Indication: Non-insulin-dependent (type II) diabetes, whenever blood sugar levels cannot be controlled adequately by diet, physical exercise and weight reduction alone.

Dosage: In principle, the dosage of Glio is governed by the desired blood sugar level. The dosage of glimepiride must be the lowest which is sufficient to achieve the desired metabolic control.

Treatment with Glio must be initiated and monitored by a physician. Glio must be taken at the times and in the doses prescribed. Mistakes, e.g. forgetting to take a dose, must never be corrected by subsequently taking a larger dose. Measures for dealing with such mistakes (in particular forgetting a dose or skipping a meal) or situations where a dose cannot be taken at the prescribed time must be discussed and agreed between physician and patient beforehand. A physician must be notified immediately if the dose taken is too high, or an extra dose has been taken.

The initial and the maintenance doses are set based on the results of regular checks of glucose in blood and urine. Monitoring of glucose levels in blood and urine also serves to detect either primary or secondary failure of therapy.

Initial dose and dose titration: The usual initial dose is 1mg Glio once daily. If necessary, the daily dose can be increased. Any increase should be based on regular blood sugar monitoring, and should be gradual, i.e., at intervals of one to two weeks, and carried out stepwise, as follows: 1mg - 2mg - 3mg - 4mg - 6mg, and - in exceptional cases 8mg.

Dose range in patients with well-controlled diabetes: The usual dose range in patients with well controlled diabetes is 1 to 4 mg Glio daily. Only some patients benefit from daily doses of more than 6 mg.

Distribution of doses: Timing and distribution of doses are decided by the physician, in consideration of the patient's current life-style. Normally, a single daily dose of Glio is sufficient. This should be taken immediately before a substantial breakfast or- if none is taken-immediately before the first main meal. It is very important not to skip meals after taking Glio.

Secondary dosage adjustment: As the control of diabetes improves, sensitivity to insulin increases; therefore, glimepiride requirements may fall as treatment proceeds. To avoid hypoglycaemia, a timely dose reduction or cessation of Glio therapy must be considered.

A dose adjustment must also be considered whenever the patient's weight or life-style changes, or other factors arise which cause an increased susceptibility to hypo - or hyperglycaemia (see under “Special warnings and precautions”).

Duration of treatment: Treatment with Glio is normally a long-term therapy.

Changeover from other oral antlialliduatics to Glio: There is no exact dosage relationship between Glio and other oral blood-sugar-lowering agents, When substituting Glio for other such agents, the initial daily dose is 1 mg; this applies even in changeovers from the maximum dose of another oral blood-sugar-lowering agent. Any Glio dose increase should be in accordance with guidelines given above in "Initial dose and dose titration".

Consideration must be given to the potency and duration of action of the previous blood-sugar-lowering agent. It may be necessary to interrupt treatment to avoid additive effects, which would increase the risk of hypoglycaemia.

Administration: Glio tablets must be swallowed without chewing and with sufficient amounts of liquid (approx. 1/2 glass).

Contraindications: Glio is not suitable for the treatment of insulin-dependent (type 1) diabetes mellitus (e.g., for the treatment of diabetics with a history of ketoacidosis), of diabetic ketoacidosis, or of diabetic precoma or coma.
Glio must not be used in patients hypersensitive to glimepiride, other sulfonylureas, other suffonamides, or any of the excipients (risk of hypersensitivity reactions).

No experience has been gained concerning the use of Glio in patients with severe impairment of liver function and dialysis patients. In patients with severe impairment of renal or hepatic function, a changeover to insulin is indicated, not least to achieve optimal metabolic control.

Use in pregnancy and lactation: To avoid risk of harm to the child, Glio must not be taken during pregnancy, a changeover to insulin is necessary. Patients planning a pregnancy must inform their physician, and should change over to insulin.

Ingestion of glimepiride with the breast milk may harm the child. Therefore, Glio must not be taken by breast-feeding women. Either a changeover to insulin or a complete discontinuation of breast-feeding is necessary.

Special warnings and precautions:
To achieve optimal control of blood sugar, a correct diet, regular and sufficient physical exercise and, if necessary, reduction of body weight are just as important as regular intake of Glio. Clinical signs of insufficiently lowered blood sugar (hyperglycaemia) are, e.g., increased urinary frequency, intense thirst, dryness of the mouth, and dry skin.

When starting treatment, the patient must be informed about the effects and risks of Glio and about its role in conjunction with dietary measures and physical exercise; the importance of adequate co-operation must also be stressed.

In the initial weeks of treatment, the risk of hypoglycaemia may be increased and necessitates especially careful monitoring.

Factors favouring hypoglycaemia include: Unwillingness or
(more commonly in older Patients) incapacity of the patient to cooperate,
- under- nutrition, irregular mealtimes, or skipped meals,
- imbalance between physical exertion and carbohydrate intake, - alterations of diet,
- consumption of alcohol, especially in combination with skipped meals, - impaired renal function.
- severe impairment of liver function,
- overdosage with Glio
- certain uncompensated disorders of the endocrine system affecting carbohydrate metabolism or counter-regulation of hypoglycaemia (as for example in certain disorders of thyroid function and in anterior pituitary or adrenocortical insufficiency),
- concurrent administration of certain other medicines (see "Interactions")
The physician must be informed about such factors and about hypoglycaemia episodes, since these require particularly careful monitoring.

