Glimepiride - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) 102.8 mg, microcrystalline cellulose 14.0 mg, pregelatinized starch 4.0 mg, sodium lauryl sulfate (sodium dodecyl sulfate) 1.9 mg, magnesium stearate 0.6 mg, indigocarmine 0.1 mg , carboxymethyl starch sodium (sodium glycolate starch) 2.6 mg.

Description:

Round, flat-cylindrical tablets from light-blue or gray-gray to blue, with incrustations with a facet and a risk.

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 of insulin by beta cells of the pancreas by enhancing the formation and release of endogenous insulin from the secretory granules of these cells (through the closure of ATP-sensitive potassium channels) (pancreatic action). Glimepiride complexed with a polypeptide SURX receptor sulfonylureas faster than other sulfonylurea derivatives, thereby increasing the rate of response of the pancreatic beta cells to physiological stimulation with glucose.The affinity of glimepiride for the sulfonylurea receptor is lower than that of other sulfonylureas,it catches the high rate of dissociation of the drug with the receptor and the secretion of a much smaller amount of insulin. The shortest stimulating effect of glimepiride on insulin secretion provides a lower risk of hypoglycemia with maximum hypoglycemic effect. In addition to this, glimepiride has an extra-pancreatic action - the ability to improve the sensitivity of peripheral tissues (muscle, fat) to the action of their own insulin, reduce the absorption of insulin by the liver and inhibit the production of glucose in the liver. Glimepiride selectively inhibits cyclooxygenase and reduces the conversion of arachidonic acid to thromboxane A2, which promotes platelet aggregation, thus providing an antiaggregant effect.

Glimepiride promotes the normalization of lipids in the blood serum, reduces the content of malonic aldehyde in the blood, which leads to a significant decrease in lipid peroxidation and an additional 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.

Glycemic control with a single glimepiride intake is achieved within 24 hours.

Pharmacokinetics:

Absorption is high. With repeated administration of glimepiride in a daily dose of 4 mg, the maximum concentration in serum (C_max) is achieved 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 the area under the concentration-time curve (AUC). Bioavailability of glimepiride for oral administration 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 low volume of distribution (about 8.8 liters), approximately equal to the albumin distribution volume, a high degree of protein binding (more than 99%) and low clearance (about 48 ml / min).

Metabolised in the liver.

After a single dose glimepirid dose in the kidneys is withdrawn 58% and through the intestine - 35%. An unchanged substance in the urine was not detected.

Half-life (T_1/2) at plasma concentrations of the drug, corresponding to a multiple dosing regimen, is 5-8 hours. After taking high doses, the elimination half-life increases slightly.

In urine and feces, two inactive metabolites are identified, most likely formed as a result of metabolism in the liver, one of them is a hydroxy derivative, and the other is a carboxy derivative.

After ingestion of glimepiride, the terminal half-life of these metabolites is 3-5 hours and 5-6 hours, respectively.

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 was a tendency to increase the clearance of glimepiride and to reduce its average serum concentrations, which is likely due to a faster release of the drug due to a lower binding to the protein.Thus, in this category of patients there is no additional risk of cumulation of the drug.

Indications:

The drug is indicated for the treatment of type 2 diabetes with ineffectiveness of diet and exercise.

With the ineffectiveness of monotherapy with glimepiride, its use in combination therapy with metformin or insulin is possible.

Contraindications:

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

Carefully:

In the first weeks of treatment (increased risk of developing hypoglycemia); if there are risk factors for developing hypoglycemia (seesection "Special instructions"); conditions requiring the transfer of a patient to insulin therapy: extensive burns, severe multiple injuries, large surgical interventions; malabsorption of food and drugvestinal funds in the gastrointestinal tract - intestinal obstruction, paresis of the stomach, etc .; 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 during lactation. In this case, you need to switch to insulin therapy or stop breastfeeding.

Dosing and Administration:

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

This form of release of glimepiride is intended only for doses of 2 mg, 4 mg or 6 mg per day. If you need to take 2 mg glimepirid tablet should be divided into two halves for risk,if you need to take 4 mg of glimepiride, you need to take a whole pill, if you need to take 6 mg glimepiride, you need to take a whole pill and half the pill.

