GLIBENCLAMIDE

Glibenclamide should be taken with or immediately after food. There were no changes to the reference product information in the report period. The total daily dosage is preferably given as a single dose at breakfast or with the first main meal, but due consideration should be given to the patients meal habits and daily activity when apportioning dosage.

5mg in debilitated or elderly patients. 5mg at intervals of one week, or as directed by the clinician. The total daily dosage rarely exceeds 15mg and increasing the daily dosage above this does not generally produce any additional effect.

Transfer from other oral sulphonylureas:

Transfer to Glibenclamide can usually be carried out without any break in therapy. Treatment is commenced with the equivalent dose of glibenclamide without exceeding an initial dose of 10mg. If response is inadequate, the dose can be raised in a stepwise fashion to 15mg daily.

One 5mg tablet of glibenclamide is approximately equivalent to 1g tolbutamine or glymidine, 250mg chlorpropamide or tolazamide, 500mg acetohexamide, 25mg glibornuride or 5mg glipizide. 5mg tablet. 5mg to achieve control.

Combination with biguanides:

If adequate control is not possible with diet and 15mg of glibenclamide, control may be established by combined administration of glibenclamide and a biguanide derivative.

Changeover from insulin:

While it is appreciated that most patients who are on insulin therapy will continue to need it, there may be few patients, particularly those on low dosage, who will remain stabilised if transferred to Glibenclamide.

Patients aged 65 years and older:

Starting and maintenance doses of glibenclamide must be carefully adjusted to reduce the risk of hypoglycaemia. 4).

Children:

No dosage recommendations can be made for the administration of Glibenclamide to children.

Method of administration:

Oral

Blood disorders Potentially life-threatening changes in the blood picture may occur. g. g. due to myelosupression), haemolytic anaemia, erythrocytopenia, granulocytopenia. Immune system disorders Hypersensitivity including dyspnoea and swelling of the lips, face, throat or tongue.

Endocrine disorders Infrequently a syndrome of inappropriate secretion of antidiuretic hormone may be induced which may give rise to reduced serum sodium levels.

Metabolism and nutritional disorders:

Hypoglycaemia Hypoglycaemia, sometimes prolonged and even life-threatening, may occur as a result of the blood glucose lowering action of Glibenclamide. Possible symptoms of hypoglycaemia include headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressiveness, impaired concentration, 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.

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.

The symptoms of hypoglycaemia nearly always subside when hypoglycaemia is corrected. Increased appetite and weight gain may occur. Eye disorders Temporary visual impairment. Gastrointestinal disorders Gastrointestinal symptoms such as nausea, vomiting, heartburn, anorexia, metallic taste, sensations of pressure or fullness in the epigastrium, abdominal pain, diarrhoea may occur.

g. with cholestatic jaundice and hepatitis which can regress after withdrawal of Glibenclamide, although they may lead to life-threatening liver failure). g. in the form of itching or rashes. In isolated cases, photosensitivity may occur, and mild reactions in the form of urticaria may develop into serious and even life-threatening reactions.

Treatment with sulphonylureas has been associated with occasional disturbances of liver function and cholestatic jaundice. If clinical jaundice occurs, glibenclamide should be discontinued.

Care is necessary in the following patients: • Elderly patients:

Age 65 years and older has been identified as a risk factor for hypoglycaemia in patients treated with sulfonylureas. Hypoglycaemia can be difficult to recognise in the elderly. 2). • Debilitated or malnourished patients who are particularly susceptible to the hypoglycaemic effects of sulphonylureas • During excessive exercise as hypoglycaemia may be provoked.

• Patients with mild to moderate renal impairment, in long-term clinical trials with renal insufficiency have been treated satisfactorily using glibenclamide at reduced doses with careful patient monitoring. • Patients with adrenal or pituitary insufficiency.

Glibenclamide should not be used in the following groups: i. 1. ii. Those patients who have or have ever had diabetic ketoacidosis or diabetic coma/precoma. iii. Insulin dependent diabetes mellitus. iv. The treatment of juvenile or unstable diabetes.

v. Severe impairment of renal, hepatic, thyroid or adrenocortical function. vi. Circumstances of unusual stress such as surgery, severe infection and trauma. vii. Pregnancy. viii. Breast feeding women. ix. In patients treated with bosentan.

x. Patients with porphyria.