Glimepirid Kanon

General characteristics. Structure:

Dosage of 1 mg
1 tablet contains:
active agent: глимепирид 1 mg;
excipients: hydrophosphate calcium dihydrate of 24,4 mg, croscarmellose sodium of 3 mg, starch of corn 14 mg, Mannitolum of 45 mg, magnesium stearate of 0,6 mg, povidon-K30 2 mg.

Dosage of 2 mg
1 tablet contains:
active agent: глимепирид 2 mg;
excipients: hydrophosphate calcium dihydrate of 30 mg, croscarmellose sodium of 3,7 mg, starch of corn 16 mg, Mannitolum of 55 mg, magnesium stearate of 0,8 mg, povidon-K30 2,5 mg.

Dosage of 3 mg
1 tablet contains:
active agent: глимепирид 3 mg;
excipients: hydrophosphate calcium dihydrate of 40,5 mg, croscarmellose sodium of 5 mg, starch of corn 22,1 mg, Mannitolum of 75 mg, magnesium stearate of 1 mg, povidon-K30 3,4 mg.

Dosage of 4 mg
1 tablet contains:
active agent: глимепирид 4 mg;
excipients: hydrophosphate calcium dihydrate of 53,3 mg, croscarmellose sodium of 6,7 mg, starch of corn 30 mg, Mannitolum of 100 mg, magnesium stearate of 1,5 mg, povidon-K30 4,5 mg.

Description:
Tablets are round, ploskotsilindrichesky, with a facet (a dosage of 1 mg and 3 mg); round, ploskotsilindrichesky, with a facet and risky (dosages of 2 mg and 4 mg), white or almost white color.

Pharmacological properties:

Pharmacodynamics. Glimepirid stimulates secretion and release of insulin from pancreas beta cells (pancreatic action). Increase in reaction of beta cells of a pancreas at physiological stimulation by glucose is the cornerstone of this effect, at the same time the amount of the cosecreted insulin is much less, than at action of other derivatives of sulphonylurea, thus, the smaller risk of development of a hypoglycemia is provided. In addition, глимепирид possesses extra pancreatic action - ability to improve sensitivity of peripheral fabrics (muscular, fatty) to effect of own insulin, to reduce insulin absorption by a liver; inhibits products of glucose in a liver. Glimepirid selectively inhibits cyclooxygenase and reduces, transformation of arachidonic acid into A2 thromboxane which promotes aggregation of thrombocytes, thus having antiagregantny effect.
Glimepirid contributes to normalization of maintenance of lipids, reduces concentration of low-new aldehyde in blood that leads to considerable decrease in peroxide oxidation of lipids, it promotes anti-atherogenous effect of drug. Glimepirid promotes decrease in expressiveness of an oxidizing stress in an organism of the patient which constantly is present at a diabetes mellitus of the 2nd type.

Pharmacokinetics. At multiple dose of a glimepirid in a daily dose of 4 mg the maximum concentration in blood (Cmax) is reached in 2,5 h and makes 309 ng/ml. There is a linear ratio between a dose and Cmax, and also between a dose and the area under a curve "concentration time" (AUC). At intake of a glimepirid its bioavailability makes 100%. Meal has no significant effect on absorption, except for insignificant delay of speed of absorption. The volume of distribution is-8,8 l. Communication with proteins - 99%, clearance - 48 ml/min.
It is metabolized in a liver. It is removed preferential in the form of metabolites by kidneys (60% of the entered dose) and intestines (40%). Glimepirid is allocated with breast milk and gets through a placental barrier. Badly gets through a blood-brain barrier. An elimination half-life (T1/2) - 5-8 h.
At patients with renal failures (with low clearance of creatinine) the tendency to increase in clearance of a glimepirid and to decrease in its average concentration in blood serum is observed that, most likely, is caused by more bystry removal of a glimepirid owing to its lower linkng with proteins of plasma. Thus, this category of patients does not have an additional risk of cumulation of drug.

Indications to use:

Diabetes mellitus of the 2nd type at inefficiency of a dietotherapy and exercise stress (in monotherapy or as a part of a combination therapy with metformin or insulin).

