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in special clinical stressful conditions such as trauma, surgery, infection, leaking with febrile temperature, possibly worsening the metabolic control in patients with diabetes mellitus, so to maintain adequate metabolic control may require a temporary transfer to insulinoterapiu.
in the first weeks of treatment may increase the risk of hypoglycemia that requires particularly careful monitoring concentrations of glucose in the blood.
to factors contributing to the risk of hypoglycemia include: LF-patient’s unwillingness or inability to (more frequently observed in patients older) to cooperate with the doctor;
— malnutrition, irregular meal or meal passes;
is the imbalance between the physical activity and consumption of carbohydrates; LF-change of diet;
— the use of alcohol, especially when combined with a decal of the meal;
— severe violations of the kidneys;
— severe violations of the liver (in patients with severe violations of the liver shows a translation into insulinoterapiu, at least, to achieve metabolic control);
— glimepiride overdose;
— some urological endocrine disorders, violating carbohydrate Exchange or adrenergic kontrregulâciû in response to hypoglycemia (e.g., certain violations of the thyroid gland and the pituitary gland, anterior failure napochechnikov crust);
— simultaneous intake of certain medicines; LF-admission of glimepiride in the absence of evidence to his admission.
Treatment of derivatives sulfonylureas, which include glimepiride, can lead to hemolytic anemia, so patients with insufficient glukozo-6-fosfatdegidrogenaza caution when assigning glimepirida, preferably use gipoglikemicakie means not derived sulfonylureas.
in the case of the above risk factors of hypoglycemia as well as when an intercurrent diseases during treatment or lifestyle changes the patient may require dose adjustment or glimepiride therapy.
Symptoms of hypoglycemia resulting from adrenergic kontrregulâcii of an organism in response to hypoglycemia, may be poorly expressed or absent when the gradual development of hypoglycemia in elderly patients, in patients with violations on the part of the autonomic nervous system, or in patients receiving beta-adrenoblokatora, clonidine, guanetidin, rezerpin and other simpatolitičeskie means.Hypoglycemia can be quickly resolved if immediate admission quickly absorbed carbohydrate (glucose or sugar). How and when taking other derivatives sulfonylureas, despite the initial success of mild hypoglycemia, hypoglycemia can resume. Therefore, patients should remain under constant surveillance. In heavy gipoglikemii requires immediate treatment and doctor, and, in some cases, hospitalization of the patient.
glimepiridom during treatment requires regular monitoring of liver function and picture peripheral blood (especially the number of white blood cells and platelets).
side effects such as severe hypoglycemia, serious changes in the blood picture, severe allergic reactions, liver failure can be life-threatening, so in the case of similar reactions the patient should immediately inform the attending doctor, stop taking the drug and not to renew the appointment without the advice of a doctor.
the use in Pediatrics.
data on long-term effectiveness and safety of drugs in children are missing.
influence on the ability to drive vehicles and management mechanisms of in the beginning of treatment, after treatment or changes with frequent reception of glimepiride may be due to hypo-or Hyperglycemia reduced concentration and psychomotor speed reactions. This may adversely affect the ability to drive vehicles or to manage a variety of machines and mechanisms.
Overdose. LF: Symptoms of acute overdose, as well as long-term care glimepiridom in excessively high doses may develop severe life-threatening hypoglycemia.
treatment: hypoglycemia can almost always be quickly was cupped off immediate taking of carbohydrates (glucose, or sugar, sweet slices of fruit juice or tea). In this regard, the patient must always carry at least 20 g of glucose (4 slices of sugar). Sugar substitutes are ineffective for treating hypoglycemia.
until a physician decides that a patient is out of danger, the patient requires careful medical supervision. It should be borne in mind that hypoglycemia can resume after the initial restoration of the concentration of glucose in the blood.
If the patient suffering from diabetes, treat different doctors (for example, during a stay in the hospital after the accident in case of sickness during the weekend), he must inform them about their disease and prior treatment.Sometimes the patient may need to be hospitalized, even if as a precaution. A large overdose and severe reaction with such manifestations, such as loss of consciousness, or other serious neurological disorders are urgent medical conditions and require immediate treatment and hospitalization.
