GLIMEWIN

GLIMEPIRIDE EG is indicated in the treatment of type 2 diabetes mellitus when diet, exercise and weight reduction alone are not sufficient.

The simultaneous intake of glimépiride with certain other medicines may lead to an undesirable increase or decrease in the hypoglycemic effect of glimépiride. Therefore, the intake of any other medicine should only take place with the agreement (or on prescription) of a doctor.

Glimépiride is metabolized by the cytochrome P450 isoenzyme 2C9 (CYP2C9). Its metabolism is modified by the concomitant administration of inducers (e.g., rifampicin) or inhibitors (e.g., fluconazole) of the CYP2C9 isoenzyme.

The results of an in vivo interaction study published in the literature show that fluconazole, one of the most potent inhibitors of the CYP2C9 isoenzyme, leads to a doubling of the area under the curve (AUC) of glimépiride.

Based on clinical experience with glimépiride and other sulfonylureas, the following interactions must be mentioned.

Potentiation of the hypoglycemic effect and consequently risk of hypoglycemia in certain cases in the event of simultaneous administration of one of the following medicines:

· phenylbutazone, azapropazone and oxyphenbutazone,

· insulin and oral antidiabetics, notably metformin,

· salicylates and para-aminosalicylic acid,

· anabolic steroids and androgens,

· chloramphenicol, certain long-acting sulfonamides, tetracyclines, quinolones and clarithromycin,

· coumarin anticoagulants,

· fenfluramine,

· fibrates,

· angiotensin-converting enzyme inhibitors,

· fluoxetine, monoamine oxidase inhibitors,

· allopurinol, probenecid, sulfinpyrazone,

· sympatholytics,

· cyclophosphamide, trophosphamide and iphosphamide,

· miconazole, fluconazole

· pentoxifylline (at high dose parenterally),

· tritoqualine.

Decrease of the hypoglycemic effect and consequently risk of hyperglycemia in the event of simultaneous administration of one of the following medicines:

· estrogens and progestogens,

· salidiuretics and thiazide diuretics,

· thyroid agents, glucocorticoids,

· phenothiazine derivatives, chlorpromazine,

· adrenaline and sympathomimetics,

· nicotinic acid (high doses) and nicotinic acid derivatives.

· laxatives (long-term use),

· phenytoin, diazoxide,

· glucagon, barbiturates and rifampicin,

· acetazolamide.

H2 antihistamines, beta-blockers, clonidine and reserpine may lead to a potentiation or a decrease of the hypoglycemic effect.

Under the influence of sympatholytics, notably beta-blockers, clonidine, guanethidine and reserpine, the signs of an adrenergic counter-regulation of hypoglycemia may be reduced or absent.

Alcohol consumption may potentiate or decrease the hypoglycemic effect of glimépiride in an unpredictable way.

Glimépiride may either potentiate or decrease the effects of coumarin derivatives.

Pregnancy

Risk related to diabetes

Abnormal blood glucose levels during pregnancy are associated with an increased incidence of congenital malformations and perinatal mortality. Blood glucose levels must therefore be closely monitored during pregnancy to reduce the teratogenic risk. Insulin therapy must therefore be initiated throughout pregnancy. 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.

Studies in animals have shown toxicity likely related to the pharmacological action (hypoglycemia) of glimépiride (see section 5.3).

Consequently, glimépiride must not be used throughout the duration of pregnancy.

If a pregnancy is planned or discovered during treatment with glimépiride, the treatment must be replaced as soon as possible by insulin therapy.

Breastfeeding

In humans, no data are available on the passage of glimépiride into breast milk. In rats, glimépiride is excreted in breast milk. Since other sulfonylureas are excreted in breast milk and given the risk of hypoglycemia in breastfed children, breastfeeding is contraindicated during treatment with glimépiride.

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

Concentration ability 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 particular importance (for example, driving vehicles or using machines).

It is necessary to inform patients to take all possible precautions to avoid hypoglycemia while driving vehicles. These precautions are particularly important in patients having little or no awareness of hypoglycemia warning symptoms or presenting frequent episodes of hypoglycemia. It is not recommended to drive a vehicle or use machines in these circumstances.

The following adverse effects are based on available data with glimépiride and other sulfonylureas:

Hematological and lymphatic system disorders

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

Immune system disorders

Very rare: leukocytoclastic vasculitis, mild hypersensitivity reactions that may progress to serious reactions accompanied by dyspnea, decreased blood pressure and sometimes shock.

Cross-allergy with sulfonylureas, sulfonamides and related substances is possible.

Metabolism and nutrition disorders

Rare: hypoglycemia.

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

Eye disorders

Changes in blood glucose levels may lead to transient visual disturbances, especially at the start of treatment.

Gastrointestinal disorders

Very rare: nausea, vomiting, diarrhea, abdominal distension, abdominal discomfort and abdominal pain which can rarely lead to discontinuation of treatment.

Hepatobiliary disorders

Elevation of liver enzymes.

Very rare: impairment of hepatic function (with e.g. cholestasis and jaundice), hepatitis and hepatic failure.

Skin and subcutaneous tissue disorders

Hypersensitivity reactions may occur, notably pruritus, urticaria, skin rashes and photosensitivity.

Investigations

Very rare: hyponatremia.

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorization 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 .