Statiglin pills 3.5mg, 120pcs

Composition

Composition per tablet:

Active ingredient:

glibenclamide 3.5 mg

Auxiliary substance:

lactose monohydrate – 93.0 mg;

povidone K 30-3.5 mg;

low-substituted hyprolose-23.0 mg;

microcrystalline cellulose-47.0 mg;

sodium carboxymethyl starch-8.0 mg;

colloidal silicon dioxide-1.0 mg;

sodium stearyl fumarate-1.0 mg

Pharmacological action

Glibenclamide has pancreatic and extra-pancreatic effects. It stimulates insulin secretion by lowering the threshold of glucose irritation of pancreatic beta cells, increases sensitivity to insulin and the degree of its binding to target cells, increases insulin release, increases the effect of insulin on glucose uptake by muscles and liver, and inhibits lipolysis in adipose tissue (extra-pancreatic effects).

It acts in the second stage of insulin secretion. It has a hypolipidemic effect, reduces the thrombogenic properties of blood. The hypoglycemic effect develops in 2 hours, reaches a maximum in 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 when the endocrine function of the pancreas is preserved.

Pharmacokinetics:

Absorption rate

When taken orally, absorption from the gastrointestinal tract is 48-84%. The time to reach the maximum blood concentration (Tmax) is 1-2 hours. The bioavailability of glibenclamide is 100%. Simultaneous food intake does not significantly affect the absorption of glibenclamide.

Distribution

Volume of distribution (Vd) 9-10 liters. The binding to plasma proteins is 95-99%. The placental barrier passes poorly.

Metabolism

Glibenclamide is almost completely metabolized in the liver to form two inactive metabolites.

Deduction

One of the inactive metabolites is excreted by the kidneys, the other-through the intestines in approximately equal proportions. The half-life (T 1/2) is from 3 to 10-16 hours.

Pharmacokinetics in patients with hepatic impairment

In patients with impaired liver function, the elimination of the Active ingredient from the blood plasma is slowed down.

Pharmacokinetics in patients with renal insufficiency

In patients with renal insufficiency, the excretion of metabolites through the intestine increases compensatorily. With creatinine clearance ≥ 30 ml / min, the total rate of glibenclamide elimination from the body remains unchanged, with severe renal insufficiency, accumulation is possible.

Indications

Type 2 diabetes mellitus, in addition to diet and exercise therapy, as monotherapy, or as part of combination therapy with metformin or other oral hypoglycemic drugs, other than sulfonylureas and glinides.

Contraindications

– Hypersensitivity to glyburide and/or to any accessory ingredient of the drug;

– hypersensitivity to other derivatives of sulfonylurea; sulfonamides; diuretic agents, containing in the molecule a sulfonamide group; the probenecid, as it may cross-reactions;

– diabetes mellitus type 1;

diabetic ketoacidosis, diabetic precoma and coma;

– condition after resection of the pancreas;

– liver failure, severe;

– renal failure severe (creatinine clearance < 30 ml/min);

– adrenal insufficiency, severe;

– decompensation of carbohydrate metabolism in infectious diseases, burns, injuries, or after major surgery when shown holding insulin;

intestinal obstruction, paresis of the stomach;

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

– pregnancy and the period of breastfeeding;

– children up to age 18 years (effectiveness and safety have not been studied);

– porphyria;

– simultaneous use of bosentan.

With caution:

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

Side effects

Classification of adverse reactions by frequency: common (> 1/100, > < 1/10), uncommon (> 1/1000, < 1/10), uncommon (>< 1/100), rare (> 1/10000, < 1/100), rare (>< 1/1000), very rare (

Metabolic and nutritional disorders:  common: hypoglycemia, weight gain.

Visual disturbances:  very rare: visual impairment and accommodation disorders.

Disorders of the blood and lymphatic system:  rare: thrombocytopenia, thrombocytopenic purpura, leukocytopenia; very rare: leukopenia, agranulocytosis, erythropenia, hemolytic anemia or pancytopenia, aplastic anemia, bone marrow aplasia, eosinophilia and blood clotting disorders.

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

Liver and biliary tract disorders:  very rare: 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 may regress after discontinuation of glibenclamide.

Kidney and urinary tract disorders:  very rare: increased diuresis, transient proteinuria.

Skin and subcutaneous tissue disorders:  rarely: pruritus of the skin; urticaria; erythema nodosum; erythematous, maculopapular or bullous rash; psoriasis-like skin reactions.