When loss of consciousness should be in\/with the introduction of the concentrated solution of dextrose (glucose) (for adults, starting with 40 ml of 20% solution). As an alternative to adult may enter in\/in, c\/a or\/m glucagon, for example, the dose of 0.5-1 mg.
in the treatment of hypoglycemia due to accidental drug Amaryl ® babies or young children should be carefully adjust the dose of dextrose to avoid the possibility of dangerous hyperglycemia; the introduction dekstrozy should be under the permanent control of the concentration of glucose in the blood.
When drug overdose Amaryl ® may require conducting gastric lavage and reception activated carbon.
After rapid recovery of the concentration of glucose in the blood is necessary to conduct the on\/in infusion solution dekstrozy in lower concentration to prevent the recurrence of hypoglycemia. The concentration of glucose in the blood in these patients should be continuously monitored for 12:00 am in severe cases with lingering over hypoglycemia risk reducing blood glucose levels may persist for several days,
once detected an overdose, there is an urgent need to inform your doctor.

Drug interactions.
Glimepiride metabolized cytochrome R4502S9 (CYP2C9) that should be considered while applying the product with inducers (e.g., rifampin) or inhibitors (e.g., fluconazole) CYP2C9.
Potentiation hypoglycemic activity and in some cases related to the development of hypoglycemia can occur when combining the drug Amaryl ® with one of the following drugs: insulin, other oral gipoglikemicakie means, ACE inhibitors, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclophosphamide, dizopiramid, fenfluramin, feniramidol, fibrata, fluoxetin, guanetidin, ifosfamid, MAO inhibitors, fluconazole, PASC, Pentoxifylline (high dose volume parenterals), phenylbutazone, azapropazon , oksifenbutazon, probenecid, quinolones, salicilata, sulfinpirazon, clarithromycin, sulfonamides, tetracyclines, tritokvalin, trofosfamid.Reduced hypoglycemic activity and the consequent increase of glucose in the blood may have when combined with one of the following drugs: acetazolamide, barbiturates, CORTICOSTEROIDS, diazoxide, diuretics, sympathomimetic agents (including epinephrine), glucagon, laxatives (with the long-term use), Nicotinic Acid (large doses), estrogena and progestagena, fenotiazina, phenytoin, rifampin, iodized thyroid hormones.
H2-blockers gistaminovykh receptors, beta-adrenoblokatora, clonidine and reserpine can both enhance and reduce hypoglycemic effect of glimepiride.
under the influence of simpatolitičeskih tools, such as Beta-adrenoblokatora, clonidine, guanethidine, and reserpine, signs of adrenergic kontrregulâcii in response to Hypoglycemia may be reduced or absent.
against the backdrop of the admission of glimepirida may increase or weakening of coumarin derivatives.
single or chronic use of alcohol can both enhance and undercut the hypoglycemic effect of glimepiride.
1 Tablet contains glimepiride 3 mg
LF indications: diabetes mellitus type 2 (as monotherapy or in combination therapy with metformin or insulin).
contraindications:
type 1 diabetes; Diabetic Ketoacidosis, diabetic precoma and coma; severe violations of the liver (no clinical experience); serious violations of the kidneys, including patients on hemodialysis (lack of clinical experience); pregnancy; lactation (breastfeeding); LF’s age (lack of clinical experience); rare hereditary diseases such as Galactose intolerance, lactase deficiency or glucose-galaktoznaâ malabsorption; hypersensitivity to the drug component; hypersensitivity to other derivative sulfonylureas and sulfanilamidnam drugs (risk of hypersensitivity reactions).
the caution should apply in the first weeks of treatment (increased risk of gipoglikemii); If there are risk factors for the development of hypoglycemia (may require dose adjustment or glimepiride therapy); If interkurrentnykh diseases during treatment, or if you change the lifestyle of patients (modified diets and meal time, increase or decrease in physical activity); in case of insufficiency glukozo-6-fosfatdegidrogenaza; suction disorders of food and medicines from the digestive tract (intestinal obstruction, bowel paresis). Contraindicated use in severe violations of the liver.
