Glimepirid - Teva

General characteristics. Structure:

Active agent - глимепирид - 1,000 mg / 2,000 mg / 3,000 mg;
  Excipients: lactoses monohydrate of 75,40 mg / 150,80 mg / 149,50 mg, starch of corn 2,33mg/4,66 mg / 4,66 mg, carboxymethylstarch of sodium of 5,00 mg / 10,00 mg / 10.00 mg, povidone of 3,00 mg / 6,00 mg / 7,00 mg. mg polysorbate 80 0,67 / 1,34 mg / 1,34 mg, talc of 1,0 mg / 2,0 mg / 2,00 mg, magnesium stearate of 0,60 mg / 1,20 mg / 1,20 mg, iron dye (Е 172) - / - / 0,30 mg.

Description:
Tablets of 1 mg: White, oblong, with slanted edges of a tablet
Tablets of 2 mg: White, oblong, with slanted edges of a tablet with the line of a break on one party
Tablets of 3 mg: Light yellow with a brownish shade with a marble surface, oblong, with slanted edges of a tablet with the line of a break on one party.

Pharmacological properties:

Pharmacodynamics. Glimepirid represents hypoglycemic drug for oral administration - derivative sulphonylurea of new (third) generation. Glimepirid acts, mainly stimulating secretion and release of insulin from pancreas beta cells (pancreatic action). As well as at other derivatives of sulphonylurea, this effect increase in reaction of beta cells of a pancreas at physiological stimulation by glucose is the cornerstone, at the same time the amount of the cosecreted insulin is much less, than at effect of traditional drugs - sulphonylurea derivatives. The smallest stimulating influence of a glimepirid on secretion of insulin provides also smaller risk of development of a hypoglycemia. In addition to it, 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 antitrombotichesky effect.
Glimepirid contributes to normalization of maintenance of lipids, reduces the level of malovy aldehyde in blood that leads to considerable decrease in peroxide oxidation of lipids, it promotes anti-atherogenous effect of drug.
Glimepirid   increases   the level of endogenous α-tocopherol, activity of a catalase, glyutationperoksidaza and superoxide scavenger that promotes decrease in expressiveness of an oxidizing stress in  an organism of the patient which  constantly  is present at a diabetes mellitus of type 2.

Pharmacokinetics. At multiple dose of a glimepirid in a daily dose of 4 mg the maximum concentration in blood serum (Cmax) is reached approximately in 2,5  hour and makes 309 ng/ml; there is a linear ratio between a dose and Cmax, and also between a dose and AUC (the area under a curve "concentration - time"). At intake of a glimepirid its bioavailability makes 100%. Meal has no significant effect on absorption,    except for  insignificant  delay  of speed  of absorption.  Very low volume of distribution (about 8,8 l) approximately equal to albumine distribution volume, high extent of linkng with proteins of plasma (more than 99%) and low clearance (about 48 ml/min.) is characteristic of a glimepirid.
After a single dose in a dose  of a glimepirid, kidneys remove 58% and through intestines - 35%. Not changed substance in urine was not found. The elimination half-life at the plasma concentration of drug in serum corresponding to the repeated mode of dosing makes 5-8 hours. After reception of high doses the elimination half-life increases a little.
In  urine  and  excrements    two  inactive  metabolites      most of which likely are formed      as a result of   metabolism in a liver come to light, one of them is hydroxyderivative, and another - to carboxyderivatives. After intake of a glimepirid the terminal elimination half-life of these metabolites makes 3-5 hours and 5-6 hours, respectively.
Glimepirid is allocated with breast milk and gets through a placental barrier.
Drug badly gets through a blood-brain barrier.
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 was observed that most likely, is caused by more bystry removal of drug owing to its lower linkng with protein. Thus, this category of patients does not have an additional risk of cumulation of drug.

Indications to use:

Drug is shown for treatment of a diabetes mellitus 2 types at inefficiency of earlier appointed diet and exercise stress.
At inefficiency of monotherapy by Glimepirid - Teva its use in a combination therapy with Metforminum or with insulin is possible.

