Gliclazide 80mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Gliclazide 80mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 80 mg gliclazide For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet.
White, round tablet, scored on one side and embossed "G03" on the reverse
side
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Non insulin dependent diabetes mellitus.
4.2 Posology and method of administration
For oral administration.
Adults: The total daily dose may vary from 40 to 320 mg taken orally .The dose should be adjusted according to the individual patient’s response, commencing with 40 - 80 mg daily (E2-I tablets) and increasing until adequate control is achieved..
A single dose should not exceed 160 mg (2 tablets). When higher doses are required, Gliclazide 80mg Tablets should be taken twice daily and according to the main meals of the day.
In obese patients or those not showing adequate response to Gliclazide 80mg Tablets alone, additional therapy may be required.
Elderly: Plasma clearance of gliclazide is not altered in the elderly and steady state plasma levels can therefore be expected to be similar to those in adults under 65 years. Clinical experience in the elderly to date shows that gliclazide is effective and well tolerated.
Care should be exercised, however, when prescribing sulphonylureas in the elderly due to a possible age-related increased risk of hypoglycaemia.
Children: Gliclazide 80mg Tablets, as with other sulphonylureas are not indicated for the treatment of juvenile onset diabetes mellitus.
4.3 Contraindications
Gliclazide should not be used in:
- Juvenile onset diabetes.
- Diabetes complicated by ketosis and acidosis.
- Pregnancy.
- Diabetics undergoing surgery, after severe trauma or during infections.
- Patients known to have hypersensitivity to other sulphonylureas and related drugs or any of the other tablet ingredients.
- Diabetic pre-coma and coma.
- Severe renal or hepatic insufficiency.
4.4 Special warnings and precautions for use
Hypoglycaemia:
This treatment should be prescribed only if the patient is likely to have a regular food intake (including breakfast). It is important to have a regular carbohydrate intake due to the increased risk of hypoglycaemia if a meal is taken late, if an inadequate amount of food is consumed or if the food is low in carbohydrate.
Hypoglycaemia is more likely to occur during low-calorie diets, following prolonged or strenuous exercise, alcohol intake or if a combination of hypoglycaemic agents is being used.
Hypoglycaemia may occur following administration of sulphonylureas (see 4.8.Undesirable effects). Some cases may be severe and prolonged. Hospitalisation may be necessary and glucose administration may need to be continued for several days.
Careful selection of patients, of the dose used, and clear patient directions are necessary to reduce the risk of hypoglycaemic episodes.
Factors which increase the risk of hypoglycaemia:
- patient refuses or (particularly in elderly subjects) is unable to co-operate,
- malnutrition, irregular mealtimes, skipping meals, periods of fasting or dietary changes,
- imbalance between physical exercise and carbohydrate intake,
- renal insufficiency,
- severe hepatic insufficiency,
- overdose of gliclazide,
- certain endocrine disorders: thyroid disorders, hypopituitarism and adrenal insufficiency,
- concomitant administration of certain other medicines (see Interactions).
Renal and hepatic insufficiency: the pharmacokinetics and/or pharmacodynamics of gliclazide may be altered in patients with hepatic insufficiency or severe renal failure.
A hypoglycaemic episode occurring in these patients may be prolonged, so appropriate management should be initiated.
The hypoglycaemic efficacy of any oral antidiabetic agent, including gliclazide, is attenuated over time in many patients: this may be due to progression in the severity of the diabetes, or to a reduced response to treatment. This phenomenon is known as secondary failure which is distinct from primary failure, when an active substance is ineffective as first-line treatment. Adequate dose adjustment and dietary compliance should be considered before classifying the patient as secondary failure.
Laboratory tests: Measurement of glycated haemoglobin levels (or fasting venous plasma glucose) is recommended in assessing blood glucose control. Blood glucose self-monitoring may also be useful.
Patient information:
The risks of hypoglycaemia, together with its symptoms, treatment, and conditions that predispose to its development, should be explained to the patient and to family members.
The patient should be informed of the importance of following dietary advice, of taking regular exercise, and of regular monitoring of blood glucose levels.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Care should be taken when giving gliclazide with drugs which are known to alter the diabetic state or potentiate the drug's action.
The hypoglycaemic effect of gliclazide may be potentiated by phenylbutazone, salicylates, sulphonamides, coumarin derivatives, MAOIs, beta adrenergic blocking agents, tetracycline compounds, chloramphenicol, clofibrate, disopyramide, miconazole (oral forms) and cimetidine.
It may be diminished by corticosteroids, oral contraceptives, thiazide diuretics, phenothiazine derivatives, thyroid hormones and abuse of laxatives.
4.6 Pregnancy and lactation
Pregnancy:
Gliclazide is contraindicated during pregnancy (see section 4.3 contraindications).
