Glimidstada^® (Tablets) Instructions for Use

ATC Code

A10BB01 (Glibenclamide)

Active Substance

Glibenclamide (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Oral hypoglycemic drug

Pharmacotherapeutic Group

Hypoglycemic agent for oral administration of the second-generation sulfonylurea group

Pharmacological Action

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

It acts in the second phase of insulin secretion. It has a hypolipidemic effect and reduces the thrombogenic properties of blood. The hypoglycemic effect develops within 2 hours, reaches a maximum after 7-8 hours, and lasts for 12 hours.

The drug provides a smooth increase in insulin concentration and a smooth decrease in plasma glucose, which reduces the risk of hypoglycemic conditions. The activity of glibenclamide is manifested when the endocrine function of the pancreas to synthesize insulin is preserved.

Pharmacokinetics

When taken orally, absorption from the gastrointestinal tract is 48-84%. The time to reach C_max is 1-2 hours, V_d is 9-10 liters. Plasma protein binding is 95%.

The bioavailability of glibenclamide is 100%, which allows the drug to be taken almost before meals. It crosses the placental barrier poorly. It is almost completely metabolized in the liver with the formation of two inactive metabolites, one of which is excreted by the kidneys and the other with bile. T_1/2 is from 3 to 10-16 hours.

Indications

Type 2 diabetes mellitus (when diet therapy is ineffective).

ICD codes

Dosage Regimen

Tablets

The dose is determined by the doctor and depends on age, the severity of diabetes, and blood glucose concentration on an empty stomach and 2 hours after a meal. The daily dose ranges from 1.75 mg to 10.5 mg.

At the initial stage of treatment and when transferring a patient to this drug from other oral hypoglycemic agents, it is recommended to increase the dose gradually. Treatment should be started with the appointment of 1.75 mg of Glimidstada^® (1/2 tablet of Glimidstada^® 3.5 mg) once a day. This dose can be gradually increased at intervals from several days to 1 week until a therapeutic dose is reached. The maximum effective dose is 10.5 mg of Glimidstada^®.

When replacing hypoglycemic drugs with a similar type of action, Glibenclamide is prescribed according to the scheme given above, and the previous drug is immediately discontinued. A daily dose of up to 2 tablets of Glimidstada^® is taken without chewing, with a small amount of liquid once a day before breakfast. With a higher daily dose, it is recommended to divide it into 2 doses in a ratio of 2:1 in the morning and evening. If a dose is missed, a double dose should not be taken to replace the missed one. Glimidstada^® can be used in combination with other hypoglycemic agents, including insulin.

Adverse Reactions

Classification of undesirable adverse reactions (UAR) by frequency of development: very common: ≥1/10; common: ≥ 1/100 and < 1/10; uncommon: ≥ 1/1000 and < 1/100; rare: ≥ 1/10000 and < 1/1000; very rare: < 1/10000 prescriptions or frequency not known (cannot be calculated from the available data).

Metabolism and nutrition disorders common – hypoglycemia, weight gain.

The most common adverse effect of the drug is hypoglycemia. It can be prolonged and contribute to the development of severe conditions up to coma, life-threatening or fatal. In diabetic polyneuropathy or with concomitant treatment with sympatholytic agents, the typical precursors of hypoglycemia may be mild or absent altogether.

Causes of hypoglycemia may include drug overdose; use not according to indications; irregular food intake; elderly age of the patient; vomiting, diarrhea; heavy physical exertion; diseases that reduce the need for insulin (impaired liver and kidney function, hypofunction of the adrenal cortex, pituitary gland or thyroid gland); alcohol abuse, as well as interaction with other drugs.

Symptoms of hypoglycemia are severe hunger, sudden profuse sweating, palpitations, pale skin, paresthesia in the oral cavity, tremor, general anxiety, headache, pathological drowsiness, sleep disorders, feeling of fear, impaired coordination of movements, temporary neurological disorders (for example, visual and speech disorders, manifestations of paresis or paralysis, or altered perception of sensations). With the progression of hypoglycemia, loss of self-control and consciousness is possible. Often such a patient has moist cold skin and a predisposition to convulsions.

Blood and lymphatic system disorders rare – thrombocytopenia; very rare – leukocytopenia, erythrocytopenia, granulocytopenia (up to agranulocytosis); in isolated cases – hemolytic anemia, pancytopenia.

Eye disorders very rare – visual and accommodation disorders (these phenomena are more often observed at the beginning of treatment due to changes in blood glucose levels). Gastrointestinal disorders: uncommon – nausea, stomach discomfort, feeling of heaviness and fullness in the stomach, vomiting, abdominal pain, diarrhea, belching, “metallic” taste in the mouth.

Skin and subcutaneous tissue disorders uncommon – itching, urticaria, skin rash (including scaly), photosensitivity, skin hyperemia, Quincke’s edema, purpura; very rare – generalized allergic reactions with skin rash, joint pain, fever, appearance of protein in the urine and jaundice; very rare – life-threatening allergic vasculitis.

