Description
Pharmacological action
Glibenclamide has pancreatic and extrapancreatic effects. It stimulates insulin secretion by lowering the threshold of pancreatic beta-cell glucose irritation, increases insulin sensitivity and its binding to target cells, increases insulin release, enhances the effect of insulin on muscle and liver glucose uptake, and inhibits lipolysis in adipose tissue (extra-pancreatic effects) . Acts in the second stage of insulin secretion. It has a lipid-lowering effect, reduces the thrombogenic properties of blood. The hypoglycemic effect develops after 2 hours, reaches a maximum after 7-8 hours and lasts 12 hours. The drug provides a smooth increase in insulin concentration and a smooth decrease in glucose concentration in blood plasma, which reduces the risk of hypoglycemic conditions. Glibenclamide activity is manifested with preserved endocrine pancreatic function.
Pharmacokinetics:
Absorption of
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 eating does not significantly affect the absorption of glibenclamide.
Distribution
Distribution volume (Vd) 9-10 l. Communication with 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 excreted by the kidneys, the other through the intestines in approximately equal proportions. The half-life (T1 / 2) is from 3 to 10-16 hours.
Pharmacokinetics in patients with impaired liver function
In patients with impaired liver function, the excretion of the active substance from blood plasma is slowed down.
Pharmacokinetics for renal failure
In patients with renal insufficiency, excretion of metabolites through the intestines increases compensatory. With creatinine clearance 30 ml / min. The total rate of removal of glibenclamide from the body remains unchanged, with severe renal failure, cumulation is possible.
Indications
Type 2 diabetes mellitus, in addition to diet therapy and exercise, as monotherapy or as part of combination therapy with metformin or other oral hypoglycemic drugs, except for sulfonylureas and clayides.
Contraindications
– Hypersensitivity to glibenclamide and / or any excipient of the
preparation – hypersensitivity to other sulfonylurea derivatives sulfonamides diuretics containing a sulfonamide group in the molecule probenecide, because cross reactions may occur
– type 1 diabetes mellitus
– diabetic ketoacidosis, diabetic precoma and coma
– condition after pancreatic resection
– severe hepatic insufficiency
– severe renal failure (creatinine clearance <30 ml / min) – severe adrenal insufficiency – decompensation of carbohydrate metabolism or after major surgeries when insulin therapy is indicated – intestinal obstruction, gastric paresis – hereditary lactose intolerance, lactase deficiency and whether glucose and lactose malabsorption syndrome – pregnancy and lactation – children under 18 years of age (efficacy and safety have not been studied) – porphyria – simultaneous use with bosentan. Caution: Glibenclamide should be used with caution in cases of febrile thyroid disease (with decreased function) deficiency of the anterior pituitary or adrenal cortex, glucose-6-dehydrogenase deficiency, chronic alcoholism, acute alcohol intoxication, accompanied by malabsorption and prolonged hypoglycemia insufficient intake of carbohydrates from food, excessive physical activity, diarrhea or vomiting) renal failure is easy th and moderate severity (creatinine clearance 30 ml / min) of mild and moderate hepatic insufficiency of cerebral atherosclerosis in elderly patients over 65 years of age due to the risk of 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 the drug and the diet. The doctor should carefully consider the appointment of glibenclamide in patients with impaired liver and kidney function, as well as with hypofunction of the thyroid gland, anterior pituitary or adrenal cortex. A dose adjustment of glibenclamide is necessary with physical and emotional overstrain, a change in diet. Factors contributing to the risk of developing hypoglycemia include: – unwillingness or inability of the patient (often observed in elderly patients) to cooperate with a doctor – malnutrition, irregular eating or skipping meals – imbalance between physical activity and carbohydrate intake – changing diet – drinking, especially in combination skipped meals – severe renal dysfunction – severe liver dysfunction – overdose of glibenclamide – diarrhea, vomiting – some decompensated endocrine disorders, disturbing carbohydrate metabolism or adrenergic counterregulation in response to hypoglycemia (for example, some dysfunctions of the thyroid gland and the anterior pituitary gland, adrenal cortex insufficiency) – the simultaneous use of certain drugs. Large surgical interventions and injuries, extensive burns, infectious diseases with febrile syndrome may require discontinuation 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 hemolytic anemia, therefore hypoglycemic agents that are not sulfonylurea derivatives should be used. The simultaneous use of drugs that have an effect on the central nervous system, lowering blood pressure (including beta-blockers), as well as autonomic neuropathy can mask the symptoms of hypoglycemia. In elderly patients, the risk of developing hypoglycemia is slightly higher, therefore 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 a meal, especially at the beginning of treatment, are necessary. Alcohol can provoke the development of hypoglycemia, as well as the development of a disulfiram-like reaction (nausea, vomiting, abdominal pain, sensation of heat of the face and upper body, tachycardia, dizziness, headache), so you should refrain from taking alcohol during treatment with glibenclamide. Each time a doctor is changed (for example, during hospitalization in a hospital, or if he is sick on vacation), the patient must inform the attending physician about that. that he has diabetes. Fertility No data on the effect of glibenclamide on fertility. Impact on the ability to drive transp. Wed and fur .: When taking glibenclamide, the development of hypoglycemia is possible, and, as a consequence, a decrease in 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 that require concentration and speed psychomotor reactions. Composition Composition per tablet: Active ingredient: glibenclamide 3.5 mg Excipient: lactose monohydrate – 93.0 mg povidone K30 – 3.5 mg low-substituted hypolerosis – 23.0 mg microcrystalline cellulose – 47.0 mg sodium carboxymethyl starch – 8.0 mg of silicon colloidal dioxide – 1.0 mg of sodium stearyl fumarate – 1.0 mg. Dosage and Administration Inside. The drug should be taken before meals, without chewing and drinking plenty of fluids. The drug should be taken at the same time of day. The dose of the drug is selected individually depending on age, severity of diabetes mellitus, fasting blood glucose concentration and 2 hours after eating. A dose adjustment is necessary when changing the body weight and lifestyle of the patient. Regular monitoring of the concentration of glucose in blood and urine, glycated hemoglobin, and indicators of lipid metabolism is also necessary. tablets 5 mg. The tablet can be divided into 2 equal parts. The daily dose range is from up to 3 tablets (from 2.5 mg to 15 mg). The initial dose is 2.5-5 mg ( – 1 tablet) per day. The maximum daily dose is 15 mg (3 tablets). An increase in dose should be carried out at intervals from several days to 1 week until the desired 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 per 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 it is necessary to take more than three tablets, they switch to taking tablets with a dosage of 3.5 mg. An increase in dose should be carried out at intervals from several days to 1 week until the desired therapeutic dose is reached, which should not exceed the maximum. Tablets 3.5 mg. The initial dose is usually – 1 tablet 1 time per 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 up to 2 tablets are usually taken once a day, in the morning. Higher doses are divided into 2 doses – morning and evening doses in a ratio of 2: 1. If you skip one dose of the drug, the next dose should be taken at the usual time, and you are not allowed to take a higher dose. Transition from other hypoglycemic drugs When switching from other hypoglycemic drugs with a similar type of action, glibenclamide is prescribed according to the scheme above, and the previous drug is immediately canceled. Use as part of combination therapy with other hypoglycemic drugs Glibenclamide can be used as part of 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, with the initial stage of secondary resistance to glibencamide with insulin. In the case of complete secondary resistance to glibencamide – insulin monotherapy. Use in the elderly, debilitated patients and patients with reduced nutrition In the elderly, debilitated patients or patients with reduced nutrition, the initial and maintenance doses must be reduced because of the risk of hypoglycemia. Children and adolescents 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 and moderate renal failure (creatinine clearance 30 ml / min) and mild and moderate hepatic insufficiency, the initial and maintenance doses must be reduced because of the risk of hypoglycemia. Side effects Classification of unwanted side reactions by developmental frequency: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000, <1/1000 ), very rarely (<1/10000), including individual messages. Metabolism and nutritional disorders: often: hypoglycemia, weight gain. Disorders of the organ of vision: very rarely: impaired vision and disturbance of accommodation. Disorders from the blood and lymphatic system: rarely: thrombocytopenia, thrombocytopenic purpura, very rare leukocytopenia: leukopenia, agranulocytosis, erythropenia, hemolytic anemia or pancytopenia, aplastic anemia, bone marrow aplasia, eosinophilia and. Disorders of 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 of the liver and biliary tract: 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 can regress after stopping glibenclamide. Disorders of the kidneys and urinary tract: very rare: increased diuresis, transient proteinuria. Disorders of the skin and subcutaneous tissue: rarely: skin itching urticaria erythema nodosum erythema, maculopapular or bullous rash psoriasis-like skin reactions. Immune system disorders: very rarely, urticaria reactions can initiate the development of severe conditions, accompanied by shortness of breath and lowering blood pressure until a life-threatening shock occurs. Some cases of severe generalized allergic reactions with a skin rash, joint pain, fever, the appearance of protein in the urine and jaundice are described. If symptoms of urticaria appear, consult a doctor immediately. Cross-allergy is possible with other sulfonylurea derivatives, sulfonamides. In some cases, the development of allergic vasculitis is possible, in some cases – life-threatening. To other side effects, observed in isolated cases include photosensitivity hyponatremia late cutaneous porphyria pellagropodobny symptoms. It is possible to develop an acute reaction of alcohol intolerance after drinking it, expressed by complications of the circulatory and respiratory organs (disulfiram-like reaction: vomiting, sensation of heat in the face and upper body, tachycardia, dizziness, headache). Overdose In case of overdose, hypoglycemia may develop. This condition can take a protracted nature and contribute to the development of severe conditions, up to a comatose, life-threatening patient or ending fatally. In case of diabetic polyneuropathy or with concomitant treatment with sympatholytic agents (see Interaction with other medicinal products section), typical precursors of hypoglycemia may be mild or absent altogether. Symptoms of hypoglycemia: severe hunger, sudden profuse sweating, palpitations, pallor and decreased skin temperature, paresthesia of the oral mucosa, trembling, general anxiety, headache, pathological drowsiness, sleep disturbances, feelings of fear, impaired coordination of movements, temporary neurological disorders (e.g., visual and speech disorders, paresis and paralysis, or altered sensory perceptions). With the progression of hypoglycemia, loss of self-control and consciousness is possible, a predisposition to seizures develops. Treatment: For mild or moderate hypoglycemia, dextrose (glucose) or a sugar solution must 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 must be given carbohydrate-rich foods to prevent the re-development of hypoglycemia. Storage conditions In a dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children. Expiration 3 years. Do not use after expiration date. Terms and conditions prescription Dosage form tablets