If such risk factors for hypoglycaemia are present, it may be necessary to adjust the dosage of Glio or the entire therapy. This also applies whenever illness occurs during therapy or the patient's life-style changes. Those symptoms of hypoglycaemia which reflect the body's adrenergic counter-regulation (see under "Adverse effects") may be milder or absent in those situations where hypoglycaemia develops gradually, in the elderly, and in patients with autonomic neuropathy or those receiving concurrent treatment with beta-blockers, clonidine, reserpine. guanethidine, or other sympatholytic drugs.

Hypoglycaemia can almost always be promptly controlled by immediate intake of carbohydrates (glucose or sugar, e.g., in the form of sugar lumps, sugar-sweetened fruit juice or sugar-sweetened tea). For this purpose, patients must carry a minimum of 20 grams of glucose with them at all times. They may require the assistance of other persons to avoid complications. Artificial sweeteners are ineffective in controlling hypoglycaemia.

It is known from other sulfonylureas that, despite initially successful countermeasures, hypoglycaemia may reoccur. Therefore, continued close observation is necessary. Severe hypoglycaemia requires, in addition, immediate treatment and follow-up by a physician and, in some circumstances, hospitalization.
If treated by different physicians (e.g., hospital stay, after an accident, illness while on holiday), the patients must inform them of their diabetic condition and previous treatment.

In exceptional stress situations (e.g., trauma, surgery, infections with fever) blood sugar control may deteriorate, and a temporary change to insulin may be necessary.

During treatment with Glio, glucose levels in blood and urine must be checked regularly, as should, additionally, the proportion of glycated haemoglobin.

Alertness and reactions may be impaired due to hypo- or hypoglycaemia, especially when beginning or after altering treatment, or when Glio is not taken regularly, This may, for example, affect the ability to operate a vehicle or machinery.

Interactions: Patients who take or discontinue taking certain other medicines while undergoing treatment with Glio may experience changes in blood sugar control.

Based on experience with glimepiride and on what is known of other sulfonylureas, the following interactions must be considered:

- Potentiation of the blood-sugar-lowering effect and, thus, in some instances hypoglycaernia may occur when one of the following medicines is taken, for example: insulin and other, oral Antidiabetics, ACE inhibitors, allopurinol, anabolic steroids and male sex hormones; chloramphenicol, cournarin derivatives, cyclophosphamide, disopyramide, fenfluramine, fenyramidol, fibrates, fluoxetine, guanethidine, ifosfamide, MAO-inhibitors, miconazole, para-aminosalicylic acid, pentoxifylline (high dose parenteral), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpyrazone, sulfonamides, tetracyclines, tritoqualine, trofosfamide.

Weakening of the blood-sugar-lowering effect and, thus, raised blood sugar levels may occur when one of the following medicines is taken, for example: acetazolamide, barbiturates, corticosteroids, diazoxide, diuretics, epinephrine (adrenaline) and other sympathomimetic agents, glucagon, laxatives (after protracted use), nicotinic acid (in high doses). oestrogens and progestogens, phenothiazines, phenytoin, rifampicin, thyroid hormones.

H2 receptor antagonists, clonidine and reserpine may lead to either potentiation or weakening of the blood-sugar-lowering effect.

Beta-blockers decrease glucose tolerance. In patients with diabetes mellitus, this may lead to deterioration of metabolic control. In addition, beta-blockers may increase the tendency to hypoglycaemia (due to impaired counter-regulation).

Under the influence of sympatholytic drugs such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation to hypoglycaemia may be reduced or absent.

Both acute and chronic alcohol intake may potentiate or weaken the blood-sugar-lowering action of Glio unpredictably.

The effect of coumarin derivatives may be potentiated or weakened.
Adverse effects:
Based on experience with Glimepiride and on what is known of other sulfonylureas, the following adverse effects must be considered.

Hypoglycaemia: As a result of the blood-sugar-lowering action of Glio, hypoglycaemia may occur, and may also be prolonged.

Possible symptoms of hypoglycaemia include headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressiveness, impaired concentration, unpaired alertness and reactions, depression, confusion. speech disorders, aphasia, visual disorders. tremor, pareses, 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. Once hypoglycaemia has been corrected, all of the above-mentioned symptoms almost always subside.

Eyes: Especially at the start of treatment, temporary visual impairment may occur due to the change in blood sugar levels.

Digestive tract: Occasionally, gastrointestinal symptoms such as the following may occur: nausea, vomiting, sensations of pressure or fullness in the epigastrium, abdominal pain, and diarrhoea.

In isolated cases, liver enzymes levels may increase, and impairment of liver function (e.g., with cholestasis and jaundice) and hepatitis may develop, possibly resulting in liver failure.

Blood: Severe changes in the blood picture may occur: Rarely, thrombopenia and, in isolated cases, leucopenia, haemolytic anaemia or, e.g., erythrocytopenia, granulocytopenia, agranuloytosis, and pancytopenia (e.g.,due to myelosuppression) may develop.

Other adverse reactions: Occasionally, allergic or pseudoallergic reactions may occur, e.g,. in the form of itching, urticaria or rashes. Such reactions are mild, but may become more serious and be accompanied by dyspnoea and a fall in blood pressure, sometimes progressing to shock. if urticaria occurs, a physician must be notified immediately.

In isolated cases, the following may occur: allergic vasculitis, hypersensitivity of the skin to light, and a decrease in serum sodium.

Please consult a physician if you notice any of the adverse effects listed in this package insert or any other undesired effects or unexpected changes.

Since some adverse effects, such as severe hypoglycaemia, certain changes in blood picture, severe allergic or pseudoallergic reactions, or liver failure, may under certain circumstances become life-threatening, it is essential that, if sudden or severe reactions do occur, you inform a physician at once, and on no account continue taking the drug without a physician's express guidance.