Pharmacodynamics:
Oral hypoglycemic drug-derived sulfonylureas (III) generation.Glimepiride lowers the concentration of glucose in the blood, mainly due to the stimulation of insulin release from the?-cells of the pancreas. Its effect is mostly associated with improving the ability of?-pancreatic cells respond to the physiological stimulation of glucose. In comparison with glibenclamide, glimepiride in low doses causes the release of fewer insulin when it reaches approximately equal concentrations of glucose in the blood. This fact testifies in favor of having a hypoglycemic èkstrapankreatičeskih glimepiride effects (increased sensitivity of tissues to insulino and insulinomimetičeskij effect).
the secretion of insulin. Like all other derivatives sulfonylureas, glimepiride regulates insulin secretion by interacting with ATP-sensitive potassium channels in membranes?-cells. Unlike other derivatives sulfonylureas glimepiride selectively binds to a protein with a molecular mass of 65 in kilodal′ton membranes?-cells of the pancreas. This interaction of glimepiride from communicating with him protein regulates the opening or closing of ATP-sensitive potassium channels.
Glimepiride closes potassium channels. This causes depoliarizatia?-cells and leads to the opening of voltage-sensitive calcium channels and calcium entry into the cell. As a result, increased intracellular calcium concentration activates insulin secretion by exocytosis.
Glimepiride much faster and consequently often enters into relationship and released from the connection with communicating with him in protein than glibenclamide. It is anticipated that this property is a high speed exchange of glimepirida with communicating with him protein determines its pronounced effect of sensitization?-cells to glucose and their protection from desensitization and premature exhaustion.
Effect increase the sensitivity of tissues to insulino. Glimepiride increases the effects of insulin on the absorption of glucose perifericescimi tissues.
Insulinomimetičeskij effect. Glimepiride has effects similar to the effects of insulin on the absorption of glucose perifericescimi tissues, and the output of glucose from the liver.
the absorption of glucose perifericescimi tissues is carried out by transport inside muscle cells and adipocytes. Glimepiride directly increases the amount of transporting glucose molecules in the plasma membranes of muscle cells and mainly. Increase income inside cells glucose leads to activation of glycophosphatidylinositol-specific phospholipase c. As a result, the intracellular calcium concentration decreases, causing a decrease in the activity of protein kinase a, which in turn leads to stimulation of glucose metabolism.Glimepiride inhibits glucose output from the liver by increasing the concentration of fructose-biphosphate-2.6, which inhibits the gluconeogenesis.
impact on agregatia platelets and formation of atherosclerotic plaques. Glimepiride reduces platelet aggregation in vitro and in vivo. This effect appears to be associated with selective inhibition of COX, which is responsible for the education of thromboxane a, an important endogenous factors of platelet aggregation.
antiaterogennoe. Glimepiride helps normalize lipid content, reduces the level of malonic aldehyde in the blood, which leads to significant reduction of peroxide oxidation of lipids.
the reduction of expressiveness of oxidative stress, which is constantly present in patients with diabetes mellitus type 2. Glimepiride increases the level of endogenous?-tocopherol, the activity of catalase, superoxide dismutase.
cardiovascular effects. Through the ATP-sensitive potassium channels derivatives sulfonylureas also have an impact on the cardiovascular system. Compared with traditional derived sulfonylureas, glimepiride has a reliably less effect on the cardiovascular system. It reduces agregatia platelets and leads to significant reduction of the formation of atherosclerotic plaques.
in healthy volunteers the minimum effective dose of glimepiride is 0.6 mg. The effect of glimepiride is reversible and repeatable. The physiological reaction to physical activity (reduction of insulin secretion) when receiving glimepirida is saved.
no reliable differences in effects depending on the drug was passed for 30 minutes before eating, or immediately before a meal. In patients with diabetes mellitus can reach sufficient metabolic control within 24 hours of the one-time admission preparation. Moreover, in a clinical study at 12 of 16 patients with renal insufficiency (KK 4-79 mL\/min) has also been made sufficient metabolic control.
combination therapy with metformin. In patients who have not achieved adequate metabolic control when applying the maximum dose of glimepiride may be triggered in combination therapy with metformin and glimepiridom. In two studies in conducting combined therapy has been proven to improve metabolic control compared with that in the treatment of each of these drugs individually.Combination therapy with insulin. In patients with inadequate achievement metabolic control when taking the maximum dose of glimepiride may be initiated concurrent therapy with insulin. According to the results of two studies in the application of this combination is achieved the same improvement of metabolic control, as when applying only one insulin. However, combination therapy requires a lower dose of insulin.
