Metformin HCl, sitagliptin phosphate monohydrate.
Each film-coated tablet contains sitagliptin phosphate monohydrate 64.25 mg equivalent to sitagliptin 50 mg and metformin hydrochloride 1000 mg.
Pharmacotherapeutic Group: Oral hypoglycemic. ATC Code: A10BD07.
Pharmacology: Sitagliptin is a highly selective DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones, thereby increasing the concentration and prolonging the action of these hormones. lncretin 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, GLP-1 and GIP increase insulin synthesis and release from pancreatic β-cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic α-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. These changes lead to a decrease in hemoglobin A1c (HbA1c) levels, as well as a lower fasting and postprandial glucose concentration. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.
Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
Metformin may act via 3 mechanisms: 1) By reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis. 2) In muscle, by modestly increasing insulin sensitivity, improving peripheral glucose uptake and utilization. 3) By delaying intestinal glucose absorption.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase. Metformin increases the transport capacity of specific types of membrane glucose transporters (GLUT-1 and GLUT-4).
For adult patients with type 2 diabetes mellitus.
The dose of Ziglip-M should be individualized on the basis of the patient's current regimen, effectiveness and tolerability while not exceeding the maximum recommended daily dose of sitagliptin 100 mg and metformin 2000 mg.
Recommended Dose: 1 tab daily.
In the event of an overdosage, it is reasonable to employ the usual supportive measures eg, remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram) and institute supportive therapy if required.
Hypersensitivity to sitagliptin phosphate monohydrate, metformin hydrochloride or to any of the excipients of Ziglip M.
Diabetic ketoacidosis, diabetic precoma, moderate and severe renal impairment (CrCl <60 mL/min).
Acute conditions with the potential to alter renal function eg, dehydration, severe infection, shock, intravascular administration of iodinated contrast agents.
Acute or chronic disease which may cause tissue hypoxia eg, cardiac or respiratory failure. Hepatic impairment, acute alcohol intoxication, alcoholism, breastfeeding.
General: It should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Pancreatitis: If pancreatitis is suspected, sitagliptin phosphate monohydrate and other potentially suspect medicinal products should be discontinued.
Lactic Acidosis: Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure.
Renal Function: Metformin and sitagliptin are known to be substantially excreted by the kidney. Metformin-related lactic acidosis increases with the degree of impairment of renal function, therefore, serum creatinine concentrations should be determined regularly.
Hypoglycemia: Patients receiving Ziglip M, in combination with a sulphonylurea or with insulin may be at risk for hypoglycemia. Therefore, a reduction in the dose of the sulphonylurea or insulin may be necessary.
Use in pregnancy: Studies in animals have shown reproductive toxicity at high doses. The potential risk for humans is unknown. Due to lack of human data, Ziglip-M should not be used during pregnancy.
Use in pregnancy: Studies in animals have shown reproductive toxicity at high doses. The potential risk for humans is unknown. Due to lack of human data, Ziglip-M should not be used during pregnancy.
Use in lactation: Contraindicated in breastfeeding patients.
The most commonly reported adverse reactions during treatment are hypoglycaemia, headache, somnolence, diarrhoea, nausea, flatulence, constipation, upper abdominal pain, vomiting and dry mouth.
Co-administration of multiple twice daily doses of metformin 1000 mg with sitagliptin 50 mg did not meaningfully alter the pharmacokinetics of sitagliptin and metformin in patients with type 2 diabetes.
Ciclosporin: Co-administration of a single 100-mg oral dose of sitagliptin and a single 600-mg oral dose of ciclosporin increased the AUC and Cmax of sitagliptin by approximately 29% and 68%, respectively. These changes in sitagliptin pharmacokinetics were not considered to be clinically meaningful. The renal clearance of sitagliptin was not meaningfully altered. Therefore, meaningful interactions would not be expected with other p-glycoprotein inhibitors.
Digoxin: Sitagliptin had a small effect on plasma digoxin concentrations. However, patients at risk of digoxin toxicity should be monitored for this when sitagliptin and digoxin are administered concomitantly.
Store below 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.
FC tab 1 x 10's, 3 x 10's, 10 x 10's, 30's, 100's.
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