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

Glibenclamide has pancreatic and extra-pancreatic effects. Stimulates insulin secretion by lowering the threshold of stimulation of pancreatic beta cells by glucose, increases insulin sensitivity and the degree of its binding to target cells, increases insulin release, enhances insulin effect on glucose uptake by muscles and liver, inhibits fat lipolysis (extra-pancreatic effects) . It operates in the second stage of insulin secretion. Has hypo-lipidemic action, reduces thrombogenic properties of blood.

Hypoglycemic effect develops after 2 hours, reaches a maximum after 7-8 hours and lasts 12 hours. The drug provides a smooth increase in the concentration of insulin and a smooth decrease in glucose in the plasma, which reduces the risk of hypoglycemic conditions. The activity of glibenclamide is manifested with the preserved endocrine function of the pancreas to synthesize insulin.

Pharmacokinetics:

When administered, absorption from the gastrointestinal tract is 48-84%. The time to reach the maximum concentration is 1-2 hours, the volume of distribution is 9-10 liters. The connection with plasma proteins is 95-99%.Bioavailability of glibenclamide is 100%, which allows you to take the drug almost before eating. The placental barrier passes badly. Almost completely metabolized in the liver with the formation of two inactive metabolites, one of which is excreted by the kidneys, and the other - with bile. Half-life is from 3 to 10-16 hours.

Indications:

Diabetes mellitus type 2 with ineffectiveness of diet therapy.

Contraindications:

type 1 diabetes mellitus;
diabetic ketoacidosis, diabetic precoma and coma;
condition after resection of the pancreas;
severe violations of liver function;
severe renal dysfunction;
known from the history of hypersensitivity to glibenclamide and / or other derivatives of sulfonylureas, sulfonamides, diuretics containing a sulfonamide group in the molecule, and probenecid, t. there may be cross reactions;
decompensation of carbohydrate metabolism in infectious diseases or after large surgical operations, when insulin therapy is shown;
leukopenia;
intestinal obstruction, paresis of the stomach;
conditions, accompanied by a violation of food intake and development of hypoglycemia;
pregnancy and the period of breastfeeding.

Carefully:

Glibenclamide should be used when:

febrile syndrome;
thyroid disease (with impaired function);
hypofunction of the anterior lobe of the pituitary gland or adrenal cortex;
alcoholism;
in elderly patients because of the danger of developing hypoglycemia.

Dosing and Administration:

The dose of the drug is selected individually. The initial dose is 2.5 mg (½ tablets) per day. If necessary, the dose is gradually increased by 2.5 mg (½ tablets) per week until the carbohydrate metabolism is compensated.

The maintenance daily dose of the drug is usually 5-10 mg (1-2 tablets). The maximum daily dose is 15 mg (3 tablets).

A dose of more than 15 mg is used in rare cases and does not cause a significant increase in the hypoglycemic effect.

For elderly patients, the initial dose is 1 mg per day.

Multiplicity of drug intake is 1-3 times a day. Tablets should be taken whole, not liquid, with a small amount of liquid for 20-30 minutes before meals.

Side effects:

The most common undesirable effect in the treatment with Glibenclamide is hypoglycemia. This condition can take a protracted character and contribute to the development of severe conditions up to a comatose, life-threatening patient or ending lethally.With diabetic polyneuropathy or with concomitant treatment with sympatholytic drugs (see section "Interaction with other drugs"), typical precursors of hypoglycemia may be mild or absent altogether.

The reasons for the development of hypoglycemia can be: drug overdose; incorrect reading; irregular eating; elderly patients; vomiting, diarrhea; large physical exercise; diseases that reduce the need for insulin (violations of liver and kidney function, hypofunction of the adrenal cortex, pituitary gland or thyroid gland); alcohol abuse, as well as interaction with other medicines (see section "Interaction with other drugs"). Symptoms of hypoglycemia are: a strong feeling of hunger, sudden profuse sweating, palpitations, pallor of the skin, paresthesia in the mouth, trembling, general anxiety, headache, pathological drowsiness, sleep disorders, fear, coordination of movements, temporary neurological disorders (for example, visual and speech disorders, manifestations of paresis or paralysis, or altered perception of sensations).With the progression of hypoglycemia, patients may lose self-control and consciousness. Often such a patient has moist cold skin and a predisposition to convulsions.

Along with hypoglycemia are possible:

Disorders from the digestive system: rare nausea, eructation, vomiting, "metallic" taste in the mouth, a feeling of heaviness and fullness in the stomach, abdominal pain and diarrhea. In some cases, a temporary increase in the activity of "hepatic" enzymes (alkaline phosphatase, glutamic-oxaloacetic aminotransferase, glutamine-pyruvic aminotransferase) in the blood serum was described; drug hepatitis and jaundice.

Rarely appear skin allergic reactions: rash, itching of the skin, urticaria, reddening of the skin, Quincke edema, pinpoint bleeding in the skin, flaky rash on large skin surfaces and increased photosensitivity. Very rarely skin reactions can serve as the beginning of the development of severe conditions, accompanied by shortness of breath and lowering blood pressure until the onset of shock, threatening the life of the patient. Separate cases are described severe generalized allergic reactions with skin rash, pain in the joints, fever, the appearance of protein in the urine and jaundice.

