AMAREL

This medicine is indicated in diabetes mellitus (type 2), when diet, physical exercise and weight reduction alone are not sufficient to restore glycemic control.

Pregnancy

Risk related to diabetes

Abnormal blood glucose during pregnancy is associated with an increased incidence of congenital malformations and perinatal mortality. Blood glucose must be closely monitored during pregnancy to reduce the teratogenic risk. Diabetes in pregnant women requires insulin therapy. Patients planning a pregnancy should inform their doctor.

Risk related to glimépiride

There are currently no sufficient data on the use of glimépiride in pregnant women. Animal studies have highlighted reproductive toxicity probably related to the pharmacological action (hypoglycemia) of glimépiride ( see section 5.3 ).

As a consequence, glimépiride should not be used during the entire duration of pregnancy.

If a pregnancy is planned or in case of incidental discovery of a pregnancy during treatment with glimépiride, the treatment must be replaced as quickly as possible by insulin.

Breastfeeding

In women, no data concerning the passage of glimépiride into breast milk is available. In rats, glimépiride is excreted in breast milk. Given that other sulfonylureas are excreted in breast milk and considering the risk of neonatal hypoglycemia, breastfeeding is not recommended in case of treatment with this medicine.

Fertility

No data on fertility is available.

The effects on the ability to drive vehicles and use machines have not been studied.

Concentration abilities and reflexes may be decreased in case of hypoglycemia or hyperglycemia or, for example, visual disturbances. This may represent a risk in situations where these faculties are of primary importance (for example driving a car or using machines).

Patients must be informed of the precautions to take before driving to avoid hypoglycemia, particularly if the precursor symptoms of hypoglycemia are absent or decreased or if episodes of hypoglycemia are frequent. It is not recommended to drive a vehicle or use machines in these circumstances.

The following adverse effects, reported during clinical studies and based on available data with glimépiride and other sulfonylureas, are listed below by organ system class and in descending order of frequency (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; unknown frequency (cannot be estimated on the basis of available data)).

Hematological disorders

· Rare: thrombocytopenia, leucopenia, neutropenia, agranulocytosis, erythrocytopenia, hemolytic anemia and pancytopenia, generally reversible upon discontinuation of treatment.

· Unknown frequency: severe thrombocytopenia (platelet count < 10 000/mm 3 or 10 giga/l) and thrombocytopenic purpura.

Immune system disorders

· Very rare: leukocytoclastic vasculitis, moderate hypersensitivity reactions which may progress to more serious reactions with dyspnea, blood pressure drop or even shock.

· Unknown frequency: cross-allergy with sulfonylureas, sulphonamides and their derivatives is possible.

Metabolic and nutritional disorders

· Rare: hypoglycaemias.

These hypoglycaemias most often appear at the onset, can be severe and sometimes difficult to correct. The occurrence of these hypoglycaemias depends, as for any hypoglycaemic treatment, on individual factors such as dietary habits and the dose of the hypoglycaemic (see section 4.4).

Visual disorders

· Unknown frequency: glycemic changes may lead to transient visual disturbances, especially at the start of treatment.

Gastrointestinal disorders

· Very rare: nausea, vomiting, diarrhoea, abdominal distension, abdominal discomfort and abdominal pains, which can exceptionally lead to discontinuation of treatment.

· Rare: dysgeusia.

Hepatobiliary disorders

· Unknown frequency: elevation of liver enzymes.

· Very rare: impairment of hepatic function (with for example cholestasis and jaundice), or even hepatitis which may progress to hepatic failure.

Skin disorders

· Unknown frequency: hypersensitivity reactions (pruritus, urticaria, skin rashes and photosensitivity) may occur.

· Rare: alopecia.

Investigations

· Very rare: hyponatraemia.

· Rare: weight gain.

Reporting of suspected adverse effects

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