Glibenclamide + Metformin - instructions for use, dose, side effects, contraindications

The sulfonylurea compound II generation, by reducing the threshold of stimulation of pancreatic β-cells by glucose stimulates the secretion of insulin, increases its release and the degree of binding to target cells. The hypoglycemic effect depends on the number of functioning β-cells.

Suppresses platelet aggregation, has fibrinolytic, hypolipidemic and weak diuretic action.

Metformin

Reduces the absorption of glucose from the intestine and enhances its peripheral utilization, increasing the sensitivity of tissues to insulin, inhibits gluconeogenesis in the liver.Reduces the level of low density lipoproteins and triglycerides in blood plasma. Does not cause hypoglycemic reactions, does not affect the secretion of insulin β-cells of the pancreas. By suppressing the inhibitor of the tissue plasminogen activator, it has a fibrinolytic effect. Stabilizes or reduces body weight.

Pharmacokinetics:

Glibenclamide

After oral intake absorbed in the gastrointestinal tract by 90%. The maximum concentration in the blood plasma is reached after 2 hours. The connection with plasma proteins is 95%.

The maximum therapeutic effect develops 7-8 hours after admission. The duration of action is 12 hours. Metabolism in the liver.

The half-life is 2-10 hours. Elimination by the kidneys and with feces.

Metformin

After oral administration, up to 50-60% is absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is achieved after 2.5 hours. Does not bind to plasma proteins.

It accumulates in muscle tissue, salivary glands, kidneys and liver.

The half-life is 6 hours. Elimination of the kidneys unchanged.

Indications:

It is used for the treatment of non-insulin dependent diabetes mellitus.

ICD-10

IV.E10-E14.E11 Non-insulin-dependent diabetes mellitus

Contraindications:

Diabetes I type (insulin-dependent), coma, ketoacidosis, individual intolerance.

Carefully:Concomitant diseases of the endocrine system affecting carbohydrate metabolism: adenohypophysis and adrenocortical insufficiency, dysfunction of the thyroid gland.

Pregnancy and lactation:

Recommendations for FDA - Category C. Contraindicated in pregnancy and lactation.

Dosing and Administration:

Replacement of previous combination therapy with metformin and glibenclamide: the initial dose should not exceed the daily dose of glibenclamide (or the equivalent dose of another sulfonylurea drug) and metformin taken earlier. Every 2 or more weeks after the start of treatment, the dose of the drug is adjusted depending on the level of glycemia.

Inside, during meals, in an initial dose of 2.5 mg glibenclamide and 500 mg metformin (1 tablet) 2 times a day. It is possible to increase or decrease the dose (depending on the level of glucose in the blood).

The highest daily dose (2.5 or 5 mg glibenclamide and 500 mg metformin): 4 tablets.

The highest single dose (2.5 mg glibenclamide and 500 mg metformin): 1 tablet.

Side effects:

Glibenclamide

Hemopoietic system: rarely - thrombocytopenia, erythrocytopenia, granulocytopenia, hemolytic anemia.

Digestive system: dyspepsia, nausea, vomiting, diarrhea, hepatitis, cholestatic jaundice.

Musculoskeletal system: arthralgia.

Dermatological reactions: a rash.

Urinary system: proteinuria.

Metformin

Central and peripheral nervous system: insomnia, paresthesia, emotional lability.

The cardiovascular system: tachycardia.

Digestive system: loss of appetite, constipation, sometimes - exacerbation of hemorrhoids.

Musculoskeletal system: symptoms of lactic acidosis - cramps of the calf muscles.

Allergic reactions.

Overdose:

Development of hypoglycemia.

Treatment: sugar inside, with loss of consciousness - intravenous injection of 40% dextrose solution.

Interaction:

Increase the concentration of the drug in the blood plasma inhibitors of the isoenzyme 3A4 cytochrome P450: ketoconazole, ciclosporin, erythromycin.

The control of a level of a glycemia at simultaneous application of a preparation with thiazide diuretics decreases,blockers of slow calcium channels, lithium preparations, glucocorticoids, isoniazid, sympathomimetics, nicotinic acid, phenytoin, phenothiazines, thyroid hormones.

With simultaneous application with furosemide, a dose reduction is necessary.

The use of alcohol (especially on an empty stomach) during treatment causes disulfiram-like reactions, contributes to an increase in the concentration of lactic acid in the blood plasma and the risk of hypoglycemia.

Special instructions:

During pregnancy and lactation, as well as in conditions after injuries and extensive operations, the drug is canceled, the treatment of diabetes continues with injections of insulin.

Instructions

Glibenclamide + Metformin (Glibenclamidum + Methforminum)