Glibenclamide, tablets 5 mg 120 pcs

ATX code: A10BB01

Pharmacological properties

Pharmacodynamics

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

It acts in the second stage of insulin secretion. It has a hypolipidemic effect, reduces the thrombogenic properties of the blood. Hypoglycemic effect develops after 2 hours, reaches its maximum after 7-8 hours and lasts 12 hours. The drug provides smooth increase of insulin concentration and smooth decrease of plasma glucose concentration, which reduces the risk of hypoglycemic states. The activity of glibenclamide occurs with preserved endocrine function of the pancreas.

Pharmacokinetics

Absorption

In oral administration, absorption from the gastrointestinal tract is 48-84%. Time of reaching maximum concentration in blood (T mah) is 1-2 hours. Bioavailability of glibenclamide is 100%. Concomitant intake of food has no significant effect on the absorption of glibenclamide.

Distribution

The volume of distribution (Vd) is 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.

Excretion

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

Pharmacokinetics in patients with hepatic impairment
In patients with hepatic impairment the excretion of the active substance from the blood plasma is delayed.

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

Indications

Active ingredient

Composition

How to take, the dosage

Ingestion. The drug should be taken before meals, without chewing and with plenty of liquid. The drug should be taken at the same time of the day. The dose of the drug is chosen individually, depending on age and severity of diabetes mellitus, blood glucose concentration at an empty stomach and 2 hours after a meal.

Tablets 5 mg. The tablet may be divided into 2 equal parts. The daily dose range is ½ to 3 tablets (2.5 mg to 15 mg). The starting dose is 2.5 to 5 mg (½ to 1 tablet) per day. The maximum daily dose is 15 mg (3 tablets).
The dose should be increased at intervals of several days to 1 week until the required therapeutic dose is reached, which should not exceed the maximum dose.

The tablets are 1.75 mg. The initial dose is usually 1-2 tablets (1.75 mg to 3.5 mg) once daily. The average daily dose is 3.5 mg (2 tablets). If necessary, the dose is gradually increased until compensation of carbohydrate metabolism is achieved. The maximum daily dose is 6 tablets (10.5 mg). If it is necessary to take more than three tablets, the dose is switched to 3.5 mg tablets. The dose should be increased at intervals of several days to one week until the desired therapeutic dose is reached, which should not exceed the maximum dose.

The 3.5 mg tablets. The initial dose is usually ½ to 1 tablet once daily. The average daily dose is 3.5 mg (1 tablet). If necessary, the dose is gradually increased until compensation of carbohydrate metabolism is achieved. The maximum daily dose is 10.5 mg (3 tablets).

Daily doses of up to 2 tablets are usually taken once a day – in the morning. Higher doses are divided into 2 doses – morning and evening doses at a ratio of 2:1. If one dose of the drug is missed, the next dose should be taken at the usual time, and the higher dose should not be taken.

Transition from other hypoglycemic drugs

When switching from other hypoglycemic drugs with a similar type of action, Glibenclamide is administered according to the scheme above, and the preceding drug is immediately withdrawn.

In combination therapy with other hypoglycemic drugs
Glibenclamide may be used in combination therapy with metformin and other oral hypoglycemic drugs that do not stimulate insulin secretion by pancreatic beta-cells.

The use in elderly, frail patients, and malnourished patients
In elderly, frail patients or malnourished patients, the initial and maintenance doses should be reduced because of the risk of hypoglycemia.

The use of Glibenclamide 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 because of the risk of hypoglycemia.

Interaction

Glibenclamide is metabolized by cytochrome CYP2C9, which should be considered when using it simultaneously with inducers or inhibitors of CYP2C9. Increased hypoglycemic action of glibenclamide is observed with concomitant use of angiotensin-converting enzyme inhibitors, anabolic agents and male sex hormones, other oral hypoglycemic drugs (eg, acarbose, biguanides) and insulin, nonsteroidal anti-inflammatory drugs (NSAIDs), azapropazone, beta-adrenoblockers, guanethidine, quinine, quinolone derivatives, chloramphenicol, clofibrate, coumarin derivatives, disopyramide, fenfluramine, pheniramidol, fluoxetine, monoamine oxidase inhibitors, antifungal agents (miconazole, fluconazole), para-aminosalicylic acid, pentoxifylline (in high doses given parenterally), Perhexiline, pyrazolone derivatives, phenylbutazones, phosphamides (e.g., cyclophosphamide, ifosfamide, trophosphamide), probenecid, salicylates, sulfinpyrazone, sulfonamides, tetracyclines, clarithromycin and tritoqualine.

The urine acidifying agents (ammonium chloride, calcium chloride) enhance the effect of glibenclamide by reducing its degree of dissociation and increasing its reabsorption.

