Glemaz - instructions for use, dose, side effects, contraindications

Excipients: croscarmellose sodium - 5,000 mg, cellulose - 32,500 mg, magnesium stearate - 0,375 mg, microcrystalline cellulose - q.s. up to 150,000 mg.

Description:

Flat rectangular tablets are almost white with a risk on both sides of the width, which divides the tablet into 2 equal parts.

Pharmacotherapeutic group:Hypoglycemic agent for oral use of the sulfonylurea group of the third generation

ATX: & nbsp

A.10.B.B.12 Glimepiride

Pharmacodynamics:

Glimepiride stimulates the secretion and release of insulin from the beta cells of the pancreas (pancreatic action), improves the sensitivity of peripheral tissues (muscle and fat) to the action of your own insulin (extra-pancreatic action).

Pancreatic action (release of insulin)

Derivatives of sulfonylureas regulate the secretion of insulin by blocking ATP-dependent potassium channels located in the cytoplasmic membrane of the pancreatic beta cells. Blocking the potassium channels, they cause depolarization of beta cells, which helps to open calcium channels and increase calcium intake inside cells. Glimepiride with high replacement rate is connected and disconnected from the beta-cell protein of the pancreas (SURX protein with a molecular weight of 65 kD), which is associated with ATP-dependent potassium channels, but differs from the usual binding site of the traditional sulfonylurea derivatives (SUR1 protein with a molar mass 140 kD). This process results in the release of insulin by exocytosis, while the amount of insulin secreted is significantly less than that of the sulfonylurea derivatives of the 1st generation. The least stimulating effect of glimepiride on the secretion of insulin provides a lower risk of hypoglycemia.

Extrapancreatic activity

In addition, the expressed extrapancreatic effects of glimepiride (reduction of insulin resistance, less effect on the cardiovascular system, anti-atherogenic, antiplatelet and antioxidant effect) were also shown, which also have derivatives of sulfonylureas of the 1st generation, but to a much lesser extent. Increasing the utilization of glucose from the blood by peripheral tissues (muscle and fat) occurs with the help of special transport proteins (GLUT1 and GLUT4), located in cell membranes. The transport of glucose into these tissues in type 2 diabetes is a rate-limiting step in the utilization of glucose. Glimepiride very quickly increases the number and activity of molecules transporting glucose (GLUT1 and GLUT4), which leads to an increase in the assimilation of glucose by peripheral tissues. Glimepiride has a weaker inhibitory effect on ATP-dependent potassium channels of cardiomyocytes. When glimepiride is taken, the ability of metabolic adaptation of the myocardium to ischemia remains. Glimepiride increases the activity of glycosyl-phosphatidylinositol-specific phospholipase C, with which lipogenesis and glycogenesis caused by the drug can correlate in isolated muscle and fat cells.

Glimepiride inhibits the production of glucose in the liver by increasing intracellular concentrations of fructose-1,6-bisphosphate, which in turn inhibits gluconeogenesis. Glimepiride selectively inhibits cyclooxygenase and reduces the conversion of arachidonic acid to thromboxane A2, which promotes platelet aggregation, thus providing an antithrombotic effect. Glimepiride promotes the normalization of lipid content, reduces the level of malonic aldehyde in the blood, which leads to a significant decrease in lipid peroxidation, this contributes to the anti-atherogenic effect of the drug. Glimepiride increases the concentration of endogenous, alpha-tocopherol, catalase activity, glutathione peroxidase and superoxide dismutase, which contributes to the reduction of the oxidative stress in the patient's body, which is constantly present in type 2 diabetes.

Pharmacokinetics:

With multiple administration of glimepiride in a daily dose of 4 mg, the maximum concentration in serum (C_max) is reached after about 2.5 hours and is 309 ng / ml; there is a linear relationship between dose and C_max, as well as between the dose and AUC (area under the curve "concentration-time"). When administered glimepiride, its bioavailability is 100%. Eating does not have a significant effect on absorption, except for a slight slowing of the absorption rate. Glimepiride is characterized by a very low volume of distribution (about 8.8 liters), approximately equal to the volume of distribution of albumin, high, the degree of binding to plasma proteins (more than 99%) and low clearance (about 48 ml /m). After Single ingestion of glimepiride dose by kidneys is deduced 58% and through the intestine - 35%. An unchanged substance in the urine was not detected. Half-life, at plasma concentrations of the drug in the serum, corresponding to a multiple, dosing regimen, is 5-8 hours. After taking high doses, the elimination half-life increases somewhat.