Route of administration and doses:

Drug is used inside. The initial and supporting Glimepirid's doses - Tev are established individually on the basis of results of regular control of concentration of glucose in blood.
Initial dose and selection of a dose
 In an initiation of treatment appoint 1 mg of Glimepirid - Teva once a day. At achievement of optimum therapeutic effect it is recommended to accept this dose as supporting. In case of lack of glycemic control the daily dose has to be step by step increased under regular control of concentration of glucose in blood (bucketed in 1-2 weeks) to 2 mg, 3 mg or 4 mg a day. Doses of over 4 in days are effective only in exceptional cases. The maximum recommended daily dose - 6 mg. Use in a combination with Metforminum
 In case of lack of glycemic control at the patients accepting Metforminum the accompanying therapy by Glimepirid - Teva can be begun. At preservation of a dose of Metforminum at the previous level treatment by Glimepirid - Teva begins with the minimum dose, and then the dose gradually increases depending on the desirable level of glycemic control, 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 glycemic control by reception of the maximum dose of Glimepirid - Teva, in monotherapy or in a combination with the maximum dose of Metforminum, Glimepirid's combination - Teva with insulin is possible. In this case the last, Glimepirid's dose appointed to the patient - Teva, remains invariable. At the same time treatment by insulin begins with the minimum dose, with possible subsequent gradual increase in its dose under control of concentration of glucose in blood. The combined treatment demands obligatory medical control.
Time and frequency rate of reception of a daily dose is defined by the doctor with a way of life of the patient. As a rule, purpose of a daily dose in one step just before is enough or during a big breakfast or the first main meal. Glimepirid's pill - Tev is taken entirely, without chewing, with enough liquid (about 0,5 glasses). It is very important not to miss meal after Glimepirid's reception - Teva.
Treatment duration
 As a rule, treatment by Glimepirid - Teva, happens long.
Transfer of the patient from other peroral hypoglycemic drug on глимепирид.
At transfer of the patient from other peroral hypoglycemic drug on Glimepirid - Teva the initial daily dose of the last has to make 1 mg (even if the patient is transferred on Glimepirid - Teva from the maximum dose of other peroral hypoglycemic drug). Any increase in a dose of Glimepirid - Teva should be carried out step by step according to the stated above recommendations. It is necessary to take efficiency, a dose and duration of action of the used hypoglycemic means into account. In certain cases, especially at reception of hypoglycemic drugs with a big elimination half-life (for example, Chlorproramidum) 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 Glimepirid-Tev
 In exceptional cases, when performing insulin therapy at patients with a diabetes mellitus of type 2, at compensation of a disease and at safe secretory function (3 cells of a pancreas, insulin replacement with Glimepirid - Teva is possible. Transfer has to be carried out under careful observation of the doctor. At the same time transfer of the patient on Glimepirid - Tev is begun with the minimum dose in 1 mg.

Features of use:

Glimepirid - Tev should be accepted 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.
If at the patient hypoglycemic reaction at reception of 1 mg of Glimepirid - Teva in days developed, it indicates that at this patient normalization of level of glucose in blood can be reached by means of one diet.
At   achievement   of compensation   of a diabetes mellitus of type 2 sensitivity to insulin increases. In this regard in the course of treatment the need for Glimepirida - Teva can decrease. In order to avoid development of a hypoglycemia it is necessary to reduce temporarily a dose or to cancel Glimepirid - Teva. Dose adjustment has to be carried out also  at  change  of body weight  of the patient,  at  change  of his  way of life  or  at  emergence  of other factors promoting increase in risk of development hypo - or a hyperglycemia. The adequate diet, regular and sufficient physical exercises and, if necessary, decrease in body weight have the same importance for achievement of optimum control of level of glucose in blood, as well as regular reception of Glimepirid - Teva.
Clinical symptoms of a hyperglycemia (insufficient decrease in level of glucose in blood) are: increase in frequency of urinations, strong thirst, dryness in a mouth and dryness of integuments. In the first weeks of treatment the risk of development of a hypoglycemia can increase that demands especially careful observation of the patient. Against the background of treatment by Glimepirid - Teva at irregular meal or the admission of meal can develop a hypoglycemia. Its possible symptoms are: a headache, feeling of hunger, nausea, vomiting, feeling of fatigue, drowsiness, sleep disorders, concern, aggression, disturbances of concentration, attention and reaction, a depression, confusion of consciousness, speech and visual frustration, aphasia, a tremor, paresis, touch disturbances, dizziness, a delirium, cerebral spasms, confusion or a loss of consciousness, including coma, shallow breathing, bradycardia. Besides, perspiration, concern, tachycardia, increase in arterial pressure, stenocardia and disturbances of a cordial rhythm can result from an adrenergic feedback mechanism. Treat the factors promoting development of a hypoglycemia:
1.nezhelaniye or (especially at advanced age) insufficient ability of the patient to cooperation with the doctor;
2.nepolnotsennoye, irregular food, admission of meals, starvation, changes of a usual diet;
3.disbalans between an exercise stress and consumption of carbohydrates;
4.upotrebleniye alcohol, especially in combination with the admission of meal;
5.narusheniye functions of kidneys;
6.tyazheloye abnormal liver function;
7.peredozirovka Glimepirida - Teva;
8.nekotorye  the noncompensated  diseases  of endocrine  system  exerting impact on carbohydrate metabolism (for example, dysfunctions of a thyroid gland, pituitary insufficiency or insufficiency of bark of adrenal glands);
9.odnovremennoye use of the medicines strengthening Glimepirid's action - Teva (see the section "Interaction with Other Medicines").

