TREVIAMET Tablet

- Initial therapy in patients with type 2 diabetes mellitus to improve glycemic control when diet and exercise do not provide adequate glycemic control.

- As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus inadequately controlled on Metformin HCl or Sitagliptin alone or in patients already being treated with the combination of Sitagliptin and Metformin HCl.

- In triple combination with a sulphonylurea as an adjunct to diet and exercise in patients with type 2 diabetes mellitus inadequately controlled on their maximal tolerated dose of Metformin HCl and a sulphonylurea.

- In triple combination with a peroxisome proliferator-activated receptor exercise in patients inadequately controlled on their maximal tolerated dose of Metformin HCl and a PPARɤ agonist.

- In patients with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control in combination with insulin.

Dosage and administration

The dosage should be individualized on the basis of patient’s current regimen, effectiveness and tolerability while not exceeding the maximum recommended daily dose of 100mg Sitagliptin.

It should be given twice daily with meals, with meals, with gradual dose escalation, to reduce the gastrointestinal side effects associated with Metformin HCl.

As initial therapy

For patients with type 2 diabetes mellitus, whose hyperglycemic is inadequately controlled with diet and exercise alone, the recommended starting dose of TREVIAMET is 50mg of Sitagliptin + 500mg of Metformin HCl twice daily. Patients may be titrated upto 50mg of Sitagliptin + 1000mg of Metformin HCl twice daily.

For patients inadequately controlled on metformin monotherapy

The usual starting dose of TREVIAMET should provide Sitagliptin dosed as 50mg twice daily (100mg total daily dose), plus Metformin HCl dose already being taken.

For patients inadequately controlled on Sitagliptin monotherapy

The usual starting dose of TREVIAMET is 50mg Sitagliptin+500mg Metformin HCl twice daily. Patients may be titrated upto 50mg Sitagliptin+1000mg Metformin twice daily.

For patient switching from Sitagliptin co-administered with Metformin HCl

For patients switching from co-administration of Sitagliptin and Metformin HCl. TREVIAMET may be initiated at the dose of Sitagliptin and Metformin HCl already being taken.

For patients inadequately controlled on dual combination therapy with any two of following three antihyperglycemic agents. Sitagliptin, Metformin HCl or PPARɤ agonist (thiazolidinedione).

The usual starting dose should provide Sitagliptin dosed as 50mg twice daily. In determining the starting dose of Metformin HCl component, the patients level of glycemic control and current dose (if any) of Metformin HCl should be considered.

For patients inadequately controlled on dual combination therapy with any two of following three antihyperglycemic agents: Sitagliptin, Metformin HCl or Insulin.

The usual starting dose should provide Sitagliptin dose of Metformin HCl component, the patients level of glycemic control and current dose (if any) of Metformin HCl should be considered.

- Patients with type 1 diabetes.

- Renal disease or renal dysfunction, e.g., as suggested by serum creatine levels≥1.5mg/mL (males) ≥1.4mg/mL (females), or abnormal creatinine clearance, which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia.

- Known hypersensitivity to Sitagliptin, Metformin HCl or any other component of Sitagliptin+Metformin HCl.

- Acute or chronic metabolic acidosis, including ketoacidosis, with or without coma.

- Children below 18 years of age.

Sitagliptin with Metformin HCl

Common: nausea.

Uncommon: somnolence, diarrhea, upper abdominal pain and blood glucose decreased.

Sitagliptin with Metformin HCl and Sulphonylurea

Very common: hypoglycemia

Common: constipation.

Sitagliptin with Metformin HCl and a PPARɤ agonist

Common: hypoglycemia, headache, diarrhea, vomiting, peripheral edema.

Sitagliptin with Metformin HCl and Insulin

Very common: hypoglycemia.

Uncommon: headache, dry mouth.

Sitagliptin: Digoxin:

Metformin HCl: Furosemide, Nifedipine, Cationic drugs (e.g. amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin), Certain medicines tend to produce hyperglycaemia and may lead to loss of glycaemic control (e.g. thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, isoniazid).

Pregnancy

The safety of Sitagliptin+ Metformin HCl in pregnant women is not known. It is not recommended for use in pregnancy.

Nursing Mother

It is not known whether Sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, Sitagliptin+Metformin HCl should not be administered during nursing.

See the package insert about the details below.

- Monitoring of renal function.

- Impaired hepatic function

- Hypoglycemia

- Sitagliptin: Pancreatitis

- Metformin HCl: Lactic acidosis, Administration of iodinated contrast agent.

Sitagliptin

It 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, including 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 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 increase insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner.

Metformin HCl

It is a biguanide with antihyperglycemic effects, lowering both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycemia.

Metformin HCl may active via three mechanisms:

- by reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis.

- in muscle, by modestly increasing insulin sensitivity, improving peripheral glucose uptake and utilization.

- by delaying intestinal glucose absorption.