Glimepiride is excreted in breast milk and "penetrates" through the placental barrier.

Glimepiride poorly penetrates the blood-brain barrier.

In patients with impaired renal function (with low creatinine clearance), there is a tendency to increase the clearance of glimepiride and to reduce its average serum concentrations, which is likely due to a faster elimination of the drug due to its lower binding to plasma proteins. Thus, in this category of patients there is no additional risk of cumulation of the drug.

Indications:

Diabetes mellitus type 2 (in monotherapy or as part of combination therapy with metformin or with insulin).

Contraindications:

type 1 diabetes mellitus;
diabetic ketoacidosis, diabetic precoma and coma;
leukopenia;
severe violations of liver function;
severe violations of kidney function (including patients on hemodialysis);
hypersensitivity to glimepiride or to any, inactive drug component, to other derivatives, sulfonylureas or to sulfonamide preparations (risk of developing hypersensitivity reactions);
pregnancy and lactation;
children's age till 18 years.

Carefully:

Conditions requiring the transfer of a patient to insulin therapy (extensive burns, severe multiple injuries, major surgical interventions, as well as impaired absorption of food and drugs in the gastrointestinal tract - intestinal obstruction, paresis of the stomach, etc.); in the first weeks of treatment (increased risk of hypoglycemia); if there are risk factors for the development of hypoglycemia; with insufficiency of glucose-6-phosphate dehydrogenase.

Pregnancy and lactation:

Glimepiride is contraindicated for use in pregnant women. In the case of a planned pregnancy or at the onset of pregnancy, a woman should be transferred to insulin therapy.

As glimepiride penetrates into breast milk, it should not be prescribed to women in the lactation period. In this case, you need to switch to insulin therapy or stop breastfeeding.

Dosing and Administration:

The drug is administered orally. The initial and maintenance doses of glimepiride are set individually based on the results of regular monitoring of the glucose concentration in the blood.

Initial dose and dose selection

At the beginning of treatment, 1 mg glimepiride is prescribed, once a day. When the optimal therapeutic effect is achieved, it is recommended to take this dose as a supporting dose. In the absence of glycemic control, the daily dose should be gradually increased by regular monitoring of blood glucose concentrations (at intervals of 1-2 to 1 week) to 2 mg, 3 mg, 4 mg, 6 mg or 8 mg per day. Doses over 6 mg per day are effective only in exceptional cases. The maximum recommended daily dose is 8 mg.

Time and frequency of admission The daily dose is determined by the doctor taking into account the lifestyle of the patient. The daily dose is given at one time just before or during the time. a hearty breakfast, or the first main meal.Glimepiride tablets are taken whole, without chewing, with a sufficient amount of liquid (about 0.5 cup). Not it is recommended to skip meals after taking glimepiride.

Duration of treatment

Treatment with glimepiride for a long time, under the control of glucose in the blood.

Use in combination with metformin

In the absence of glycemic control in patients taking metformin, may be initiated concomitant therapy with glimepiride. If the dose of metformin remains at the same level, treatment with glimepiride begins with a minimal dose, and then the dose gradually increases depending on the desired concentration of glucose in the blood, up to the maximum daily dose. Combination therapy should be conducted under close medical supervision.

Use in combination with insulin

In cases where it is not possible to achieve glycemic control by taking the maximum dose of glimepiride in monotherapy or in combination with the maximum dose of metformin, a combination of glimepiride with insulin is possible. In this case, the last dose of glimepiride prescribed to the patient remains unchanged.In this case, treatment with insulin begins with a minimal dose, with the possible subsequent gradual increase in its dose under the control of the concentration of glucose in the blood. Combined treatment requires compulsory medical supervision.

Transfer of a patient from another oral hypoglycemic preparation to glimepiride

When transferring a patient from another oral hypoglycemic drug to a glimepiride the initial daily dose of the latter should be 1 mg (even if the patient is transferred to glimepiride with a maximum dose of another oral hypoglycemic drug). Any increase in the dose of glimepiride should be carried out in stages in accordance with the recommendations given above. It is necessary to take into account the effectiveness, dose and duration of action of the hypoglycemic agent used. In some cases, especially when taking hypoglycemic drugs with a long half-life, there may be a need for a temporary (within a few days) cessation of treatment to avoid an additive effect that increases the risk of developing hypoglycemia.