The doctor has to be informed on the factors stated above and on hypoglycemia episodes as they demand especially strict observation of the patient. In the presence of such factors increasing risk of development of a hypoglycemia it is necessary to correct Glimepirid's dose - Teva or all scheme of treatment. It needs to be made also in case of an intercurrent disease or change of a way of life of the patient.
Symptoms of a hypoglycemia can be maleficiated or be absent absolutely at elderly patients,   at   the patients   having   vegetative   neuropathy   or   receiving simultaneous treatment by β-adrenoblockers, a clonidine, Reserpinum, guanetidiny or other sympatholytics. 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 inefficient in treatment of a hypoglycemia.
From experience of use of other drugs of sulphonylurea it is known that, despite initial success of stopping of a hypoglycemia,  its recurrence is possible.     In this regard, continuous and careful observation of the patient is necessary. The heavy hypoglycemia demands immediate treatment under observation of the doctor, and under certain circumstances and hospitalization of the patient.
If the patient suffering from a diabetes mellitus is treated by different doctors (for example, during stay in hospital after accident, at a disease on the weekend), he has to report surely to them about the disease and about the previous treatment.
During treatment by Glimepirid - Teva is required carrying out regular control of function of a liver and a picture of peripheral blood (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 Glimepirid - Teva at 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 by Glimepirid - Teva regular control of concentration of glucose in blood, and also concentration of glikozilirovanny hemoglobin is necessary.
In an initiation of treatment, upon transition from one medicine to another, or at irregular reception of Glimepirid - Teva can take place the decrease    in concentration of attention  and  speed of psychomotor reactions of the patient  caused hypo - or a hyperglycemia.   It  can     have an adverse effect  on  ability   to  driving of motor transport or to control of various cars and mechanisms.

Side effects:

Seldom:
From a metabolism: development of hypoglycemic reactions. These reactions, mainly, arise soon after administration of drug, and they not always manage to be stopped easily.
From organs of sight: during treatment (especially at its beginning) the tranzitorny decrease in sight caused by change of concentration of glucose in blood can be observed.
From system of digestive organs: increase in activity of liver 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.
Sometimes:
 From system  of digestive organs: nausea, vomiting,   heavy feeling  or discomfort in the epigastriums, abdominal pains, diarrhea which are very seldom leading to the treatment termination.
Allergic reactions: emergence of symptoms of a small tortoiseshell (itch, skin rash). Such reactions happen, as a rule, moderately expressed, but can progress, being followed by falling of arterial pressure, диспноэ, up to development of an acute anaphylaxis. At emergence of symptoms of a small tortoiseshell it is necessary to see a doctor immediately. The cross allergy with other derivatives of sulphonylurea, streptocides, or similar to them substances is possible, development of an allergic vasculitis is also possible.
In exceptional cases:
Other side effects: development of a photosensitization, hyponatremia is possible.
As separate side effects, such, as: the heavy hypoglycemia, serious changes of a picture of blood, heavy allergic reactions, a liver failure, can represent under certain circumstances threat for life, in case of development of undesirable or heavy reactions the patient needs to inform at once on them the attending physician and not to continue administration of drug without its recommendation at all.

