Metformin HCl is 1,2-dimethyl biguanide hydrochloride.
Each Diamet-SR tablet also contains titanium dioxide as colouring agent.
Pharmacotherapeutic Group: Antidiabetic agent.
Pharmacology: Metformin is an oral antihyperglycaemic agent used in the management of non-insulin dependent diabetes mellitus (NIDDM). It reduces blood glucose levels, predominantly by improving hepatic and peripheral tissue sensitivity to insulin without affecting the secretion of this hormone. Metformin possesses similar antihyperglycaemic efficacy to sulfonylureas in obese and non-obese patients with NIDDM.
Pharmacokinetics: Metformin has an absolute oral bioavailability of 50-60% and gastrointestinal absorption is apparently complete within 6 hrs of ingestion. Higher oral doses are proportionately less bioavailable than lower doses (observed with doses ranging from 500-1500 mg).
The appearance of metformin in plasma from Diamet SR is slower and more prolonged compared to immediate-release metformin. Distribution studies with Diamet SR have not been conducted. The apparent volume of distribution (V/F) of metformin following single oral doses of immediate-release metformin 850 mg averaged 654±358 L. Metformin is negligibly bound to plasma proteins.
Metformin is partially absorbed from the genitourinary tract. Half-life is 1.5-3 hrs. It is not bound to plasma proteins. It is eliminated by the renal route.
Renal clearance of metformin is approximately 3.5 times greater than creatinine clearance which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the 1st 24 hrs, with a plasma elimination half-life of approximately 6.2 hrs. In the blood, the elimination half-life is approximately 17.6 hrs, suggesting that the erythrocyte mass may be a compartment of distribution.
Obese non-insulin dependent diabetes mellitus (NIDDM) patients who do not respond to dietary control and who have a moderately elevated glycosylated haemoglobin levels with normal kidney functions.
Primary or secondary sulfonylurea failures. In these cases, metformin can be used alone or in combination with sulfonylureas, depending on the response to such treatment before considering transfer to insulin therapy.
Very unstable juvenile or maturity onset diabetes where a combination of insulin and metformin is beneficial.
Overweight NIDDM patients who will benefit with weight control by the use of metformin along with insulin therapy.
Diamet: 500 mg 3 times daily or 850 mg twice daily, with maximum daily dose not exceeding 2.5 g/day, with or after meals, gradually increased if necessary to a maximum of 3 g/day.
Diamet SR: 1000 mg once daily with the evening meal, although 500 mg may be utilised when clinically appropriate. Dosage increases should be made in 500-mg increments weekly, up to a maximum of 2500 mg once daily with the evening meal.
Hypoglycaemia has not been seen even with ingestion of up to 85 g of immediate-release metformin, although lactic acidosis has occurred in such circumstances. Metformin is dialysable with a clearance of up to 170 mL/min under good haemodynamic conditions. Therefore, haemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.
Hypersensitivity to metformin.
Patients with renal and hepatic failure which may also result from conditions eg, cardiovascular collapse (shock), acute myocardial infarction and septicaemia.
Congestive heart failure requiring pharmacologic treatment.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma. Diabetic ketoacidosis should be treated with insulin.
Dehydration, acute or chronic alcoholism or any other condition which may predispose to lactic acidosis.
Metformin should not be used alone in insulin-dependent diabetes mellitus.
Metformin is not recommended in patients with severe impairment of thyroid function.
Metformin is known to be substantially excreted by the kidneys and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function.
Concomitant medication(s) that may affect renal function or result in significant haemodynamic change or may interfere with the disposition of metformin eg, cationic drugs that are eliminated by renal tubular secretion should be used with caution.
Cardiovascular collapse (shock) from whatever cause, acute congestive heart failure, acute myocardial infarction and other conditions characterised by hypoxaemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur in patients on metformin therapy, Diamet/Diamet SR should be promptly discontinued.
Metformin therapy should be temporarily suspended for any surgical procedure (except minor procedures not associated with restricted intake of food and fluids) and should not be restarted until the patient's oral intake has resumed and renal function has been evaluated as normal.
Alcohol is known to potentiate the effect of metformin on lactate metabolism.
Since impaired hepatic function has been associated with some cases of lactic acidosis, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease.
Use in pregnancy & lactation: Metformin is not recommended for use in pregnancy and lactation.
Use in children: Metformin is not recommended for use in patients <17 years.
Metformin is not recommended for use in pregnancy and lactation.
Metformin causes gastrointestinal adverse effects including anorexia, nausea and diarrhoea which normally subside on continued therapy. Absorption of various substances including vitamin B12 may be impaired.
Patients may experience a metallic taste and weight loss.
Lactic acidosis occurred with the administration of metformin, but it is generally accepted that lactic acidosis usually occurs in patients whose condition contraindicates the use of metformin.
Drug interactions are less of a problem with metformin. In a few cases, cimetidine administration resulted in increased plasma-metformin concentration. The renal clearance of metformin was reduced, competition for proximal tubular excretion was considered responsible.
Furosemide: Furosemide increases the metformin plasma and blood Cmax and area under the curve (AUC) without any significant change in metformin renal clearance.
Nifedipine: Co-administration of nifedipine increased plasma metformin Cmax and AUC by 20% and 9%, respectively and increased the amount excreted in the urine.
Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on nifedipine.
Store in a cool and dry place.
Shelf-Life: 36 months.
A10BA02 - metformin ; Belongs to the class of biguanides. Used in the treatment of diabetes.
Diamet: FC tab 500 mg x 10 x 10's.
Diamet SR: FC tab (sustained-release) 500 mg x 10 x 10's. 1 g x 10 x 10's.
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