GLICLAZIDE

Posology Adults The total daily dose may vary from 40-320mg. The dose should be adjusted according to the individual's response, commencing with 40-80mg daily and increasing until adequate control is achieved. A single dose should not exceed 160mg.

When higher doses are required, gliclazide 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 alone, additional therapy may be required. Special Populations 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 sulfonylureas in the elderly due to a possible age-related increased risk of hypoglycaemia.

Paediatric population Gliclazide, as with other sulfonylureas, is not indicated for the treatment of juvenile onset diabetes mellitus. Method of administration For oral use.

Based on the experience with gliclazide and with other sulfonylureas, the following undesirable effects have to be mentioned. Hypoglycaemia The most frequent adverse reaction with gliclazide is hypoglycaemia. As for other sulfonylureas, treatment with Gliclazide can cause hypoglycaemia, if mealtimes are irregular and, in particular, if meals are skipped.

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 sulfonylureas 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 are required.

Gastrointestinal disturbances, including abdominal pain, nausea, vomiting, dyspepsia, diarrhoea and constipation have been reported. These can be avoided or minimised if gliclazide is taken with breakfast. The following undesirable effects have been more rarely reported: - Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria, angioedema, erythema, maculopapular rashes, bullous reactions, (such as Stevens-Johnson syndrome and toxic epidermal necrolysis and autoimmune bullous disorders), and exceptionally, drug rash with eosinophilia and systemic symptoms (DRESS).

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. 8). 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. 5). 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. 8), 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. 5), fever, trauma, infection or surgical intervention. In some cases, it may be necessary to administer insulin.

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. Dysglycaemia Disturbances in blood glucose, including hypoglycaemia and hyperglycaemia have been reported, in diabetic patients receiving concomitant treatment with fluoroquinolones, especially in elderly patients.

6), Gliclazide should, where possible, be avoided in porphyria.