INFORMATION FOR HEALTH PROFESSIONALS
Home | Consumers | Health Professionals | Regulatory | Other | Hot Topics | Search
Home | Consumers | Health Professionals | Regulatory | Other | Hot Topics | Search
Metformin hydrochloride BP as:
500mg tablets: White, film-coated, biconvex tablets of 11mm diameter embossed with dp on one side and 500 on the other.
850mg tablets: White, film-coated, biconvex tablets of 13mm diameter embossed with dp on one side and 850 on the other.
Metformin hydrochloride is a biguanide oral hypoglycaemic agent. Its mode of action is thought to be multifactoral and includes delayed uptake of glucose from the intestinal tract, increased peripheral glucose utilisation mediated by increased insulin sensitivity and inhibition of increased hepatic and renal gluconeogenesis.
The administration of metformin HCl results in improved glucose assimilation and reduced levels of plasma cholesterol, triglycerides and prebetalipoproteins. Weight may also be reduced.
The degree of absorption of metformin HCl after oral administration is only about 50-60%, and it is thought that the percentage absorbed from the gastrointestinal tract may decrease as the dose increases. Absorption may be affected by food.
The peak concentration after a 500mg dose of metformin HCl has been measured as approximately 1µg/mL between 2-2.5h. After a 850mg dose it is approximately 1.8µg/mL at about 3 hours. Metformin HCl is not significantly bound to plasma protein and is excreted almost unchanged in the urine. Reports indicate that elimination may be biphasic.
Metformin hydrochloride is a biguanide hypoglycaemic agent and is used in diet-failed, non-insulin-dependent diabetes mellitus, especially if overweight. It may be used alone as initial therapy or, in sulphonylurea failures either alone or in combination with a sulphonylurea.
Metformin may also be used as adjuvant therapy in insulin-dependent diabetic patients who are usually obese and not well controlled by insulin.
Adults: Metformin HCl tablets should be taken in divided doses with meals. Initially either 500mg three times a day or 850mg twice daily.
Good diabetic control may be achieved in a few days, but can take up to two weeks. If control is incomplete, the dose may be gradually increased up to a maximum of 3g per day. Once control has been obtained it may be possible to reduce the dosage.
Metformin therapy in combination with a sulphonylurea or insulin should be monitored by blood-glucose readings as hypoglycaemia may occur.
When using metformin HCl and insulin in combination, working out the correct ratio of the two medicines to be given should be carried out in hospital due to the risk of hypoglycaemia.
Metformin HCl is contraindicated in the following conditions: dehydration, diabetic coma, ketoacidosis, marked renal impairment, chronic liver disease, cardiac failure, recent myocardial infarction, alcoholism (both acute and chronic), conditions associated with hypoxaemia, states associated with lactic acidosis such as shock or pulmonary insufficiency in patients with a history of lactic acidosis and in the period around surgery (see Warnings and Precautions).
The use of metformin is not advised in infantile diabetics, except in hospital.
As metformin HCl is excreted by the kidney, care is therefore necessary in patients with decreased renal function and the elderly.
Patients receiving continuous metformin therapy should have an annual estimation of vitamin B12 absorption. However, no case of pernicious anaemia has ever been reported.
The use of metformin is not advised in conditions which may cause dehydration, in patients suffering from serious infections or trauma, and in those undergoing surgery because of the additional risk of lactic acidosis. Metformin should be stopped 24h before surgery and should not be recommenced until patients have recovered sufficiently to be taking food and liquid by mouth.
The use of metformin is also not advised in certain investigations such as intravenous urography and intravenous angiography (therapy should be stopped 2 days before and restarted after the investigation is completed).
It is prudent to stop metformin therapy temporarily if any of the above conditions exist, particularly if gastrointestinal disturbances are noted or acidosis is suspected. After ketoacidosis and lactic acidosis have been excluded, metformin treatment may be resumed.
Use in pregnancy and lactation: Metformin has been associated with the development of foetal lactic acidosis. It should, therefore, not be used during pregnancy but replaced by insulin. If metformin is required during lactation, it is recommended that an alternative method to breast feeding be used.
Metformin HCl is generally well tolerated, but can cause minor transient gastrointestinal upsets. These can generally be avoided by taking metformin with meals or, occasionally, by temporarily lowering the dose.
Approximately 3% of patients may have to discontinue treatment because of this complication. In the majority of patients who show signs of intolerance, gastrointestinal upsets disappear by the time the diabetes is controlled and do not return. It is, therefore, important not to discontinue therapy at the first signs of intolerance to metformin.
Lactic acidosis, sometimes fatal, has occurred. It is generally accepted, however, that the lactic acidosis occurred in patients whose condition contraindicated the use of metformin.
Lactic acidosis is characterised by decreased blood pH, electrolyte disturbances with an increased anion gap and an increased lactate level with altered lactate/pyruvate ratio. Azotaemia may also be present. Lactic acidosis often has an insidious onset and non-specific symptomatology. Marked anorexia or unexplained weight loss may indicate the onset and precede the full clinical manifestations of lactic acidosis presenting with nausea, vomiting, hyperventilation, malaise and/or abdominal pain.
Lactic acidosis is a medical emergency, which must be treated in hospital immediately. In patients with a metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonaemia) lactic acidosis should be suspected.
Other adverse effects which patients may experience include: impaired absorption of vitamin B12, metallic taste and weight loss, which in some diabetics could be an advantage.
Alcohol should only be taken in moderation in patients on metformin HCl.
Combined therapy of metformin with sulphonylurea or insulin should be monitored by blood-sugar readings because of the possibility of hypoglycaemia.
There is a possible interaction between anticoagulants and metformin HCl. Patients receiving these two medicines concomitantly need an adjustment of the anticoagulant dosage.
Hypoglycaemia does not occur with metformin HCl monotherapy (fifty tablets have been ingested with no untoward effects). However, when metformin is taken with a sulphonylurea, insulin or alcohol, hypoglycaemia can occur. Glucose or glucagon may be required for treatment of hypoglycaemia.
Acute poisoning with metformin calls for intensive supportive therapy and should be particularly directed at correcting fluid loss and metabolic disturbance. Lactic acidosis can occur and may require treatment with sodium bicarbonate.
Store below 30°C. Protect from light and moisture. Keep out of reach of children.
Prescription Medicine.
500mg tablets: Packs of 100.
850mg tablets: Packs of 60.
Metformin hydrochloride is 1,1-dimethyl-biguanide hydrochloride. It has a molecular formula and weight of C4H11N5.HCl and 165.6 respectively.
Other ingredients of the tablets are: Polyvinylpyrrolidinone K-25, Microcrystalline cellulose, Magnesium stearate, Talc and Silicon dioxide.
Douglas Pharmaceuticals Ltd
P.O. Box 45-027
Auckland 8
New Zealand
Ph: (09) 835-0660
Fax: (09) 835-0665
16 March 1999