Route of administration and doses:

In an initiation of treatment drug Glimepirid Kanon is used inside in a dose by 1 mg of 1 times a day (just before or during a plentiful breakfast), if necessary gradually increasing a dose by 1 mg in 1-2 weeks prior to 2 mg, 3 mg, 4 mg, 6 mg, 8 mg.
The maximum recommended daily dose - 6 mg. Doses over 6 mg are effective only in exceptional cases.
It is very important not to miss meal after reception of a glimepirid.
The admission of administration of drug cannot be eliminated by the subsequent reception of its higher dose conducting to a hypoglycemia. A pill is taken entirely, without chewing, washing down with enough water (about 0,5 glasses).
Prolonged treatment, under control of content of glucose in blood.

Use in a combination with Metforminum
In case of insufficient stabilization of concentration of glucose in blood at the patients accepting Metforminum the accompanying therapy glimepiridy can be begun. At preservation of a dose of Metforminum at the previous level treatment glimepiridy begins with the minimum dose in 1 mg, and then its dose gradually increases depending on desirable concentration of glucose in blood, up to the maximum daily dose. The combination therapy has to be carried out under careful medical observation.

Use in a combination with insulin
In cases when it is not possible to reach normalization of concentration of glucose in blood reception of the maximum dose of a glimepirid in monotherapy or in a combination with the maximum dose of Metforminum, the combination of a glimepirid with insulin is possible.
In this case the last, the dose of a glimepirid appointed to the patient remains invariable. At the same time treatment by insulin begins with the minimum dose, with possible subsequent gradual increase in a dose of insulin under control of concentration of glucose in blood.
The combined treatment demands obligatory medical control.
Transfer of the patient from other peroral hypoglycemic drug on глимепирид
There is no exact ratio between doses of a glimepirid and other peroral hypoglycemic drugs. At transfer from such drugs on глимепирид the initial daily dose of the last has to make 1 mg (even if the patient is transferred on глимепирид from the maximum dose of other peroral hypoglycemic drug). Any increase in a dose of a glimepirid should be carried out step by step taking into account the answer on глимепирид according to the stated above recommendations. It is necessary to take the used dose and duration of effect of the previous hypoglycemic means into account. In certain cases, especially at reception of hypoglycemic drugs with a big elimination half-life, there can be a need in temporary (within several days) the termination of treatment in order to avoid the additive effect increasing risk of development of a hypoglycemia.

Transfer of the patient from insulin on глимепирид
In exceptional cases, when performing insulin therapy at patients with a diabetes mellitus 2 types, at compensation of a disease and at safe secretory function of beta cells of a pancreas, can be shown transfer on глимепирид. Transfer has to be carried out under careful observation of the doctor. At the same time transfer of the patient on глимепирид is begun with the minimum dose of a glimepirid in 1 mg.

Features of use:

