DIAMICRON

Non-insulin-dependent diabetes (type 2) in adults, when diet, exercise and weight reduction alone are not sufficient to achieve glycemic control.

Pregnancy

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

Animal studies have not shown teratogenic effects of gliclazide (see section 5.3).

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

Control of diabetes must be achieved before conception in order to reduce the risk of congenital malformations due to uncontrolled diabetes.

During pregnancy, oral antidiabetic drugs are not appropriate, insulin is the treatment of choice 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 contraindicated in breastfeeding women. A risk to the newborns/infants cannot be excluded.

Fertility

No effect on fertility or reproductive performance was demonstrated in male and female rats (see section 5.3).

GLICLAZIDE SANDOZ has no effect or only a negligible effect on the ability to drive vehicles and use machines. However, patients should be informed that their concentration could be affected if their diabetes is not satisfactorily controlled, especially at the start of treatment (see section 4.4).

Based on clinical experience with gliclazide, the following adverse effects have been reported:

Adverse effects are listed according to frequency and system organ class (SOC). Frequency categories are defined as follows:

· Very common ( ≥ 1/10 ) ,

· Common ( ≥ 1/100 to < 1/10 ) ,

· Uncommon ( ≥ 1/1000 to < 1/100 ) ,

· Rare ( ≥ 1/10 0 0 0 to < 1/1 0 00 ) ,

· Very rare ( < 1/ 1 0 0 00) ,

· Not known (cannot be estimated from the available data).

Blood and lymphatic system disorders:

Rare: haematological changes which may include anaemia, leucopenia, thrombocytopenia, granulocytopenia. These abnormalities are generally reversible upon discontinuation of treatment.

Metabolism and nutrition disorders:

Not known: hypoglycaemia.

Eye disorders:

Not known: transient visual disturbances.

These disturbances may appear particularly at the beginning of treatment, due to changes in blood glucose levels.

Gastrointestinal disorders:

Not known: abdominal pain, nausea, vomiting, dyspepsia, diarrhoea and constipation.

These symptoms may appear, they can however be avoided or minimised if gliclazide is taken during breakfast.

Hepatobiliary disorders:

Not known: raised liver enzyme levels (AST, ALT, alkaline phosphatase), hepatitis (isolated cases). Discontinue treatment if cholestatic jaundice appears. In general, these symptoms regress upon discontinuation of treatment.

Mucocutaneous eruptions :

Not known: rash, pruritus, urticaria, angioedema, erythema, maculopapular rashes, bullous reactions (such as Stevens-Johnson syndrome and toxic epidermal necrolysis and bullous autoimmune diseases), and exceptionally, drug rash with eosinophilia and systemic symptoms (DRESS).

Class effects:

As for other sulphonylureas, the following adverse effects have been observed: erythrocytopenia, agranulocytosis, haemolytic anaemia, pancytopenia, allergic vasculitis, hyponatraemia, elevated liver enzyme levels, hepatic impairment (cholestasis and jaundice) and even hepatitis which have regressed upon discontinuation of treatment; only a few cases have led to life-threatening hepatic failure.

Description of selected adverse effects

Hypoglycaemia:

As for other sulphonylureas, treatment with GLICLAZIDE SANDOZ can cause hypoglycaemia, especially if meals are taken at irregular intervals and in case of skipping a meal. Possible symptoms are: headache, intense hunger, nausea, vomiting, fatigue, sleep disorders, agitation, aggression, poor concentration, reduced alertness and reaction, depression, confusion, visual and speech disorders, aphasia, tremor, paresis, sensory disorders, dizziness, feeling of helplessness, loss of self-control, delirium, convulsions, shallow respiration, bradycardia, drowsiness, loss of consciousness or even coma and potentially leading to a fatal outcome.

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

Symptoms generally disappear after intake of carbohydrates (sugars). On the other hand, artificial sweeteners have no effect. Experience with other sulfonylurea hypoglycemic agents shows that despite initially effective measures, hypoglycemia may recur.

In case of severe or prolonged hypoglycemia, even if temporarily controlled by sugar intake, immediate medical treatment or even hospitalization may be required.

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorization of the medicine is important. It allows 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 network of Regional Pharmacovigilance Centres - Website: www.signalement-sante.gouv.fr .