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

Excipient: lactose monohydrate - 46.5 mg / 93.0 mg / 50.0 mg; povidone K30 - 1.75 mg / 3.5 mg / 5.0 mg; giprolose low-substituted - 11.5 mg / 23.0 mg / 23.0 mg; cellulose microcrystalline - 23.5 mg / 47.0 mg / 47.0 mg; sodium carboxymethyl starch 4.0 mg / 8.0 mg / 8,0 mg; silicon dioxide colloidal - 0.5 mg / 1.0 mg / 1.0 mg; sodium stearyl fumarate 0.5 mg / 1,0 mg / 1.0 mg.

Description:

Tablets 1.75 mg: round biconvex tablets white or white with a yellowish hue.

Tablets 3,5 mg: round flat-cylindrical tablets white or white with a yellowish tinge color with a bevel.

Tablets 5 mg: round flat-cylindrical tablets white or white with a yellowish shade of color with a risk on one side and a facet.

Pharmacotherapeutic group:Hypoglycemic agent for oral use of the second-generation sulfonylurea group

ATX: & nbsp

A.10.B.B.01 Glibenclamide

Pharmacodynamics:

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

Pharmacokinetics:

Absorption

When administered, absorption from the gastrointestinal tract is 48-84%. Time to reach the maximum concentration in the blood (T_m_Oh) - 1-2 hours Bioavailability of glibenclamide is 100%. Simultaneous food intake does not have a significant effect on the absorption of glibenclamide.

Distribution

Volume of distribution (Vd) 9-10 liters. The connection with plasma proteins is 95-99%. The placental barrier passes badly.

Metabolism

Glibenclamide is almost completely metabolized in the liver with the formation of two inactive metabolites.

Excretion

One of the inactive metabolites is excreted by the kidneys, the other through the intestine in approximately equal proportions. The half-life (T_1/2) - from 3 to 10-16 hours.

Pharmacokinetics in patients with impaired hepatic function

In patients with impaired hepatic function, excretion of the active substance from the blood plasma is slowed down.

Pharmacokinetics in renal failure

In patients with renal failure, the excretion of metabolites through the intestine is compensated.When creatinine clearance is ≥ 30 ml / min, the overall rate of removal of glibenclamide from the body remains unchanged, with renal failure of severe degree, cumulation is possible.

Indications:

Type 2 diabetes mellitus, in addition to diet and exercise, as a monotherapy or as part of a combination therapy with metformin or other oral hypoglycemic drugs, in addition to sulfonylurea derivatives and clays.

Contraindications:

- Hypersensitivity to glibenclamide and / or any auxiliary substance of the drug;

- hypersensitivity to other sulfonylurea derivatives; sulfonamides; diuretics containing a sulfonamide group in the molecule; probenecid, t. there may be cross reactions;

- Type 1 diabetes mellitus;

- diabetic ketoacidosis, diabetic precoma and coma;

- condition after resection of the pancreas;

hepatic failure of severe degree;

- renal failure of severe degree (creatinine clearance <30 ml / min);

- Adrenal insufficiency of a serious degree;

- decompensation of carbohydrate metabolism in infectious diseases, burns, injuries or after major surgical operations, when insulin therapy is indicated;

- intestinal obstruction, paresis of the stomach;

- hereditary lactose intolerance, lactase deficiency or glucose malabsorption syndrome and lactose;

- pregnancy and the period of breastfeeding;

- Children under 18 years of age (effectiveness and safety not studied);

- porphyria;

- simultaneous application with bosentan.

Carefully:

Glibenclamide should be used with caution in febrile syndrome; diseases of the thyroid gland (with a decrease in function); insufficiency of the function of the anterior lobe of the pituitary gland or the adrenal cortex; insufficiency of glucose-6-dehydrogenase; chronic alcoholism, acute alcohol intoxication; conditions associated with impaired absorption of food and the risk of hypoglycemia (prolonged starvation, insufficient intake of carbohydrates from food, excessive exercise, diarrhea or vomiting); renal failure of mild to moderate severity (creatinine clearance ≥ 30 ml / min); hepatic insufficiency of mild and moderategravity; cerebral atherosclerosis; In elderly patients over 65 years of age due to the risk of developing hypoglycemia.

Pregnancy and lactation:

The use of glibenclamide during pregnancy is contraindicated. At the onset of pregnancy, the drug should be stopped. When planning pregnancy, oral hypoglycemic therapy should be replaced with insulin therapy.

