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

croscarmellose sodium 10,000 mg, cellulose 65,000 mg, magnesium stearate 0.750 mg, quinoline yellow color 0.250 mg, brilliant blue dye 0.125 mg; microcrystalline cellulose q.s. up to 300,000 mg.

Description:

Flat rectangular tablets of light green color with 3 parallel incisions on all sides of the width of the tablet, which divide the tablet into 4 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 a high replacement rate is connected and disconnected from the protein of the beta cells of the pancreas (protein SURX with a molecular weight of 65 kDa), which is associated with ATP-dependent potassium channels, but differs from the usual binding site of other sulfonyl urea derivatives (protein SUR1 with a molar mass of 140 kDa). This process results in the release of insulin by exocytosis, while the amount of insulin secreted is significantly less than that of other sulfonyl urea derivatives. The least stimulating effect of glimepiride on the secretion of insulin provides a lower risk of hypoglycemia.

Extrapancreatic activity

In addition, expressed extrapancreatic effects of glimepiride (decrease in insulin resistance, less effect on the cardiovascular system, anti-atherogenic, antiplatelet and antioxidant effect) have been shown, which also have other sulfonylmerchene derivatives, 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. Transport of glucose into these tissues in type 2 diabetes mellitus is a rate-limited 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 reduction in lipid peroxidation, this contributes to the anti-atherogenic effect of the drug. Glimepiride increases the concentration of endogenous alpha-tocopherol, the activity of catalase, 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 repeated administration of glimepiride in a daily dose of 4 mg, the maximum concentration in serum (C_max) is reached after approximately 2.5 hours and is 352 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 9 liters), approximately equal to the volume of albumin distribution, a high degree of binding to plasma proteins (more than 99%) and low clearance (about 48 ml / min).

After a single intake of glimepiride dose, 60% are excreted by the kidneys and 40% through the intestine. An unchanged substance in the urine was not detected. The 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 slightly.

Glimepiride is excreted in breast milk and penetrates the placental barrier. The drug penetrates poorly through 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;
conditions, accompanied by a violation of food intake and development of hypoglycemia (including infectious diseases);
leukopenia;
severe violations of liver function;
severe violations of kidney function (including patients on hemodialysis);
hypersensitivity to glimepiride or to any inactive component drug, to other derivatives of sulfonylureas or to sulfanilamide 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, large surgical interventions, as well as impaired absorption of food and drugs in the gastrointestinal tract - intestinal obstruction, paresis of the stomach, etc.).

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 during lactation.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 1 time per 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 weeks) to 2 mg, 3 mg or 4 mg per day. Doses over 4 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 prescribed in one session immediately before or during a hearty breakfast, or the first basic meal. Glimepiride tablets are taken whole, not liquid, with a sufficient amount of liquid (about 0.5 cup). It is not 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, concomitant therapy with glimepiride may be initiated. 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 drug 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 in attention to 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 glimeopioid

In exceptional cases, with insulin therapy in patients with type 2 diabetes mellitus, with disease compensation and with the secretory function of pancreatic p-cells, insulin replacement with glimepiride is possible.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:

Co 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.

Co 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.

Co side 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).

Co hematopoiesis side: thrombocytopenia (from moderate to severe), leukopenia, hemolytic or aplastic anemia, erythrocytopenia, granulocytopenia, agranulocytosis, and pancytopenia.

Allergic reactions: possibly the appearance of urticaria, skin rash, itching). Such reactions are usually mild, 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 side effects: in exceptional cases, the development of headache, asthenia, hyponatremia, photosensitization, late cutaneous porphyria is possible.

Overdose:

After ingestion of a large dose of glimepiride, the development of hypoglycemia, lasting from 12 to 72 hours, may occur, which may recur after the initial restoration of the glucose concentration in the blood. In most cases, monitoring in a hospital is recommended.

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

Treatment includes induction of vomiting, a plentiful drink with activated carbon (adsorbent) and sodium picosulfate (laxative). When receiving a large amount of the drug shows gastric lavage, followed by the introduction of sodium picosulphate and activated carbon. As soon as possible, start the injection of dextrose, if necessary in the form of intravenous jet injection of 50 ml of a 40% solution, followed by infusion of 10% solution, with careful monitoring of the concentration of glucose in the blood. In the future, treatment should be symptomatic.

Interaction:

The simultaneous use of glimepiride with certain drugs can cause both an increase and a decrease in 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, fenfluramine, fibrates, fluoxetine, sympatholytics (guanethidine), monoamine oxidase (MAO) inhibitors, miconazole, pentocaine ifillinom (when administered parenterally in high doses), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, materials- antimicrobial quinolone derivatives, salicylates (including at aminosalicylic acid, sulfinpyrazone, some sulfonamides prolonged action, tetracyclines, tritokvalinom, 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 (with prolonged use), nicotinic acid (in high doses) and nicotinic acid derivatives, estrogens and progestogens, phenothiazine derivatives, including chlorpromazine, phenytoin, rifampicin, thyroid hormones, lithium salts .

Blockers H₂-gistaminovyh receptors, clonidine and reserpine are able both to potentiate and weaken the hypoglycemic action of glimepiride.

Under the action of β-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 if too high a dose is taken.

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 observation of the patient. On the background of treatment with glimepiride with irregular intake of food or skipping meals can develop hypoglycemia.

Symptoms of hypoglycemia can be smoothened or completely absent in the elderly, in patients with autonomic neuropathy or receiving concurrent treatment with beta-adrenoblockers, 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.

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 liver and kidney function 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, hypoglycemia or hyperglycaemia may develop, so caution should be exercised when practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 4 mg.

Packaging:

For 5 or 10 tablets are placed in a blister of PVC / aluminum.

For 3 or 6 blisters are placed in a cardboard box together 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:П N016150 / 01

Date of registration:18.01.2010 / 03.12.2013

The owner of the registration certificate:VALEANT, LLC VALEANT, LLC Russia

Manufacturer: & nbsp

QUIMICA MONTPELLIER, S.A. Argentina

Representation: & nbspVALEANT LLC VALEANT LLC Russia

Information update date: & nbsp26.04.2017

Illustrated instructions

Instructions

Glemaz® (Glemaz®)