Gluconorm tablets 400 + 2.5mg, No. 40

Type 2 diabetes mellitus in adults:

• with the ineffectiveness of diet therapy, exercise and previous therapy with metformin or glibenclamide;

• to replace previous therapy with two drugs (metformin and glibenclamide) in patients with stable and well-controlled blood glucose levels.

The drug is taken orally during meals. The dose of the drug is determined by the doctor individually for each patient, depending on the blood glucose level.

Usually the initial dose is 1 tab. (400 mg / 2.5 mg) / day. Every 1-2 weeks after the start of treatment, the dose of the drug is adjusted depending on the blood glucose level. When replacing the previous combination therapy with metformin and glibeklamide, 1-2 tablets are prescribed. Gluconorm depending on the previous dose of each component.

The maximum daily dose is 5 tab.

Film-coated tablets of white or almost white color, round, biconvex; at the break from white to white with a grayish tinge.

1 tab. glibenclamide 2.5 mg

metformin hydrochloride 400 mg

Excipients: microcrystalline cellulose - 100 mg, corn starch - 20 mg, colloidal silicon dioxide - 20 mg, gelatin - 10 mg, glycerol - 10 mg, magnesium stearate - 7 mg, purified talc - 15 mg, croscarmellose sodium - 30 mg, sodium carboxymethyl starch - 18.3 mg, cellacephate - 2 mg, diethyl phthalate - 0.2 mg.

• Type 1 diabetes mellitus;

• diabetic ketoacidosis, diabetic precoma, diabetic coma;

• hypoglycemia;

• severe renal dysfunction;

• acute conditions that can lead to changes in kidney function (dehydration, severe infection, shock);

• acute or chronic diseases accompanied by tissue hypoxia (heart or respiratory failure, recent myocardial infarction, shock);

• liver failure;

• porphyria;

• simultaneous administration of miconazole;

• infectious diseases, major surgical interventions, trauma, extensive burns and other conditions requiring insulin therapy;

• chronic alcoholism, acute alcohol intoxication;

• lactic acidosis (including history);

• application for at least 48 hours before and within 48 hours after carrying out radioisotope or X-ray studies with the introduction of an iodine-containing contrast agent;

• adherence to a hypocaloric diet (less than 1000 calories / day);

• pregnancy;

• breastfeeding period;

• hypersensitivity to metformin, glibenclamide or other sulfonylurea derivatives, as well as to excipients.

It is not recommended to use the drug in persons over 60 years of age who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis in them.

With care: febrile syndrome, adrenal insufficiency, hypofunction of the anterior pituitary gland, thyroid disease with impaired function.

pharmachologic effect

GluconormЃ is a fixed combination of two oral hypoglycemic agents of different pharmacological groups: metformin and glibenclamide.

Metformin belongs to the biguanide group and lowers serum glucose levels by increasing the sensitivity of peripheral tissues to the action of insulin and enhancing glucose uptake. Reduces the absorption of carbohydrates in the gastrointestinal tract and inhibits gluconeogenesis in the liver. The drug also has a beneficial effect on blood lipid profile by lowering total cholesterol levels. LDL and triglycerides. Does not cause hypoglycemic reactions.

Glibenclamide belongs to the group of II generation sulfonylurea derivatives. Stimulates insulin secretion by lowering the threshold of glucose irritation of pancreatic ?-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 liver, inhibits lipolysis in adipose tissue. Acts in the second stage of insulin secretion.

Pharmacokinetics

Glibenclamide

When taken orally, absorption from the gastrointestinal tract is 48-84%. Time to reach Cmax - 1-2 hours. Vd - 9-10 liters. The connection with plasma proteins is 95%.

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 by the intestine. T1 / 2 - from 3 to 10-16 hours

Metformin

After oral administration, it is absorbed from the gastrointestinal tract quite completely, 20-30% of the dose is found in the feces. Absolute bioavailability ranges from 50 to 60%. With the simultaneous intake of food, the absorption of metformin is reduced and delayed. It is quickly distributed in tissues, practically does not bind to plasma proteins.

It is metabolized to a very weak extent and excreted by the kidneys. T1 / 2 is approximately 9-12 hours.

Side effect

From the side of carbohydrate metabolism: hypoglycemia is possible.

From the gastrointestinal tract and liver: rarely - nausea, vomiting, abdominal pain, loss of appetite, 'metallic' taste in the mouth; in some cases - cholestatic jaundice, increased activity of liver enzymes, hepatitis.

From the hematopoietic system: rarely - leukopenia, thrombocytopenia, erythrocytopenia; very rarely - agranulocytosis, hemolytic or megaloblastic anemia, pancytopenia.

From the side of the central nervous system: headache, dizziness, weakness, fatigue; rarely - paresis, sensitivity disorders.

