COMPOSITION: Each tablet contains 80 mg of gliclazide
PHARMACOLOGICAL CLASSIFICATION: A 21.2 Oral hypoglycaemics
PHARMACOLOGICAL ACTION: Gliclazide is a sulphonylurea hypoglycaemic agent which stimulates the secretion of insulin by the beta cells of the pancreas.
In addition to this pancreatic action it has been demonstrated that gliclazide administration may improve the metabolic utilisation of glucose at a peripheral level. Gliclazide is readily absorbed from the gastro-intestinal tract. It is extensively bound to plasma proteins. The half-life is about 10 to 12 hours. Gliclazide is extensively metabolised in the liver to metabolites without significant hypoglycaemic activity. Metabolites and a small amount of unchanged medicine are excreted in the urine.
INDICATIONS: Treatment of non-insulin-dependent diabetes mellitus where dietary management alone has been insufficient.
CONTRA-INDICATIONS: Hypersensitivity to sulphonylureas and related substances. Not to be used for: juvenile onset diabetes; diabetes complicated by ketosis or acidosis; diabetics undergoing surgery, after severe trauma or during infections; diabetic precoma and coma; severe renal or hepatic insufficiency; porphyria, hyperthyroidism, pregnancy and lactation.
The administration of oral hypoglycaemics may be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet and insulin.
A reduction in dosage may be necessary in patients with renal dysfunction.
Effects on Ability to Drive and Use Machines: Patients should be informed that their concentration may be affected if their diabetes is not satisfactorily controlled, especially at the beginning of treatment.
DOSAGE AND DIRECTIONS FOR USE: Adults: The total daily dose may vary from 40-320 mg. The dose should be adjusted according to the individual's response, commencing with 40-80 mg daily and increasing until adequate control is achieved. A single dose should not exceed 160 mg. When higher doses are required, gliclazide 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 alone, additional therapy may be required. Elderly: Plasma clearance of gliclazide is not altered in the elderly and steady state plasma levels can therefore be expected to be similar to those in adults under 65 years. Clinical experience in the elderly to date shows that gliclazide is effective and well tolerated. Care should be exercised however, when prescribing sulphonylureas in the elderly due to a possible age-related increased risk of hypoglycaemia. Children: Gliclazide, as with other sulphonylureas, is not indicated for the treatment of juvenile onset diabetes mellitus.
SIDE EFFECTS AND SPECIAL PRECAUTIONS:
Hypoglycaemia: All sulphonylurea medicines are capable of producing moderate to severe hypoglycaemia, particularly in the following conditions: in patients controlled by diet alone; in case of accidental overdose; when calorie or glucose intake is deficient; in patients with hepatic and/or renal impairment, however, in long-term clinical trials, patients with renal insufficiency have been treated satisfactorily, using gliclazide at reduced doses. In order to reduce the risk of hypoglycaemia it is therefore recommended: to initiate treatment for non-insulin diabetics by diet alone, if this is possible; - to take into account the age of the patient: blood sugar levels not strictly controlled by diet alone might be acceptable in the elderly; to adjust the dose of gliclazide according to the blood glucose response and to the 24 hour urinary glucose during the first days of treatment. Dosage adjustments may be necessary, on the occurrence of mild symptoms of hypoglycaemia (sweating, pallor, hunger pangs, tachycardia, sensation of malaise). Such findings should be treated with oral glucose and adjustments made in medicine dosage and/or meal patterns; on the occurrence of severe hypoglycaemic reactions (coma or neurological impairment, see overdosage), loss of control of blood glucose (hyperglycaemia). When a patient stabilised on any diabetic regimen is exposed to stress such as fever, trauma, infection or surgery, a loss of control may occur. At such times it may be necessary to progressively increase the dosage of gliclazide and if this is insufficient, to discontinue the treatment of gliclazide and to administer insulin.
Abnormalities of hepatic function may occur during gliclazide therapy. There are less frequent reports of hepatic failure, hepatitis and jaundice following treatment with gliclazide.
Mild gastrointestinal disturbances including nausea, dyspepsia, diarrhoea and constipation have been reported, but this type of adverse reaction can be avoided if gliclazide is taken with a meal.
Weight changes: most studies report no significant overall change in weight.
Skin reactions including rash, pruritus, erythema, bullous eruption, blood dyscrasia including anaemia, leucopenia, thrombocytopenia and granulocytopenia have been observed during treatment with gliclazide. Facial flushing may develop in patients receiving sulphonylureas.
Care should be exercised in patients with hepatic and/or renal impairment and a small starting dose should be used with careful patient monitoring. As with other sulphonylureas, hypoglycaemia will occur if the patient's dietary intake is reduced or if they are receiving a larger dose of gliclazide than is required.
Interactions with Other Medicaments: Care should be taken when using gliclazide with medicines which are known to alter the diabetic state or potentiate the medicine's action. The hypoglycaemic effect of gliclazide may be potentiated by phenylbutazone, salicylates, sulphonamides, coumarin derivatives; monoamine oxidase inhibitors, beta-adrenergic blocking agents, tetracycline compounds, chloramphenicol, clofibrate, disopyramide, oral forms of miconazole and cimetidine. The hypoglycaemic action of Ziclin may be diminished by corticosteroids, oral contraceptives, thiazide diuretics, phenothiazine derivatives, thyroid hormones and abuse of laxatives.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: Hypoglycaemic reactions should be treated by gastric lavage and correction of the hypoglycaemia by the administration of glucose. The patient's blood sugar should be continuously monitored until the effect of the medicine has ceased. Hypoglycaemic reactions should alert the physician to the possibility of renal dysfunction.
IDENTIFICATION: White, circular, flat bevelled-edge uncoated tablets impressed with "G" and "Z" on either side of a central division line on one side and COXon the reverse.
PRESENTATION: Packs of 60 and 500 tablets in securitainers or blister packs.
STORAGE INSTRUCTIONS: Store below 25°C in a dry place. Keep out of reach of children.
REGISTRATION NUMBER: 31/21.2/0687
NAME AND BUSINESS ADDRESS OF THE APPLICANT: Knoll Pharmaceuticals SA (Pty) Ltd.
Cnr. George Rd. and Sixteenth Str.
DATE OF PUBLICATION OF THIS PACKAGE INSERT: 8 April 1997