Glimepirid it is necessary to accept in the recommended doses and in due time. Mistakes in drug use, for example, the admission of reception, it is never impossible to eliminate by means of the subsequent reception of higher dose. The doctor and the patient have to discuss in advance measures which should be accepted in case of such mistakes (for example, the admission of administration of drug or meal) or in situations when reception of the next dose of drug at the scheduled time is impossible. The patient has to inform immediately the doctor in case of reception of too high dose of drug.
Development of a hypoglycemia in the patient after reception of 1 mg of a glimepirid a day means a possibility of control of a glycemia only by means of a diet. At achievement of compensation of a diabetes mellitus 2 types raise sensitivity to insulin. In this regard in the course of treatment the need for a glimepirida can decrease. In order to avoid development of a hypoglycemia it is necessary to reduce temporarily a dose or to cancel глимепирид. Dose adjustment has to be carried out also at change of body weight of the patient, his way of life or at emergence of other factors promoting increase in risk of development hypo - or a hyperglycemia.
In the first weeks of treatment the risk of development of a hypoglycemia can increase that demands especially careful observation of the patient. Treat the factors promoting risk of development of a hypoglycemia:
- unwillingness or inability of the patient to cooperation with the doctor (more often observed at patients of advanced age);
- malnutrition, irregular meal or admissions of meal;
- an imbalance between exercise stresses and the use of carbohydrates;
- change of a diet;
- alcohol intake, especially in combination with admissions of meal;
- heavy renal failures;
- overdose of a glimepirid;
- some dekompensirovanny endocrine frustration breaking carbohydrate metabolism or adrenergic counterregulation in response to a hypoglycemia (for example, dysfunction of a thyroid gland and front department of a hypophysis, insufficiency of bark of adrenal glands);
- a concomitant use of some medicines (see the section "Interaction with other medicines);
- reception of a glimepirid in the absence of indications to its reception.
Symptoms of a hypoglycemia can be maleficiated or be absent absolutely at elderly, at patients with vegetative neuropathy or receiving simultaneous treatment (b-adrenoblockers, a clonidine, Reserpinum, guanetidiny. The hypoglycemia can be almost always quickly stopped by immediate reception 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 has to have always at himself not less than 20 g of glucose (4 pieces of sugar).
Sweeteners are not effective in treatment of a hypoglycemia.
Treatment by sulphonylurea derivatives which treats and глимепирид, can lead to development of hemolitic anemia therefore at patients with insufficiency glyukozo-6-fosfatdegidrogenazy it is necessary to observe extra care at purpose of a glimepirid and is better to apply the hypoglycemic means which are not sulphonylurea derivatives.
During treatment glimepiridy carrying out regular control of function of a liver and a picture of peripheral blood is required (especially quantities of leukocytes and thrombocytes).
In stressful situations (for example, at an injury, surgical intervention, infectious diseases which are followed by fever) there can be a need for temporary transfer of the patient on an insulin therapy.
There is no experience of use of a glimepirid for patients with heavy abnormal liver functions and kidneys or the patients who are on a hemodialysis. And a liver transfer into an insulin therapy is shown to patients with heavy renal failures.
During treatment glimepiridy regular control of concentration of glucose in blood, and also concentration of glikozilirovanny hemoglobin is necessary.

Influence on ability to control of vehicles and mechanisms:
During treatment it is necessary to be careful at control of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From a metabolism: development of hypoglycemic reactions is possible. These reactions, mainly, arise soon after administration of drug, can have a severe form and a current and they not always manage to be stopped easily. Approach of these symptoms depends on individual factors, such as feeding habits and dosing.
From an organ of sight: during treatment (especially at its beginning) the tranzitorny vision disorders caused by change of concentration of glucose in blood can be observed.
From system of digestive organs: nausea, vomiting, heavy feeling or discomfort in the epigastriums, an abdominal pain, diarrhea which are very seldom leading to the treatment termination; increase in activity of "hepatic" enzymes, a cholestasia, jaundice, hepatitis (up to development of a liver failure).
From system of a hemopoiesis: thrombocytopenia (from moderated to heavy), a leukopenia, hemolitic or aplastic anemia, an erythrocytopenia, a granulocytopenia, an agranulocytosis and a pancytopenia.
Allergic reactions: emergence of a small tortoiseshell, skin rash, itch is possible. Such reactions happen, as a rule, moderately expressed, but can progress, being followed by a lowering of arterial pressure, short wind, up to development of an acute anaphylaxis. At emergence of a small tortoiseshell it is necessary to see a doctor immediately. The cross allergy with other derivatives of sulphonylurea, streptocides or other sulfonamides is possible, development of an allergic vasculitis is also possible.
Others: development of a headache, an adynamy, hyponatremia, photosensitization, late skin porphyria is in exceptional cases possible.

Interaction with other medicines:

