2010/09/20

Amaryl

Composition, structure and packing

Tablets are oblong, with a dividing groove, pink.

1 tab. glimepirid 1 mg.

Excipients: lactose monohydrate, sodium starch glycolate, polyvidone 25 000, microcrystalline cellulose, magnesium stearate, iron oxide red (E172). Tablets are oblong, with a dividing groove, green.

1 tab. glimepirid 2 mg.

Excipients: lactose monohydrate, sodium starch glycolate, polyvidone 25 000, microcrystalline cellulose, magnesium stearate, iron oxide yellow (E172), indigo (E132). Tablets are oblong, with a dividing groove, pale yellow.

1 tab. glimepirid 3 mg.

Excipients: lactose monohydrate, sodium starch glycolate, polyvidone 25 000, microcrystalline cellulose, magnesium stearate, iron oxide yellow (E172). Tablets are oblong, with a dividing groove, blue.

1 tab. glimepirid 4 mg.

Excipients: lactose monohydrate, sodium starch glycolate, polyvidone 25 000, microcrystalline cellulose, magnesium stearate, indigo (E132).

Clinico-pharmacological group: oral hypoglycemic drug.

Pharmacological action

Oral hypoglycemic drug - derived primarily long-acting sulfonylureas. It stimulates the secretion and release of insulin from β-cells of the pancreas (pancreatic effect), increases the sensitivity of peripheral tissues (muscle and adipose) to insulin (ekstrapankreaticheskoe action).

Derivative sulfonylureas regulate insulin secretion by closing ATP-dependent potassium channels located in the cytoplasmic membrane β-cells of the pancreas. In closing the potassium channels, they cause depolarization of β-cells, which promotes opening of calcium channels and increase calcium entry into cells.

Glimepirid with a high replacement rate is connected and disconnected from the protein β-cells of the pancreas (molecular mass 65 kDa / SURX), which is associated with ATP-dependent potassium channels, but differs from the usual binding sites of traditional sulfonylurea derivatives (protein molecular weight of 140 kD/SUR1 ).

This process leads to the release of insulin by exocytosis, while the number of insulin secreted significantly less than during the traditional sulfonylureas derivatives.

The least stimulating effect glimepirida on insulin secretion and provides less risk of hypoglycemia. In addition, the drug has ekstrapankreaticheskoe action that includes the reduction of insulin resistance, lower impact on the cardiovascular system, antiatherogenic, antiplatelet, anti-oxidant action.

Increased utilization of glucose from the blood to peripheral tissues (muscle and fat) is by special transport proteins located in cell membranes. Transport of glucose in these tissues in insulin-dependent diabetes is limited by the speed stage of glucose utilization. Amaryl very rapidly increases the number and activity of transport proteins, which leads to an increase in glucose uptake by peripheral tissues. Amaryl is weaker inhibitory effect on ATP-dependent potassium channels in cardiomyocytes.

When receiving Amaryl preserved the ability of metabolic adaptation to myocardial ischemia. Amaryl increases the activity of glycosyl-phosphatidylinositol-specific phospholipase C, which in isolated muscle and fat cells may correlate drug induced adipogenesis and glikogenez. Amaryl inhibits production of glucose in the liver by increasing the intracellular concentration of fructose-2 ,6-bisfosfata, which in turn inhibits gluconeogenesis. Amaryl selectively inhibits cyclooxygenase and reduces the conversion of arachidonic acid to thromboxane A2, which promotes platelet aggregation, thereby exerting antithrombotic effect. Amaryl increases the level of endogenous α-tocopherol, catalase activity, glutationperoxydaze and superoxide dismutase, which reduces the severity of oxidative stress in the patient, which is constantly present in diabetes mellitus.

Pharmacokinetics

Pharmacokinetic parameters are similar in patients of different gender and different age groups. When comparing the data obtained with single and multiple (2 times / day) admission glimepirida not revealed significant differences in the pharmacokinetics of the drug, and intraindividualnaya variability of pharmacokinetic parameters was very low. The significant accumulation of the drug was absent.

Absorption

Repeatedly taking the drug orally in a daily dose of 4 mg Cmax in serum reached approximately 2.5 h and was 309 ng / ml, there is a linear relationship between dose and Cmax, as well as between dose and AUC. Glimepirid has absolute bioavailability. Eating does not have a significant impact on the suck, except for slight slowing the rate of absorption.