Initial dose and dose selection

At the beginning of treatment, the smallest therapeutic dose of glimepiride, 1 mg per day, should be used. During the dose selection, it is necessary to use another preparation of glimepiride with the appropriate dosage in one tablet. When the optimal therapeutic effect is achieved when taking 1 mg of glimepiride, it is recommended to take this dose as a supporting dose. In the absence of glycemic control, the daily dose should be incrementally (at intervals of 1-2 weeks) increased by 1 mg under regular control of blood glucose concentrations until optimal glycemic control is achieved. The maximum recommended daily dose is 6 mg. Doses over 6 mg per day (8 mg) are effective only in exceptional cases.

Drug administration and dosing regimen

The time and frequency of daily intake 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 main meal, without chewing, with a sufficient amount of liquid (about 0.5 cup).It is not recommended to skip meals after taking glimepiride to avoid the development of hypoglycemia.

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 in the maximum tolerated dose, 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 glycemic control, 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, insulin treatment begins with a minimal dose, followed by a possible gradual increase in the dose under control of blood glucose concentration.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 preparation to 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.

Side effects:

From the side of metabolism: In rare cases, the development of hypoglycemic reactions that depend on individual factors, such as nutrition and dosing characteristics, is possible.These reactions occur, mainly shortly after taking the drug, can have a prolonged course and do not always stop easily.

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: sometimes there may be nausea, vomiting, a feeling of heaviness or discomfort in the epigastrium, abdominal pain, diarrhea, very rarely leading to cessation of treatment; in rare cases - increased activity of "liver" enzymes, cholestasis, jaundice, hepatitis (until the development of liver failure).

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

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

Other side effects: in exceptional cases, the development of headache, asthenia, hyponatremia, photosensitization, late cutaneous porphyria is possible.

Certain side effects (severe hypoglycemia, severe changes in the blood picture, severe allergic reactions, liver failure) can under certain circumstances pose a threat to the life of the patient.

If you notice any adverse reactions, including those not indicated in the instructions, when taking the drug, you should immediately inform the doctor about it.

Overdose:

When ingesting a large dose of glimepiride, development of hypoglycemia with a duration of 12-72 hours is possible, which can be repeated after the initial restoration of the glucose concentration in the blood (see "Special instructions" for symptoms). Treatment: if the patient is conscious - immediate intake of carbohydrates (glucose or a piece of sugar, sweet fruit juice or tea).In most cases, monitoring in a hospital is recommended. Treatment includes induction of vomiting, fluid intake. When receiving a large amount of the drug is shown washing the stomach, followed by the introduction of activated carbon (adsorbent) and sodium sulfate (laxative), the injection of dextrose intravenously struino in an amount of 50 ml of 40% solution, then infusion of 10% solution. An alternative treatment for severe hypoglycemia may be a subcutaneous or intramuscular injection of a solution of glucagon in a dose of 0.5-1 ml (administered by a relative of the patient). It is necessary to constantly monitor and maintain vital functions, the concentration of glucose in the blood (at least 5.5 mmol / l) for as a minimum 24-48 hours (repeated episodes of hypoglycemia are possible). After the restoration of consciousness, it is necessary to give the patient food rich in easily digestible carbohydrates (in order to avoid the re-development of hypoglycemia). In the future, treatment should be symptomatic.

In the treatment of hypoglycemia, which has developed due to the unintentional administration of glimepiride by a thoracic or small child, a dose of dextrose (50 ml of 40% solution) should be carefully monitored in order to avoid dangerous hyperglycemia.

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.

The increase in 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), inhibitors mo oaminooksidazy (MAO), miconazole, pentoxifylline (when administered parenterally in high doses), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolone antibiotics, salicylates and aminosalicylic acid, sulfinpyrazone, some sulfonamides prolonged action, tetracyclines, tritokvalinom, fluconazole.

Weakening of hypoglycemic action, and associated increase in blood glucose concentration, 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 nicotinic acid derivatives, estrogens and progestogens, phenothiazine, chlorpromazine, phenytoin, p ifampticin, thyroid hormones, lithium salts.