Immune system disorders:  very rarely, reactions in the form of urticaria can serve as the beginning of the development of severe conditions, accompanied by shortness of breath and a decrease in blood pressure until the onset of life-threatening shock. Isolated cases of severe generalized allergic reactions with skin rash, joint pain, fever, protein in the urine and jaundice are described. If you experience symptoms of urticaria, you should immediately consult a doctor. Possible cross-allergy with other derivatives of sulfonylureas, sulfonamides.

In some cases, allergic vasculitis may develop, in some cases – life-threatening.

Other side effects observed in isolated cases include photosensitization; hyponatremia; late cutaneous porphyria; and pellagra-like symptoms. It is possible to develop an acute reaction of alcohol intolerance after its use, which is expressed by complications from the circulatory and respiratory organs (disulfiram-like reaction: vomiting, a feeling of heat in the face and upper body, tachycardia, dizziness, headache).

Interaction

Glibenclamide is metabolized by the cytochrome CYP2C9, which should be taken into account when it is co-administered with inducers or inhibitors of CYP2C9.

Increased hypoglycemic effect of glibenclamide is observed with the simultaneous use of angiotensin-converting enzyme inhibitors, anabolic agents and male sex hormones, other oral hypoglycemic drugs (for example, acarbose, biguanides) and insulin, nonsteroidal anti-inflammatory drugs (NSAIDs), azapropazone. beta-blockers, guanethidine, quinine, quinolone derivatives, chloramphenicol, clofibrate, coumarin derivatives, disopyramide, fenfluramine, phenyramidol, fluoxetine, monoamine oxidase inhibitors. antifungal agents (miconazole, fluconazole), para-aminosalicylic acid, pentoxifylline (in large doses administered parenterally), perhexylin, derivatives of pyrazolones, phenylbutazones, phosphamides (for example, cyclophosphamide, ifosfamide, trophosfamide), probenecid, salicylates, sulfinpyrazone, sulfonamides, tetracyclines, clarithromycin and tritoqualin.

Urine acidifying agents (ammonium chloride, calcium chloride) enhance the effect of glibenclamide by reducing the degree of its dissociation and increasing its reabsorption. The hypoglycemic effect of glibenclamide may decrease with the simultaneous use of barbiturates, isoniazid, cyclosporine, diazoxide, glucocorticosteroids, glucagon, epinephrine, nicotinates (in large doses), phenytoin, phenothiazines, rifampicin, ritordine, clonidine, thiazide diuretics, acetazol amide, estrogens (for example, oral hormonal contraceptives), preparations of iodine-containing thyroid hormones, slow calcium channel blockers, sympathomimetic agents and lithium salts.

When used concomitantly with pentamidine in isolated cases, a pronounced decrease or increase in the concentration of glucose in the blood is possible.

H2-histamine receptor blockers, clonidine and reserpine can both enhance and weaken the hypoglycemic effect 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.

Single or chronic alcohol consumption can both enhance and weaken the hypoglycemic effect of glibenclamide.

Glibenclamide may enhance or weaken the effects of coumarin derivatives. Glibenclamide can increase the plasma concentration of cyclosporine and potentially lead to increased toxicity, so it is recommended to monitor the concentration and adjust the dose of cyclosporine when used simultaneously with glibenclamide. When using glibenclamide simultaneously with bosentan, an increase in cases of increased activity of “liver” enzymes was noted, since glibenclamide and bosentan inhibit the transfer of bile acids from liver cells, which leads to their intracellular accumulation and an increase in their cytotoxic effect. In this regard, the simultaneous use of glibenclamide and bosentan is contraindicated.

Medications that inhibit bone marrow hematopoiesis increase the risk of myelosuppression.

How to take, course of use and dosage

Inside. The drug should be taken before meals, without chewing and with a sufficient amount of 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 diabetes mellitus, fasting blood glucose concentration and 2 hours after meals. It is necessary to adjust the dose if the patient’s body weight and lifestyle change. It is also necessary to regularly monitor the concentration of glucose in the blood and urine, glycated hemoglobin, and lipid metabolism indicators.

Tablets 5 mg. The tablet can be divided into 2 equal parts. The daily dose range is from ½ to 3 tablets (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).

Dose increases should be made at intervals of several days to 1 week until the required therapeutic dose is reached, which should not exceed the maximum.

Tablets 1.75 mg. The initial dose is usually 1-2 tablets (1.75 mg – 3.5 mg) 1 time 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 you need to take more than three tablets, switch to taking tablets with a dosage of 3.5 mg.

