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

Excipients: lactose monohydrate - 107,800 mg; 106.148 mg or 104.498 mg; cellulose microcrystalline - 14,000 mg; 14,000 mg or 14,000 mg; pregelatinized starch - 3,900 mg; 3.900 mg or 3.900 mg; sodium lauryl sulfate - 1,300 mg; 1,950 mg or 2,600 mg; magnesium stearate - 1,000 mg; 1,000 mg or 1,000 mg; dye quinoline yellow [E104] 0.002 mg (for a dosage of 3 mg), dye azorubin [E122] 0.002 mg (for a dosage of 4 mg).

Description:

Dosage 2 mg: round, flat-cylindrical tablets, from white to white with a creamy shade of color, with a bevel.

Dosage 3 mg: round, flat-cylindrical tablets, light yellow color, with a bevel.

Dosage 4 mg: round, flat-cylindrical tablets, light-pink color, with a bevel. Marble is allowed.

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 acts mainly by stimulating the secretion and release of insulin from the beta cells of the pancreas (pancreatic action). As with other derivatives sulfonylureas, the basis of this effect is an increase in the response of beta cells of the pancreas to physiological stimulation with glucose,while the amount of insulin secreted is significantly less than when exposed to traditional sulfonylurea derivatives, when the blood glucose concentration is approximately the same. 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; inhibits the production of glucose in the liver. Glimepiride selectively inhibits cyclooxygenase and reduces the conversion of arachidonic acid to thromboxane A, which promotes platelet aggregation, thus providing an antiaggregant effect.

Glimepiride promotes the normalization of lipid content, reduces the concentration 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 level of endogenous a-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:

Suction. With repeated 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 ig / 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 about 100%. Eating does not have a significant effect on absorption, except for a slight slowing of the absorption rate.

Distribution. Glimepiride is characterized by a very low volume of distribution (about 8.8 liters), approximately equal to the volume of distribution of albumin, a high degree of binding to plasma proteins (more than 99%) and low clearance (about 48 mg / min). Glimepiride penetrates into breast milk and through the placental barrier. The drug penetrates poorly through the blood-brain barrier.

Metabolism. In urine and feces, two metabolites, formed as a result of metabolism in the liver, were detected (mainly with the help of CYP2C9), one of them is a hydroxy derivative, and the other is a carboxy derivative. After glimepiride intake, the half-life of these metabolites was 3-5 hours and 5-6 hours, respectively.

Excretion. 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. After a single oral glimepiride dose, 58% are excreted by the kidneys and through the intestine 35%. An unchanged substance in the urine was not detected.

Pharmacokinetics in specific patient groups

Impaired renal function

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.

Pharmacokinetic parameters are similar in patients of different sex and different age groups.

Indications:

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

Contraindications:

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

Carefully:

In the first weeks of treatment (increased risk of developing hypoglycemia); if there are risk factors for the development of hypoglycemia; conditions requiring the transfer of the 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.); with insufficiency of glucose-6-phosphate dehydrogenase; with intercurrent diseases during treatment or when changing the lifestyle of patients (changing diet and eating time, increasing or decreasing physical activity).

If you have any of these diseases, consult a doctor before taking the drug.

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.

Glimepiride penetrates into breast milk, so its use during breastfeeding is contraindicated.

Dosing and Administration:

Inside, not liquid and squeezed with enough liquid.

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

Initial dose and dose selection

At the beginning of treatment, the smallest therapeutic dose of glimepiride should be applied - 1 mg once a day (it is necessary to use the preparation of glimepiride in the indicated dosage of another manufacturer). 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 phased (from the intershafts 1-2 weeks) increased by 1 mg under regular control of blood glucose and in accordance with the next step increasedDose of dose: 1 mg -2 mg - 3 mg -4 mg - 6 mg (-8 mg). The usual daily dose of glimepiride in patients with well-controlled diabetes mellitus is 1-4 mg. Doses over 6 mg per day (8 mg) are effective only in a small number of patients.

