(Metformin Hydrochloride 500mg)
Each caplet contains metformin hydrochloride 500mg.
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 three mechanisms:
- Reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis.
- In muscle, by increasing insulin sensitivity, improving peripheral glucose uptake and utilization.
- Delay of intestinal glucose absorption.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen syntethase.
The blood glucose-lowering action does not depend on the presence of functioning pancreatic β cells. It only acts in the presence of endogenous insulin.
Glucoform® is the drug of choice in grossly obese patients in whom strict dieting has failed to control diabetes. Hypoglycaemia is not a problem with Glucoform®.
Other advantages are the lower incidence of weight gain and lower plasma insulin concentration. It does not exert a hypoglycaemic action in non-diabetic subjects unless given in overdose.
Metformin in Glucoform® is rapidly absorbed from the gut. After oral dose of metformin, maximum time (Tmax) is reached in 2.5hours.Absolute bioavailability of 500mg metformin caplet is approximately 50 – 60% in healthy subjects. At the usual metformin doses and dosing schedules, steady state plasma concentrations are reached within 24 to 48 hours and are generally less than 1µg/ml, plasma protein binding is negligible. Metformin partitions into erythrocytes. The blood peak is lower than the plasma peak and appears at approximately the same time. The mean volume of distribution (Vd) ranged between 63 – 276L.
Metfomin is excreted unchanged in the urine. No metabolites have been identified in humans. Renal clearance of metformin is >400ml/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. Following an oral dose, the apparent terminal half-life is approximately 6.5 hours.
When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of metfomin in plasma.
Treatment of non-insulin dependent diabetes, especially in overweight patients, when dietary management and exercise alone does not result in adequate glycemic control.
Glucoform® may be used as monotherapy or in combination with other oral antidiabetic agents, or with insulin.
Metformin in Glucoform® caplets is contraindicated in impaired renal or hepatic function, cardiovascular collapse, congestive heart failure(CHF), acute myocardial infarction(acute MI); diabetes mellitus complicated by acidosis, infection or gangrene, surgery and alcoholism.
- Alcohol – Do not take alcohol when you are on metformin therapy.
- Metformin may decrease vitamin B12 and folic acid absorption.
- Furosemide and cimetidine may increase metformin blood levels.
- Nifedipine enhances absorption of metformin.
- Co-administration with sulphonylurea may cause hypoglycaemia.
- Drugs which tend to produce hyperglycemia (e .g diuretics, corticosteroids, phenothiazines, thyroid products, oestrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics and isoniazid) may lead to loss of glucose control.
Animal studies do not indicate harmful effects with respect to pregnancy, embryonal or foetal development, parturition or postnatal development. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.
Metformin is excreted into milk in lactating rats. Similar data is not available in humans. Insulin therapy should be considered in breast-feeding women.
KEEP OUT OF THE REACH OF CHILDREN!
Monitor renal function regularly to reduce the risk of lactic acidosis; stop therapy 2-3 days before surgery and clinical investigations involving the use of iodinated materials; condition which may cause dehydration or in patients suffering from serious infection or trauma.
All patients should continue their diet with a regular distribution of carbohydrate intake during the day.
Overweight patients should continue their energy restricted diet. The usual laboratory tests for diabetes monitoring should be performed regularly.
- Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite are very common: these occur most frequently during initiation of therapy and resolve spontaneously in most cases. To prevent these gastrointestinal symptoms, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.
- Metallic taste.
- Lactic acidosis is very rare.
SYMPTOMS OF OVERDOSE AND ANTIDOTE:
Hypoglycaemia has not been seen with metformin doses of up to 85g, 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 effective method to remove lactate and metformin is haemodialysis.
DOSAGE AND ADMINISTRATION:
500mg 8hourly or 750mg 12hourly with meals; up to a maximum of 3g daily if necessary.
Glucoform® is available as 500mg metformin hydrochloride in a blister pack of 10×10’s.
Store in a cool dry place below 30oC. Protect from light.