GLYCEMAT

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 data or limited data (less than 300 pregnancies) concerning the use of gliclazide in pregnant women; data with other hypoglycaemic sulphonamides are limited.

Animal studies have not demonstrated a teratogenic effect of gliclazide (see section 5.3).

As a precautionary measure, it is preferable to avoid using gliclazide during pregnancy.

Glycaemic control should be achieved before conception to reduce the risk of congenital malformations due to poorly controlled diabetes.

Oral antidiabetics are not appropriate during pregnancy; insulin is then the treatment of choice. Switching from an oral antidiabetic to insulin is recommended when pregnancy is planned or as soon as it is discovered.

Breastfeeding

The excretion of gliclazide or its metabolites in human breast milk is unknown. Given the risk of neonatal hypoglycaemia, gliclazide is therefore contraindicated in breastfeeding women. A risk to newborns/infants cannot be excluded.

Fertility

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

gliclazide has no influence or a negligible influence on the ability to drive vehicles and use machines. However, patients should be made aware of the symptoms of hypoglycemia and exercise caution when driving vehicles or using machines, especially at the start of treatment.

Based on the clinical experience of gliclazide and other hypoglycaemic sulphonamides, the following adverse effects should be mentioned:

The frequencies are defined as follows:

Very frequent (≥ 1/10)

Frequent (≥ 1/100 to < 1/10)

Uncommon (≥ 1/1 000 to < 1/100)

Rare (≥ 1/10 000 to < 1/1 000)

Very rare (< 1/10 000)

Frequency unknown (cannot be estimated on the basis of available data).

Hematological and lymphatic system disorders

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

Metabolism and nutrition disorders

Frequent: the most frequent adverse effect with gliclazide is hypoglycaemia.

As with other hypoglycaemic sulphonamides, gliclazide treatment may frequently lead to hypoglycaemia in case of irregular meal times and notably if a meal is skipped. Possible symptoms are: headache, intense hunger, nausea, vomiting, fatigue, sleep disorders, agitation, aggressiveness, difficulties of concentration, decreased vigilance and decreased reactions, depression, confusion, vision and speech disorders, aphasia, tremors, paresis, sensory disorders, dizziness, sensation of helplessness, loss of self-control, delirium, convulsions, shallow breathing, bradycardia, drowsiness and loss of consciousness, which may lead to coma and a fatal outcome.

Signs of adrenergic counter-regulation may also be observed: hyperhidrosis, moist and cold skin, anxiety, tachycardia, hypertension, palpitations, angina and cardiac arrhythmias.

Symptoms generally disappear after ingestion of carbohydrates (sugars). But artificial sweeteners have no effect. Experience with other hypoglycaemic sulphonamides shows that hypoglycaemic episodes may recur despite initially effective measures.

In case of a severe or prolonged hypoglycaemic episode, even if temporarily controlled by sugar absorption, immediate medical treatment, or even hospitalisation, is required.

Eye disorders

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

Gastrointestinal disorders

Uncommon: gastrointestinal disorders, including abdominal pain, nausea, vomiting, dyspepsia, diarrhoea and constipation: these may be avoided or minimised if gliclazide is taken during breakfast.

Hepatobiliary disorders

Rare: elevation of liver enzymes (ASAT, ALAT, alkaline phosphatases), hepatitis (isolated cases). Discontinue treatment in case of appearance of cholestatic jaundice. These symptoms generally disappear after discontinuation of treatment.

Skin and subcutaneous tissue disorders

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

Class effects

As with other hypoglycaemic sulphonamides, the following adverse effects have been observed:

Cases of erythrocytopenia, agranulocytosis, haemolytic anaemia, pancytopenia, allergic vasculitis, hyponatraemia, 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 life-threatening prognosis.

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorisation of the medicinal product is important. It allows continuous monitoring of the benefit/risk ratio of the medicinal product. 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/ .