Transfer of a patient from insulin to glimepiride

In exceptional cases, when carrying out insulin therapy in patients with diabetes mellitus 2 types, with compensation of the disease and with the preserved secretory function of beta cells of the pancreas, it is possible to replace insulin with glimepiride. The translation should be carried out under the close supervision of a physician. In this case, the patient's transfer to glimepiride begin with a minimum dose of 1 mg.

Side effects:

From the side of metabolism: hypoglycemic reactions may develop. These reactions, mainly occur shortly after taking the drug, can have severe form and course and they can not always be easily stopped. The onset of these symptoms depends on individual factors, such as eating habits and dosing.

From the side of the organ of vision: During treatment (especially at the beginning), transient visual impairments due to changes in glucose concentration in the blood can be observed.

On the part of the digestive system: nausea, vomiting, a feeling of heaviness or discomfort in the epigastrium, abdominal pain, diarrhea, very rarely leading to discontinuation of treatment; increased activity of "hepatic" enzymes, cholestasis, jaundice, hepatitis (up to the development of liver failure).

On the part of the hematopoiesis system: thrombocytopenia (from moderate to severe), leukopenia, hemolytic or aplastic anemia, erythrocytopenia, granulocytopenia, agranulocytosis and pancytopenia.

Allergic reactions: there may be urticaria, skin rashes and itching. Such reactions happen, as a rule, moderately expressed, but can progress, accompanied by a decrease in blood pressure, shortness of breath, until the development of anaphylactic shock. When urticaria appears, consult a doctor immediately. A cross-allergy with other derivatives of sulfonylurea, sulfonamides or other sulfonamides is possible, and allergic vasculitis is also possible.

Other by-products actions: in exceptional cases, the development of headache, asthenia, hyponatremia, photosensitization, late cutaneous porphyria is possible.

Overdose:

After ingestion of a large dose of glimepiride, hypoglycemia may develop, from 12 to 72 hours, which can be repeated after the initial restore blood glucose. In most cases, monitoring in a hospital is recommended.

Symptoms of hypoglycemia: increased sweating, anxiety, tachycardia, increased blood pressure, palpitations, chest pain, arrhythmia, headache, dizziness, sharp increase in appetite, nausea, vomiting, lethargy, drowsiness, restlessness, aggressiveness, impaired concentration, depression, confusion consciousness, tremor, paresis, impaired sensitivity, convulsions of the central genesis. Sometimes the clinical picture of hypoglycemia may resemble a stroke. Possible the development of coma.

As soon as possible, start the injection of dextrose, if necessary in the form of intravenous jet administration of 50 ml of a 40% solution, followed by an infusion of 40 % a solution with careful monitoring of the concentration of glucose in the blood. When taking a large amount of the drug may require carrying out gastric lavage and 1 reception of activated charcoal. In the future, treatment should be symptomatic.

Interaction:

The simultaneous use of glimepiride with certain drugs may cause both strengthening and weakening of the hypoglycemic effect of the drug.Therefore, other medications can be taken only after consultation with the doctor.

Increased hypoglycemic action and associated with this, the possible development of hypoglycemia can be observed with the simultaneous use of glimepiride with insulin; metformin or other oral hypoglycemic agents, angiotensin-converting enzyme (ACE) inhibitors, allopurinol, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclophosphamide, trophosphamide and ifosfamide, fenfetramine, fibrates, fluoxetine, sympatholytics (guanethidine), monoamine oxidase (MAO) inhibitors, miconazole, pentoxifylline (for parenteral administration at high doses), phenylbutazone, azaprozone, oxyphenbutazone, probenecid, antimicrobial agents - quinolone derivatives, salicylates (including aminosalicylic acid ), sulfinpyrazone, some prolonged-action sulfanilamides, tetracyclines, tritokvaline, fluconazole.

Weakening of hypoglycemic action, and associated with this,an increase in the concentration of glucose in the blood can be observed with the simultaneous use of glimepiride with acetazolamide, barbiturates, glucocorticosteroids, diazoxide, saluretic, thiazide diuretics, epinephrine and other sympathomimetic agents, glucagon, laxatives (for prolonged use), nicotinic acid (in high doses) and derivatives nicotinic acid, estrogens and progestogens, phenothiazine derivatives, including chlorpromazine, phenytoin, rifampicin, thyroid hormones, lithium salts.

The blockers of H2-histamine receptors, clonidine and reserpine are able to both enhance and weaken the action of glimepiride.

