Glibenklamid-Zdorovye, the tab. on 5 mg No. 50

General characteristics. Structure:

International and chemical names: Glibenclamidum; 5-hlor-N-[2-[4-[[[(cyclohexyl-amino) a carbonyl] amine] - sulphonyl] phenyl] ethyl] - 2-metoksibenzamid; 
main physical and chemical properties: tablets of white color, a ploskotsilindrichesky form with a facet;
structure: 1 tablet contains Glibenclamidum 5 mg; 
excipients: Mannitolum, potato starch, povidone, calcium stearate.

Pharmacological properties:

Pharmacodynamics. Hypoglycemic means derivative of sulphonylurea of the second generation. The antihyperglycemic effect of drug is caused by the complex mechanism of pancreatic and ekstrapankreatichesky action.
Pancreatic action consists in insulin secretion stimulation by pancreas b-cells that is followed by mobilization and strengthening of emission of endogenous insulin. This effect is caused by interaction of Glibenclamidum with the receptors integrated into structure of K+ ATP-dependent - channels of plasma membranes of the functioning pancreas b-cells, depolarization of a cellular membrane, activation of potentsialzavisimy Sa2+-channels. Slows down release of a glucagon pancreas cells.
Ekstrapankreatichesky action consists in increase in sensitivity of peripheral fabrics to effect of endogenous insulin, oppression of synthesis of glucose and a glycogen in a liver.
Increase in level of insulin in blood and lowering of the level of glucose happens gradually that reduces risk of emergence of hypoglycemic reactions. Hypoglycemic action develops in 2 h after reception, reaches a maximum in 7–8 hour and 8–12 hour proceed.
Glibenclamidum strengthens secretion of pancreatic and gastric somatostatin (but not a glucagon), has moderate diuretic effect (due to increase in renal clearance of free water). Reduces risk of development of all complications of a non-insulin-dependent diabetes mellitus (vascular, retinopathies, a nephropathy, a cardiopathy) and the mortality connected with a diabetes mellitus. Has cardiotyre-tread and antiarrhytmic effect.

Pharmacokinetics. After oral administration it is quickly and almost completely soaked up from digestive tract. The concomitant use of food can slow down absorption. 
The maximum concentration in blood after a single dose is reached in 1–2 h. Linkng with blood proteins – more than 98%. Badly gets through a placental barrier.
It Biotransformirutsya in a liver on two inactive metabolites (approximately in equal quantities), one of which is brought by kidneys, and another – with bile. An elimination half-life – 6–10 hour. In an organism does not kumulirut.
Pharmacokinetics in special clinical cases. At patients with a renal failure of easy and average degree clinically significant differences in pharmacokinetics of drug are absent; at a heavy renal failure (clearance of creatinine less than 30 ml/min.) cumulation is possible.

Indications to use:

Diabetes mellitus ІІ type (non-insulin-dependent), at adults as monotherapy at insufficient efficiency of a dietotherapy and purpose of exercise stresses; a combination therapy with insulin. 

Route of administration and doses:

Appoint inside, in 20–30 min. prior to food, without chewing, washing down with a small amount of liquid (about ½ glasses).
The initial and supporting doses, time of reception and distribution of a daily dose are established individually on the basis of results of regular determination of level of glucose in blood and urine.
The initial dose of drug makes 2,5 mg (1/2 tablets) of 1 times a day. If necessary, increase in a daily dose is carried out at regular control of level of glucose to blood, gradually increasing a dose with an interval from several days to 1 week by 2,5 mg (1/2 tablets) before achievement therapeutic of an effective dose. The maximum effective dose makes 15 mg (3 tablets). Doses higher than 15 mg/days do not increase expressiveness of hypoglycemic effect.
The daily dose to 10 mg (2 tablets) is accepted 1 time a day, before a breakfast. At higher daily dose it is recommended to be divided into two receptions in the ratio 2:1, in the morning and in the evening.
At patients of advanced age treatment is begun with a half dose which is raised further no more than on 2,5 mg/days with a week interval.
At change of body weight or a way of life of the patient, and also at emergence of the factors promoting increase in risk of development hypo - or a hyperglycemia, it is necessary to carry out dose adjustment.
Use in a combination with insulin. Glibenclamidum in a combination with insulin is appointed in case it is not possible to reach normalization of concentration of glucose in blood reception of the maximum dose of Glibenclamidum in monotherapy. At the same time against the background of the last Glibenclamidum dose appointed to the patient, treatment with insulin begins with its minimum dose, with possible subsequent gradual increase in a dose of insulin under control of concentration of glucose in blood. The combined treatment demands obligatory medical control. At Glibenclamidum combination with insulin the dose of the last can be lowered by 25–50%.
Now there is no information on use of drug for treatment of children.

