Glibenclamidum

General characteristics. Structure:

Active ingredients: glibenclamide;

1 tablet contains Glibenclamidum 5 mg in terms of 100% dry matter;

excipients: lactoses monohydrate, potato starch, povidone, понсо   4R (E 124), magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Treats peroral antihyperglycemic means, sulphonylurea derivatives ІІ generation. Promotes stimulation of β-cells of a pancreas which is followed by mobilization and strengthening of emission of endogenous insulin. Drug is effective in the presence in a pancreas of functionally capable β-cells which produce endogenous insulin. Promotes decrease in aggregation of thrombocytes.

Pharmacokinetics. At oral administration of Glibenclamidum on an empty stomach there is bystry and its almost full absorption in a digestive tract. Drug more than for 98% contacts blood proteins (albumine) and is metabolized in a liver. In the course of metabolism 3 cishydroxyglibenclamidum and 4 transhydroxyglibenclamidum are formed. It is brought out of an organism with urine and bile. Glibenclamidum elimination half-life from a blood plasma – 1,5-3,5 hours. The hypoglycemic effect lasts till 12 o'clock.

At patients with reduced function of a liver removal of drug is slowed down. At states which are followed by moderate insufficiency of kidneys (at clearance of creatinine           of 30 ml/min.) process of removal of metabolites does not change, but their cumulation at the expressed renal failure is possible.

Pharmaceutical characteristics.

Main physical and chemical properties: tablets of a ploskotsilindrichesky form with risky and a facet, light pink color. On a surface of tablets the insignificant mramornost and impregnations are allowed.

Indications to use:

Non-insulin-dependent diabetes at adults ( a diabetes mellitus ІІ type), if other measures as, for example, strict observance of a diet, decrease in excessive body weight, sufficient physical activity did not lead to satisfactory correction of level of glucose in blood.

Route of administration and doses:

Drug should be used only on doctor's orders and surely with correction of a diet. The dosage depends on results of a research of a condition of a metabolism (sugar level in blood and urine).

The first and posleduyushchiyenaznacheniya. Therapy is begun, whenever possible, with as it is possible smaller doses, first of all it concerns patients with the increased tendency to a hypoglycemia and body weight to a mensha of 50 kg. The first appointment makes from ½ to 1 tablets (that corresponds to 2,5-5 mg of Glibenclamidum) a day. At insufficient correction of a metabolism the dose is gradually raised bucketed from several days to one week, to a necessary daily therapeutic dose which makes 3 tablets (that corresponds to 15 mg of Glibenclamidum) a day.

Переводбольногос primeneniyadrugy anti-diabetic drugs. A transfer into the drug Glibenclamidum should be made very carefully and to begin from ½ to 1 tablet (that corresponds to 2,5-5 mg of Glibenclamidum a day).

Selection of a dose. The patient of advanced age weakened or the patient with a hyponutrient, and also with easy and moderate disturbances of functions of kidneys or a liver it is necessary to lower an initial and maintenance dose because of a possibility of development of a hypoglycemia. At decrease in body weight of the patient or change of a way of life it is necessary to resolve an issue of dose adjustment.

Combination sdrugy anti-diabetic means. In reasonable cases additional purpose of drugs of group of a glitazon can be shown to patients with intolerance of Metforminum (розиглитазон, пиоглитазон). Glibenclamidum can be combined with peroral anti-diabetic drugs which do not stimulate emission by beta cells of endogenous insulin (гуармель or acarbose). At emergence of secondary inefficiency of therapy by Glibenclamidum (decrease in products of insulin as a result of decrease in beta cells) it is possible to try the combined treatment with insulin. However at complete cessation of secretion of own insulin the organism showed monotherapy by insulin.

Way and duration of treatment. A pill should be taken before food. Not to chew and wash down with enough liquid (1 glass of water is better). At a daily dose, a component more than 2 tablets of drug, all quantity on one morning and one evening reception in the ratio 2:1 is recommended to distribute. It is very important to use drug every time at the same time. If the patient missed one reception, it is never impossible to supplement it with reception of higher dose. Duration of treatment depends on disease. Throughout treatment it is necessary to carry out regular control of a condition of a metabolism.

Features of use:

Use during pregnancy or feeding by a breast.

Glibenclamidum use to pregnant women and during feeding by a breast contraindicated.
Children.

