Glibenclamide

Pharmacological properties

refers to oral hypoglycemic agents derived sulfonylurea ii generation. promotes the stimulation of β-cells of the pancreas, accompanied by mobilization and increased release of endogenous insulin. the drug is effective in the presence of functionally capable β-cells in the pancreas that produce endogenous insulin. helps reduce platelet aggregation.

Pharmacokinetics With oral administration of glibenclamide on an empty stomach, its rapid and almost complete absorption in the gastrointestinal tract occurs. The drug binds to blood proteins (albumin) by more than 98% and is metabolized in the liver. In the process of metabolism, 3-cis-hydroxy-glibenclamide and 4-trans-hydroxy-glibenclamide are formed. It is excreted in the urine and bile. T_½ glibenclamide from blood plasma - 1.5-3.5 hours. The hypoglycemic effect lasts up to 12 hours.

In patients with decreased liver function, drug excretion slows down. In conditions accompanied by moderate renal failure (with creatinine clearance of 30 ml / min), the process of excretion of metabolites does not change, but their accumulation is possible with severe renal failure.

Indications

Non-insulin-dependent diabetes in adults (type II diabetes mellitus), if other measures, such as strict diet, weight loss, sufficient physical activity, have not led to a satisfactory correction of blood glucose.

Application

The drug should be used only as prescribed by the doctor and be sure to correct the diet. the dosage depends on the results of a study of the state of metabolism (glucose levels in the blood and urine).

First and subsequent appointments. The therapy is started as soon as possible with the smallest possible doses, first of all, this concerns patients with an increased tendency to hypoglycemia and body weight less than 50 kg. The first appointment is from ½ to 1 tablet (which corresponds to 2.5-5 mg of glibenclamide) per day. With insufficient metabolic correction, the dose is gradually increased at intervals from several days to one week to the required daily therapeutic dose of 3 tablets (which corresponds to 15 mg of glibenclamide) per day.

Transfer of the patient with the use of other antidiabetic drugs. Transfer to the drug Glibenclamide should be carried out very carefully and start with ½ to 1 tablet (which corresponds to 2.5-5 mg of glibenclamide per day).

Dose selection. Elderly patients, weakened or patients with malnutrition, as well as mild to moderate impaired renal or hepatic function, the initial and maintenance dose must be reduced due to the possibility of hypoglycemia. With a decrease in the patient’s body weight or a change in lifestyle, the question of dose adjustment should be addressed.

Combination with other antidiabetic agents. In justified cases, patients with metformin intolerance may be shown the additional purpose of the glitazone group of drugs (rosiglitazone, pioglitazone).Glibenclamide can be combined with oral antidiabetic drugs that do not stimulate β-cell release of endogenous insulin (guarmel or acarbose). With the appearance of secondary inefficiency of glibenclamide therapy (a decrease in insulin production as a result of a decrease in β-cell activity), you can try a combination treatment with insulin. However, with the complete cessation of the secretion of their own insulin by the body, insulin monotherapy is indicated.

The method and duration of treatment. Tablets should be taken before meals. Do not chew and drink with a sufficient amount of liquid (preferably 1 glass of water). With a daily dose of more than 2 tablets of the drug, it is recommended that the entire amount be distributed to one morning and one evening dose in a ratio of 2: 1. It is very important to use the drug every time at the same time. If the patient missed one dose, you should never supplement this with a higher dose. The duration of treatment depends on the course of the disease. During treatment, regular monitoring of the state of metabolism is necessary.

Contraindications

Hypersensitivity to glibenclamide or excipients, sulfonylureas, sulfonamides, diuretics, sulfonamide derivatives and probenecid. in cases where insulin treatment is required: type I diabetes mellitus, complete secondary inefficiency of glibenclamide therapy for type II diabetes mellitus, metabolic disorders in the direction of acidosis, precoma or diabetic coma. condition after pancreatic resection. severe dysfunction of the liver. severe renal impairment.

Side effects

When evaluating adverse reactions, the following values ​​of the frequency of occurrence were taken as the basis: very often (≥10%), often (10%, ≥1%), sometimes (1%, ≥0.1%), rarely (0.1%, ≥ 0.01%), very rarely (0.01% or cases are unknown).

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

Visual disorders: very rarely - visual and accommodation disorders, especially at the beginning of treatment.

Disorders from the gastrointestinal tract: sometimes - nausea, a feeling of fullness of the stomach, vomiting, abdominal pain, diarrhea, belching, metallic taste in the mouth. These phenomena are reversible and do not require discontinuation of the drug.

Dysfunction of the liver and gall bladder: very rarely - a transient increase in AsAT and ALAT, alkaline phosphatase, drug-induced hepatitis, intrahepatic cholestasis, which may be caused by an allergic reaction of the hyperergic type of liver cells. These disorders are reversible after discontinuation of the drug, but can lead to life-threatening liver failure.

Disorders from the skin and subcutaneous tissue: sometimes - itching, urticaria, erythema nodosum, measles or maculopapular exanthema, purpura, photosensitivity. These phenomena of hypersensitivity reactions are reversible, but very rarely can go into life-threatening conditions, accompanied by suffocation and a decrease in blood pressure, up to the development of shock.Very rarely - generalized hypersensitivity reactions, accompanied by skin rash, arthralgia, fever, proteinuria and jaundice; allergic vasculitis, life-threatening. If skin reactions occur, consult a doctor.

Violations of the blood system and lymphatic system: rarely - thrombocytopenia. Very rarely - leukopenia, erythropenia, granulocytopenia, up to the development of agranulocytosis. In some cases - pancytopenia, hemolytic anemia, aplastic anemia, eosinophilia. The above changes in the blood picture are reversible after discontinuation of the drug, but very rarely can be a threat to life.

