GLYAZID

Non-insulin-dependent diabetes, in association with an appropriate diet, when this diet is not sufficient alone to restore glycemic control.

Pregnancy

There are no or limited data (less than 300 pregnancy outcomes) from the use of gliclazide in pregnant women; limited data are available with other sulfonylureas.

Animal studies do not indicate teratogenic effects (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of gliclazide during pregnancy.

Blood glucose control should be maintained before conception to reduce the risk of congenital malformations linked to uncontrolled diabetes.

During pregnancy, oral antidiabetic drugs are not appropriate, insulin is the first-line treatment for diabetes. It is recommended to switch from oral antidiabetic therapy to insulin when a pregnancy is planned or discovered.

Breastfeeding

It is unknown whether gliclazide or its metabolites are excreted in human milk. Given the risk of neonatal hypoglycaemia, gliclazide is therefore contraindicated in breastfeeding women.

A risk to the newborns/infants cannot be excluded.

Fertility

No effect on fertility or reproduction was observed in male and female rats (see section 5.3).

GLICLAZIDE BIOGARAN has no effect or a negligible effect on the ability to drive vehicles and use machines. However, patients should be made aware of the symptoms of hypoglycemia and should be cautious when driving and/or using machines, especially at the start of treatment.

According to clinical experience with gliclazide, the following adverse effects have been reported:

Hypoglycaemia

The most frequent adverse effect with gliclazide is hypoglycaemia.

As with other hypoglycaemic sulphonamides, treatment with GLICLAZIDE BIOGARAN can lead to hypoglycaemia, particularly in the case of meals taken at irregular intervals and in the case of skipping a meal.

Possible symptoms are: headache, intense hunger, nausea, vomiting, fatigue, sleep disturbances, agitation, aggressiveness, decreased concentration, vigilance and reactions, depression, confusion, visual disturbances and speech disturbances, aphasia, tremors, paresis, sensory disturbances, dizziness, sensation of helplessness, loss of self-control, delirium, convulsions, shallow breathing, bradycardia, drowsiness, loss of consciousness or even coma and can lead to a fatal outcome.

On the other hand, signs of adrenergic counter-regulation may be observed: hyperhidrosis, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina and cardiac arrhythmia.

Symptoms generally disappear after intake of carbohydrates (glucides). On the other hand, artificial sweeteners have no effect. Experience with other hypoglycaemic sulphonamides shows that despite initially effective measures, hypoglycaemia may recur.

In case of severe or prolonged hypoglycaemia, even if temporarily controlled by sugar absorption, immediate medical treatment or even hospitalisation may be necessary.

Other adverse effects

Gastrointestinal disorders, such as abdominal pain, nausea, vomiting, dyspepsia, diarrhoea, constipation, have been reported; they can be avoided or reduced if the treatment is taken during a meal or by splitting the doses.

The following adverse effects have been reported less frequently:

· cutaneous-mucosal eruptions: rash, pruritus, urticaria, angioedema, erythema, maculopapular eruptions, bullous reactions (such as Stevens-Johnson Syndrome and toxic epidermal necrolysis and bullous autoimmune diseases) and exceptionally, DRESS syndrome (drug eruption with eosinophilia and systemic symptoms);

· haematological disorders: they are rare and include anaemia, leucopenia, thrombocytopenia, granulocytopenia. These abnormalities are generally reversible upon discontinuation of treatment;

· hepatobiliary disorders: elevation of liver enzymes (ASAT, ALAT, alkaline phosphatases), hepatitis (isolated cases). Discontinue treatment in case of appearance of cholestatic jaundice. As a general rule, these symptoms regress upon discontinuation of treatment;

· visual disturbances: transient visual disturbances due to variations in blood glucose may occur, particularly during the initiation of treatment.

Class effect

As with other hypoglycemic sulfamides, the following adverse effects have been observed: erythrocytopenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, hyponatremia, increase in liver enzyme levels, hepatic insufficiency (cholestasis and jaundice) or even hepatitis which regressed upon discontinuation of treatment; only a few cases led to hepatic insufficiency involving the vital prognosis.

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorization of the medicine is important. It allows for continuous monitoring of the benefit/risk ratio of the medicine. Healthcare professionals report any suspected adverse effect via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/.