Simultaneous use of a glimepirid with some medicines can cause both strengthening, and weakening of hypoglycemic effect of drug. Therefore other medicines can be accepted only after approval of the doctor.
Strengthening of hypoglycemic action and, the connected with it, possible development of a hypoglycemia can be observed at simultaneous use of a glimepirid with the insulin, metformin or other peroral hypoglycemic drugs, inhibitors of an angiotensin-converting enzyme (APF), Allopyrinolum, anabolic steroids and male sex hormones, chloramphenicol derivative of coumarin, cyclophosphamide, trofosfamidy and ifosfamidy, fenfluraminy, fibrata, fluoxetine, sympatholytics (guanetidiny), inhibitors of a monoaminooxidase (MAO), Miconazolum, pentoksifilliny (at parenteral administration in high doses), phenylbutazone, azapropazony, oksifenbutazony, probenetsidy, antimicrobic means - derivatives of a hinolon, salicylates (including aminosalicylic acid), Sulfinpyrazonum, some streptocides of the prolonged action, tetracyclines, tritokvaliny, flukonazoly.
Weakening of hypoglycemic action, and connected with it increase in concentration of glucose in blood can be observed at simultaneous use of a glimepirid with acetazoleamide, barbiturates, glucocorticosteroids, diazoxide, saluretics, thiazide diuretics, Epinephrinum and other sympathomimetic means, a glucagon, purgatives (at prolonged use), niacin (in high doses) and the niacin derivatives, estrogen and progestogens derivative of a fenotiazin, including Chlorpromazinum, Phenytoinum, rifampicin, hormones of a thyroid gland, lithium salts.
Blockers of H2-histamine receptors, clonidine and Reserpinum are capable both to potentiate, and to weaken hypoglycemic action of a glimepirid.
Under the influence of b-adrenoblockers, a clonidine, guanetidin and Reserpinum easing or lack of clinical signs of a hypoglycemia is possible. Against the background of reception of a glimepirid strengthening or weakening of action of derivatives of coumarin can be observed.
At simultaneous use with the medicines oppressing a marrowy hemopoiesis the risk of a miyelosupressiya increases.
Single or chronic alcohol intake can both strengthen, and to weaken hypoglycemic action of a glimepirid.

Contraindications:

- diabetes mellitus of the 1st type;
- hypersensitivity to a glimepirid or other components of drug, other derivatives of sulphonylurea or streptocides;
- diabetic ketoacidosis, diabetic prekoma and coma, giperosmolyarny coma;
- a heavy liver and renal failure (including the patients who are on a hemodialysis);
- leukopenia;
- pregnancy, lactation period;
- children's age up to 18 years.

With care:
- in the first weeks of treatment (the increased risk of development of a hypoglycemia);
- with risk factors for development of a hypoglycemia;
- in the presence of the states demanding transfer into an insulin therapy (extensive burns, a severe multiple injury, extensive surgical interventions);
- at disturbances of absorption of food and medicines in the digestive tract (DT) (including intestinal impassability, intestines paresis);
- at insufficiency glyukozo-6-fosfatdegidrogenazy.

Use at pregnancy and in the period of a lactation:
Glimepirid is contraindicated to use for pregnant women. In case of the planned pregnancy or at pregnancy approach the woman should be transferred to an insulin therapy.
As глимепирид gets into breast milk, women should not appoint it in the period of a lactation. In that case it is necessary to pass to an insulin therapy or to stop feeding by a breast.

Overdose:

At intake of a high dose of a glimepirid development of a hypoglycemia lasting 12-72 hours which can repeat after initial recovery of concentration of glucose in blood is possible.
Treatment: if the patient in consciousness - immediate reception of carbohydrates (glucose or a piece of sugar, sweet fruit juice or tea). Observation in the conditions of a hospital is in most cases recommended. At reception of a large amount of drug the gastric lavage with the subsequent administration of absorbent carbon (adsorbent) and sodium sulfate (laxative), introduction of a dextrose intravenously struyno is shown: 50 ml of 40% of solution, then infusion of 10% of solution. Constant observation and maintenance of the vital functions, concentration of glucose in blood is necessary (it is not lower than 5,5 mmol/l) during at least 24-48 h (repeated episodes of a hypoglycemia are possible). After recovery of consciousness it is necessary to give to the patient the food rich with digestible carbohydrates (in order to avoid repeated development of a hypoglycemia). Further treatment has to be symptomatic.
At treatment of the hypoglycemia which developed owing to unintentional reception of a glimepirid by the chest or small child, the dose of a dextrose has to be controlled carefully to avoid a dangerous hyperglycemia.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets of 1 mg, 2 mg, 3 mg, 4 mg.
On 10, 20 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 1, 3, 6 blister strip packagings on 10 tablets or on 3, 5 blister strip packagings on 20 tablets or on 1, 2, 3, 4 blister strip packagings on 30 tablets together with the application instruction place in a pack from a cardboard.