Very rarely, skin reactions can be the beginning of the development of severe conditions, accompanied by shortness of breath and a decrease in blood pressure up to the onset of shock, life-threatening to the patient.

Liver and biliary tract disorders very rare – temporary increase in the activity of “liver” enzymes (alkaline phosphatase, ALT, AST), drug-induced hepatitis, intrahepatic cholestasis.

Others very rare – increased diuresis, transient proteinuria, hyponatremia, acute intolerance reaction to alcohol after its consumption, expressed by complications from the circulatory and respiratory organs (disulfiram-like reaction: vomiting, feeling of heat in the skin of the face and upper body, tachycardia, dizziness, headache).

Contraindications

• Type 1 diabetes mellitus;
• Diabetic ketoacidosis, diabetic precoma and coma;
• Condition after pancreatic resection;
• Severe liver dysfunction; severe renal dysfunction;
• Known history of hypersensitivity to glibenclamide and/or other sulfonylurea derivatives, sulfonamides, diuretic drugs containing a sulfonamide group in the molecule, and probenecid, because cross-reactions may occur;
• Decompensation of carbohydrate metabolism in infectious diseases or after major surgical operations, when insulin therapy is indicated;
• Leukopenia;
• Intestinal obstruction, gastric paresis;
• Conditions accompanied by impaired food absorption and the development of hypoglycemia;
• Lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose);
• Children under 18 years of age.

With caution. Febrile syndrome, adrenal insufficiency, thyroid diseases (with impaired function), hypofunction of the anterior pituitary lobe or adrenal cortex, alcoholism, elderly age (due to the danger of developing hypoglycemia).

Use in Pregnancy and Lactation

The use of the drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction.

Use in Renal Impairment

Contraindicated in severe renal dysfunction.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in the elderly.

Special Precautions

It is necessary to regularly monitor the glucose content in the blood on an empty stomach and after meals, the daily curve of blood glucose content.

Major surgical interventions and injuries, extensive burns, infectious diseases with febrile syndrome may require the withdrawal of oral hypoglycemic drugs and the appointment of insulin. Patients should be warned about the increased risk of hypoglycemia in cases of ethanol intake (including the possible development of disulfiram-like reactions: abdominal pain, nausea, vomiting, headache), non-steroidal anti-inflammatory drugs, during fasting.

During treatment, it is not recommended to stay in the sun for a long time.

Dose adjustment is necessary during physical and emotional stress, changes in diet.

Clinical manifestations of hypoglycemia may be masked when taking beta-blockers, clonidine, reserpine, guanethidine.

During treatment, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms hypoglycemia (hunger, increased sweating, sharp weakness, palpitations, tremor, anxiety, headache, dizziness, insomnia, irritability, depression, cerebral edema, speech and vision impairment, impaired consciousness), hypoglycemic coma.

Treatment if the patient is conscious, take sugar orally, if consciousness is lost – intravenous administration of dextrose (IV bolus – 50% dextrose solution, then infusion of 10% solution), 1-2 mg of glucagon subcutaneously, IM or IV, diazoxide 30 mg IV for 30 minutes, control of glucose concentration every 15 minutes, as well as determination of pH, blood urea nitrogen, creatinine, electrolytes. After regaining consciousness, it is necessary to give the patient food rich in easily digestible carbohydrates (to avoid repeated development of hypoglycemia). For cerebral edema – mannitol and dexamethasone.

Drug Interactions

Angiotensin-converting enzyme inhibitors (captopril, enalapril), H2-histamine receptor blockers (cimetidine), antifungal drugs (miconazole, fluconazole), non-steroidal anti-inflammatory drugs (phenylbutazone, azapropazone, oxyphenbutazone), fibrates (clofibrate, bezafibrate), anti-tuberculosis (ethionamide) drugs, salicylates, coumarin anticoagulants, anabolic steroids, beta-blockers, MAO inhibitors, long-acting sulfonamides, cyclophosphamide, biguanides, chloramphenicol, fenfluramine, acarbose, fluoxetine, guanethidine, pentoxifylline, tetracycline, theophylline, tubular secretion blockers, reserpine, bromocriptine, disopyramide, pyridoxine, insulin, allopurinol enhance the effect.

Barbiturates, glucocorticosteroids, adrenomimetics (epinephrine, clonidine), antiepileptic drugs (phenytoin), “slow” calcium channel blockers, carbonic anhydrase inhibitors (acetazolamide), thiazide diuretics, chlorthalidone, furosemide, triamterene, asparaginase, baclofen, danazol, diazoxide, isoniazid, morphine, ritodrine, salbutamol, terbutaline, glucagon, rifampicin, iodine-containing thyroid hormones, lithium salts, in high doses – nicotinic acid, chlorpromazine, oral contraceptives and estrogens weaken the effect.

Drugs that acidify urine (ammonium chloride, calcium chloride, ascorbic acid in large doses) enhance the action by reducing the degree of dissociation and increasing the reabsorption of glibenclamide.

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

Storage Conditions

In a dry place protected from light at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 5 years. Do not use the drug after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.