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

Excipients: lactose monohydrate 107.8 mg, microcrystalline cellulose 14.0 mg, pregelatinized starch 3.9 mg, sodium lauryl sulfate 1.3 mg, magnesium stearate 1.0 mg;

for a dosage of 3 mg:

active substance: glimepiride - 3 mg;

Excipients: lactose monohydrate - 106.1452 mg, microcrystalline cellulose - 14.0 mg, pregelatinized starch - 3.9 mg, sodium lauryl sulfate - 1.95 mg, magnesium stearate 1.0 mg, dye sunset yellow (E110) -0, 00056 mg, dye quinoline yellow (E104) -0.00424 mg.

Description:

Ploskotsilindricheskie tablets white or almost white color with a facet and a risk (a dosage of 2 mg) and flat-cylindrical tablets of light yellow color with a facet and risk (a dosage of 3 mg).

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 is a hypoglycemic preparation for oral use - a derivative of sulfonylureas of the third generation.

Glimepiride acts mainly by stimulating the secretion and release of insulin from the beta cells of the pancreas (pancreatic action).As with other sulfonylureas, this effect is based on an increase in the response of beta cells of the pancreas to physiological stimulation with glucose, while the amount of secreted insulin is significantly less than that of traditional sulfonylureas. The least stimulating effect of glimepiride on the secretion of insulin provides a lower risk of hypoglycemia. 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 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 level of endogenous alpha-tocopherol, catalase activity, Glutathione peroxidase and superoxide dismutase, which contributes to a decrease in severity oxidative stress in the patient's body, which is constantly present in type 2 diabetes mellitus.

Pharmacokinetics:

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 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, a high degree of binding to the protein (more than 99%) and low clearance (about 48 ml / min).

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.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.

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 elimination of the drug due to its 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 a previously prescribed diet and exercise.

If glomepiride monotherapy is ineffective, its use in combination therapy with metformin or with insulin is possible.

Contraindications:

Type 1 diabetes mellitus;
diabetic ketoacidosis, diabetic precoma and coma;
conditions, accompanied by a violation of food intake and development of hypoglycemia (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 of the drug, to other derivatives of sulfonylureas or to sulfonamide preparations (risk of developing hypersensitivity reactions);
lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
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, extensive 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, apparently, 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 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 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 6 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 and urine.

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 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 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 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 (eg, chlorpropamide), 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 insulin therapy is performed in patients with type 2 diabetes mellitus, with disease compensation and with the secretory function of beta cells of the pancreas, replacement of insulin 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:

From the side of metabolism: in rare cases, the development of hypoglycemic reactions is possible. 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 the concentration of glucose 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 discontinuation 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 it is possible the appearance of urticaria (itching, skin rash). Such reactions are, as a rule, moderately expressed, but can progress, accompanied by a drop 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 may develop headaches, fatigue, hyponatremia, photosensitivity, late cutaneous porphyria.

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 case should continue taking the drug without his recommendation.

Overdose:

After oral high dose glimepiride may develop hypoglycemia, lasting from 12 to 72 hours, which may be repeated after the initial restore blood glucose. In most cases, monitoring in a hospital is recommended. May experience increased sweating, anxiety, tachycardia, hypertension, palpitations, pain in the heart, arrhythmia, headache, dizziness, sharp increase in appetite, nausea, vomiting, lethargy, drowsiness, restlessness, 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.

In the treatment of hypoglycemia, which has developed due to the occasional use of glimepiride in infants or young children, in order to avoid hyperglycemia, the dose of dextrose (50 ml of 40% solution) should be monitored and the glucose concentration in the blood monitored continuously.

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, quinolone antibiotics, salicylates and aminosalicylic acid, sulfinpyrazone, some sulfonamides prolonged action, tetracyclines, tritokvalinom, fluconazole.

Weakening of hypoglycemic action, and the associated increase in the concentration of glucose in the blood,may occur while the application glimepiride with acetazolamide, barbiturates, corticosteroids, diazoxide, saluretics, thiazide diuretics, epinephrine and other sympathomimetic agents, glucagon, laxatives (with prolonged use), nicotinic acid (at high doses) and nicotinic acid derivatives, estrogens and progestogens, phenothiazines, chlorpromazine, phenytoin, rifampin, thyroid hormones, lithium salts.

Blockers H₂-gistaminovyh 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.

While the use of drugs which suppress bone marrow hematopoiesis, increased risk mielosupreseii.

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.

At achievement of indemnification of a diabetes of type 2 sensitivity to an insulin raises. 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 just as important for achieving optimal control of blood glucose levels, as is the regular intake of glimepiride.

Clinical symptoms 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. On the background of treatment with glimepiride with irregular intake of food or skipping meals can develop hypoglycemia. Its possible symptoms are: headache, hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, anxiety, aggressiveness, attention and reaction disorders, 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.

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.

Symptoms of hypoglycemia can be smoothened or completely absent in the elderly, in patients suffering from autonomic neuropathy or receiving concurrent treatment with beta-blockers, clonidine, reserpine, guanethidine or other sympatholytic agents. 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.

From the experience with other sulfonylureas, it is known that despite the initial success of stopping hypoglycemia, its relapse is possible. 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 suffering from diabetes mellitus is treated by different doctors (for example, during a hospital stay after an accident, during a weekend illness), he must necessarily inform them about his illness and about the previous treatment.

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:

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 psychomotor reactions of the patient. This can adversely affect the ability to drive vehicles or to manage various machines and mechanisms.

Form release / dosage:

Tablets 2 mg and 3 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 instructions for use in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 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:LSR-009962/09

Date of registration:08.12.2009 / 10.03.2016

Expiration Date:Unlimited

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)