Features of use:

With care use drug at a feverish syndrome, alcoholism, adrenal insufficiency, diseases of a thyroid gland (hypo - or a hyperthyroidism), at patients of advanced age and at patients with abnormal liver functions.
At long monotherapy (more than 5 years) development of secondary resistance is possible.
Control of laboratory indicators. At treatment it is necessary to carry out by drug regular control of level of glucose in blood and urine (during selection of a dose – several times a week), and also concentration of glikozilirovanny hemoglobin (at least 1 time in 3 months) that will allow to reveal primary or secondary resistance to drug in time. Besides, it is necessary to control function of a liver and a picture of peripheral blood (especially quantity of thrombocytes and leukocytes).
The states demanding transfer of the patient from Glibenclamidum on an insulin therapy: extensive burns, a severe multiple injury, extensive surgical interventions, disturbances of absorption of food and medicines in digestive tract (intestinal impassability, intestines paresis), heavy abnormal liver functions and kidneys, including stay on a hemodialysis. Need of temporary transfer on insulin can arise in stressful situations (injuries, surgical interventions, infectious diseases which are followed by fever).
Risk of development of a hypoglycemia in an initiation of treatment Glibenclamidum. In the first weeks of treatment the risk of development of a hypoglycemia (can increase especially at irregular meal or the admission of meal). Its development can be promoted by the following factors:
unwillingness or (especially at advanced age) insufficient ability of the patient to cooperation with the doctor;
irregular food, admission of meal, malnutrition;
imbalance between exercise stresses and the use of carbohydrates;
changes in a diet;
alcohol intake, especially at a hyponutrient or the admission of meal;
renal failures;
heavy abnormal liver functions;
drug overdose;
the noncompensated associated diseases of endocrine system influencing carbohydrate metabolism or counterregulation of a hypoglycemia (including dysfunction of a thyroid gland, pituitary or adrenocortical insufficiency);
concomitant use of some other drugs (see Interaction with other medicines).
Symptoms of a hypoglycemia can be poorly expressed or even to be absent at its gradual development in patients of advanced age, and also in patients with vegetative dysfunction or the b-adrenoceptors which are at the same time receiving treatment by blockers, a clonidine, Reserpinum, guanetidiny or other sympatholytics.

Drug should be accepted only in the appointed doses and in a certain time of day. 

Time of reception and distribution of a daily dose of drug is defined by the doctor with features of a day regimen of the patient. 
Meal is obligatory no later than in 1 h after administration of drug.
For achievement of optimum control of level of a glycemia at purpose of Glibenclamidum it is necessary to keep in addition to the corresponding diet, to carry out physical exercises and, in case of need, to reduce body weight. It is necessary to refuse long stay in the sun and to limit the use of greasy food.
Errors in Glibenclamidum reception (the admission of reception of a dose because of forgetfulness) cannot be corrected by the subsequent reception of higher dose at all. The doctor and the patient have to discuss previously measures which should be accepted in case of mistakes in drug use (the admission of reception of a dose, the admission of reception of food) or in situations when administration of drug at the scheduled time is impossible. 
The patient has to inform immediately the doctor in case of accidental reception of too high or excess dose of drug.
Transfer of the patient into Glibenclamidum from other drugs of sulphonylurea (except for a hlorpramid) and insulin (a daily dose – more than 40 PIECES). At transfer of the patient into Glibenclamidum it is recommended to raise a dose gradually. At an insulin therapy in the first day appoint a half dose of insulin and 5 mg of Glibenclamidum.
Influence on ability to manage motor transport and to work with mechanisms. In an initiation of treatment or at irregular use of Glibenclamidum it can be noted caused hypo - or a hyperglycemia decrease in concentration of attention and speed of psychomotor reactions of the patient. In such situations it is necessary to abstain from occupations potentially dangerous types of activity requiring special attention and speed of psychomotor reactions.

Side effects:

From a metabolism. Hypoglycemia, including night (headache, feeling of hunger, nausea, feeling of fatigue, sleep disorder, dreadful dreams, alarm, similar to intoxication state, trembling, confusion of consciousness, speech and visual frustration; very seldom – spasms, a coma). Besides, as a result of an adrenergicheskoy feedback mechanism there can sometimes be following symptoms: cold clammy sweat, tachycardia. Hypersensitivity to alcohol, increase in body weight, a dislipidemiya, adjournment of fatty tissue; after long use – hypofunction of a thyroid gland.
From digestive tract. Sometimes – nausea, vomiting, heavy feeling or discomfort in epigastriums, an abdominal pain, diarrhea, a meteorism, heartburn, loss or increase in appetite; very seldom – an abnormal liver function, cholestatic jaundice, a porphyria, hepatitis. 
From system of blood. Very seldom – hemolitic or aplastic anemia, an agranulocytosis, a leukopenia, a pancytopenia, thrombocytopenia, an eosinophilia.
Allergic reactions. Seldom – a multiformny erythema, exfoliative dermatitis, a photosensitization. The cross allergy with other derivatives of sulphonylurea, streptocides and tiazidopodobny drugs is possible. 
Others. Hyponatremia, hypoosmolarity or syndrome of inadequate secretion of antidiuretic hormone (depression, dizziness, lethargy, face edemas, anklebones and hands, spasms, stupor, coma), passing disorder of accommodation.