Other side effects: very rarely - weak diuretic effect, syndrome of inadequate secretion of antidiuretic hormone, reversible proteinuria, hyponatremia, disulfiram-like reaction, cross allergy with sulfonamides, sulfonamide derivatives and probenecid. Ponso 4R may cause an allergic reaction.

special instructions

When using the drug in patients with impaired renal or hepatic function of the liver of mild or moderate degree or decreased function of the thyroid gland, pituitary or adrenal cortex, special care is required.

In elderly patients, there is a risk of prolonged hypoglycemia, therefore, they are prescribed glibenclamide with extreme caution and carefully monitor their condition at the beginning of treatment. In this age group, under certain conditions, it is first more advisable to use sulfonylurea preparations with a shorter duration of action. Patients with diabetes with signs of cerebral sclerosis and patients with difficult contact in general are more prone to the risk of developing hypoglycemia. Significant intervals between meals, inadequate carbohydrate intake, unusual physical activity, diarrhea or vomiting can increase the risk of hypoglycemia.

With the simultaneous use of the drug Glibenclamide with clonidine, β-adrenoreceptor blockers, guanethidine and reserpine, the patients perception of symptoms may be impaired - precursors of hypoglycemia.

The effect of the drug Glibenclamide can unexpectedly increase or decrease with the use of alcohol repeatedly in significant quantities and with its constant use.

The constant abuse of laxatives can lead to a deterioration in the state of metabolism.

If the treatment regimen is not observed, the hypoglycemic effect of the drug is insufficient or there are stressful situations (trauma, surgery, infectious disease, which is accompanied by an increase in body temperature), blood glucose levels can sometimes rise so much that temporary transfer of the patient to insulin may be required. Symptoms of hyperglycemia may include feelings of extreme thirst, dry mouth, frequent urination, itching, dry skin, fungal or infectious skin diseases, and decreased performance.The patient should know that if other diseases appear during treatment with Glibenclamide, he should immediately consult a doctor.

In patients with a deficiency of glucose-6-phosphate dehydrogenase in the body, treatment with sulfonylureas, including glibenclamide, can cause hemolytic anemia, so the issue of switching to drugs alternative to sulfonylurea derivatives should be addressed.

In patients with hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome, glibenclamide should not be used.

Use during pregnancy and lactation. The use of glibenclamide in pregnant women and during lactation is contraindicated.

Children. Do not use in children.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Patients should apply safety measures to prevent hypoglycemia while driving and working with other mechanisms. This is especially important for those patients who often have cases of hypoglycemia or have no symptoms - precursors of hypoglycemia. In such cases, it is necessary to resolve the issue of the appropriateness of driving.

Interactions

Drugs that enhance the effects of glibenclamide with simultaneous use: other antidiabetic drugs and insulin, apf inhibitors, anabolic steroids and male sex hormones, antidepressants (fluoxetine, mao inhibitors), β-adrenoreceptor blockers, quinolone derivatives, chloramphenicol and its clofibrate , disopyramide, fenfluramine, miconazole, pasc, pentoxifylline (administered parenterally in a high dose), perhexiline, pyrazolone derivatives, probenecid, salicylates, sulfonamides, antibiotics ratsiklinovogo series tritokvalin, cytotoxic agents such as cyclophosphamide.

Drugs that reduce the effect of glibenclamide with simultaneous use: acetazolamide, β-adrenoreceptor blockers, barbiturates, diazoxide, diuretics, glucagon, isoniazid, corticosteroids, nicotinates, phenothiazine derivatives, phenytoin, rifampicin, thyroid hormones, female genes sympathomimetics.

Blockers H₂receptors, clonidine and reserpine can both reduce and enhance the hypoglycemic effect of the drug. In some cases, pentamidine can lead to severe hypoglycemia or hyperglycemia. The effect of coumarin derivatives can both increase and decrease.

Overdose

A single overdose or the use of slightly increased doses for a long time can lead to severe prolonged hypoglycemia, which is life threatening.

Symptoms of an overdose (hypoglycemia): sudden sweating, increased palpitations, trembling, hunger, anxiety, paresthesia in the mouth, pallor of the skin, headache, drowsiness, sleep disorders, shyness, lack of movement, temporary neurological disorders (speech and vision disorders paralysis or sensory disturbance). With progressive hypoglycemia, the patient may lose control of his condition and lose consciousness (hypoglycemic shock).In such cases, the skin feels moist and cold to the touch, tachycardia, hyperthermia, motor excitement, hyperreflexion, paresis and a positive Babinsky reflex are noted, convulsions may appear.

Treatment. Mild or moderate severity of hypoglycemia can be resolved by the patient by consuming sugar, food, or drinks with a high content. If hypoglycemia is severe, you should immediately consult a doctor. In case of accidental poisoning and provided that contact with the patient can be established, vomiting should be performed, gastric lavage should be carried out (in the absence of a tendency to cramps) and injected into / into glucose. If the patient has lost consciousness, you should immediately start the on / in the introduction of glucose (40–80 ml of 40% solution in the form of an injection, then continue to infuse 5-10% solution of glucose). If necessary, you can additionally introduce 1 mg of glucagon in / in or / m. If the patient does not regain consciousness, these measures are repeated, and in the future, intensive therapy may be necessary. With prolonged hypoglycemia, monitoring the patient for several days is required with regular monitoring of blood glucose levels and, if necessary, carrying out infusion therapy.

Storage conditions

In the dark place at a temperature of no higher than 25 ° c.