Drug administration and dosing regimen

The time and frequency of taking a daily dose is determined by the doctor, taking into account the patient's lifestyle. The daily dose is prescribed in one session immediately before a hearty breakfast or the first main 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 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 or glimepiride in the maximum tolerated dose, therapy can be started with a combination of these two drugs.If the dose of metformin or glimepiride remains at the same level, treatment with glimepiride or metformin begins with a minimal dose, and then the dose gradually increases depending on the desired level of 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, a combination of glimepiride and 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 a possible subsequent gradual increase in the dose of insulin 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

There is no exact correlation between doses of glimepiride and other oral hypoglycemic drugs. When transferring a patient from another oral hypoglycemic preparation 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.

Use in patients with renal insufficiency

There is a limited amount of information available but the use of glimepiride in patients with renal insufficiency. Patients with impaired renal function may be more sensitive to the hypoglycemic effect of glimepiride (see the sections "Pharmacokinetics", "Contraindications"),

Use in patients with hepatic impairment

There is limited information on the use of glimepiride in liver failure (see "Contraindications").

Use in children

A study of the safety and efficacy of the drug in children with type 2 diabetes mellitus was not conducted.

Side effects:

The frequency of unwanted reactions is given in accordance with the following scale: very often (> 10%); often (> 1% and <10%); infrequently (> 0.1% and <1%); rarely (> 0.01% and <0.1%); very rarely (<0.01 %).

Disorders from the metabolism and nutrition: 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.

Disorders 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.

Disorders from the gastrointestinal tract: rarely - nausea, vomiting, a feeling of heaviness or discomfort in the epigastrium, abdominal pain,diarrhea, very rarely leading to discontinuation of treatment; very rarely - increased activity of "liver" enzymes, cholestasis, jaundice, hepatitis (until the development of liver failure).

Violations from the blood and lymphatic system: rarely - thrombocytopenia (from moderate to severe); very rarely - leukopenia, hemolytic anemia, erythrocytopenia, granulocytopenia, agranulocytosis and pancytopenia. In the post-marketing application of glimepiride, cases of severe thrombocytopenia with a platelet count of less than 10,000 / μL and thrombocytopenic purpura (frequency unknown) have been reported.

Immune system disorders: rarely - allergic and pseudoallergic reactions, such as itching, hives, skin rashes are possible. Such reactions are almost always of an easy form, but they can progress, accompanied by a decrease in blood pressure, dyspnea, until the development of anaphylactic shock. When urticaria appears, consult a doctor immediately. Possible cross-allergy to other derivatives of sulfonylureas, sulfonamides and other sulfonamides also may develop allergic vasculitis.

Other side effects: in some cases, the development of hyponatremia, photosensitivity.

Certain side effects, such as 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 unwanted or severe reactions of the patient develop or if you notice any other side effects - it is necessary immediately inform them about the doctor and not to continue taking the drug without his recommendation.

Overdose:

Acute overdose, as well as prolonged use of glimepiride in too high doses can lead to the development of severe life-threatening hypoglycemia.

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

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. In case of drug overdose Glimepiride it may be necessary to perform gastric lavage and receive activated charcoal. In the unconscious state of the patient, the administration of dextrose is started as soon as possible,if appropriate in the form of an intravenous bolus of 50 ml of 40% solution, followed by introducing the infusion of 10% solution, with careful monitoring of blood glucose concentration (not less than 5.5 mmol / l) for at least 24-48 hours (possible recurrent episodes hypoglycemia). As an alternative to adults, intravenous, subcutaneous, intramuscular administration of glucagon in a dose of 0.5-1 mg is possible. In the treatment of hypoglycemia in children accidentally taking them glimenirida should carefully adjust the dose administered dextrose under the constant control of blood glucose concentration due to the potential development of dangerous hyperglycemia.

In severe cases with prolonged course, the risk of hypoglycemia may persist for several days. 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.

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.

Glimepiride is metabolized by cytochrome P450 2C9 (isoenzyme CYP2C9). Its metabolism is affected by the simultaneous use of isoenzyme inducers CYP2C9, for example, rifampicin (the risk of reducing the hypoglycemic effect of gliemiride when used simultaneously with isoenzyme inducers CYP2C9 and an increased risk of developing hypoglycemia in the event of their withdrawal without correction of the dose of glimepiride) and inhibitors of the isoenzyme CYP2C9, for example, fluconazole (increased risk of hypoglycemia and side effects of gliwimiride when taken concomitantly with isoenzyme inhibitors CYP2C9 and the risk of reducing the hypoglycemic effect when they are withdrawn without correction of the dose of glimepiride).