Lactation:
It has not been established whether gliclazide is transferred to human milk. However, other sulphonylureas have been found in milk and there is no evidence to suggest that gliclazide differs from the group in this respect. Gliclazide should, therefore, not be taken while the mother is breast-feeding.
4.7 Effects on ability to drive and use machines
Patients should be informed that their concentration may be affected if their diabetes is not satisfactorily controlled, especially at the beginning of treatment (see special warnings and precautions).
4.8 Undesirable effects
Based on the experience with gliclazide and with other sulphonylureas, the following undesirable effects may occur:-
Frequencies are defined as: very common (>1/10); common (>1/100, <1/10); uncommon ( > 1/1000, <1/100); rare ( > 1/10,000, <1/1000); very rare ( <1/10,000), including isolated reports; not known (cannot be estimated from the available data).
Common: Hypoglycaemia
As for other sulphonylureas, treatment with Gliclazide 80 mg Tablets can cause hypoglycaemia (see special warnings and precautions).
Possible symptoms of hypoglycaemia are: headache, intense hunger, nausea, vomiting, lassitude, sleep disorders, agitation, aggression, poor concentration, reduced awareness and slowed reactions, depression, confusion, visual and speech disorders, aphasia, tremor, paresis, sensory disorders, dizziness, feeling of powerlessness, loss of self-control, delirium, convulsions, shallow respiration, bradycardia, drowsiness and loss of consciousness, possibly resulting in coma and lethal outcome.
In addition, signs of adrenergic counter-regulation may be observed: sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmia.
Usually, symptoms disappear after intake of carbohydrates (sugar). However, artificial sweeteners have no effect. Experience with other sulphonylureas shows that hypoglycaemia can recur even when measures prove effective initially.
If a hypoglycaemic episode is severe or prolonged, and even if it is temporarily controlled by intake of sugar, immediate medical treatment or even hospitalisation is required.
Gastrointestinal disorders
Common: Nausea, dyspepsia, diarrhoea, constipation.
If these adverse reactions should occur they can be avoided or minimised if gliclazide is taken during a meal.
Skin and subcutaneous tissue disorders
Not known: rash, pruritus, erythema, bullous reactions.
Blood and lymphatic system disorders
Rare: anaemia, leukopenia, thrombocytopenia, granulocytopenia.
Hepato-biliary disorders
Rare: hepatic failure, hepatitis, jaundice.
4.9 Overdose
The symptom to be expected of overdose would be hypoglycaemia. The treatment is gastric lavage and correction of the hypoglycaemia by appropriate means with continual monitoring of the patient's blood sugar until the effect of the drug has ceased.
5.1 Pharmacodynamic properties
A10B B09 Oral Blood Glucose Lowering Drugs
Gliclazide is a hypoglycaemic sulphonylurea oral antidiabetic active substance differing from other related compounds by an N-containing heterocyclic ring with an endocyclic bond.
Gliclazide reduces blood glucose levels by stimulating insulin secretion from the P-cells of the islets of Langerhans. Increase in postprandial insulin and C-peptide secretion persists after two years of treatment.
In addition to these metabolic properties, gliclazide has haemovascular properties.
Effects on insulin release in type 2 diabetics, gliclazide restores the first peak of insulin secretion in response to glucose and increases the second phase of insulin secretion. A significant increase in insulin response is seen in response to stimulation induced by a meal or glucose.
Haemovascular properties:
Gliclazide decreases microthrombosis by two mechanisms which may be involved in complications of diabetes:
• a partial inhibition of platelet aggregation and adhesion, with a decrease in the markers of platelet
activation (beta thromboglobulin, thromboxane B2).
• an action on the vascular endothelium fibrinolytic activity with an increase in tPA activity.
5.2 Pharmacokinetic properties
The drug is well absorbed and its half-life in man is approximately 10-12 hours. Gliclazide is metabolised in the liver; less than 5% of the dose is excreted unchanged in the urine.
5.3 Preclinical safety data
Preclinical data reveal no special hazards for humans based on conventional studies of repeated dose toxicity and genotoxicity. Long term carcinogenicity studies have not been done. No teratogenic changes have been shown in animal studies, but lower fxtal body weight was observed in animals receiving doses 25 fold higher than the maximum recommended dose in humans.
6.1 List of excipients
Lactose monohydrate Silicon Dioxide Pregelatinized Maize Starch Talc
Magnesium Stearate
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
36 months
6.4 Special precautions for storage
Do not store above 25°C
6.5 Nature and contents of container
The tablets are packaged into polyvinyl chloride (PVC)/aluminium foil blister packs. Boxes of 28 and 60 tablets are available. Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
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Pramod Rajani Organisation Limited
Foster Avenue, unit 5, Aragon Park
Dunstable
Bedfordshire
LU5 5TA
UK
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Date of first authorisation: 29 August 2003 Date of latest renewal: 27 February 2009
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20/04/2011