia.
Dosage and Administration:
The recommended dose of Sitagliptin is 100 mg once daily. Sitagliptin can be taken with or without food.
Patients with Renal Insufficiency: For patients with mild renal insufficiency (creatinine clearance [CrCl] greater than or equal to 50 mL/min), no dosage adjustment for Sitagliptin is required.
For patients with moderate renal insufficiency: (CrCl greater than or equal to 30 to less than 50 mL/min), the dose of Sitagliptin is 50 mg once daily.
For patients with severe renal insufficiency : (CrCl less than 30 mL/min), or with end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis, the dose of Sitagliptin is 25 mg once daily. Sitagliptin may be administered without regard to the timing of dialysis.
Because there is a need for dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of Sitagliptin and periodically thereafter.
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