Distribution

For glimepirida characterized by very low Vd (about 8.8 liters), approximately equal to Vd albumin, high plasma protein binding (99%) and low clearance (approximately 48 ml / min). Glimepirid excreted in breast milk and crosses the placental barrier. Poorly penetrates the BBB.

Metabolism

Glimepirid biotransformiruetsya in the body for 2 metabolite formed, probably as a result of glimepirida metabolism in the liver and detected in urine and in feces, are hydroxylated and carboxylated derivative glimepirida.

Withdrawal

T1 / 2, with plasma concentrations of the drug in serum, corresponding to a multiple dose regimen is 5-8 hours after taking glimepirida high-dose T1 / 2 increases slightly. After a single oral dose glimepirida labeled with radionuclides, 58% of the tracer was detected in the urine and 35% - in the feces. The unmodified active substance in the urine is not discovered.

T1 / 2 hydroxylated and carboxylated metabolites glimepirida were respectively about 3-6 h and 5-6 h.

Pharmacokinetics in special clinical situations

Patients with impaired renal function (low QC) tended to increase the clearance glimepirida and to reduce its average concentration in the blood serum, which was likely due to more rapid excretion of the drug due to a lower binding to proteins.

Thus, this category of patients there is no additional risk of cumulation glimepirida.

Statement
Type 2 diabetes as monotherapy or in combination with metformin or insulin.

Dosage regimen

The initial dose and supportive set individually on the basis of regular monitoring of blood glucose and urine. At the beginning of treatment prescribed Amaryl 1 mg 1 time / day. If necessary, the daily dose may be gradually increased (at intervals of 1-2 weeks) and in the following order: 1 mg-2 mg-3 mg-4 mg-6 mg of Amaryl a day.

The maximum recommended daily dose - 6 mg. Time and the multiplicity of the drug the doctor determines, in the way of life the patient. The daily dose administered in a reception, usually before or during a hearty breakfast or, if the daily dose was not accepted, immediately before or during the first heavy meal. Treatment of long-term.

The use of Amaryl in combination with metformin

In case of insufficient stabilization of the concentration of glucose in the blood of patients receiving metformin, may be initiated concomitant therapy Amarillo.

When you save a dose of metformin at the same level Amarillo treatment begins with a minimal dose of 1 g, and then the dose is gradually increased depending on the desired level of glycemic control, up to a maximum daily dose of 6 mg.

The use of Amaryl in combination with insulin

In case you can not achieve normalization of blood glucose concentration receiving maximum doses of Amaryl as monotherapy or in combination with a maximum dose of metformin can be a combination glimepirida with insulin. In this case, the latter assigned patient dose of Amaryl remains unchanged.

At the same time insulin treatment starts with a minimal dose, with possible subsequent gradual increase in dose of insulin under the control of blood glucose concentration. Combined treatment requires mandatory medical monitoring.

In maintaining long-term glycemic control this combination therapy may reduce insulin requirements by almost 40%. Transfer of patients with other oral hypoglycemic drugs on Amaryl There is no exact correlation between the doses of Amarah and other oral hypoglycemic drugs. Upon transfer to such drugs on Amaryl initial daily dose of the latter should be 1 mg (even if the patient is transferred to a maximum dose of Amaryl with other oral hypoglycemic drug).

Any increase in the dose Amaryl should be phased manner, taking into account the answer to glimepirid in accordance with the above recommendations. Should take into account the used dose and duration of hypoglycemic effect of prior means. In some cases, especially when taking hypoglycemic agents with a large half-life (eg, hlorpropamid), it may be necessary over time (several days) the termination of treatment in order to avoid the additive effect, increases the risk of hypoglycemia.

Translation of a patient with insulin on Amaryl In exceptional cases, when patients with diabetes mellitus type 2 (insulin-dependent) are insulin, with compensation for illness and intact secretory function of β-cells of the pancreas, they may be shown to translate Amaryl.

The translation must be conducted under the close supervision of a physician. This translation of the patient to begin with Amaryl glimepirida minimum dose of 1 mg. Tablets should be taken as a whole, without chewing, drinking plenty of fluids (about 1 / 2 cup).

It is important not to skip meals after taking Amaryl.

Side effect

On the part of metabolism: rarely - the development of hypoglycemic reactions. These reactions primarily occur shortly after taking the drug, and they can not easily be cut short.

There may be headache, hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbance, anxiety, aggressiveness, impaired concentration, and reaction, depression, confusion, speech and visual disorders, aphasia, tremor, paresis, sensory disorders, dizziness , violations of coordination, helpless condition, the loss of self-control, delirium, cerebral convulsions, confusion or loss of consciousness, including coma, shallow breathing, bradycardia.