It is not known whether the glibenclamide in breast milk. Since other derivatives of sulfonylureas penetrate into breast milk, the use of glibenclamide in the period of breastfeeding is contraindicated.

Dosing and Administration:

Inside. The drug should be taken before eating, without chewing and squeezed with enough liquid. The drug should be taken at the same time of day.

The dose of the drug is selected individually depending on the age, severity of the course of diabetes, blood glucose concentration on an empty stomach and 2 hours after eating. It is necessary to correct the dose when changing the patient's body weight and lifestyle. It is also necessary to regularly monitor the concentration of glucose in the blood and urine, glycated hemoglobin,indicators of lipid metabolism.

Tablets 5 mg. The tablet can be divided into 2 equal parts. The range of daily dose is from ½up to 3 tablets (from 2.5 mg to 15 mg). The initial dose is 2.5-5 mg (½ - 1 tablet) per day. The maximum daily dose is 15 mg (3 tablets).

The dose increase should be carried out at intervals of several days to 1 week before reaching the required therapeutic dose, which should not exceed the maximum.

Tablets 1.75 mg. The initial dose is usually 1-2 tablets (1.75 mg - 3.5 mg) once a day. The average daily dose is 3.5 mg (2 tablets). If necessary, the dose is gradually increased until adequate glycemic control is achieved. The maximum daily dose is 6 tablets (10.5 mg). If more than three tablets are taken, they switch to taking the tablets in a dosage of 3.5 mg.

The dose increase should be carried out at intervals of several days to 1 week before reaching the required therapeutic dose, which should not exceed the maximum.

Tablets 3,5 mg. The initial dose is usually ½ - 1 tablet once a day. The average daily dose is 3.5 mg (1 tablet). If necessary, the dose is gradually increased until adequate glycemic control is achieved.The maximum daily dose is 10.5 mg (3 tablets).

Daily doses of the drug to 2 tablets are usually taken 1 time per day - in the morning. Higher doses are divided into 2 doses - morning and evening receptions in a ratio of 2: 1.

If you miss one dose of the drug, the next dose of the drug should be taken at the usual time, while not allowed to take a higher dose.

Transition from other hypoglycemic drugs

When switching from other hypoglycemic agents with a similar type of action glibenclamide appoint according to the scheme given above, and the previous drug is immediately canceled.

Application in combination therapy with other hypoglycemic drugs

Glibenclamide can be used in combination therapy with metformin and other oral hypoglycemic drugs that do not stimulate insulin secretion (guar gum or acarbose). In case of intolerance to metformin, a combination of glibenclamide with thiazolidinediones (rosiglitazone, pioglitazone), with the initial stage of secondary resistance to glibencamide - with insulin.In the case of complete secondary resistance to glibencamide, insulin monotherapy.

Use in elderly, debilitated patients and patients with reduced diet

In elderly, debilitated patients or patients with reduced diet, the initial and maintenance doses should be reduced because of the risk of developing hypoglycemia.

Children and teens

Data on the efficacy and safety of glibenclamide in this age group are not available.

Use in patients with impaired renal and hepatic function

The use of glibenclamide in patients with severe renal and hepatic impairment is contraindicated. In patients with mild to moderate renal insufficiency (creatinine clearance ≥ 30 mL / min) and mild to moderate hepatic insufficiency the severity of the initial and maintenance dose should be reduced because of the risk of developing hypoglycemia.

Side effects:

Classification of undesirable adverse reactions according to the frequency of development: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000, <1/1000), very rarely <1/10000), including individual messages.

Disorders from the metabolism and nutrition: often: hypoglycemia, weight gain.

Disorders from the side of the organ of vision: very rarely: visual impairment and accommodation disorders.

Violations from the blood and lymphatic system: rarely: thrombocytopenia, thrombocytopenic purpura, leukocytopenia; very rarely: leukopenia, agranulocytosis, erythropenia, hemolytic anemia or pancytopenia, aplastic anemia, bone marrow aplasia, eosinophilia and bleeding disorders.

Disorders from the gastrointestinal tract: infrequently: nausea, heartburn, anorexia, belching, vomiting, "metallic" taste in the mouth, a feeling of heaviness and overflow in the stomach, abdominal pain and diarrhea; rarely - pancreatitis.

Disorders from the liver and bile ducts: very rarely: increased activity of "liver" enzymes (ACT, ALT), cholestasis, cholestatic hepatitis, granulomatous hepatitis and bilirubinemia. In some cases, hepatitis, increased activity of "liver" enzymes and / or cholestasis and jaundice can lead to life-threatening liver failure, but can regress after stopping the intake of glibenclamide.