. The hypoglycemic effect of glibenclamide may be reduced with concomitant use of barbiturates, isoniazid, cyclosporine, diazoxide, glucocorticosteroids, glucagon, epinephrine, nicotinate (in high doses), phenytoin, phenothiazines, rifampicin, Ritordine, clonidine, thiazide diuretics, acetazolamide, estrogens (e.g., oral hormonal contraceptives), iodine-containing thyroid hormone preparations, slow calcium channel blockers, sympathomimetic agents, and lithium salts.

In concomitant use with pentamidine in single cases a marked decrease or increase in blood glucose concentration may occur.

H 2-histamine receptor blockers, clonidine and reserpine can both potentiate and attenuate the hypoglycemic effects of glibenclamide. Under the influence of sympatholytic agents such as beta-adrenoblockers, clonidine, guanethidine and reserpine, signs of adrenergic counterregulation in response to hypoglycemia may be reduced or absent.

Single or chronic alcohol consumption may either enhance or impair the hypoglycemic effects of glibenclamide.

Glibenclamide may potentiate or attenuate the effects of coumarin derivatives. Glibenclamide may increase plasma concentrations of cyclosporine and potentially lead to increased toxicity of cyclosporine, so it is recommended to control the concentration and adjust the dose of cyclosporine during concomitant use with glibenclamide.

When using glibenclamide concomitantly with bosentan, an increase in the activity of “hepatic” enzymes has been noted because glibenclamide and bosentan inhibit the transport of bile acids from liver cells, which leads to their intracellular accumulation and enhances their cytotoxic effect.

In this regard, concomitant use of glibenclamide and bozentan is contraindicated.

Drugs that inhibit medullary hematopoiesis increase the risk of myelosuppression.

Special Instructions

The drug should be taken regularly and, if possible, at the same time. The drug regimen and dietary intake should be carefully observed.

The physician should carefully consider prescribing glibenclamide to patients with impaired hepatic and renal function, as well as hypothyroidism, anterior pituitary gland or adrenal cortex hypofunction. It is necessary to adjust the dose of glibenclamide in case of physical and emotional overexertion, changes in diet.

Factors contributing to the risk of hypoglycemia include:

Contraindications

Side effects

Classification of adverse reactions by frequency of development: frequently (> 1/100, < 1/10), infrequently (> 1/1000, < 1/100), rarely (> 1/10000, < 1/1000), very rarely (< 1/10000), including individual reports.

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

Visual organ disorders: very rare: visual impairment 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: infrequent: nausea, heartburn, anorexia, belching, vomiting, “metallic” taste in the mouth, a feeling of heaviness and fullness in the stomach, abdominal pain and diarrhea; rarely – pancreatitis.

Liver and biliary tract disorders: very rarely: increased activity of “liver” enzymes (ACT, ALT), cholestasis, cholestatic hepatitis, granulomatous hepatitis and bilirubinemia.

In individual cases, hepatitis, increased activity of “liver” enzymes and/or cholestasis and jaundice may 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: skin itching; urticaria; erythema nodosa; erythematous, maculopapular or bullous rash; psoriasis-like skin reactions.

Immune system disorders: very rarely, reactions in the form of urticaria may trigger severe states accompanied by shortness of breath and decrease in blood pressure, up to and including life-threatening shock.

Some cases of severe generalized allergic reactions with skin rash, joint pain, fever, appearance of protein in the urine and jaundice have been described. If symptoms of urticaria occur, seek medical attention immediately. Cross-allergy with other sulfonylurea derivatives and sulfonamides is possible.

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

Other side effects observed in isolated cases include photosensitization; hyponatremia; late cutaneous porphyria; pellagro-like symptoms.

An acute alcohol intolerance reaction may develop after drinking, manifested by circulatory and respiratory complications (disulfiram-like reaction: vomiting, fever in the face and upper torso, tachycardia, dizziness, headache).

Overdose

In case of overdose, hypoglycemia may develop. This condition may be prolonged and contribute to the development of severe states up to comatose, life-threatening or lethal.

In diabetic polyneuropathy or concomitant treatment with sympatholytic agents (see section “Interaction with other drugs”), typical precursors of hypoglycemia may be mild or absent.

Symptoms of hypoglycemia: Strong feelings of hunger, sudden profuse sweating, palpitations, pallor and decreased skin temperature, paresthesias of the oral mucosa, trembling, general restlessness, headache, abnormal somnolence, sleep disturbances, feelings of fear, movement coordination disorders, temporary neurological disorders (such as visual and speech disorders, paresis and paralysis or altered sensation perception).

In the progression of hypoglycemia, loss of self-control and consciousness may occur, and a predisposition to seizures develops.

Treatment: In mild or moderate hypoglycemia it is necessary to take dextrose (glucose) or sugar solution orally.

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

Pregnancy use

Similarities