Interaction with other medicines:

Glimepirid  is metabolized  with  по­мощью P450 2C9 cytochrome (CYP2C9). At  simultaneous   use  with   CYP2C9 isoenzyme inductors, for example,  rifampicin,  reduction of hypoglycemic action of a glimepirid and  increase in risk of development of a hypoglycemia in case of their cancellation without dose adjustment of a glimepirid is possible. At a simultaneous priyomeneniye with CYP2C9 isoenzyme inhibitors, for example, flukonazoly, vozyomozhno  strengthening of hypoglycemic action of a glimepirid and increase in a risyok of development of a hypoglycemia and side effects of a glimepirid, and also reduction of its hypoglycemic action at their cancellation without dose adjustment of a glimepirid is possible. Strengthening of gipoglikeyomichesky action and the possible development of a hypoglycemia connected with it can be observed at a simultaneous primeyoneniye of a glimepirid with the insulin or other peroral hypoglycemic drugs, Metforminum, ingiyobitor of an angiotensin-converting enzyme (APF), Allopyrinolum, anaboyolichesky steroids and men's poyolovy hormones, chloramphenicol derivative of coumarin, tsiklo-, tro-and isophosphamides, fenfluraminy, Disopyramidum, fibrata, fluoxetine, sympatholytics (guanetidiny), ingiyobitor of a monoaminooxidase (MAO), Miconazolum, flukonazoly, pentoksifilliny (at parenteral administration in high doses), phenylbutazone, azapropazony, oksifenbutazony, probenitsidy, hinolona, salicylates and aminosalicylic acid, Sulfinpyrazonum, some sulfanilamiyoda of long action, tetracyclines, tritokvaliny. Easing hypoglycemic a deystyoviya and the increase in a konyotsentration of glucose connected with it in blood can nayoblyudatsya at simultaneous primeneyoniya of a glimepirid with acetazoleamide, baryobiturata, glucocorticosteroids, a glucagon, purgatives (at prolonged use), nikotiyonovy acid (in high doses) and proyoizvodny niacin, estroyogena and progestogens, fenotiazina, Chlorpromazinum, Phenytoinum, riyofampitsiny, hormones of a thyroid gland, lithium salts. H2 blockers - histamine receptors, a clonidine and Reserpinum, are capable both to potentiate, and to weaken hypoglycemic action of a glimepirid. Under the influence of such  sympatholytics  as beta adrenoblockers, a clonidine, гуанетидин 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 a deyyostviye of derivatives of coumarin can nayoblyudatsya. At simultaneous use with the leyokarstvenny means oppressing a marrowy hemopoiesis the risk of a miyelosupressiya uvelichiyovatsya. The single or chronic upotrebyoleniye of alcohol can both strengthen, and to weaken hypoglycemic action of a glimepirid.

Contraindications:

Diabetes mellitus  of 1 type; diabetic ketoacidosis, diabetic prekoma and koyoma; giperosmolyarny coma; hypersensitivity to a glimepirid or to any   inactive   component of drug, to  other derivatives of sulphonylurea  or  to sulfanilamidyony drugs (risk of development of reactions of hypersensitivity); heavy abnormal liver functions; heavy renal failures (including the patients who are on a gemodialiyoza); lactose intolerance, deficit of lactase,  glkzhozo-galaktozny  malabsorption; children's age up to 18 years; insufficiency dehydrogenase glyukozo-6-phosphate; pregnancy and period of breastfeeding.

With care - the states demanding transfer of the patient into an insulinotsrapiya (extensive burns, a severe multiple injury, extensive surgical interventions); adrenal insufficiency; zaboyolevaniye of a thyroid gland (hypothyroidism, thyrotoxicosis); disturbances a vsasyvayoniya of food and medicines in digestive tract, including intestinal impassability, paresis of a kishechyonik; infectious fever; alkogoyolizm; in the first days of treatment (povyshenyony risk of development of a hypoglycemia); at the increased risk of development of a hypoglycemia (see the section "Special Instructions"); at intercurrent diseases during treatment or at change of a way of life of the patient (change of a diet and time of meal, increase or umensheyony physical activity).
Use during pregnancy and 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, apparently, 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:

Symptoms: a hypoglycemia (nausea, vomiting and pains in epigastric area, concern, a tremor, visual frustration, lacks of coordination, drowsiness, a coma and spasms). Treatment: if the patient in consciousness - induction of vomiting, plentiful drink, absorbent carbon and laxative. In case of heavy overdose - intravenous bolyusny administration of solution of a dextrose (50 ml of 40% of solution), then - infusional introduction of 10% of solution. Constant observation of the patient, maintenance of the vital functions and control of concentration of glucose in blood is necessary (repetition of episodes of a hypoglycemia is possible). Further symptomatic treatment.

Storage conditions:

At a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity 4 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets 1 of mg, 2 mg, 3 mg.
On 10 tablets in the blister from PVC/PVDH / aluminum foil. On 3 or 6 blisters with the application instruction in a cardboard pack.