This 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.
Combination Oral hypoglycemic preparations
This tablet combines two antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes. Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and Metformin HCl, a member of the biguanide class. 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. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated then 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 increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. The pharmacologic mechanism of action of Metformin HCl is different from other classes of oral antihyperglycemic agents. Metformin HCl decreases hepatic glucose production, decreases intestinal absorption of glucose and increases peripheral glucose uptake and utilization.
The dosage of Sitagliptin & Metformin 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. Initial combination therapy or maintenance of combination therapy should be individualized and left to the discretion of the health care provider. Sitagliptin & Metformin should generally be given twice daily with meals, with gradual dose escalation, to reduce the gastrointestinal (GI) side effects due to metformin. The starting dose of Sitagliptin & Metformin should be based on the patient's current regimen. 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 Sitagliptin & Metformin is 50 mg sitagliptin/1000 mg metformin hydrochloride twice daily. Co-administration of Sitagliptin & Metformin 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. No studies have been performed specifically examining the safety and efficacy of Sitagliptin & Metformin in patients previously treated with other oral antihyperglycemic agents and switched to Sitagliptin & Metformin. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.
Cationic Drugs: Cationic drugs eliminated by renal tubular secretion: Use with caution.
Phenprocoumon: Metformin may decrease the anticoagulant effect of phenprocoumon. Therefore, close monitoring of the INR is recommended.
Levothyroxine: Levothyroxine can reduce the hypoglycemic effect of metformin. Monitoring of blood glucose levels is recommended, especially when thyroid hormone therapy is initiated or stopped, and the dosage of metformin must be adjusted if necessary.
Sitagliptin + Metformin HCl is contraindicated in patients with: Renal disease or renal dysfunction, e.g., as suggested by serum creatinine levels 1.5 mg/dL [males], 1.4 mg/dL [females]. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. History of a serious hypersensitivity reaction to the combination or sitagliptin, such as anaphylaxis or angioedema. 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.
The most common adverse reactions reported in > 5% of patients simultaneously started on sitagliptin and metformin and more commonly than in patients treated with placebo were diarrhea, upper respiratory tract infection, and headache. Nasopharyngitis was the only adverse reaction reported in > 5% of patients treated with sitagliptin monotherapy. Hypoglycemia was also reported more commonly in patients treated with the combination of Sitagliptin and sulfonylurea, with or without Metformin, than in patients given the combination of placebo and sulfonylurea, with or without Metformin. The most common established adverse reactions due to initiation of metformin therapy are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.
Pregnancy Category B. 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. Lactation: It is not known whether Sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this combination is administered to a nursing woman.
Sitagliptin: 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 indicated by the patient's clinical status. Sitagliptin is modestly dialyzable. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.
Metformin hydrochloride: Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams. Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected. Pancreatitis may occur in the context of a metformin overdose.
Store below 25°C in a dry place away from light. Keep the medicines in a safe place, out of the reach of children. Do not use later than the date of expiry. To be dispensed only on the prescription of a registered physician.
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