Disorders from the kidneys and urinary tract: very rare: increased diuresis, transient proteinuria.

Disturbances from the skin and subcutaneous tissues: rarely: itching of the skin; hives; nodal erythema; erythematous, maculopapular or bullous rash; psoriasis-like skin reactions.

Immune system disorders: very rarely, urticaria reactions can trigger the development of severe conditions, accompanied by shortness of breath and lowering blood pressure until the onset of life-threatening shock. Separate cases of severe generalized allergic reactions with skin rash, pain in the joints, fever, the appearance of protein in the urine and jaundice are described. When symptoms of urticaria appear, consult a doctor immediately. A cross-allergy with other derivatives of sulfonylurea, sulfonamides is possible.

In some cases, the development of allergic vasculitis, in some cases - life-threatening.

To other side effects observed in isolated cases; are photosensitization; hyponatremia; Late skin porphyria; pellagrope-like symptoms. Perhaps the development of an acute reaction of alcohol intolerance after its use, expressed by complications from the circulatory and respiratory organs (disulfiramoid-like reaction: vomiting, sensation of heat in the face and upper body, tachycardia, dizziness, headache).

Overdose:

In case of an overdose, hypoglycemia may develop. This condition can take a protracted character and promote the development of severe conditions up to a comatose, life-threatening patient or ending lethal. 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.

Symptoms of hypoglycemia: strong feeling of hunger, sudden profuse sweating, palpitations, pallor and lowering of the temperature of the skin, paresthesia of the oral mucosa, trembling, general anxiety, headache, pathological drowsiness, sleep disorders, fear, coordination of movements, temporary neurological disorders , visual and speech disorders, manifestations of paresis and paralysis, or altered perception of sensations).With the progression of hypoglycemia, loss of self-control and consciousness is possible, a predisposition to convulsions develops.

Treatment: For hypoglycemia of mild or moderate severity, dextrose (glucose) or a solution of sugar must be taken internally.

In case of severe hypoglycemia accompanied by loss of consciousness, 40% solution of dextrose or intravenously glucagon intravenously, intramuscularly, subcutaneously. After restoring consciousness, the patient should be given food rich in carbohydrates, in order to avoid the re-development of hypoglycemia.

Interaction:

Glibenclamide is metabolized by cytochrome CYP2C9, which should be taken into account when it is used simultaneously with inducers or inhibitors CYP2C9.

An increase in the hypoglycemic effect of glibenclamide is observed with simultaneous use of angiotensin-converting enzyme inhibitors, anabolic agents and male sex hormones, other oral hypoglycemic drugs (eg, acarbose, biguanides) and insulin, non-steroidal anti-inflammatory drugs (NSAIDs), and azapropion. beta-adrenoblockers, guanethidine, quinine, quinolone derivatives, chloramphenicol, clofibrate,derivatives of coumarin, disopyramide, fenfluramine, pheniramidol, fluoxetine, monoamine oxidase inhibitors. antifungal agents (miconazole, fluconazole), p-aminosalicylic acid, pentoxifylline (in large doses administered parenterally), perhexiline derivatives, pyrazolones, phenylbutazone, phosphamide (e.g., cyclophosphamide, ifosfamide, trofosfamide), probenecid, salicylates, sulfinpirazona, sulfonamides, tetracyclines , clarithromycin and tritvaline.

Urine acidifying agents (ammonium chloride, calcium chloride) increase the effect of glibenclamide due to a decrease in the degree of its dissociation and increase its reabsorption. The hypoglycemic effect of glibenclamide may decrease with simultaneous use of barbiturates, isoniazid, cyclosporine, diazoxide, glucocorticosteroids, glucagon, epinephrine, nicotinate (in high doses), phenytoin, phenothiazines, rifampicin, ritordine, clonidine, thiazide diuretics, acetazole amide, estrogens (eg, oral hormonal contraceptives), preparations of iodine-containing hormones of the thyroid gland, blockers of "slow" calcium channels, sympathomimetic agents and lithium salts.

With simultaneous use with pentamidine in isolated cases, there may be a marked decrease or increase in the concentration of glucose in the blood.

The blockers of H2-histamine receptors, clonidine and reserpine are capable, both to strengthen, and to weaken hypoglycemic action of glibenclamide.

Under the influence of sympatholytic agents, such as beta-blockers, clonidine, guanethidine and reserpine, signs of adrenergic counterregulation in response to hypoglycemia may decrease or be absent.

