Glimepiride-Teva - instructions for use, dose, side effects, contraindications

1 tablet contains: active substance glimepiride 4.00 mg, Excipients: lactose monohydrate 199.34 mg, corn starch 6.21 mg, sodium carboxymethyl starch type A 13.33 mg, povidone-KZO 9.33 mg, polysorbate 80 1.79 mg, talc 2.67 mg, magnesium stearate 1 , 60 mg, ferric oxide, yellow oxide (E 172) 0.40 mg.

Description:

Tablets of oblong form of yellow color with light marble with chamfered edges and risk on one side.

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 sulfonylurea derivatives, 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 other sulfonyl urea derivatives. 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, providing an antiaggregant effect.

Glimepiride promotes the normalization of lipid content, reduces the concentration of malonic aldehyde in plasma, which leads to a significant decrease in lipid peroxidation, which contributes to the manifestation of anti-atherogenic action of glimepiride.

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 intake of glimepiride in a daily dose of 4 mg, its maximum concentration in the blood serum (Cmax) is reached after about 2.5 hours and is 309 ng / ml; there is a linear relationship between dose and Cmax,and also between the dose and the area under the "concentration-time" curve. Bioavailability of glimepiride is 100%. The intake of food has no significant effect on absorption, except for a slight slowing down, the absorption rate: Glimepiride has a very low volume of distribution (about 8.8 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 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 (T1 / 2) at plasma serum glimepiride concentrations corresponding to a multiple dosing regimen is 5-8 hours. After taking high doses, T1 / 2 slightly increases.

Glimepiride is excreted in breast milk and penetrates the placental barrier. Poorly penetrates the blood-brain barrier.

In patients with impaired renal function (with low creatinine clearance (CC)), there is a tendency to increase the clearance of glimepiride and to reduce its average serum concentrations, which is most likely due to the faster elimination of glimepiride 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 with ineffectiveness of diet and exercise (in monotherapy or as part of combination therapy with metformin or 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);
increased sensitivity to glimepiride or other components of the drug, to other derivatives of sulfonylureas or to sulfonamide preparations (risk of developing hypersensitivity reactions);
pregnancy and lactation;
lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
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 burn, severe multiple trauma, extensive surgical intervention,as well as a violation of absorption of food and drugs in the gastrointestinal tract (GI tract), including intestinal obstruction, intestinal paresis, infectious fever, alcoholism); insufficiency of glucose-6-phosphate dehydrogenase (G6PD).

Pregnancy and lactation:

Glimepiride is contraindicated 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 such a case, it is necessary to switch to insulin therapy or stop breastfeeding.

Dosing and Administration:

Inside.

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 incrementally increased by regular monitoring of blood glucose concentrations (at intervals of 1-2 weeks) to 2 mg, 3 mg, 4 mg, 6 mg, (8 mg).The maximum recommended daily dose is 6 mg. Doses over 6 mg per day are effective only in exceptional cases.

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 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.

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. When the dose of metformin is maintained, treatment with glimepiride begins with a minimal dose, and then the dose gradually increases, depending on the desired blood glucose concentration, up to the maximum daily dose. Combination therapy should be conducted under careful 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 a possible subsequent gradual increase, 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

The initial daily dose of glimepiride 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 step by step in accordance with the above recommendations. 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 large T1 / 2,there may be a need for a temporary (within a few days) cessation of treatment in order to avoid an additive effect that increases the risk of developing hypoglycemia.

Transfer of a patient from insulin to glimepiride

In exceptional cases, with insulin therapy in patients with type 2 diabetes mellitus, with disease compensation and with the secretory function of beta cells of the pancreas, insulin replacement with glimepiride is possible. The translation should be done 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:

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including isolated cases.

From the side of metabolism: rarely, a hypoglycemic reaction (this reaction mainly occurs shortly after taking glimepiride, it can have a severe form and flow and it is not always possible to easily stop it, in addition, its appearance depends on the individual characteristics of nutrition and dosing).

From the side of the organ of vision: frequency is not known - during the treatment (especially at the beginning), transient visual impairments due to changes in the concentration of glucose in the blood can be observed.

From the digestive system: very rarely - nausea, vomiting, a feeling of heaviness or discomfort in the epigastric abdominal pain, diarrhea (in extreme cases leading to discontinuation of treatment), cholestasis, jaundice, hepatitis (until the development of liver failure); frequency is not known - increased activity of "liver" enzymes.

From the side of the blood and lymphatic system: rarely - thrombocytopenia (moderate to severe), leukopenia, hemolytic and aplastic anemia, eritrotsigopeniya, granulocytopenia, agranulocytosis and pantsigopeniya.