Interaction with other medicines:

Strengthening of hypoglycemic effect of glibenclamide can be observed at simultaneous use with insulin or other hypoglycemic drugs, inhibitors of an angiotensin-converting enzyme, Allopyrinolum, anabolic steroids and male sex hormones, chloramphenicol, Cimetidinum, coumarin derivatives, tsiklo-, tro-and isophosphamide, fenfluraminy, feniramidoly, fibrata, fluoxetine, guanetidiny, MAO inhibitors, Miconazolum, flukonazoly, pentoksifilliny, phenylbutazone, oksifenbutazony, azapropanony, probenitsidy, salicylates, Sulfinpyrazonum, streptocides of long action, tetracyclines, tritokvaliny.
Weakening of hypoglycemic effect of glibenclamide is possible at simultaneous use with acetazoleamide, barbiturates, glucocorticosteroids, diazoxide, saluretics, thiazide diuretics, Epinephrinum (adrenaline) and other sympathomimetics, a glucagon, purgatives (at prolonged use), niacin (in high doses) and its derivatives, estrogen and progestogens, fenotiaziny, Phenytoinum, rifampicin, hormones of a thyroid gland, lithium salts, Chlorpromazinum.
Both strengthening, and weakening of hypoglycemic effect of glibenclamide can be observed at simultaneous use with blockers of histamine H2 receptors, a clonidine and Reserpinum, single or chronic alcohol intake.
Against the background of reception of Glibenclamidum strengthening or weakening of action of derivatives of coumarin can be observed.

Contraindications:

Insulin-dependent diabetes mellitus (І type), including at children's and youthful age, diabetic ketoacidosis, a diabetic prekoma and a coma, a pancreatectomy, a giperosmolyarny coma, a heavy liver and/or renal failure (clearance of creatinine less than 30 ml/min., including the patients who are on a hemodialysis), the extensive burns, a severe multiple injury, big surgical interventions, intestinal impassability, paresis of a stomach, states which are followed by disturbance of absorption of food and development of a hypoglycemia (infectious diseases, etc.), a leukopenia, hypersensitivity to Glibenclamidum, other derivatives of sulphonylurea or sulfanamide drugs, pregnancy, feeding by a breast, children's age up to 14 years (efficiency and safety of use for children is not proved).
Patients during pregnancy and planning pregnancy have to be transferred to insulin. Nursing mothers have to be transferred to insulin or refuse completely feeding by a breast.

Overdose:

At overdose by Glibenclamidum the hypoglycemia develops. Symptoms: sweating strengthening, feeling of alarm, tachycardia, increase in arterial pressure, a heart consciousness, pains in heart, arrhythmia, a headache, sharp increase in appetite, nausea, vomiting, apathy, drowsiness, concern, aggression, disturbance of concentration of attention, a depression, confusion of consciousness, a tremor, paresis, disturbance of sensitivity, a spasm of the central genesis. The clinical picture of a hypoglycemia can sometimes remind a stroke. Development of a coma is possible. 
Treatment: The easy and moderate hypoglycemia can be quickly stopped by immediate reception of carbohydrates (glucose or sugar, for example, in the form of pieces of sugar, sweet fruit juice or tea). In this regard the patient has to have always at himself not less than 20 g of glucose (4 pieces of sugar). Sweeteners at treatment of a hypoglycemia are inefficient. In hard cases of a hypoglycemia, owing to overdose, the patient needs to be hospitalized. It is necessary to cause vomiting, to appoint liquid reception (water or lemonade with the activated coal/adsorbent and sulfate sodium/laxative). To immediately begin administration of glucose, if necessary – in the form of intravenous jet administration of 50 ml of 40% of solution with the subsequent infusions more diluted (10%) solution with careful monitoring of level of glucose in blood for maintenance of an easy hyperglycemia of 100 mg/dl, then 1–2 mg of a glucagon intramusculary (for mobilization of hepatic glucose), diazoxide of 300 mg intravenously within 30 min. or 200 mg inside each 4 h during the monitoring of level of sodium and control of arterial pressure. Each 1–3 h carry out monitoring of a glycemia, definition to blood рН, an urea nitrogen, creatinine, electrolytes. Further carry out a symptomatic treatment. At wet brain enter a mannitol intravenously and dexamethasone, at a hypopotassemia – potassium drugs. At treatment of the hypoglycemia which developed owing to accidental reception of Glibenclamidum by babies or small children to avoid a hyperglycemia, it is necessary to control a dextrose dose (50 ml of 40% of solution) and to continuously monitorirovat concentration of glucose in blood. It is necessary to consider that provocation of an acute/excessive hyperglycemia introduction of hypertonic salt solution of glucose stimulates additional emission of insulin that aggravates a hypoglycemia.

Storage conditions:

To store in the place protected from light at a temperature from 8 °C to 25 °C. To store in the place, unavailable to children.

Period of validity – 3 years.

Issue conditions:

According to the recipe

Packaging:

On 50 tablets in a container plastic and in a pack; No. 10х5 in a blister strip packaging and in a pack; No. 20х6 in a blister strip packaging and in a pack.