In addition, as a result of adrenergic feedback mechanism may occur symptoms such as cold, clammy sweat, anxiety, tachycardia, hypertension, angina and cardiac arrhythmia. On the part of the organ of vision: during treatment (especially in the beginning of treatment) may experience transient visual disturbances caused by changing the concentration of glucose in the blood.

On the part of the digestive system: sometimes - nausea, vomiting, feeling of heaviness or discomfort in the epigastric, abdominal pain, diarrhea (very rarely lead to cessation of treatment); rarely - increased activity of hepatic transaminases, cholestasis, jaundice, hepatitis (until the development of liver failure ).

On the part of the hemopoietic system: rarely - thrombocytopenia (moderate to severe), leukopenia, hemolytic or aplastic anemia, erythropenia, granulocytopenia, agranulocytosis and pancytopenia. Allergic reactions: sometimes - itching, rash, skin rash. Such reactions are usually moderately expressed, but may progress, accompanied by falling blood pressure, dyspnoea, until the development of anaphylactic shock.

Possible cross allergy to other derivatives of sulfonylureas, sulfonamides, or similar substances, it is also possible the development of allergic vasculitis. Other: In isolated cases - photosensitivity, hyponatremia.

Contraindications
diabetes mellitus type 1;
diabetic ketoacidosis, diabetic coma and precoma;
severe liver problems;
severe renal dysfunction (including patients on dialysis);
Pregnancy
lactation (breastfeeding);
Hypersensitivity to glimepiridu or other components of the drug, other derivatives of sulfonylurea and sulfanilamide preparations.

Pregnancy and lactation

Amaryl is contraindicated in pregnancy. In the case of planned pregnancy or if pregnancy occurs the woman should be transferred to insulin. Found that glimepirid excreted in breast milk. In lactating woman should be transferred to insulin or to stop breast-feeding.

Application for violations of liver function

Do not use this in cases of severe liver problems.

Application for violations of renal function

Do not use this with severely impaired renal function (including patients on hemodialysis).

Cautions

It should pay particular attention to the condition requiring the transfer of a patient on insulin: extensive burns, severe multiple trauma, extensive surgery, malabsorption of food and medicines in the digestive tract (intestinal obstruction, intestinal paresis). In stressful situations (in trauma, surgery, infectious diseases accompanied by fever) may necessitate a temporary transfer of the patient to insulin.

Keep in mind that patients with insufficient controlled type 2 diabetes when used in monotherapy with maximal doses of metformin observed a significant improvement in metabolic control upon acceding to the treatment glimepirida. Keep in mind that patients with insufficient controlled type 2 diabetes while taking maximum doses of metformin and glimepirida can be initiated with combination therapy glimepirida inculinom.

With this combination there is a significant improvement in metabolic control. In the first weeks of treatment with irregular eating or skipping meals may increase the risk of hypoglycemia, which requires the most stringent monitoring of patients. Factors contributing to the development of hypoglycemia include: unwillingness or (particularly in old age) lack of ability to cooperate with the patient's physician, irregular and insufficient food, skipping meals, fasting, changes in habitual diet, alcohol consumption, especially when combined with the omission of a meal ; imbalance between physical activity and intake of carbohydrates, renal dysfunction, severe dysfunction of liver overdose Amar; uncompensated concomitant diseases of the endocrine system affecting carbohydrate metabolism (including thyroid, pituitary insufficiency or deficiency of the adrenal cortex); simultaneous reception of other medicines.

Please note that the symptoms of hypoglycemia can be smoothed out or completely absent in older patients, patients with NCD or receiving simultaneous treatment of beta-blockers, clonidine, reserpine, guanetidinom or other sympatholytic. Dosage Amaryl determined by the level of glucose in the blood. Amaryl should be taken at the designated doses and at the appointed time. Skipping the drug should never be corrected by a subsequent admission to the higher dose. The patient must immediately inform the doctor if you receive too high a dose. In pursuing compensation for type 2 diabetes mellitus increases insulin sensitivity, in this connection in the course of treatment may decrease the need for glimepiride. For the avoidance of hypoglycemia should be timely dose reduction or repeal Amaryl. Dose adjustment should also be carried out with the change in body weight or change their way of life with the appearance of other factors contributing to the development of hypo-or hyperglycemia. Proper diet, regular exercise and, if necessary, weight loss are equally important to achieve optimal control of blood glucose, as well as the regular reception glimepirida.

