Glimecomb tablets 40 + 500mg, No. 60

• type 2 diabetes mellitus (non-insulin dependent) with the ineffectiveness of diet therapy, exercise and previous therapy with metformin or gliclazide;

• replacement of previous therapy with two drugs (metformin and gliclazide) in patients with type 2 diabetes mellitus (non-insulin dependent) with a stable and well-controlled blood glucose level.

The drug is taken orally during or immediately after a meal. The dose of the drug is determined by the doctor individually for each patient, depending on the blood glucose level.

The initial dose is, as a rule, 1-3 tablets / day with a gradual selection of the dose until a stable compensation of the disease is achieved. The maximum daily dose is 5 tab. Usually the drug is taken 2 times / day (morning and evening).

Tablets from white to white with a creamy or yellowish tinge of color, flat-cylindrical, with a beveled and scored; presence of marbling is allowed.

1 tab.

gliclazide 40 mg

metformin hydrochloride 500 mg

Excipients: sorbitol, povidone, croscarmellose sodium, magnesium stearate.

• type 1 diabetes mellitus (insulin dependent);

• 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 failure, respiratory failure, recent myocardial infarction, shock;

• liver failure;

• porphyria;

• pregnancy;

• lactation period (breastfeeding);

• simultaneous administration of miconazole;

• conditions requiring insulin therapy, incl. infectious diseases, major surgical interventions, trauma, extensive burns;

• 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);

• hypersensitivity to drug components;

• hypersensitivity to other sulfonylurea derivatives.

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

The drug should be used with caution in febrile syndrome, adrenal insufficiency, hypofunction of the anterior pituitary gland, thyroid diseases with impaired function.

pharmachologic effect

Combined oral hypoglycemic drug. GlimecombЃ is a fixed combination of two oral hypoglycemic agents of the biguanide group and the sulfonylurea group of derivatives.

Has pancreatic and extra-pancreatic action.

Gliclazide is a sulfonylurea derivative. Stimulates the secretion of insulin by the pancreas, increases the sensitivity of peripheral tissues to insulin. Stimulates the activity of intracellular enzymes - muscle glycogen synthetase. Restores the early peak of insulin secretion, shortens the time interval from the moment of eating to the beginning of insulin secretion, and reduces postprandial hyperglycemia. In addition to the effect on carbohydrate metabolism, it affects microcirculation, reduces adhesion and aggregation of platelets, delays the development of parietal thrombosis, normalizes vascular permeability and prevents the development of microthrombosis and atherosclerosis, restores the process of physiological parietal fibrinolysis, counteracts the increased reaction to vascular adrenaline in patients.Slows down the development of diabetic retinopathy at the non-proliferative stage; with diabetic nephropathy against the background of long-term use, there is a significant decrease in proteinuria. Does not lead to an increase in body weight, because has a predominant effect on the early peak of insulin secretion and does not cause hyperinsulinemia; helps to reduce body weight in obese patients with an appropriate diet.

Metformin belongs to the biguanide group. Reduces the concentration of glucose in the blood by inhibiting gluconeogenesis in the liver, reducing the absorption of glucose from the gastrointestinal tract and increasing its utilization in tissues. Reduces the concentration in serum of triglycerides, cholesterol and LDL (determined on an empty stomach) and does not change the concentration of lipoproteins of a different density. Helps stabilize or reduce body weight. In the absence of insulin in the blood, the therapeutic effect is not manifested. Does not cause hypoglycemic reactions. Improves the fibrinolytic properties of blood by suppressing the tissue-type activator profibrinolysin (plasminogen) inhibitor.

Pharmacokinetics

Gliclazide

Absorption and distribution

After oral administration, absorption is high. When taken at a dose of 40 mg, Cmax in blood plasma is achieved after 2-3 hours and is 2-3 ?g / ml. Plasma protein binding is 85-97%.

Metabolism and excretion

It is metabolized in the liver. T1 / 2 - 8-20 hours. It is excreted mainly in the form of metabolites by the kidneys - 70%, through the intestines - 12%.

In elderly patients, there are no clinically significant changes in pharmacokinetic parameters.

Metformin

Absorption and distribution

After oral administration, absorption is 48-52%. It is rapidly absorbed from the gastrointestinal tract. Absolute bioavailability (on an empty stomach) is 50-60%. Cmax in blood plasma is reached after 1.81-2.69 hours and does not exceed 1 ?g / ml. Reception with food reduces Cmax in plasma by 40% and slows down its achievement by 35 minutes. Plasma protein binding is negligible. Metformin is able to accumulate in red blood cells.

Withdrawal

T1 / 2 is 6.2 hours. It is excreted by the kidneys, mainly unchanged (glomerular filtration and tubular secretion) and through the intestines (up to 30%).

Side effect

From the endocrine system: hypoglycemia (in case of violation of the dosage regimen and inadequate diet) - headache, fatigue, hunger, increased sweating, severe weakness, palpitations, dizziness, impaired coordination of movements, temporary neurological disorders; with the progression of hypoglycemia, loss of self-control, loss of consciousness is possible.