Allergic and immunopathological reactions: rarely - urticaria, erythema, pruritus, fever, arthralgia, proteinuria.

Dermatological reactions: rarely - photosensitization.

From the side of metabolism: lactic acidosis.

Others: an acute reaction of alcohol intolerance after drinking it, 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).

Application during pregnancy and lactation

During pregnancy, the use of Gluconorm is contraindicated. When planning pregnancy, as well as in case of pregnancy during the period of taking Gluconorm, the drug should be canceled and insulin therapy should be prescribed.

GluconormЃ is contraindicated during breastfeeding, since metformin passes into breast milk. In this case, it is necessary to switch to insulin therapy or stop breastfeeding.

Application for violations of liver function

Contraindicated in liver failure

Application for impaired renal function

Contraindicated for use in severe renal impairment and acute conditions that can lead to changes in renal function (dehydration, severe infection, shock);

Use in elderly patients

It is not recommended to use the drug in persons over 60 years of age who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis in them.

special instructions

Major surgical interventions and trauma, extensive burns, infectious diseases with a febrile syndrome may require discontinuation of the drug and the appointment of insulin therapy.

It is necessary to regularly monitor fasting blood glucose and after meals.

Patients should be warned about the increased risk of hypoglycemia in cases of taking ethanol, NSAIDs, and fasting.

Dose correction is necessary in case of physical and emotional overstrain, changes in diet.

It is not recommended to take alcohol during treatment.

48 hours before surgery or intravenous administration of an iodine-containing X-ray contrast agent, Gluconorm should be discontinued. It is recommended to resume treatment with Gluconorm after 48 hours.

Influence on the ability to drive vehicles and use mechanisms

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Overdose or the presence of risk factors can provoke the development of lactic acidosis, because the drug contains metformin. If symptoms of lactic acidosis appear (vomiting, abdominal pain, general weakness, muscle cramps), you must stop taking the drug. Lactic acidosis is a medical emergency; treatment of lactic acidosis should be carried out in a hospital. The most effective treatment is hemodialysis.

Overdose can also lead to the development of hypoglycemia due to the presence of glibenclamide in the preparation. Symptoms of hypoglycemia: hunger, increased sweating, weakness, palpitations, pallor of the skin, paresthesia of the oral mucosa, tremors, general anxiety, headache, pathological drowsiness, sleep disorders, fear, impaired coordination of movements, temporary neurological disorders. With the progression of hypoglycemia, patients may lose self-control and consciousness.

For mild to moderate hypoglycemia, dextrose (glucose) or sugar solution is taken orally. In the case of severe hypoglycemia (loss of consciousness), a 40% dextrose (glucose) solution or glucagon is administered intravenously, intramuscularly, subcutaneously. After the restoration of consciousness, the patient must be given food rich in carbohydrates in order to avoid the re-development of hypoglycemia.

Drug interactions

The hypoglycemic effect of the drug is enhanced by ACE inhibitors (captopril, enalapril), histamine H2 receptor blockers (cimetidine), antifungal agents (miconazole, fluconazole), NSAIDs (phenylbutazone, azapropazone, oxyphenbutazone), etilophilic acid), fibrates , salicitates, coumarin anticoagulants, anabolic steroids, beta-blockers, MAO inhibitors, long-acting sulfonamides, cyclophosphamide, chloramphenicol, fenfluramine, fluoxetine, guanetidine, pentoxifylline, tetracycline, sekridirami, pyrophyllinum, others hypoglycemic drugs (acarbose, biguanides, insulin), allopurinol.

Weaken the effect of barbiturates, corticosteroids, adrenostimulants (epinephrine, clonidine), antiepileptic drugs (phenytoin), blockers of 'slow' calcium channels, carbonic anhydrase inhibitors (acetazolamide), thiazide diuretics, chlorthalidone, furosemlophenol, triamterazole , morphine, ritodrin, salbutamol, terbutaline, glucagon, rifampicin, iodine-containing thyroid hormones, lithium salts, in high doses - nicotinic acid, chlorpromazine, oral contraceptives and estrogens.

Medicines acidifying urine (ammonium chloride, calcium chloride, ascorbic acid in large doses) enhance the effect by reducing the degree of dissociation and increasing the reabsorption of glibenclamide.

Ethanol increases the likelihood of developing lactic acidosis.

Metformin reduces the Cmax and T1 / 2 of furosemide by 31% and 42.3%, respectively.

Furosemide increases the Cmax of metformin by 22%.

Nifedipine increases absorption, Cmax slows down the excretion of metformin.

Cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, and vancomycin) secreted in the tubules compete for tubular transport systems and, with prolonged therapy, can increase the Cmax of metformin by 60%.