Not to apply to children.

At drug use by the patient with a renal failure or a liver of easy or moderate degree, or reduced function of a thyroid gland, hypophysis or bark of adrenal glands extra care is required.

Patients of advanced age have a risk of development of the prolonged hypoglycemia therefore by it Glibenclamidum is appointed with extra care and carefully control their state in an initiation of treatment. In this age group under certain conditions at first it is more reasonable to use sulphonylurea drugs with shorter time of action. Patients with diabetes with signs of a cerebral sclerosis and patients with whom the contact in general is complicated are more inclined to threat of development of a hypoglycemia. Considerable intervals between meals, insufficient providing with carbohydrates, an unusual exercise stress, diarrhea or vomiting can cause increase in risk of development of a hypoglycemia.

At simultaneous use of the drug Glibenclamidum with a clonidine, beta adrenoblockers, guanetidiny and Reserpinum perception by the patient of symptoms harbingers of a hypoglycemia can be broken.

Effect of the drug Glibenclamidum can amplify or be weakened in an unexpected way at alcohol intake repeatedly in a significant amount and at its constant use.

Constant abuse of purgatives can lead to a metabolism aggravation of symptoms.

At non-compliance with the scheme of treatment, at insufficient antihyperglycemic effect of drug or in the presence of stressful situations (an injury, operation, an infectious disease which is followed by fervescence) sugar level in blood can sometimes increase so that can demand temporary convertion of the patient on insulin. Feelings of strong thirst, dryness in a mouth, a frequent urination, an itch, a xeroderma, fungus or infectious diseases of skin and decrease in working capacity can be symptoms of a hyperglycemia. The patient has to know that at emergence of other diseases during treatment of the drug Glibenclamidum he has to consult immediately with the doctor.

At patients with insufficiency in an organism glyukozo-6-fosfatdegidrogenazy treatment with sulphonylurea drugs, including Glibenclamidum, can cause hemolitic anemia therefore it is necessary to resolve an issue of convertion on the drugs alternative to sulphonylurea derivatives.

Patients with hereditary intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption should not apply Glibenclamidum.

Ability to influence speed of response at control of motor transport or work with other mechanisms.

 

Patients should apply security measures to prevention of a hypoglycemia during driving and in operating time with other mechanisms. It is especially important for those patients who often have cases of a hypoglycemia or there are no symptoms - hypoglycemia harbingers. In such cases it is necessary to resolve an issue of expediency of driving.

Side effects:

At assessment of side reactions the following values of frequency of emergence are assumed as a basis: very often (≥ 10%), it is frequent (<10%, ≥ 1%), sometimes (<1%, ≥0,1%), is rare (<0,1%, ≥ 0,01%), is very rare (<0,01% or cases are unknown).

Disbolism and food: often – a hypoglycemia, increase in body weight.

Disturbances from organs of sight: very seldom – visual disturbances and accommodations, especially in an initiation of treatment.

Disturbances from a digestive tract: sometimes – nausea, feeling of overflow of a stomach, vomiting, an abdominal pain, diarrhea, an eructation, metal smack in a mouth. These complaints have reversible character and do not demand drug withdrawal.

Abnormal liver function and gall bladder: very seldom – passing increase in ASAT and ALAT, alkaline phosphobasins, medicamentous hepatitis, an intra hepatic cholestasia which, perhaps, are caused by allergic reaction of giperergichesky type of cells of a liver. These disturbances have reversible character after drug withdrawal, but can lead to a liver failure that threatens life.

Disturbances from skin and hypodermic cellulose: sometimes – an itch, urtikarny rash, erythema nodosum, a korepodobny or makulopapulyozny dieback, a purpura, a photosensitization. These phenomena of hypersensitivity reactions have reversible character, but very seldom can pass into the states menacing for life which is followed by suffocation and a lowering of arterial pressure, up to development of shock. Very seldom – generalized hypersensitivity reactions which are followed by skin rash, an arthralgia, fever, a proteinuria and jaundice; an allergic vasculitis that makes threat for life. At emergence of skin reactions it is necessary to see a doctor.

