Galet M

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This tablet is indicated as an adjunct to diet and exercises to improve glycaemic control in patients with type 2 diabetes mellitus whose diabetes is not adequately controlled on Metformin Hydrochloride or Vildagliptin alone or who are already treated with the combination of Vildagliptin and Metformin Hydrochloride, as separate tablets.

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This combination is contraindicated in patients with known hypersensitivity to Vildagliptin or Metformin Hydrochloride or to any of the excipients. It is contraindicated in patients with renal disease or renal dysfunction, acute myocardial infarction, and septicaemia. It is also contraindicated in patients with congestive heart failure patients and in patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. It should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function.

Vildagliptin acts primarily by inhibiting DPP-4 (Dipeptidyl peptidase-4), the enzyme responsible for the degradation of the incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). The administration of Vildagliptin results in a rapid and complete inhibition of DPP-4 activity resulting in increased fasting and postprandial endogenous levels of the incretin hormones GLP-1 and GIP. By increasing the endogenous levels of these incretin hormones, Vildagliptin increases insulin secretion from the pancreatic beta cell and decreases glucagon secretion from alpha cell. The enhanced increase in the insulin/glucagon ratio during hyperglycaemia due to increased incretin hormone levels results in a decrease in fasting and postprandial hepatic glucose production, leading to reduced glycaemia.Metformin Hydrochloride is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Glucomin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

No clinically relevant pharmacokinetic interaction was observed when Vildagliptin (100 mg once daily) was co-administered with Metformin Hydrochloride (1,000 mg once daily). Vildagliptin has a low potential for drug interactions. Since Vildagliptin is not a cytochrome P (CYP) 450 enzyme substrate nor does it inhibit nor induces CYP 450 enzymes, it is not likely to interact with co-medications that are substrates, inhibitors or inducers of these enzymes. As a result of these studies no clinically relevant interactions with other oral antidiabetics (glibenclamide, pioglitazone, metformin hydrochloride), amlodipine, digoxin, ramipril, simvastatin, valsartan or warfarin were observed after co-administration with vildagliptin. On the other hand, furosemide, nifedipine and glyburide increase Cmax and blood AUC of Metformin with no change in renal clearance of Metformin.

The most common side effects are headache, tremor, dizziness, nausea, hypoglycaemia etc.

There are no adequate and well controlled studies in pregnant women and therefore, this combination should not be used during pregnancy unless the potential benefit justifies the potential risk to the foetus. No studies have been conducted with the components of this combination. As it is not known whether Vildagliptin and/or Metformin Hydrochloride is excreted in human milk this combination should not be administered to breast-feeding women.

Lactic acidosis can occur due to Metformin accumulation. If metabolic acidosis is suspected, treatment should be discontinued and the patient should be hospitalized immediately. Serum creatinine should be monitored at least once a year in patients with normal renal function and 2–4 times a year in patients with serum creatinine levels at the upper limit of normal and in elderly patients. Special caution should be exercised in elderly patients where renal function may become impaired (e.g. when initiating antihypertensives, diuretics or NSAIDs). It is recommended that Liver Function Tests (LFTs) are monitored prior to initiation of this drug, at three-monthly intervals in the first year and periodically thereafter. If transaminase levels are increased, patients should be monitored with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality return to normal. If AST or ALT persist at 3 x ULN, Vildagliptin & Metformin tablets should be stopped Patients who develop jaundice or other signs of liver dysfunction. Following withdrawal of treatment with Vildagliptin & Metformin and LFT normalization, treatment with Vildagliptin & Metformin should not be reinitiated. Vildagliptin & Metformin tablets should be discontinued 48 hours before elective surgery with general anaesthesia and should not usually be resumed earlier than 48 hours afterwards.

Use in pediatric patients: The safety and effectiveness of this combination in pediatric patients have not been established. Therefore, this combination is not recommended for use in children below 18 years of age. Use in geriatric patients: As Metformin is excreted via the kidney, and elderly patients have a tendency to decreased renal function, elderly patients taking this combination should have their renal function monitored regularly. This combination should only be used in elderly patients with normal renal function. Patients with renal impairment: This combination should not be used in patients with renal failure or renal dysfunction, e.g. serum creatinine levels > 1.5 mg/dl (>135 micro mol/L) in males and > 1.4 mg/dl (>110 micro mol/L) in females. Patients with hepatic impairment: This combination is not recommended in patients with hepatic impairment including patients with a pre-treatment ALT or AST >3 X the upper limit of normal.