GLICLAZIDE

Posology Initial dose 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 (1 – 2 tablets) and increasing until adequate control is achieved.

A single dose should not exceed 160 mg (4 tablets). When higher doses are required, Gliclazide 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 tablets alone, additional therapy may be required.

Switching from another oral antidiabetic agent to Gliclazide 40 mg tablets:

Gliclazide 40mg Tablets can be used to replace other oral antidiabetic agents. The dosage and the half-life of the previous antidiabetic agent should be taken into account when switching to Gliclazide 40 mg Tablets. A transitional period is not generally necessary.

A starting dose of 40-80 mg ( 1 to 2 tablets) should be used and this should be adjusted to suit the patient’s blood glucose response, as described above. When switching from a hypoglycaemic sulfonylurea with a prolonged half- life, a treatment free period of a few days may be necessary to avoid an additive effect of the two products, which might cause hypoglycaemia.

• Combination treatment with other antidiabetic agents: Gliclazide Tablets can be given in combination with biguanides, alpha glucosidase inhibitors or insulin. In patients not adequately controlled with Gliclazide Tablets, concomitant insulin therapy can be initiated under close medical supervision.

Special Populations Elderly:

Gliclazide Tablets should be prescribed using the same dosing regimen recommended for patients under 65 years of age.

Renal impairment:

In patients with mild to moderate renal insufficiency, the same dosing regimen can be used as in patients with normal renal function with careful patient monitoring. These data have been confirmed in clinical trials. Patients at risk of hypoglycaemia: • undernourished or malnourished, • severe or poorly compensated endocrine disorders (hypopituitarism, hypothyroidism, adrenocorticotrophic insufficiency), • withdrawal of prolonged and/or high dose corticosteroid therapy, • severe vascular disease (severe coronary heart disease, severe carotid impairment, diffuse vascular disease); It is recommended that the minimum daily starting dose of 40-80 mg is used.

Based on the experience with gliclazide, the following undesirable effects have been reported. The most frequent adverse reaction with gliclazide is hypoglycaemia. As for other sulphonylureas, treatment with Gliclazide tablets 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 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 hospitalization is required.

Gastrointestinal disturbances, including abdominal pain, nausea, vomiting dyspepsia, diarrhoea, and constipation have been reported: if these should occur, they can be avoided or minimised if Gliclazide tablets are 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 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. Hospitalization may be necessary and glucose administration may need to be continued for several days.

Careful selection 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.

Poor blood glucose control:

Blood glucose control in a patient receiving antidiabetic treatment may be affected by any of the following: St. 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.

1, other sulfonylureas, sulfonamides • Type 1 diabetes • Diabetic pre-coma and coma, diabetic keto-acidosis. • Severe renal or hepatic insufficiency: in these cases, the use of insulin is recommended. 6)