GLIMEPIRIDE

Posology For oral administration. 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 cannot compensate if the patient does not keep to the recommended diet.

Dose 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 dose should be used for maintenance therapy. For the different dose regimens appropriate strengths are available.

If control is unsatisfactory the dose 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 dose 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 can 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, 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. 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. Change in dose may also be necessary, if there are changes in weight or lifestyle of the patient, or other factors that increase the risk of hypo- or hyperglycaemia.

The following adverse reactions from clinical investigations were based on experience with glimepiride and other sulphonylureas, were listed below by system organ class and in order of decreasing incidence: very common (≥ 1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Blood and lymphatic system disorders Rare: thrombocytopenia, leucopenia, granulocytopenia, agranulocytosis, erythropenia, haemolytic anaemia and pancytopenia, which are in general reversible upon discontinuation of medicinal product.

Not known: severe thrombocytopenia with platelet count less than 10,000/μl and thrombocytopenic purpura. , mild hypersensitivity reactions that may develop into serious reactions with dyspnoea, a fall in blood pressure and sometimes shock.

Not known: cross allergenicity with sulphonylureas, sulphonamides or related substances is possible. Metabolism and nutrition disorders Rare: hypoglycaemia. These hypoglycaemic reactions mostly occur immediately, may be severe and are not always easy to correct.

4). Eye disorders Not known: visual disturbances, transient, may occur especially on initiation of treatment, due to changes in blood glucose levels. Gastrointestinal disorders Rare: dysgeusia. Very rare: nausea, vomiting, diarrhoea, abdominal distension, abdominal discomfort and abdominal pain, which seldom lead to discontinuation of therapy.

g. with cholestasis and jaundice), hepatitis and hepatic failure. Not known: hepatic enzymes increased. Skin and subcutaneous tissue disorders Rare: alopecia. Not known: hypersensitivity reactions of the skin may occur as pruritus, rash, urticaria and photosensitivity.

Investigations Rare: weight gain. Very rare: blood sodium decrease. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Glimepiride must be taken shortly before or during a meal. When meals are taken at irregular hours or skipped altogether, treatment with glimepiride may lead to hypoglycaemia . Possible symptoms of hypoglycaemia include: headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, 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 up 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 can almost always be promptly controlled by immediate intake of carbohydrates (sugar). Artificial sweeteners have no effect. It is known from other sulphonylureas that, despite initially successful countermeasures, hypoglycaemia may recur.

Severe hypoglycaemia or prolonged hypoglycaemia, only temporarily controlled by the usual amounts of sugar, require immediate medical treatment and occasionally hospitalisation. 5). Treatment with glimepiride requires regular monitoring of glucose levels in blood and urine.

In addition determination of the proportion of glycosylated haemoglobin is recommended. Regular hepatic and haematological monitoring (especially leucocytes and thrombocytes) are required during treatment with glimepiride. g. ) a temporary switch to insulin may be indicated.

No experience has been gained concerning the use of glimepiride in patients with severe impairment of liver function or dialysis patients. In patients with severe impairment of renal or liver function change over to insulin is indicated.

3. Paediatric population There are no data available on the use of glimepiride in patients under 8 years of age. 2). The available data on safety and efficacy are insufficient in the paediatric population and therefore such use is not recommended.

Method of administration Tablets should be swallowed whole with some liquid. 1, - diabetes mellitus type 1, - diabetic coma, - ketoacidosis, - severe renal or hepatic function disorders. In case of severe renal or hepatic function disorders, a change over to insulin therapy is required.