If hypoglycaemic coma is diagnosed or suspected, the patient should be given a rapid I.V. injection of 50 mL of concentrated glucose solution (20 to 30 %). This should be followed by continuous infusion of a more dilute glucose solution (10 %) at a rate that will maintain blood glucose levels above 1 g/L. Patients should be monitored closely and, depending on the patient's condition after this time, the doctor will decide if further monitoring is necessary.

Dialysis is of no benefit to patients due to the strong binding of gliclazide to proteins.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

 SULFONAMIDES, UREA DERIVATIVES

ATC code: A10BB09

Gliclazide is a hypoglycaemic sulphonylurea oral antidiabetic active substance differing from other related compounds by an N-containing heterocyclic ring with an endocyclic bond.

Gliclazide reduces blood glucose levels by stimulating insulin secretion from the β-cells of the islets of Langerhans. Increase in postprandial insulin and C-peptide secretion persists after two years of treatment.

In addition to these metabolic properties, gliclazide has haemovascular properties.

Effects on insulin release

In type 2 diabetics, gliclazide restores the first peak of insulin secretion in response to glucose and increases the second phase of insulin secretion. A significant increase in insulin response is seen in response to stimulation induced by a meal or glucose.

Haemovascular properties:

Gliclazide decreases microthrombosis by two mechanisms which may be involved in complications of diabetes:

• a partial inhibition of platelet aggregation and adhesion, with a decrease in the markers of platelet activation (beta thromboglobulin, thromboxane B2).

• an action on the vascular endothelium fibrinolytic activity with an increase in tPA activity.

5.2 Pharmacokinetic properties

 Plasma levels increase progressively during the first 6 hours, reaching a plateau which is maintained from the sixth to the twelfth hour after administration.

Intra-individual variability is low.

Gliclazide is completely absorbed. Food intake does not affect the rate or degree of absorption.

The relationship between the dose administered ranging up to 120 mg and the area under the concentration time curve is linear.

Plasma protein binding is approximately 95%.

Gliclazide is mainly metabolised in the liver and excreted in the urine: less than 1% of the unchanged form is found in the urine. No active metabolites have been detected in plasma.

The elimination half-life of gliclazide varies between 12 and 20 hours.

The volume of distribution is around 30 litres.

No clinically significant changes in pharmacokinetic parameters have been observed in elderly patients.

A single daily dose of Diamicron MR 30 mg maintains effective gliclazide plasma concentrations over 24 hours.

5.3 Preclinical safety data

 Preclinical data reveal no special hazards for humans based on conventional studies of repeated dose toxicity and genotoxicity. Long term carcinogenicity studies have not been done. No teratogenic changes have been shown in animal studies, but lower fœtal body weight was observed in animals receivi