Metformin Tablets 850mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Metformin Tablets 850mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains metformin hydrochloride Ph Eur 850mg.
3 PHARMACEUTICAL FORM
Film-coated tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Metformin Tablets are indicated for treatment of non-insulin dependent diabetes mellitus (Type II/maturity onset-type diabetes) when dietary measures are inadequate to control the diabetes, especially if the patient is overweight, or if attempts to achieve control with sulphonylureas and exercise have been unsuccessful. Metformin may be used in conjunction with sulphonylureas, but close medical supervision is required.
4.2. Posology and method of administration
Adults and the elderly:
The usual initial dose of metformin is 500mg 3 times daily, or 850mg twice daily, with meals. Adequate diabetic control may occur in a few days, but can often take up to 2 weeks. The dose may be cautiously increased, if necessary, to a maximum dose of 3,000mg (3g) daily. Once control is obtained it may be possible to reduce the dosage.
Metformin Tablets may be given to elderly patients if there is no renal impairment.
Children:
Not recommended for children.
Method of administration: oral.
4.3 Contraindications
Metformin Tablets are contra-indicated in any of the following circumstances:
- hypersensitivity to metformin, or any of the other ingredients;
- diabetic coma and ketoacidosis;
- renal impairment;
- chronic liver disease;
- cardiac failure or recent myocardial infarction;
- lactic acidosis, shock or pulmonary insufficiency;
- conditions associated with hypoxaemia; and
- alcoholism (acute or chronic).
- intravascular administration of iodinated contrast agents (see section 4.4 special warnings and precautions for use).
4.4 Special warnings and precautions for use
Lactic acidosis can occur due to metformin accumulation. Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure. The incidence of lactic acidosis can and should be reduced by also assessing other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia. If metabolic acidosis is suspected, metformin should be discontinued and the patient should be hospitalised immediately (see section 4.9).
Blood glucose levels must be regularly monitored.
As metformin is excreted by the kidney, serum creatine levels should be determined before initiating treatment and regularly thereafter:
• At least annually in patients with normal renal function
• At least two to four times a year in patients with serum creatine levels at the upper limit of normal and in elderly subjects.
Regular monitoring of renal function is advised.
Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with an NSAID.
An annual estimation of vitamin B12 levels should be made as there have been reports of decreased vitamin B12 absorption.
Treatment with Metformin Tablets should be stopped 2-3 days before surgery and clinical investigations such as intravenous angiography or IV pyelography and resumed only after control of renal function has been regained.
Metformin treatment is not recommended in conditions which may cause dehydration, in patients suffering from serious infections, or trauma.
Alcohol should be avoided as it may increase the risk of lactic acidosis.
As the intravascular administration of iodinated contrast materials in radiologic studies can lead to renal failure, metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal (see section Interactions with other Medicines and other forms of Interaction section 4.5).
Caution is advised when metformin is used in combination with insulin or sulphonylureas as hypoglycaemia may occur.
All patients should continue their diet with 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.
4.5 Interaction with other medicinal products and other forms of interaction
Blood glucose should be monitored if metformin is given with a sulphonylurea because the combination may cause hypoglycaemia.
If insulin is to be given with metformin, the patient should be stabilised in hospital because of possible hypoglycaemia until the correctly balanced ratio between insulin and metformin is achieved.
Concomitant administration of cimetidine and metformin may lead to reduced renal clearance of the latter, so a dose reduction should be considered.
Anticoagulants may interact with metformin, therefore dosage adjustment may be required for the anticoagulant.
Co-administration of metformin with ACE inhibitors may result in an enhanced hypoglycaemic effect.
Ketotifen and metfornin co-administration could cause depressed thrombocyte count.
MAOIs are thought to enhance the hypoglycaemic effect of metformin,
Octreotide may reduce the requirements of oral hypoglycaemic drugs like metformin in diabetes mellitus
Intravascular administration of iodinated contrast agents may lead to renal failure, resulting in metformin accumulation and a risk of lactic acidosis. Metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal (see Special Warnings and Precautions for Use section 4.4)
4.6. Pregnancy and lactation
Metformin Tablets are not recommended for use during pregnancy or lactation.
4.7. Effects on ability to drive and use machines
Patients’ ability to drive and use machines is not usually impaired when they are being treated with metformin alone but diabetics who experience dizziness or hypoglycaemia should be warned about the risks and their obligations to notify the UK vehicle licensing centre.
4.8. Undesirable effects
Gastrointestinal disturbances such as diarrhoea, abdominal pain, nausea and vomiting sometimes occur. These are usually minor and can often be avoided by taking metformin with or after meals. Sometimes, a temporary lowering of the dose may be required. Initial intolerance has been found to often resolve on its own. Also there are reports of a metallic taste in the mouth as relatively common side effect.
Megaloblastic anaemia may occur as a result of decreased vitamin Bi2 absorption and therefore vitamin Bi2 deficiency which may be caused by taking metformin.
Hypoglycaemia may occur, particularly in association with sulphonylurea therapy, but is less commonly associated with biguanides alone.
Reports of the occurrence of lactic acidosis have been made, most often in patients with contra-indications to metformin treatment. Lactic acidosis should be suspected in patients with a metabolic acidosis without evidence of ketoacidosis (ketonuria and ketonaemia), and metformin treatment must be stopped. Lactic acidosis must be treated in hospital immediately as a medical emergency.
Additionally there have been reports of skin rashes.
Other undesirable effects include anorexia, erythema, urticaria, pruritus and hepatitis.
Overdose
4.9.
Lactic acidosis may develop if too many tablets have been taken. Hypoglycaemia may occur if metformin has been taken with alcohol, insulin or a sulphonylurea. Intensive supportive treatment should be undertaken directed at correcting fluid loss and metabolic disturbance in particular.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Metformin is a biguanide antihyperglycaemic. It reduces high blood glucose concentrations in patients with diabetes only without increasing insulin secretion. It also encourages the muscles to take up glucose, reduces gluconeogenesis and slows intestinal glucose absorption.
5.2. Pharmacokinetic properties
Oral doses of metformin are absorbed via the gastrointestinal tract within 6 hours to give a bioavailability of 50-60%. Higher doses (over 1,500mg) are less bioavailable than lower doses.
Metformin is quickly distributed in the tissues and does not bind to plasma proteins. There is a slowly increasing binding to blood cells. The mean plasma elimination half-life is between 1.5 and 4.5 hours. This is prolonged in patients with renal impairment. Metformin does not appear to be metabolised and is excreted via the kidneys.
5.3. Preclinical safety data
There are no preclinical safety data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium starch glycollate, maize starch, povidone, colloidal anhydrous silica, magnesium stearate, methylhydroxypropylcellulose, titanium dioxide (E171), propylene glycol, polyethylene glycol 6000 and purified talc.
Incompatibilities
6.2
None known
6.3 Shelf life
36 months
6.4 Special precautions for storage
Store below 25°C in a dry place.
6.5 Nature and contents of container
Blister packs comprised of PVC/PVDC/aluminium strips enclosed in an outer carton containing* 28, 30, 56, 60, 84, 90, 100 or 112 tablets.
Not all pack sizes may be marketed
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Sandoz Ltd Woolmer Way Bordon Hampshire GU35 9QE
8 MARKETING AUTHORISATION NUMBER(S)
PL 4416/0301
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 17/05/2007
10 DATE OF REVISION OF THE TEXT
17/05/2007