Glibenclamide pills 3.5mg, 120pcs

Composition

Active ingredient:  

• glibenclamide – 3.50 mg;

Auxiliary substances:  

• lactose monohydrate (milk sugar) – 153.00 mg,
• corn starch-30.00 mg,
• povidone-K 25-6.00 mg,
• magnesium stearate-1.50 mg,
• sodium carboxymethyl starch (type A) – 6.00 mg

Pharmacological action

ATX code:  A 10 BB 01

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

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 concentration in the blood (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 impaired hepatic functionin patients with impaired liver function, the elimination of the Active ingredient from the blood plasma is slowed.

Pharmacokinetics in renal insufficiency In patients with renal insufficiency, the excretion of metabolites through the intestine compensatorily increases. If creatinine clearance is > 30 ml/min, total excretion remains unchanged; in severe renal insufficiency, accumulation is possible.

Indications

Type 2 diabetes mellitus as monotherapy or as part of combination therapy with other oral hypoglycemic drugs, except for derivatives of sulfonylureas and glinides.

Use during pregnancy and lactation

The use of glibenclamide during pregnancy is contraindicated. If pregnancy occurs, the drug should be discontinued. When planning pregnancy, therapy with oral hypoglycemic drugs should be replaced with insulin therapy. It is not known whether glibenclamide passes into breast milk. Since other derivatives of sulfonylureas pass into breast milk, the use of glibenclamide during breastfeeding is contraindicated.

Contraindications

• Hypersensitivity to glyburide and/or any subsidiary of the drug substance;
• 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;
• severe liver dysfunction;
• severe renal dysfunction (creatinine clearance <30 ml/min);
• severe adrenal insufficiency;
• decompensation of carbohydrate metabolism in infectious diseases, burns, injuries, or after major surgery when shown holding insulin;
• leukopenia;
• intestinal obstruction, paresis of the stomach;
• hereditary lactose intolerance, lactase deficiency or malabsorption syndrome glucose and lactose;
• pregnancy and lactation;
• children up to age 18 years (effectiveness and safety have not been studied).
• porphyria;
• glucose-6-phosphate dehydrogenase deficiency;
• concomitant use with bosentan.

WITH CAUTION

Glibenclamide should be used with caution in patients with febrile syndrome; thyroid diseases (with impaired function); insufficiency of the anterior pituitary or adrenal cortex function; alcoholism, acute alcohol intoxication; conditions associated with food malabsorption and the risk of hypoglycemia; mild to moderate renal failure (creatinine clearance > 30 ml/min); mild to moderate hepatic insufficiency; cerebral atherosclerosis; in elderly patients 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 disturbances and accommodation disorders.

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

Gastrointestinal disorders: 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.

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

Skin and subcutaneous tissue disorders: rare: 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 lead to 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), paraaminosalicylic acid, pentoxifylline (in large doses administered parenterally), perhexylin, pyrazolone derivatives, phenylbutazones, phosphamides (for example, cyclophosphamide, ifosfamide, and trophosphamide), 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, acetazolamide, 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.

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 compensation for carbohydrate metabolism 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 compensation for carbohydrate metabolism 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 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 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, the drug Glibenclamide is prescribed according to the scheme given above, and the previous drug is immediately canceled.

Use in combination therapy with other hypoglycemic Drugsglibenclamide can be used in combination therapy with metformin and other oral hypoglycemic drugs that do not stimulate insulin secretion by pancreatic beta cells.

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.

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 impairment (creatinine clearance >30 ml/min) and mild to moderate hepatic impairment, 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, 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: For 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::

• the unwillingness or inability of the patient (most often observed in elderly patients) to cooperate with the doctor;
• malnutrition, irregular mealtimes or omissions meal;
• the imbalance between physical exertion and carbohydrate intake;
• dietary advice;
• use of alcohol, especially in combination with skipped meals;
• severe kidney problems;
• severe disturbances of liver function;
• overdose of glibenclamide;
• diarrhea, vomiting;
• some decompensated endocrine disorders, in violation of carbohydrate metabolism or adrenergic contraregulatory in response to hypoglycemia (e. g., some disorders of thyroid function and in anterior pituitary, and adrenal insufficiency);
• simultaneous reception 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 that he has diabetes mellitus.

Fertility

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

Influence on the ability to drive vehicles and mechanisms

When taking the drug 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

In a dark place at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 3 years.

Active ingredient

Glibenclamide

Conditions of release from pharmacies

By prescription

Dosage form

Tablets