Allergic reactions: very rarely - urticaria, itching, skin rash (such reactions are usually moderate but can progress, accompanied by a decrease in blood pressure (BP), shortness of breath, until the development of anaphylactic shock); frequency is not known - the cross-allergy to other derivatives of sulfonylureas, sulfonamides and other sulfonamides also may develop allergic vasculitis.

Other: very rarely - hyponatremia; in isolated cases - headache, asthenia; frequency is not known - photosensitivity, late cutaneous porphyria.

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, sharp increase in appetite, nausea, vomiting, apathy, drowsiness, anxiety, aggressiveness, impaired concentration, depression, confusion , tremor, paresis, sensitivity disorder, convulsion of the central genesis. Sometimes the clinical picture of hypoglycemia may resemble a stroke. Possible the development of coma.

When large amounts of glimepiride are taken, gastric lavage is shown, followed by sodium picosulfate 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 inhibitors, allopurinol, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclophosphamide, trophosfamide and ifosfamide, fenfluramine , disopyramide, fibrates, fluoxetine, sympatholytics (guanethidine), inhibitors of monoamine oxidase, miconazole, fluconazole, pentoxifylline (when parenterally - administered in high doses), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, antimicrobial agents - quinolone derivatives, salicylates (including aminosalicylic acid), sulfinpyrazone, some sulfonamides prolonged action, tetracyclines, tritvaline.

Attenuation 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, saluretic, thiazide diuretics, epinephrine and other sympathomimetic agents, glucagon, laxatives (with prolonged use), nicotinic acid doses) and nicotinic acid derivatives, estrogens and progestogens, phenothiazine derivatives, including chlorpromazine, phenytoin, rifampicin, iodso ERZHAN thyroid hormones, lithium salts. The blockers of H2-histamine receptors, clonidine and reserpine can both potentiate and weaken the hypoglycemic effect of glimepiride.

Under the action of beta-adrenoblockers, clonidine, guanetidine and reserpine, weakening or lack of clinical signs of hypoglycemia is possible.

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.

Single or chronic, the 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 that should be taken in case of such mistakes (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 prescribed time. The patient should immediately inform the doctor if the dose is too high.

The patient should be warned about the need to immediately inform the doctor about the appearance of skin rashes, hives. Such allergic reactions can quickly progress up to anaphylactic shock.

Development of hypoglycemia in the patient after admission, 1 mg glimepiride per day means the ability to control glycemia solely through 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 patient's body weight, lifestyle or other factors contributing to an increased risk of hypo- or hyperglycaemia.

Adequate diet, regular and sufficient 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 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;
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. If there are such factors that increase the risk of hypoglycemia, adjust the dose of glimepiride or the entire scheme, treatment. 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 elderly patients, 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.

From the experience with other sulfonylureas, it is known that, despite the initial success of stopping hypoglycemia, a relapse of hypoglycemia is possible. 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, if he feels unwell at a weekend), he must tell 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, in trauma, surgery, infectious diseases accompanied by fever), it may be necessary to temporarily transfer 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.

Therapy of patients with G6PD deficiency derivatives of sulfonylureas, including glimepiride, can lead to the development of hemolytic anemia. Consideration should be given to the possibility of using other drugs not belonging to this group in these patients.

Some of the side effects of glimepiride (severe hypoglycemia, severe changes in the blood picture, allergic reactions, liver failure) can under certain circumstances pose a threat to the life of the patient. Patient it is necessary to warn about the need to immediately consult a doctor and inform him about the development of adverse reactions.

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, there may be a decrease in the concentration of attention and speed of psychomotor reactions caused by hypo- or hyperglycemia. This can adversely affect the ability to drive vehicles or to manage various machines and mechanisms. Patients should be given advice on preventing hypoglycemia and hyperglycemia.This is especially important for patients with a lack or decrease in the severity of symptoms-precursors of developing hypoglycemia or suffering from frequent episodes of hypoglycemia.

Form release / dosage:

Tablets 4 mg.

Packaging:

For 10 tablets in a blister of PVC / PVDC / aluminum foil.

By 3, 6 or 10 blisters together with instructions for use in cardboard pack.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

4 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001767

Date of registration:02.07.2012

Expiration Date:02.07.2017

The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia

Manufacturer: & nbsp

USV, Ltd. India

Representation: & nbspTeva Teva Israel

Information update date: & nbsp30.04.2017

Illustrated instructions

Instructions

Glimepiride-Teva (Glimepiride-Teva)