Sitagliptin, metformin hydrochloride.
Each film coated tablet contains Sitagliptin Phosphate Monohydrate INN 64.25 mg eqv. to Sitagliptin INN 50 mg and Metformin HCl BP 500 mg.
Sitagliptin phosphate is an orally-active, potent, and highly selective inhibitor of the dipeptidyl peptidase 4 (DPP-4) enzyme for the treatment of type 2 diabetes. The DPP-4 inhibitors are a class of agents that act as incretin enhancers. 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. Sitagliptin is a potent and highly selective inhibitor of the enzyme DPP-4 and does not inhibit the closely-related enzymes DPP-8 or DPP-9 at therapeutic concentrations.
By increasing and prolonging active incretin levels, Sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. The pharmacologic mechanism of action of Metformin is different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and increases peripheral glucose uptake and utilization.
Sitaglit-M is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type-2 diabetes mellitus when treatment with both Sitagliptin and Metformin is appropriate.
Dose of this combination should be individualized on the basis of the patient's current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg Sitagliptin and 2000 mg Metformin. Sitagliptin/Metformin combination should generally be given twice daily with meals, with gradual dose escalation, to reduce the gastrointestinal (GI) side effects due to Metformin. The recommended starting dose in patients not currently treated with Metformin is 50 mg Sitagliptin/500 mg Metformin hydrochloride twice daily, with gradual dose escalation recommended to reduce gastrointestinal side effects associated with Metformin. The starting dose in patients already treated with Metformin should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and the dose of Metformin already being taken. For patients taking Metformin 850 mg twice daily, the recommended starting dose of this combination is 50 mg Sitagliptin/1000 mg Metformin hydrochloride twice daily. Patients treated with an insulin secretagogue or insulin Co-administration of the combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.
Single doses of up to 800 mg sitagliptin were generally well tolerated. There is no experience with doses above 800 mg in clinical studies.
A large overdose of metformin (or co-existing risks of lactic acidosis) may lead to lactic acidosis which is a medical emergency and must be treated in hospital. The most effective method to remove lactate and metformin is haemodialysis.
In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastro-intestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy if required.
Sitaglit-M is contraindicated in patients with: Hypersensitivity to the active substances or to any of the excipients; Diabetic ketoacidosis, diabetic pre-coma; Moderate and severe renal impairment (creatinine clearance < 60 mL/min).
Do not use the combination of Sitagliptin & Metformin in patients with hepatic disease.
Before initiating the combination and at least annually thereafter, assess renal function and verify as normal.
May need to discontinue the combination and temporarily use insulin during periods of stress and decreased intake of fluids and food as may occur with fever, trauma, infection or surgery.
Use in Children: Safety and effectiveness of Sitagliptin/Metformin in pediatric patients under 18 years of age have not been established.
Use in the Elderly: Because Sitagliptin and Metformin are substantially excreted by the kidney, and because aging can be associated with reduced renal function, combination of Sitagliptin and Metformin should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function.
Pregnancy: There are no adequate and well-controlled studies in pregnant women with the combination of Metformin/Sitagliptin or its individual components; therefore, the safety of the combination in pregnant women is not known. The combination of Sitagliptin & Metformin should be used during pregnancy only if clearly needed.
Nursing Mothers: Metformin is excreted in human milk in small amounts. It is not known whether sitagliptin is excreted in human milk. Sitaglit-M must therefore not be used in women who are breast-feeding.
The most common (>5%) adverse reactions due to initiation of Metformin therapy are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.
Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems. Co-administration of Digoxin and Sitagliptin may slightly increase the mean peak drug concentration of Digoxin. But no dosage adjustment of digoxin or Sitagliptin is recommended.
Store at temperature not exceeding 30°C in a dry place. Protect from light.
A10BD07 - metformin and sitagliptin ; Belongs to the class of combinations of oral blood glucose lowering drugs. Used in the treatment of diabetes.