Metformin is a biguanide oral anti-hyperglycemic agent. Its mode of action is thought to be increased peripheral glucose utilization mediated by increased insulin sensitivity and inhibition of increased hepatic and renal gluconeogenesis
Non-insulin dependent diabetes when diet has failed and especially if the patient is overweight. Metfil can be given alone as initial therapy or can be administered in combination with a sulphonylurea. In insulin-dependent diabetes, Metfil may be given as an adjuvant to patients whose symptoms are poorly controlled
- Hypersensitivity to metformin hydrochloride or any of the excipients
- Diabetic ketoacidosis, diabetic pre-coma, or the history thereof
- Impaired renal function
- Chronic liver disease
- History of states associated with lactic acidosis such as shock or pulmonary insufficiency
- Cardiac failure and recent myocardial infarction
- Conditions associated with hypoxia
- Hepatic insufficiency, acute alcohol intoxication, alcoholism
- Safety in pregnancy and lactation has not been established
- Children-safety and efficiency have not been established
Lactic acidosis is a rare, but serious (high mortality in the absence of prompt treatment), metabolic complication that can occur due to METFIL accumulation. Reported cases of lactic acidosis in patients on METFIL have occurred primarily in diabetic patients with significant renal failure.
The incidence of lactic acidosis can and should be reduced by assessing also other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia Lactic acidosis is characterized by acidotic dysponea, abdominal pain and hypothermia followed by coma.
Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5 mmol/L, and an increased anion gap and lactate pyruvate ratio. If metabolic acidosis is suspected, metformin should be discontinued and the patients should be hospitalized immediately
METFIL should be discontinued 48 hours before elective surgery with general anaesthesia and should not be usually resumed earlier than 48 hours afterwards
Pregnancy and lactation
The use of Metformin during pregnancy is not advised. There is no information available concerning the safety of Metformin during lactation
Dosage and directions for use
It is important that Metformin tablets be taken in divided doses with meals.
Adult: initially, one 500 mg tablet three times a day, with or after food. After 10 to 15 days the dose should be adjusted or increased to 850 mg or 1000mg twice daily. A slow increase in dose may improve gastrointestinal tolerability. If control is incomplete a cautious has been obtained it may be possible to reduce the dosage of Metfil
Children: Metfil is not recommended for use in type 1 diabetes mellitus
Elderly: Metfil is indicated in the elderly, but not when renal function is impaired
Blood and the lymphatic system disorders: Less frequent; megaloblastic anaemia
Gastrointestinal disorders: Frequent; Anorexia, nausea, vomiting, constipation and diarrhea
Nervous system disorders: Frequent; Metallic taste
Renal and urinary disorders: Less frequent; Ketoacidosis and Ketonuria
Hepato-biliary disorders: Less frequent; Severe cholestatic hepatitis
General disorders: Less frequent; Hypersensitivity, hypoglycemia
Known symptoms of overdose and particulars of its treatment
Hypoglycemia can occur when Metformin is given concomitantly with a sulphonylurea, insulin or alcohol. In excessive dosage and particularly if there is a possibility of accumulation, lactic acidosis may develop. Intense symptomatic and support therapy is recommended which should be particularly directed at correcting fluid loss and correcting blood glucose levels.