Dose increases should be made at intervals of several days to 1 week until the required therapeutic dose is reached, which should not exceed the maximum.

Tablets 3,5 mg. The initial dose is usually ½ – 1 tablet 1 time 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 up to 2 tablets are usually taken 1 time a day-in the morning. Higher doses are divided into 2 doses-morning and evening doses 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, and it is not allowed to take a higher dose.

Switching from other hypoglycemic drugs

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

Use 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 metformin intolerance, a combination of glibenclamide with thiazolidinediones (rosiglitazone, pioglitazone) can be recommended, and in the initial stage of secondary resistance to glibencamide – with insulin. In case of complete secondary resistance to glibencamide, insulin monotherapy is recommended.

Use in elderly, debilitated patients and patients with reduced nutrition

In elderly, debilitated patients or patients with reduced nutrition, the initial and maintenance doses should be reduced due to the risk of hypoglycemia.

Children and teenagers

There are no data on the efficacy and safety of glibenclamide in this age group.

Use in patients with impaired renal and hepatic function

The use of glibenclamide in patients with severe renal and hepatic insufficiency is contraindicated. In patients with mild to moderate renal insufficiency (creatinine clearance ≥ 30 ml/min) and mild to moderate hepatic insufficiency, the initial and maintenance doses should be reduced due to the risk of hypoglycemia.

Overdose

In case of overdose, hypoglycemia may develop. This condition can take on a prolonged character and contribute to the development of severe conditions up to comatose, life-threatening or fatal. In diabetic polyneuropathy or in concomitant treatment with sympatholytic agents (see the section “Interaction with other drugs”), typical precursors of hypoglycemia may be mild or absent altogether.

Symptoms of hypoglycemia: severe hunger, sudden profuse sweating, palpitation of the heart, paleness and decreased skin temperature, paresthesia of the oral mucosa, trembling, general restlessness, headache, abnormal drowsiness, sleep disorders, fear, impaired coordination of movements, temporary neurological disorders (for example, 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, and a predisposition to seizures develops.

Treatment: In case of mild or moderate hypoglycemia, dextrose (glucose) or a sugar solution should be taken orally.

In case of severe hypoglycemia accompanied by loss of consciousness,40% dextrose solution or glucagon is administered intravenously, intramuscularly, subcutaneously. After regaining consciousness, the patient should be given a carbohydrate-rich diet to avoid recurrent 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 taking the drug and the diet. The doctor should carefully consider prescribing glibenclamide to patients with impaired liver and kidney function, as well as with hypofunction of the thyroid gland, anterior pituitary gland or adrenal cortex. It is necessary to adjust the dose of glibenclamide in case of physical and emotional overstrain, changing the diet.

Factors contributing to the risk of hypoglycemia include::

– unwillingness or inability of the patient (most often observed in elderly patients) to cooperate with the doctor;

– malnutrition, irregular mealtimes or skipping of meals;

– imbalance between physical exertion and carbohydrate intake;

– change the diet;

– drinking alcohol, especially in combination with skipped meals;

– severe renal dysfunction;

severe disturbances of liver function;

– overdose glibenclamide;

– diarrhea, vomiting;

– some decompensated endocrine disorders, in violation of carbohydrate metabolism or adrenergic contraregulatory in response to hypoglycemia (e. g. some dysfunction of the thyroid and anterior pituitary, and adrenal insufficiency);

– concomitant use of certain drugs.

Major surgical procedures and injuries, extensive burns, and infectious diseases with febrile syndrome may require discontinuation of oral hypoglycemic medications and insulin use.

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 may lead to the development of hemolytic anemia, so hypoglycemic agents that are not sulfonylurea derivatives should be used.

Concomitant use of medications that have an effect on the central nervous system, lower blood pressure (including beta-blockers), as well as autonomic neuropathy can mask the symptoms of hypoglycemia.

In elderly patients, the risk of hypoglycemia is slightly higher, so more careful selection of the dose of the drug and regular monitoring of fasting and post-meal blood glucose concentrations are necessary, especially at the beginning of treatment.

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

At each change of doctor (for example, when being admitted to the hospital, when being ill on vacation), the patient must inform the attending physician about the following. that he has diabetes.

Fertility

There are no data on the effect of glibenclamide on fertility.

Influence on the ability to drive vehicles and fur. :

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

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25 °C.

Keep out of reach of children.

Shelf

life is 3 years.

Do not use after the expiration date.

Active ingredient

Glibenclamide

Conditions of release from pharmacies

By prescription

Dosage form

Tablets