From the side of metabolism: in some cases - lactic acidosis (weakness, myalgia, respiratory disorders, drowsiness, abdominal pain, hypothermia, decreased blood pressure, bradyarrhythmia).

On the part of the digestive system: dyspepsia (nausea, diarrhea, a feeling of heaviness in the epigastrium, a 'metallic' taste in the mouth), decreased appetite (the severity of these reactions decreases when the drug is taken with meals); rarely - hepatitis, cholestatic jaundice (drug withdrawal is required), increased activity of hepatic transaminases, alkaline phosphatase.

From the hematopoietic system: rarely - inhibition of bone marrow hematopoiesis (anemia, thrombocytopenia, leukopenia).

Allergic reactions: itching, urticaria, maculopapular rash.

Others: visual impairment.

In cases of side effects, the dose should be reduced or the drug should be temporarily canceled.

Common side effects of sulfonylurea derivatives: erythropenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, life-threatening liver failure.

Application during pregnancy and lactation

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

GlimecombЃ is contraindicated in breastfeeding, since active substances can be excreted in 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 in severe renal dysfunction, acute conditions that can lead to changes in kidney function: dehydration, severe infection, shock.

Use in elderly patients

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

special instructions

Treatment with GlimecombЃ is carried out only in combination with a low-calorie, low-carbohydrate diet. It is necessary to regularly monitor the blood glucose level on an empty stomach and after meals, especially in the first days of drug treatment.

GlimecombЃ can only be prescribed to patients who receive regular meals, which must include breakfast and ensure an adequate intake of carbohydrates.

When prescribing the drug, it should be borne in mind that due to the intake of sulfonylurea derivatives, hypoglycemia may develop, and in some cases in a severe and prolonged form, requiring hospitalization and glucose administration for several days. Hypoglycemia often develops with a low-calorie diet, after prolonged or vigorous exercise, after drinking alcohol, or while taking several hypoglycemic drugs at the same time. In order to avoid the development of hypoglycemia, careful and individual selection of doses is necessary, as well as the provision of complete information to the patient about the proposed treatment. In case of physical and emotional stress, when changing the diet, the dose of GlimecombЃ must be adjusted.

Elderly persons are especially sensitive to the action of hypoglycemic drugs; patients who do not receive a balanced diet, with a general weakened condition; patients suffering from pituitary-adrenal insufficiency.

Beta-blockers, clonidine, reserpine, guanethidine are able to mask the clinical manifestations of hypoglycemia.

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

With major surgical interventions and injuries, extensive burns, infectious diseases with a febrile syndrome, it may be necessary to discontinue oral hypoglycemic drugs and prescribe insulin therapy.

During treatment, it is necessary to monitor kidney function. Determination of lactate in plasma should be carried out at least 2 times a year, as well as when myalgia appears. With the development of lactic acidosis, discontinuation of treatment is required.

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

During therapy with GlimecombЃ, the patient must stop drinking alcohol and / or ethanol-containing drugs and food.

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

Symptoms: possible lactic acidosis (because the drug contains metformin), hypoglycemia.

Treatment: if symptoms of lactic acidosis appear, you should stop taking the drug. Lactic acidosis is a medical emergency; treatment is carried out in a hospital. The most effective treatment is hemodialysis.

With hypoglycemia of mild to moderate severity, glucose (dextrose) 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, or 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

An increase in the hypoglycemic effect of the drug GlymecombЃ is observed when used simultaneously with ACE inhibitors (captopril, enalapril), histamine H2-receptor blockers (cimetidine), antifungal drugs (miconazole, fluconazole), NSAIDs (phenylbutazone) oxif, sapenlobutaibon, bezafibrate), anti-tuberculosis drugs (ethionamide), salicylates, coumarin anticoagulants, anabolic steroids, beta-blockers, MAO inhibitors, long-acting sulfonamides, with cyclophosphamide, chloramphenicol, phenfluramine, fluoxethylinomide, fluoxethylline reserpine, bromocriptine, disopyramide, pyridoxine, with other hypoglycemic drugs (including acarbose, biguanides, insulin), allopurinol,oxytetracycline.

A decrease in the hypoglycemic effect of the drug GlimecombЃ is observed with simultaneous use with barbiturates, corticosteroids, adrenomimetics (epinephrine, clonidine), antiepileptic drugs (phenytoin), with blockers of slow calcium channels, carbonic anhydrase inhibitors (acetazolamide), thiazide diurethics, thiazide diuretamide , with baclofen, danazol, diazoxide, isoniazid, with morphine, ritodrin, salbutamol, terbutaline, with glucagon, rifampicin, with thyroid hormones, lithium salts, with high doses of nicotinic acid, chlorpromazine, oral estrogen and oral contraceptives.

Increases the risk of developing ventricular premature beats in the presence of cardiac glycosides.

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

Ethanol increases the likelihood of developing lactic acidosis.

Pharmacokinetic interaction

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

Furosemide increases the Cmax of metformin by 22%.

Nifedipine increases absorption, increases Cmax in blood plasma, 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 in blood plasma by 60%.