SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

GLYFORMIN/Metformin

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Metformin Hydrochloride BP 500.00 mg

3    PHARMACEUTICAL FORM

Film-Coated Tablet

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Maturity onset diabetes when diet alone has failed.

Obese diabetic patients who are not well controlled on insulin but who are insulin-dependent may occasionally benefit when GLYFORMIN is used as an adjunct.

4.2    Posology and method of administration

Adults: Usually one 500mg tablet 3 times a day to be taken with meals. Should control of diabetes be incomplete a gradual increase in dosage to a maximum of 3g daily in divided doses taken together with meals may be instituted

This dosage regimen should not be increased above 3g.

Children: Not recommended

Elderly: Metformin, while indicated in the elderly should not be used when renal function is impaired Route of adminstration: Oral

4.3 Contraindications

The drug is contraindicated in diabetic coma and ketoacidosis. Chronic liver disease. Impaired renal function. Cardiac failure. Recent myocardial infarction. Shock or pulmonary insufficiency and conditions associated with lactic acidosis. Acute or chronic alcoholism. Those conditions associated with hypoxaemia. Severe infection or trauma Dehydration. Peripheral vascular disease. Hypersensitivity to the drug.

4.4 Special warnings and precautions for use

Glyformin should not be used: in conditions which may cause dehydration. Intravascular contrast studies with iodinated materials can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving metformin. Therefore, in patients in whom any such studies are planned, metformin should be discontinued at the time of, or prior to, the procedure and withheld for 48 hours subsequent to the procedure and reinstituted only after renal function has been re-evaluated and found to be normal.

In any of the above conditions Glyformin should be temporarily suspended and particularly if acidosis is suspected. Only after lactic acidosis or ketoacidosis have been excluded should treatment be resumed. Glyformin is excreted by the kidney therefore regular monitoring of renal function should be undertaken in all diabetics, especially the elderly.

An annual vitamin b12 level estimation may be considered desirable in patients on continuous metformin therapy.

4.5 Interaction with other medicinal products and other forms of interaction

There may be interactions between Glyformin and anticoagulants; accordingly patients receiving the two drugs may need adjustment of the anticoagulant dosage.

Patients receiving Glyformin over prolonged periods should have an annual estimation of b12 because of decreased b12 absorption.

Combined therapy of Glyformin with a sulphonylurea or insulin may cause hypoglycaemia. Alcohol enhances the hypoglycaemia effect of metformin and increases the risk of lactic acidosis. Glyformin and insulin therapy stabilisation should be carried out in hospital. During cimetidine therapy reduced renal clearance of metformin has been reported and accordingly a dose reduction should be considered.

4.6 Pregnancy and lactation

Glyformin should not be used in pregnancy unless there are compelling reasons for its use. Lactation: do not use during lactation unless considered absolutely essential.

4.7 Effects on ability to drive and use machines

None

4.8 Undesirable effects

While Glyformin is usually well tolerated, gastro-intestinal disturbances sometimes occur and although they are usually minor they can normally be avoided by taking Glyformin with or after food. It may, however, be necessary temporarily to lower the dose of Glyformin. Glyformin treatment should not be abandoned at the first sign of intolerance because this has been found to resolve spontaneously. Metformin may decrease vitamin B12 absorption.

Lactic acidosis has been associated with Glyformin, but in the rare cases reported it has occurred in patients with contraindications to therapy.

In patients with a metabolic acidosis lacking evidence of ketoacidosis (ketoneuria and ketonaemia )lactic acidosis should be suspected and Glyformin therapy stopped. Lactic acidosis is a medical emergency which must be treated in hospital.

4.9 Overdose

Hypoglycaemia does not occur if Glyformin is taken alone in overdosage, but it can occur when Glyformin is given concomitantly with a sulphonylurea, insulin or alcohol. In excessive dosage lactic acidosis may develop.

The treatment includes intensive supportive therapy and correcting fluid loss and metabolic disturbance.

5.1 Pharmacodynamic properties

Metformin is a biguanide oral anti-hyperglycaemic agent which is thought to act through delayed uptake of glucose from the gastro-intestinal tract and by increased peripheral glucose utilisation mediated by increased insulin sensitivity and inhibition of increased hepatic and renal gluconeogenesis.

5.2 Pharmacokinetic properties

Metformin is completely absorbed from the gastro-intestinal tract and is excreted unchanged in the urine. 37.6% of an oral dose was recovered in the urine after 48 hours. Metformin is not protein bound in plasma or metabolised.

5.3 Preclinical safety data

Not applicable.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose

Silicon Dioxide Gelatin

Sodium Starch Glycollate

Purified Water

Magnesium Stearate

Hydroxypropylmethylcellulose

Ethylcellulose

Titanium Dioxide E171

Diethylphthalate

Methanol

Dichloromethane

Incompatibilities

None known.

6.3 Shelf life

36 months for all packs.

6.4 Special precautions for storage

Store below 25°C in a dry place. Keep containers securely closed.

6.5 Nature and contents of container

High density polystyrene containers with polythene lids and/or polypropylene containers with polypropylene or polythene lids and polyurethane/polythene inserts.

Pack sizes: 28, 30, 50, 56, 60, 84, 250,500 and 1000 250 micron PVC glass-clear/bluish rigid PVC (pharmaceutical grade). 20 micron hard-tempered aluminium foil coated on the dull side with 6-7 gsm heat seal lacquer and printed on the bright side.

Pack sizes: 28, 30, 50, 56, 60, 84, 100, 250, 500 and 1000

6.6 Special precautions for disposal

No special instructions

7    MARKETING AUTHORISATION HOLDER

Chelonia Healthcare Limited 11 Boumpoulinas Street,

3^rd floor, 1060 Nicosia Cyprus

8    MARKETING AUTHORISATION NUMBER(S)

PL 33414/0059

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

25/02/2009

10    DATE OF REVISION OF THE TEXT

25/02/2009