Under the action of beta-adrenoblockers, clonidine, guanethidine and reserpine, it is possible that the clinical signs of hypoglycemia are weakened or absent.

Against the background of taking glimepiride, there may be an increase or decrease in the action of coumarin derivatives.

With simultaneous use with drugs that inhibit bone marrow hematopoiesis, the risk of myelosuppression increases.

A single or chronic use of alcohol can both enhance and weaken the hypoglycemic effect of glimepiride.

Special instructions:

Glimepiride should be taken at recommended doses and at the appointed time. Errors in the use of the drug, for example, admission, can never be eliminated by the subsequent administration of a higher dose. The doctor and the patient must preliminarily discuss the measures to be taken in case of such mistakes (for example, skipping a drug or eating a meal) or in situations where it is not possible to take the next dose of the drug at the set time. The patient should immediately inform the doctor in case of admission too high a dose of the drug.

The development of hypoglycemia in a patient after taking 1 mg of glimepiride per day means the possibility of controlling glycemia solely with the help of a diet.

When you reach the compensation of type 2 diabetes, the sensitivity to insulin increases. In this regard, the treatment process may reduce the need for glimepiride. To avoid the development of hypoglycemia, it is necessary to temporarily reduce the dose or cancel glimepiride. Correction of the dose should also be carried out with a change in the body weight of the patient, his lifestyle, or with the appearance of other factors contributing to an increased risk of hypo- or hyperglycaemia.

In the first weeks of treatment, the risk of developing hypoglycemia may increase, which requires particularly careful monitoring of the patient.

The factors contributing to the risk of developing hypoglycemia include: the patient's reluctance or inability to cooperate with a doctor (more often observed in elderly patients); malnutrition, irregular eating or skipping meals; an imbalance between exercise and carbohydrate intake; changing diet; drinking alcohol, especially with meals; severe renal dysfunction; an overdose of glimepiride; some decompensated endocrine disorders that disrupt carbohydrate metabolism or adrenergic counterregulation in response to hypoglycemia (eg, dysfunction of the thyroid gland and anterior pituitary gland, insufficiency of the adrenal cortex); concomitant use of certain medicines.section "Interaction with other drugs"); reception glimepirida in the absence of indications for its use.

Symptoms of hypoglycemia can be smoothened or completely absent in the elderly, in patients with autonomic neuropathy or receiving concurrent treatment with beta-blockers, clonidine, reserpine, guanethidine. Hypoglycemia can almost always be quickly stopped by the immediate intake of carbohydrates (glucose or sugar, for example, in the form of a piece of sugar, sweet fruit juice or tea). In this regard, the patient should always have at least 20 grams of glucose (4 pieces of sugar). Sugary substitutes are ineffective in the treatment of hypoglycemia.

Treatment with derivatives of sulfonylurea, which includes glimepiride, can lead to the development of hemolytic anemia, therefore it is better to use hypoglycemic agents that are not derivatives of sulfonylurea in patients with glucose-6-phosphate dehydrogenase deficiency.

During treatment with glimepiride, regular monitoring of liver function and peripheral blood pattern (especially the number of leukocytes and platelets) is required.In stressful situations (for example, with trauma, surgical intervention, infectious diseases accompanied by fever), there may be a need for a temporary transfer of the patient to insulin therapy.

There is no experience with glimepiride in patients with severe impairment of function liver and kidneys or patients on hemodialysis. Patients with severe impairment of kidney and liver function are indicated by a transfer to insulin therapy.

During treatment with glimepiride, regular monitoring of blood glucose concentration as well as the concentration of glycosylated hemoglobin is necessary.

Effect on the ability to drive transp. cf. and fur:

When taking glimepiride, it is possible to develop hypoglycemia or hyperglycemia in this way, caution should be exercised when engaging in potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 2 mg.

Packaging:

For 15 tablets are placed in a blister of PVC / aluminum.

Two blisters are placed in a cardboard box, along with instructions for medical use.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:PL-000724

Date of registration:29.09.2011

Expiration Date:29.09.2016

The owner of the registration certificate:Kimika Montpellier, SA, Bago Group CompanyKimika Montpellier, SA, Bago Group Company Argentina

Manufacturer: & nbsp

QUIMICA MONTPELLIER, S.A. Argentina

Representation: & nbspBBC FARMA BV BBC FARMA BV Netherlands

Information update date: & nbsp26.04.2017

Illustrated instructions

Instructions

Glemaz® (Glemaz®)