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, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclophosphamide, trophosphamide and ifosfamide, fenfluramine, fibrates, fluoxetine, sympatholytics (guaetidin), monoamine oxidase inhibitors (MAO), pentoxifylline (when administered parenterally in high doses), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolone antibiotics, salicylates and aminosalicylic acid, sulfinpyrazone us tritokvalinom, fluconazole, clarithromycin.

The weakening of hypoglycemic action, and the associated increase in the concentration of glucose in the blood, can be observed with the simultaneous use of glimepiride with acetazolamide, barbiturates, glucocorticosteroids, diazoxide, diuretics,epinefriiom and other sympathomimetic agents, glucagon, laxatives (with prolonged use), nicotinic acid (at high doses) and nicotinic acid derivatives, estrogens and progestogens, phenothiazine derivatives (including chlorpromazine), feiitoinom, rifampicin, iodine-containing thyroid hormones.

Blockers H₂histamine receptors, β-blockers, clonidine and reserpine how can potentiate or weaken the hypoglycaemic action of glimepiride. Under the action of β-blockers, clonidine, reserpine and guanethidine may weaken or absence of clinical signs of hypoglycemia.

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

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

Sequestants of bile acids: kolesevelam binds with glimepiride and reduces the absorption of glimepiride from the gastrointestinal tract. In the case of glimepiride, at least for 4 hours before receiving colesevelam,no interaction is observed. therefore glimepiride must be taken at least 4 hours prior to taking kolesevelam.

You should inform your doctor about all the medications that you are taking.

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 that should be taken in case of such errors (for example, skipping a drug or eating a meal) or in situations when it is not possible to take the next dose of the drug at the set time. The patient should immediately inform the doctor if the dose is too high.

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 patient's body weight, lifestyle, or other factors contributing to an increased risk of hypo- or hyperglycaemia.

Adequate diet, regular and sufficient physical exercise and, if necessary, weight loss are just as important for achieving optimal control of blood glucose, as is the regular intake of glimepiride. Clinical symptoms of hyperglycemia are: increased frequency of urination, severe thirst, dry mouth and dry skin.

In the first weeks of treatment, the risk of developing hypoglycemia may increase, which requires particularly careful monitoring of the patient. Against the background of treatment with glimepiride, with irregular intake of food or skipping meals, hypoglycemia may develop. 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 certain other drugs (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 illness or a change in the patient's lifestyle. Symptoms of hypoglycemia can be smoothened or completely absent in the elderly, in patients suffering from autonomic neuropathy or receiving simultaneous treatment with β-blockers, clonidine, guanethidine, reserpine. Hypoglycemia can almost always be quickly stopped by an immediate intake of digestible carbohydrates (glucose or sugar, for example, in the form of a piece of sugar, (sweet fruit juice or tea).In connection with this, the patient should always have not less than 20 g of glucose (4 slices of sugar 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 physician, 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 necessarily 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, patients with glucose-6-phosphate dehydrogenase deficiency should be especially careful in the appointment of glimepiride 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 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 translation of insulin therapy.

During treatment, regular monitoring of blood glucose concentration is required, as well as regular testing of the concentration of glycosylated hemoglobin. Some side effects (severe hypoglycemia, serious changes in the blood picture, severe allergic reactions, liver failure) may under certain circumstances constitute a threat to the life of the patient. In case of unwanted or severe reactions, the patient should immediately inform the attending physician about them and in no wayDo not continue taking the drug without his recommendation.

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 occur, a decrease in the concentration and speed of the patient's psychomotor reactions. This can adversely affect the ability to drive vehicles and work with mechanisms.

Form release / dosage:

Tablets 2 mg, 3 mg or 4 mg.

Packaging:10 tablets per contour cell package, 3 contour packs with instructions for medical use in a pack of cardboard.

Storage conditions:

In dry, the dark place at a temperature of no higher than 25 C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not apply but the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002967

Date of registration:22.04.2015

Expiration Date:22.04.2020

The owner of the registration certificate:FARMPROJECT, CJSC FARMPROJECT, CJSC Russia

Manufacturer: & nbsp

FARMPROJECT, CJSC Russia

Representation: & nbspFARM PROJECT CJSC FARM PROJECT CJSC Russia

Information update date: & nbsp30.04.2017

Illustrated instructions

Instructions

Glimepiride (Glimepiride)