The blockers of H2-histamine receptors, clonidine and reserpine how can potentiate or weaken the hypoglycaemic action of glimepiride.

Under the influence of sympatholytic agents such as beta-blockers, clonidine, guanethidine and reserpine, possibly weakening or lack of clinical signs of hypoglycemia.

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.

Adequate diet, regular and sufficient physical exercise and, if necessary, weight loss are equally important for achieving optimal glycemic control, as is the regular intake of glimepiride.

Clinical symptoms of hyperglycemia are: increased frequency of urination and volume of secreted fluid, severe thirst, dry mouth, dry skin.

In the first weeks of treatment, the risk of developing hypoglycemia may increase, which requires particularly careful monitoring of the patient. Factors contributing to the development of hypoglycemia include:

reluctance or (especially in old age) the patient's inadequate ability to cooperate with a doctor;
inadequate, irregular meals, skipping meals, fasting, changing a habitual diet;
an imbalance between exercise and carbohydrate intake;
alcohol consumption, especially when combined with a skipping meal;
impaired renal function;
severe liver dysfunction;
an overdose of glimepiride;
Some uncompensated diseases of the endocrine system affecting the carbohydrate metabolism (for example, thyroid dysfunction, pituitary insufficiency or adrenocortical insufficiency);
simultaneous use of some other medicines (see section "Interaction with other drugs").

The doctor should be informed of the above factors and episodes of hypoglycemia, because they require very strict monitoring of the patient. In the presence of such factors that increase the risk of hypoglycemia, the dose of glimepiride or the entire treatment regimen should be adjusted. This must also be done in the case of an intercurrent disease or a change in the patient's lifestyle.

Possible symptoms of hypoglycemia are: headache, hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbance, anxiety, aggressiveness, violation of concentration and reaction, depression, confusion, speech and visual disorders, aphasia, tremor, paresis, sensory disturbances, dizziness,loss of self-control, delirium, cerebral cramps, confusion or loss of consciousness, including coma, shallow breathing, bradycardia. In addition, as a result of the adrenergic feedback mechanism, symptoms such as cold, sticky sweat, anxiety, tachycardia, increased blood pressure, angina and heart rhythm disturbances can occur.

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

From experience with other sulfonylureas, it is known that, despite the initial success of stopping hypoglycemia, it is possible to relapse.In this regard, continuous and careful monitoring of the patient is necessary. Severe hypoglycemia requires immediate treatment under the supervision of a doctor, and under certain circumstances and hospitalization of the patient.

If a patient with diabetes is treated by different doctors (for example, during a hospital stay after an accident, with a disease on a weekend), he must obligatorily inform them about his illness and about the previous treatment.

Treatment with derivatives of sulfonylurea, which includes glimepiride, can lead to the development of hemolytic anemia, therefore, in patients with glucose-6-phosphate dehydrogenase deficiency, special care should be taken when prescribing gliipyride and it is better to use hypoglycemic agents that are not derivatives of sulfonylurea.

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, surgery, infectious diseases accompanied by fever), glycemic control may worsen, and there may be a need for a temporary transfer 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, regular monitoring of blood glucose concentration is required, as well as regular testing of the concentration of glycosylated hemoglobin.

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

At the beginning of treatment, when switching from one drug to another, or with an irregular intake of glimepiride, hypoglycemic or hyperglycemia may result, a decrease in the concentration and speed of the psychomotor reactions of the patient. This can adversely affect the ability to drive vehicles or machinery.

Form release / dosage:

Tablets 4.0 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

3, 6 or 10 contour packs together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

The preparation should be stored in its original packaging. At a temperature of no higher than 25 ° C.

Keep out of the reach of children!

Shelf life:

2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001795

Date of registration:10.08.2012

Expiration Date:10.08.2017

The owner of the registration certificate:PHARMSTANDART-FORESTRY, OJSC PHARMSTANDART-FORESTRY, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-FORESTRY, OJSC Russia

Information update date: & nbsp30.04.2017

Illustrated instructions

Instructions

Glimepiride (Glimepiride)