Pharmacokinetics when comparing data obtained with single and multiple (1 time\/day) admission glimepiride revealed reliable differences farmakokineticeskih parameters and their variability between different patients was very low. Significant accumulation of the drug is not available.

Induction.
receiving repeated drug inside a daily dose of 4 mg Cmax in blood serum is approximately 2.5 h at 309 ng\/ml. There is a linear relationship between dose and Cmax of glimepiride in plasma, as well as between dose and AUC. The ingestion bioavailability of glimepiride is 100%. Food intake does not significantly affect the removals, except a slight slowing down its speed.

Distribution.
for glimepirida is characterized by very low Vd (approx. 8.8 litres), approximately equal Vd albumin, high degree of binding to plasma proteins (99%) more and low ground clearance (approx. 48 mL\/min).
Glimepiride is excreted in breast milk and penetrates through the placental barrier.

Metabolism.
Glimepiride metabolised in the liver (mainly with the participation of izofermenta CYP2C9) with the formation of 2 metabolites-gidroksilirovannogo and karboksilirovannogo derivatives that are detected in the urine and feces.
T1\/2 when plasma drug concentrations in serum, relevant to multiple dosing regime, is approximately 5-8 h after administration of glimepiride in high doses, T1\/2 increases slightly.
after a single intake of 58% glimepirida kidneys displayed and 35% through the intestine. The unchanged active substance in urine is not found.
T1\/2 gidroksilirovannogo and karboksilirovannogo metabolites glimepirida were about 3-5 hours and 5-6 h.

Pharmacokinetics in special clinical cases.
pharmacokinetic parameters were similar in patients of different sexes and different age groups.
in patients with the human kidney (low CC) there is a tendency to increase clearance glimepirida and reduce its average concentrations in the serum, which is likely due to more rapid breeding of the drug due to a lower associate it with a protein. Thus, this category of patients, there is no additional risk cumulation glimepirida.
side effects:From the metabolic: hypoglycemic action of the drug may develop hypoglycemia, which like other derivatives sulfonylureas, can be prolonged.
symptoms of hypoglycemia are: headache, hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbance, anxiety, aggressiveness, concentration, alertness and speed of reactions, depression, sputannosti consciousness, speech disorders, aphasia, visual disturbances, tremors, paresis, sensory violations, dizziness, loss of self-control, deliri, cerebral convulsions, loss of consciousness, or somnolenciâ up to coma, shallow breathing, bradycardia.
in addition, kontrregulâcii adrenergic manifestations may occur in response to hypoglycemia, such as cold sticky sweat, anxiety, tachycardia, arterial hypertension, angina, palpitations and cardiac arrhythmia.
the clinical picture of severe hypoglycemia can be similar to stroke. Symptoms gipoglikemii almost always disappear after her elimination.
from the organ of vision: during treatment (especially in the beginning), you may experience transient visual disturbances caused by the change in the concentration of glucose in the blood. Their cause is to temporarily change the lens nabuhaemosti, which depends on the concentration of glucose in the blood, and this is a change in the refractive index of the lens.
from the stomach: in rare cases, nausea, vomiting, a feeling of heaviness or fullness in the epigastrium, pain in the abdomen, diarrhoea; in some cases, hepatitis, increase in liver enzymes and\/or cholestasis and jaundice, which can progress to a life-threatening liver failure, but may be the opposite of denial of drug development.
the blood and lymphatic system: seldom-B19; in some cases, lakopenia, haemolytic anaemia, eritrotsitopenia, granulocytopenia, agranulocytosis, and pancytopenia.
General violations: in rare cases, allergic and psevdoallergicakie reactions such as itching, urticaria, skin rashes. Such reactions may become severe reactions with shortness of breath, sharp decline ad, which sometimes can progress up to anaphylacticski shock. If urticarial symptoms should immediately contact a doctor. In some cases, you may experience a decrease in concentrations of serum sodium, allergic vasculit, photosensitization.