On the part of the system of hemopoiesis: rarely there is thrombocytosis or very rarely leukocytosis, agranulocytosis. In isolated cases, hemolytic anemia or pancytopenia develops.

Other side effects, observed in isolated cases, include: a weak diuretic effect, a temporary appearance of the protein in the urine, visual impairment and accommodation, as well as an acute reaction of alcohol intolerance after its use, expressed by complications from the circulatory and respiratory organs (disulfira-mopidobia reaction: vomiting, sensation heat in the face and upper body, tachycardia, dizziness, headache).

Overdose:

In case of an overdose, hypoglycemia may develop.

With mild or moderate hypoglycemia, glucose or sugar solution is taken orally.

In the case of severe hypoglycemia (loss of consciousness), a 40% solution of dextrose (glucose) or intravenously glucagon intravenously, intramuscularly, subcutaneously.

After the restoration of consciousness, the patient needs to give food rich in carbohydrates, in order to avoid the re-development of hypoglycemia.

Interaction:

An increase in the hypoglycemic effect of Glibenclamide is observed with simultaneous use of angiotensin-inhibiting enzyme inhibitors, anabolic agents.

inhibitors of other hypoglycemic agents (e.g., acarbose, biguanides) and insulin, non-steroidal anti-inflammatory drugs (NSAIDs), beta blockers, quinine, quinolone derivatives, chloramphenicol, clofibrate, coumarin derivatives, dizoiiramida, fenfluramine, feniramidola, fluoxetine, monoamine oxidase inhibitors, miconazole, para-aminosalicylic acid, pentoxifylline (at high doses administered parenterally), perhexylene, pyrazolone derivatives, phenylbutazones, phosphamides (eg, cyclophosphamide, ifos amide, trofosfamide), probenecid, salicylates, sulfinpirazona, sulphonamides, tetracyclines and tritokvalina. Urine acidifying agents (ammonium chloride, calcium chloride) enhance the action of Glybenklamid due to a decrease in the degree of its dissociation and an increase in reabsorption.

Drugs that inhibit bone marrow hematopoies increase the risk of myelosuppression.

Along with the increase in hypoglycemic action, beta-blockers, clonilip, guanethidine and reserpine, as well as drugs with a central mechanism of action, can weaken the sensation of precursors of hypoglycemia.

The hypoglycemic effect of Glybeneclamide can decrease with the simultaneous use of barbiturates, isoniazid, cyclosporine, diazoxide, glucocorticosteroids, glucagon, nicotinate (in high doses), phenytoin, phenothiazines, rifampicip, thiazide diuretics, acetazolamide, sex hormones (eg hormonal contraceptives), iodine-containing hormones thyroid gland, blockers of "slow" calcium channels, sympathomimetic agents and lithium salts.

Chronic abuse of alcohol and laxatives can aggravate the violation of carbohydrate metabolism.

H2-receptor antagonists can, on the one hand, weaken, and on the other increase the hypoglycemic effect of Glibenclamide. Pentamidine in a few cases can cause a strong decrease or increase in the concentration of glucose in the blood. The effect of coumarin derivatives may be enhanced or weakened.

Along with the increased hypoglycemic effect of beta-blockers, clonidine, guanethidine and reserpine, as well as drugs with a central mechanism of action, can weaken the sensation of precursors of hypoglycemia.

Special instructions:

The drug should be taken regularly and, if possible, at the same time. It is necessary to carefully observe the regimen of the drug and the diet.

The doctor should carefully consider the appointment of Glybenklamid to patients with impaired liver and kidney function, as well as hypothyroidism of the thyroid gland, anterior pituitary gland or adrenal cortex. Glibenclamide dose adjustment is necessary in case of physical and emotional overstrain, changes in diet. Large surgical interventions and trauma, extensive burns, infectious diseases with febrile syndrome may require the abolition of oral hypoglycemic drugs and the administration of insulin.

Patients should be warned about the increased risk of hypoglycemia in cases of alcohol intake, NSAIDs, and fasting.

During treatment it is not recommended to stay in the sun for a long time.

At the beginning of treatment, during the selection of a dose, patients prone to developing hypoglycemia are not recommended to engage in activities requiring increased attention and speed of psychomotor reactions.

When treating patients with lactase deficiency, it should be taken into account that the preparation contains lactose monohydrate.

Form release / dosage:

Tablets 5 mg.

Packaging:

10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil or paper with polyethylene coating.

20, 30 and 50 tablets are placed in a jar of dark glass such as BPS, sealed with a cap of a stretchable with sealing element or a can of polymer type BP.

Each jar or 1, 2, 3 or 5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000933

Date of registration:18.10.2011

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Representation: & nbspBIOSINTEZ JSC BIOSINTEZ JSC Russia

Information update date: & nbsp22.12.2015

Illustrated instructions

Instructions

Glibenclamide (Glibenclamide )