When you go to Amaryl with other drugs should take into account the extent and duration of effect of prior hypoglycemic drug. It may be necessary to suspend treatment to avoid the additive effect.

If the patient developed a hypoglycemic reaction while taking glimepirida 1 mg / day, this indicates that the patient has normal levels of blood glucose can be achieved with a single diet. There is currently no experience with glimepirida in patients with severely impaired liver and kidney function or in patients who are on hemodialysis. Patients with severe liver or kidney shows a transition to insulin therapy.

Patients should be informed that during the development of severe adverse reactions should seek medical advice immediately and not continue taking the drug without his advice.

Patients should be informed not only about the symptoms of hypoglycemia, but also about the symptoms of hyperglycemia (frequent urination, excessive thirst, dry mouth, dryness of the skin).

Monitoring of laboratory parameters

During treatment, Amarillo requires regular monitoring of blood glucose and urine, as well as the concentration of glycated hemoglobin. Monitor system for the above indicators helps to establish a primary or secondary resistance to the drug.

Also, during treatment glimepiridom need to monitor liver function and pattern of peripheral blood (especially the number of platelets and leukocytes). Effects on ability to drive motor vehicles, and management arrangements in the early treatment of the transition from one hypoglycemic drug to another or the irregular admission glimepirida may occur due to hypo-or hyperglycemia decrease the concentration of attention and speed of psychomotor reactions patient. Therefore, in such situations should refrain from the study of potentially hazardous activities that require attention and quickness of psychomotor reactions.

Overdose

Symptoms: After receiving glimepirida in high doses may develop hypoglycemia lasting 12-72 h, which may recur after initial restoration of blood glucose concentration, accompanied by such manifestations as sweating, anxiety, tachycardia, increased blood pressure, sensation of palpitations, pain in the heart arrhythmia, headache, dizziness, rapid increase of appetite, nausea, vomiting, lethargy, drowsiness, anxiety, aggressiveness, impaired concentration, depression, confusion, tremor, paresis, breach of sensitivity, convulsions central origin. Sometimes the clinical picture of hypoglycemia may resemble a stroke.

Perhaps the development of coma.

Treatment: hypoglycemia can be quickly cupped immediate intake of carbohydrates (glucose, or sugar, for example in the form of lumps of sugar, sweetened fruit juice or tea). In this regard, the patient should always carry at least 20 g of glucose (4 lumps of sugar). Sweeteners are not effective in the treatment of hypoglycemia. In severe cases, the patient should be hospitalized. Need to induce vomiting, an appointment liquid (water or lemonade with activated carbon / adsorbent and / sodium sulfate / laxative /). As soon as possible begin the introduction of dextrose, if necessary, as in / jet introducing 50 ml of 40% solution followed by infusion of more dilute (10%) solution with careful monitoring of blood glucose. Further treatment should be symptomatic.

In the treatment of hypoglycemia, which was developed by accidental reception Amaryl infants and young children, in order to avoid hyperglycemia, should control the dose of dextrose (50 ml of 40% solution) and continuously monitor the concentration of glucose in the blood.

Drug Interactions

Increased hypoglycemic action Amaryl may occur while the application of insulin or other hypoglycemic drugs, ACE inhibitors, allopurinol, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclo-, tro and izofosfamidom, fenfluraminom, feniramidolom, fibrates, fluoxetine, guanetidinom , MAO inhibitors, miconazole, pentoxifylline (for parenteral administration in high doses), fenilbutazonom, azapropazonom, oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpirazon, long-acting sulphonamide, tetracycline antibiotics, tritokvalinom.

Reducing the hypoglycemic action Amaryl is possible with simultaneous application of acetazolamide, barbiturates, steroids, diazoxide, saluretikami, thiazide diuretics, epinephrine (adrenaline) and other sympathomimetics, glucagon, laxatives (long-term use), nicotinic acid (high doses) and its derivatives , progestogenic and estrogen, phenothiazines, phenytoin, rifampicin, thyroid hormones, salts of lithium, chlorpromazine.

With simultaneous application of histamine H2-blockers receptors, clonidine and reserpine are capable of both strengthening and weakening hypoglycemic effect of Amarah. During the course of Amaryl may be a strengthening or weakening of coumarin derivatives. A single or chronic use of ethanol can both strengthen and weaken the hypoglycemic effect glimepirida.

Terms and Conditions of storage

List B. The drug should be stored at temperatures not above 25 ° C. Shelf life - 3 years.