Cooking method or application:
inside, alone with liquid, squeezed enough liquid (approx. 0.5 Cup).Typically, the dose is determined by the target concentration of glucose in the blood. The lowest dose should be applied, is sufficient to achieve the necessary.

Metabolic control.
during drug treatment should be regularly to determine the concentration of glucose in the blood. In addition, it is recommended that regular monitoring of the level of glikozilirovannogo hemoglobin.
an incorrect dose, such as skipping a dose must never be filled by subsequently receiving a higher dose.
the patient’s Actions when errors in the admission of the drug (in particular when skipping a dose or skipping meals) or in situations where it is not possible to take medication, must negotiate the doctor and the patient in advance.
The initial dose and dose selection.
The initial dose of 1 mg glimepiride 1 times per day.
The daily dose can be gradually (at intervals of 1-2 weeks) increased. It is recommended that the dose be under regular supervision of the concentration of glucose in the blood and in accordance with the next step of increasing the dose: 1 mg. 2 mg. 3 mg. 4 mg. 6 mg (8 mg).
range of doses in patients with well controlled diabetes
Usually daily dose in patients with well controlled diabetics is 1-4 mg glimepiride. Daily dose of more than 6 mg is better only in a small number of patients.

The dosage.
Time dose and dose distribution during the day is set by your doctor depending on the lifestyle of the patient at this time (the time of the meal, the amount of physical exertion).
it is usually enough to one administered within days. It is recommended that in this case the entire dose taken just before a full breakfast or if it had not been adopted at this time — immediately before the first main meal. It is very important not to skip the pill after taking the meal.
So as improved metabolic control is associated with increased insulin sensitivity, in the course of treatment can decrease the need for glimepiride. In order to avoid the development of hypoglycemia, need to reduce the dose or stop taking the drug.
the condition under which may require dose adjustment glimepirida:
* decrease in body mass index patient;
* lifestyle changes (changing your diet, eating time, amount of physical exertion);
* the emergence of other factors, which lead to a predisposition to the development of hypoglycemia or Hyperglycemia (see “contraindications”).
the duration of treatment.
glimepiridom Treatment is usually carried out for a long time.Translated patient with other hypoglycemic means for the reception inside.
there is no exact correlation between doses of medication and other oral gipoglikemicakih funds. When another gipoglikemicescoe means for reception inside is replaced by medication, it is recommended that the procedure for his appointment was the same as when the original drug, i.e., treatment should be initiated with low doses of 1 mg (even if the patient is transferred with a maximum dose of another hypoglycemic medication for the reception inside). Any increase in dose should be carried out in stages, taking into account the reaction to glimepiride in accordance with the above recommendations.
it is necessary to take into account the strength and duration of effect prior to hypoglycemic means for the reception inside. You may need to interrupt treatment in order to avoid any summation effects that can increase the risk of developing hypoglycemia.
The use in combination with metformin in patients with inadequately controlled diabetes when taking maximum doses or glimepiride or metformin treatment may be initiated by a combination of these two drugs. While previously conducted treatment or glimepiridom or metformin is continued at the same dose level, and additional taking metformin or glimepiride begin with a low dose, which then is titrated according to the target level of metabolic control up to a maximum daily dose. Combination therapy must begin under strict medical supervision.
The use in combination with insulin patients with inadequately controlled diabetes when taking the maximum daily dose of glimepiride may be assigned at the same time the introduction of insulin. In this case, the last assigned patient dose of glimepiride, remains unchanged. While insulin treatment begins with low doses, which gradually increased under the control of the concentration of glucose in the blood. Combined treatment requires careful medical supervision.
The application in patients with kidney failure. There is a limited amount of information on the use of the drug in patients with renal insufficiency. Patients with compromised renal function may be more susceptible to gipoglikemičeskomu effect of glimepiride (see sections “Pharmacokinetics”, “contra-indications”).
The application in patients with hepatic insufficiency. There is a limited amount of information on the use of the drug with hepatic insufficiency (see “Contraindications”) the children. Data on the use of drugs in children is not enough.

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