GLIMEPIRIDE

For oral use. The basis for successful treatment of diabetes is a good diet, regular physical activity, as well as routine checks of blood and urine. Tablets or insulin can not compensate if the patient does not keep to the recommended diet.

Dosage is determined by the results of blood and urinary glucose determinations. The starting dose is 1 mg glimepiride per day. If good control is achieved this dosage should be used for maintenance therapy. If control is unsatisfactory the dosage should be increased, based on the glycaemic control, in a stepwise manner with an interval of about 1 to 2 weeks between each step, to 2, 3 or 4 mg glimepiride per day.

A dosage of more than 4 mg glimepiride per day gives better results only in exceptional cases. The maximum recommended dose is 6 mg glimepiride per day. In patients not adequately controlled with the maximum daily dose of metformin, concomitant glimepiride therapy may be initiated.

While maintaining the metformin dose, glimepiride therapy is started with a low dose, and is then titrated up depending on the desired level of metabolic control up to the maximum daily dose. The combination therapy should be initiated under close medical supervision.

In patients not adequately controlled with the maximum daily dose of Glimepiride Tablet, concomitant insulin therapy can be initiated if necessary. While maintaining the glimepiride dose, insulin treatment is started at low dose and titrated up depending on the desired level of metabolic control.

The combination therapy should be initiated under close medical supervision. Normally a single daily dose of glimepiride is sufficient. It is recommended that this dose be taken shortly before or during a substantial breakfast or if none is taken - shortly before or during the first main meal.

If a dose is forgotten, this should not be corrected by increasing the next dose. Tablets should be swallowed whole with some liquid. If a patient has a hypoglycaemic reaction on 1 mg glimepiride daily, this indicates that they can be controlled by diet alone.

In the course of treatment, as an improvement in control of diabetes is associated with higher insulin sensitivity, glimepiride requirements may fall. To avoid hypoglycaemia timely dose reduction or cessation of therapy must therefore be considered.

Based on experience with Glimepiride Tablet and with other sulphonylureas the following side effects have to be mentioned. 000, incl. isolated reports Blood and the lymphatic system disorders Changes in the blood picture*, including: Moderate to severe thrombocytopenia, leukopenia, erythrocytopenia, granulocytopenia, agranulocytosis, haemolytic anaemia, pancytopenia Immune system disorders Mild hypersensitivity reactions may develop to severe reactions with dyspnoea, fall in blood pressure and possibly shock.

Allergic vasculitis. Cross allergy with sulfunyl ureas, sulphonamide and related substances. g. with cholestasis and icterus. Hepatitis***** Skin and subcutaneous tissue disorders Allergic skin reactions such as pruritus, rash, urticaria.

Photosensitivity Investigations Drop in serum sodium *These alterations are usually reversible upon discontinuation of treatment. ** These reactions which often occur immediately may be serious and are not always easy to correct. The incidence of hypoglycaemic reactions depends on individual parameters such as food habits and dosage as with any other diabetic medication (se also “Special warnings and precaution for use”).

*** These disorders are transient and are especially seen at the beginning of the treatment, due to changes in blood glucose levels. **** These reactions rarely cause discontinuation of treatment. ***** Hepatitis may progress to hepatic failure.

Glimepiride Tablet must be taken shortly before or during a meal. When meals are taken at irregular hours and especially if meals are omitted, treatment with Glimepiride Tablet may lead to hypoglycaemia. g. headache, ravenous hunger, nausea, vomiting, fatigue, sleepiness, sleep disorders, restlessness, aggressiveness, impaired concentration, alertness and reaction time, depression, confusion, speech and visual disorders, aphasia, tremor, paresis, sensory disturbances, dizziness, helplessness, loss of self control, delirium, cerebral convulsions, somnolence and loss of consciousness amounting to and including coma, shallow respiration and bradycardia.

In addition, signs of adrenergic counter-regulation may be present such as sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmias. The clinical picture of a severe hypoglycaemic attack may resemble that of a stroke.

Symptoms are usually promptly controlled after immediate intake of carbohydrates. Artificial sweeteners have no effect. It is known from other sulphonylureas that hypoglycaemia may recur despite initially successful countermeasures. Severe hypoglycaemia or prolonged hypoglycaemia, only temporarily controlled by the usual amounts of sugar, requires immediate medical treatment and occasionally hospitalisation.

Factors favouring hypoglycaemia include: − Unwillingness (more commonly in elderly patients) or incapacity of the patient to cooperate. − undernutrition, irregular meal times, skipped meals or periods of fasting. − Changes in diet. − Imbalance between physical activity and carbohydrate intake.

− Consumption of alcohol, especially in combination with skipped meals. − Impaired renal function. − Severe hepatic impairment. g. certain disorders of thyroid function and anterior pituitary or adrenocortical insufficiency), − Other concurrent administration of certain other medicines (see Interactions").

3 Contraindications Glimepiride Tablet must not be administered in the following cases: - Insulin dependent diabetes - diabetic coma, - ketoacidosis, - severe renal and hepatic disease, - known hypersensitivity to glimepiride, other sulphonylureas or other sulphonamides or excipients in the tablet.

In case of severe renal or hepatic disease, a switch to insulin therapy is required.