Disturbances from system of blood and lymphatic system: seldom – thrombocytopenia. Very seldom – a leukopenia, an erythropenia, a granulocytopenia up to development of an agranulocytosis. In some cases – a pancytopenia, hemolitic anemia, aplastic anemia, an eosinophilia. Above-mentioned changes of a picture of blood have reversible character after drug withdrawal, but very seldom can make threat for life.

Other side effects: very seldom – weak diuretic effect, a syndrome of inadequate secretion of antidiuretic hormone, a reversible proteinuria, a hyponatremia, disulfiramopodobny reaction, a cross allergy with the sulfonamides derivative of sulfonamides and probenetsidy. Ponso 4R can cause allergic reactions.

Interaction with other medicines:

Drugs which strengthen effect of glibenclamide at simultaneous use: other anti-diabetic drugs and insulin, inhibitors of an angiotensin-converting enzyme, anabolic steroids and male sex hormones, antidepressants (fluoxetine, MAO inhibitors), the beta adrenoblockers derivative a hinolona, chloramphenicol, Clofibratum and its analogs, coumarin derivatives, Disopyramidum, фенфлурамин, Miconazolum, p-aminosalicylic acid, пентоксифиллин (entered parenterally in a high dose), пергексилин, pyrazyl ketone derivatives, пробенецид, salicylates, sulfonamides, antibiotics of a tetracycline row, тритоквалин, cytostatics like cyclophosphamide.

The drugs reducing effect of glibenclamide at simultaneous use: acetazoleamide, beta adrenoblockers, barbiturates, diazoxide, diuretics, a glucagon, an isoniazid, corticosteroids, the nikotinata derivative a fenotiazina, Phenytoinum, rifampicin, hormones of a thyroid gland, female sex hormones (gestagena, are oestrogenic), sympathomimetics.

H2 receptors blockers, clonidine and Reserpinum can both reduce, and to strengthen antihyperglycemic effect of drug. In some cases pentamidine can lead to a heavy hypoglycemia or a hyperglycemia. Action of derivatives of coumarin can both amplify, and to decrease.

Contraindications:

Hypersensitivity to Glibenclamidum or to excipients, to sulphonylurea derivatives, to the sulfonamides, diuretics derivative of sulfonamide and a probenetsid. In cases when treatment is required by insulin: a diabetes mellitus of the I type, full secondary inefficiency of therapy by Glibenclamidum at a diabetes mellitus of the II type, metabolism with tendency towards acidosis, a prekoma or a diabetic coma. A state after a pancreatectomy. Heavy abnormal liver functions. Heavy renal failures.

Overdose:

One-time overdose or use of slightly raised doses can lead to the heavy prolonged hypoglycemia for a long time that poses a threat for life.

Symptoms of overdose (hypoglycemia): a sudden potovydeleniye, the strengthened heartbeat, a shiver, feeling of hunger, concern, paresthesias in a mouth, pallor of integuments, a headache, drowsiness, frustration of a dream, fearfulness, uncertainty in the movements, temporary neurologic frustration (disturbances of the speech and sight, emergence of paralysis or disturbance of sensitivity). At the progressing hypoglycemia of the patient can lose control over the state and faint (hypoglycemic shock). In such cases skin to the touch wet and cold, takes place tachycardia, a hyperthermia, motive excitement, a hyperreflexia, paresis and a positive Babinski's reflex, spasms can develop.

Treatment. Easy or moderate severity of the patient can independently eliminate a hypoglycemia, using sugar, food or drinks with its high content. If the hypoglycemia has difficult character, it is necessary to ask immediately for the help the doctor. At accidental poisoning and provided that it is possible to come into contact with the patient, it is necessary to cause vomiting and to carry out a gastric lavage (in the absence of tendency to spasms) and to carry out intravenous administration of glucose. If the patient fainted, it is necessary to begin immediately  intravenous administration of glucose (40-80 ml of 40% of solution in the form of an injection, further to carry out infusion of 5-10% of solution of glucose). If necessary it is possible to enter in addition 1 mg of a glucagon intravenously or intramusculary. If the patient does not recover consciousness, these actions are repeated, and carrying out an intensive care can be necessary further. At a long hypoglycemia observation of the patient for several days with regular control of level of sugar in blood and, if necessary, performing infusional therapy is required.

Storage conditions:

Period of validity. 3 years. Not to use drug after the termination of the period of validity specified on packaging. To store in the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister. On 5 or 10 blisters in a pack.