Radiglip-M 50/500

Generic

Sitagliptin+Metformin Hydrochloride

Indications

Radiglip-MTM is a dipeptidyl peptidase-4 (DPP-4) inhibitor and biguanide combination product 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.

Pharmacology

Radiglip-MTM 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 HCI, 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-I (GLP-I) 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 physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated then GLP-I and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-I 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 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.

Dosage & Administration

• Dose of this combination should be individualized on the basis of the patient's effectiveness, current and regmen, 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 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.

• Swallow whole. Never split, crush or chew.

Interaction

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.

Contraindications

Combination (Sitagliptin & Metformin) is contraindicated in patients with renal disease or renal dysfunction, e.g., as suggested by serum creatinine levels 21.5 mg/dL [males], 2 1.4 mg/dL [females] or abnormal creatinine clearance . 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.

Side Effects

Adverse reactions like upper respiratory tract infection, nasopharyngitis and headache can occur. The most common (>5%) adverse reactions due to initiation of Metformin therapy are diarrhoea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia and headache.

Pregnancy & Lactation

Pregnancy: There are no adequate and well-controlled studies in pregnant women with the combination of Sitagliptin & Metformin 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: 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.

Precautions & Warnings

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 duringperiods of stress and decreased intake of fluids and food as may occur with fever, trauma, infection or surgery.

Therapeutic Class

Antidiabetic

Storage Conditions

Do not store above 300 C, protect from light & moisture. Keep the medicine out of reach of children

Pharmaceutical Name

Radiant Pharmaceuticals Ltd.