Uses of Gemer: - Type 2 diabetes mellitus Type 2 diabetes mellitus Renal disease or renal dysfunction, as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females] or abnormal creatinine clearance, which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicaemia. Hepatic impairment. Known hypersensitivity to this product or any of its components. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin. Patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because the use of such products may result in acute alteration of renal function Pregnancy, lactation.

Combination Oral hypoglycemic preparations

Glimepiride, a member of the sulfonylurea class, and Rosiglitazone maleate, a member of the thiazolidinedione class. The primary mechanism of action of Glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta-cells. In addition, extrapancreatic effects may also play a role in the activity of sulfonylureas such as Glimepiride. This is supported by both preclinical and clinical studies demonstrating that Glimepiride administration can lead to increased sensitivity of peripheral tissues to insulin.Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin reduces hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis, and stimulates intracellular glycogen synthesis by acting on glycogen synthase. In muscle, it increases insulin sensitivity, improving peripheral glucose uptake and utilization. Metformin also delays intestinal glucose absorption. Metformin increases the transport capacity of all types of membrane glucose transporters (GLUTs) known to date.

How to use Glimepiride + Metformin: Use it as advised by your doctor or check the label for directions before use. Glimepiride + Metformin is to be taken with food. Administration: Should be taken with breakfast or first main meal of the day. Adult Dose: Oral Type 2 diabetes mellitus Adult: Each tablet contains glimepiride 1 mg or 2 mg and metformin sustained release 500 mg The initial recommended dose is one tablet once daily Maximum Recommended Dose The maximum recommended dose for glimepiride is 8 mg daily. The maximum recommended daily dose for metformin sustained-release is 2000 mg in adults. Dosage should be individualized on the basis of both effectiveness and tolerance.

Cationic drugs: Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretions (e.g: amiloride, digoxin, morphine, procainamide, quinidine, ranitidine, or vancomycin) may decrease metformin elimination by competing for common renal tubular transport systems. Hence, careful patient monitoring and dose adjustment of metformin/cationic drug is recommended. Miconazole (systemic route, oromucosal gel) and Phenylbutazone (systemic route): Increases hypoglycemic effect of glimepiride. Thiazide: Interactions between thiazide diuretics and oral antidiabetic agents decreases insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Hence diabetic patients should be monitored closely. Other: Concomitant administration of angiotensin enzyme inhibitors (captopril, enalapril), other antidiabetic drugs (insulin, acarbose) beta-blockers, fluconozole, monoamine oxidase inhibitors (MAOIs), sulphonamides and NSAIDs, increasessensitivity to insulin and potentiates blood glucose lowering effect and may in some 6 instances, cause hypoglycemia. Patients receiving estrogens or oral contraceptives, phenytoin, quinolones should be closely monitored for loss of diabetic control. Potentially Fatal: NSAIDS, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid, MAOs, and beta blockers potentiate the hypoglycemic action of glimepiride.

Renal disease or renal dysfunction, as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females] or abnormal creatinine clearance, which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicaemia. Hepatic impairment. Known hypersensitivity to this product or any of its components. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin. Patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because the use of such products may result in acute alteration of renal function Pregnancy, lactation.

Common - Hypoglycemia (low blood glucose level) - Taste change - Nausea - Diarrhea - Stomach pain - Headache - Upper respiratory tract infection Diarrhoea, vomiting, metallic taste, rash, isolated transaminase elevations, cholestatic jaundice, allergic skin reactions, photosensitivity reactions, leukopaenia, agranulocytosis, thrombocytopaenia, haemolytic anaemia, aplastic anaemia, pancytopaenia, blurred vision. Potentially Fatal: Lactic acidosis.

Pregnancy: Administration of the drug this combination is contraindicated during pregnancy because of the possible adverse effects on intrauterine fetal development. Pregnant women and women planning pregnancy should notify the doctor about this. During pregnancy and when planning, women with impaired glucose metabolism, which cannot be corrected with diet and physical activity, must receive insulin therapy in order to maintain normal blood concentrations of blood glucose level.Breast-feeding: In order to avoid transfer of medicine to the child’s body through breast milk, women should not take this medicine in breastfeeding period. In case of need for hypoglycemic therapy, the patient must be transferred to the insulin treatment, otherwise she must discontinue breastfeeding.

Precaution: Renal and hepatic impairment. Avoid alcohol consumption. Hypoglycaemic episodes.

For Glimepiride: Acute overdosage, as well as long-term treatment with too high a dose of glimepiride, may lead to severe life-threatening hypoglycaemia. As soon as an overdose of glimepiride has been discovered, a physician must be notifed without delay. The patient must immediately take sugar, if possible in the form of glucose unless a physician has already undertaken responsibility for treating the overdose. Careful monitoring is essential until the physician is confdent that the patient is out of danger. It must be remembered that hypoglycaemia may recur after initial recovery. Admission to hospital may sometimes be necessary even as a precautionary measure. In particular, signifcant overdoses and severe reactions with signs such as loss of consciousness or other serious neurological disorders are medical emergencies and require immediate treatment and admission to hospital. If, for example, the patient is unconscious, an intravenous injection of concentrated glucose solution is indicated (for adults starting with 40 ml of 20% solution, for example). Alternatively in adults, administration of glucagon, e.g. in doses of 0.5 to 1 mg i.v., s.c. or i.m., may be considered. In particular when treating hypoglycaemia due to accidental intake of glimepiride in infants and young children, the dose of glucose given must be very carefully adjusted in view of the possibility of producing dangerous hyperglycaemia, and must be controlled by close monitoring of blood glucose. Patients who have ingested life-threatening amounts of glimepiride require detoxifcation (e.g. by gastric lavage and medicinal charcoal). After acute glucose replacement has been completed it is usually necessary to give an intravenous glucose infusion in lower concentration so as to ensure that the hypoglycaemia does not recur. The patient's blood glucose level should be carefully monitored for at least 24 hours. In severe cases with a protracted course, hypoglycaemia, or the danger of slipping back into hypoglycaemia, may persist for several days.For Metformin: Hypoglycaemia has not been seen with metformin doses of up to 85 g, although Lactic acidosis has occurred in such circumstances. High overdose or concomitant risks of metformin may lead to lactic acidosis Lactic acidosis is a medical emergency and must be treated in hospital. The most efective method to remove lactate and metformin is haemodialysis. Pancreatitis may occur in the context of a metformin overdose.

Store in a cool (not exceeding 25°C) and dry place, protected from light.

Combination Oral hypoglycemic preparations

Glimepiride stimulates the insulin release from functioning pancreatic β-cells and inhibits gluconeogenesis at hepatic cells. It also increases insulin sensitivity at peripheral target sites. Metformin decreases hepatic gluconeogenesis, decreases intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilisation).

Pregnancy- For Glimepiride: Glimepiride must not be taken during pregnancy. Otherwise, there is risk of harm to the child. The patient must change over to insulin during pregnancy. Patients planning a pregnancy must inform their physician. It is recommended that such patients change over to insulin. For Metformin: When the patient plans to become pregnant and during pregnancy, diabetes should not be treated with metformin but insulin should be used to maintain blood glucose levels as close to normal as possible in order to lower the risk of fetal malformations associated with abnormal blood glucose levels. Lactation- For Glimepiride: To prevent possible ingestion with the breast milk and possible harm to the child, glimepiride must not be taken by breast-feeding women. If necessary the patient must change over to insulin, or must stop breastfeeding. For Metformin: Metformin is excreted into milk in lactating rats. Similar data is not available in humans and a decision should be made whether to discontinue nursing or to discontinue metformin, taking into account the importance of the compound to the mother.