A single or chronic use of alcohol can both enhance and weaken the hypoglycemic effect of glibenclamide.

Glibenclamide can enhance or weaken the effects of coumarin derivatives. Glibenclamide can increase the concentration in the plasma of cyclosporine and potentially lead to an increase in its toxicity, therefore, it is recommended to monitor the concentration and dose correction of cyclosporine when used simultaneously with glibenclamide.

When glibenclamide was used simultaneously with bosentan, there was an increase in the incidence of increased activity of "hepatic" enzymes. glibenclamide and bosentan inhibit the transfer of bile acids from the liver cells, which leads to their intracellular accumulation and enhancement of their cytotoxic effect. In this regard, the simultaneous use of glibenclamide and bosentan is contraindicated.

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

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 glibenclamide to patients with impaired liver and kidney function, as well as hypothyroidism of the thyroid gland, anterior pituitary gland or adrenal cortex. It is necessary to correct the dose of glibenclamide in case of physical and emotional overstrain, change in diet.

Factors that contribute to the risk of developing hypoglycemia include:

- unwillingness or inability of the patient (more often observed in elderly patients age) to cooperate with a doctor;

- malnutrition, irregular eating or skipping meals;

- imbalance between physical loads and carbohydrate intake;

- changing the diet;

- drinking alcohol, especially when combined with missing meals;

- severe renal dysfunction;

severe hepatic impairment;

- an overdose of glibenclamide;

- diarrhea, vomiting;

- Some decompensated endocrine disorders that disrupt carbohydrate metabolism or adrenergic counterregulation in response to hypoglycemia (for example, some disorders of the thyroid gland and anterior pituitary gland, insufficiency of the adrenal cortex);

- simultaneous intake of certain medicines.

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.

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

The use of sulfonylurea derivatives, which include glibenclamide, in patients with glucose-6-phosphate dehydrogenase deficiency can lead to the development of hemolytic anemia, therefore, hypoglycemic agents other than sulfonylureas should be used.

Simultaneous reception of drugs that have an effect on the central nervous system, lowering blood pressure (including beta-blockers), as well as autonomic neuropathy can mask symptoms of hypoglycemia.

In elderly patients, the risk of developing hypoglycemia is slightly higher, so a more careful selection of the dose of the drug and regular monitoring of the concentration of glucose in the blood on an empty stomach and after meals, especially at the beginning of treatment.

Alcohol can trigger the development of hypoglycemia, as well as the development of a disulfiram-like reaction (nausea, vomiting, abdominal pain, a feeling of fever in the face and upper body, tachycardia, dizziness, headache), so you should refrain from drinking alcohol during treatment with glibenclamide.

At each change of the doctor (for example, at hospitalization in hospital, at illness on holiday) the patient necessarily should inform the attending physician about that. that he has diabetes mellitus.

Fertility

Data on the effect of glibenclamide on fertility are not available.

Effect on the ability to drive transp. cf. and fur:

When taking glibenclamide, hypoglycemia may develop, and as a consequence, a decrease reaction and ability to concentrate, therefore, during treatment with the drug, care must be taken when driving vehicles and engaging in other potentially dangerous activities requiring concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 1.75 mg, 3.5 mg and 5 mg.

Packaging:

Primary packaging of medicinal product

For 7, 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

25, 30, 50, 60, 75, 80, 84. 90, 100, 112, 120, 150, 180 or 240 tablets in a polymer can of polyethylene with a lid of a pull-up with the control of the first opening. Free space is filled with cotton wool. Labels are applied to cans from paper label or written or from polymeric materials, self-adhesive.

Secondary packaging of medicinal product

By 2, 6, 8 or 10 out-of-round cell packs of 7 tablets together with the instruction for use are placed in a pack of cardboard for consumer containers.

For 2, 5 or 10 contour packs of 10 tablets together with the instructions for use are placed in a pack of cardboard for consumer containers.

On 1 bank together with the instruction on application place in a pack from a cardboard for consumer tare.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004405

Date of registration:09.08.2017

Expiration Date:09.08.2022

The owner of the registration certificate:Pharmasintez-Tyumen, Open CompanyPharmasintez-Tyumen, Open Company Russia

Manufacturer: & nbsp

FARMASINTEZ, JSC (Irkutsk) Russia

Pharmasintez-Tyumen, Open Company Russia

Information update date: & nbsp01.09.2017

Illustrated instructions

Instructions

Statiglyn (Statiglin)