Amaryl tablets 2mg, No. 30

Diabetes mellitus type 2 (in monotherapy or as part of combination therapy with metformin or insulin).

Inside, whole, without chewing, drinking plenty of liquid (about 0.5 glass).

As a rule, the dose of AmarylЃ is determined by the target blood glucose concentration. The smallest dose sufficient to achieve the desired metabolic control should be used.

During treatment with AmarylЃ, it is necessary to regularly determine the concentration of glucose in the blood. In addition, regular monitoring of the level of glycosylated hemoglobin is recommended.

An inappropriate drug intake, such as a missed dose, should never be replenished by a subsequent dose of a higher dose.

The patient's actions in case of errors in taking the drug (in particular when skipping a dose or skipping a meal) or in situations where it is not possible to take the drug should be discussed by the patient and the doctor in advance.

Initial dose and dose selection

The starting dose is 1 mg glimepiride once a day.

If necessary, the daily dose can be gradually (at intervals of 1-2 weeks) increased. It is recommended to increase the dose under regular monitoring of the blood glucose concentration and in accordance with the following dose increase step: 1 mg-2 mg-3 mg-4 mg-6 mg (-8 mg).

Dose range in patients with well-controlled diabetes mellitus

The usual daily dose in patients with well-controlled diabetes mellitus is 1-4 mg glimepiride. A daily dose of more than 6 mg is more effective in only a small number of patients.

Dosage regimen

The time of taking the drug and the distribution of doses during the day is set by the doctor, depending on the patient's lifestyle at a given time (time of eating, the amount of physical activity).

Usually, a single dose of the drug during the day is sufficient. It is recommended that in this case the entire dose of the drug should be taken immediately before a full breakfast or, if it was not taken at this time, immediately before the first main meal. It is very important not to skip meals after taking the pills.

Since improved metabolic control is associated with increased insulin sensitivity, the need for glimepiride may decrease during treatment. In order to avoid the development of hypoglycemia, it is necessary to promptly reduce the dose or stop taking the drug AmarylЃ.

Conditions in which a dose adjustment of glimepiride may also be required:

- a decrease in body weight in a patient;

- changes in the patient's lifestyle (change in diet, meal time, amount of physical activity);

- the occurrence of other factors that lead to a predisposition to the development of hypoglycemia or hyperglycemia (see section 'Special instructions').

Duration of treatment

Treatment with glimepiride is usually long-term.

Transfer of a patient from another hypoglycemic agent for oral administration to AmarylЃ

There is no exact relationship between the doses of AmarylЃ and other oral hypoglycemic agents. When another hypoglycemic agent for oral administration is replaced with AmarylЃ, it is recommended that the procedure for prescribing it be the same as for the initial administration of AmarylЃ, i.e. treatment should begin with a low dose of 1 mg (even if the patient is transferred to AmarylЃ from the maximum dose of another hypoglycemic drug for oral administration). Any dose increase should be carried out in stages, taking into account the reaction to glimepiride in accordance with the recommendations above.

It is necessary to consider the strength and duration of the effect of the previous oral hypoglycemic agent. It may be necessary to interrupt treatment in order to avoid any summation of effects, which may increase the risk of hypoglycemia.

Use in combination with metformin

In patients with insufficiently controlled diabetes mellitus, when taking the maximum daily doses of either glimepiride or metformin, treatment with a combination of these two drugs can be started. In this case, the previous treatment with either glimepiride or metformin continues at the same dose level, and additional administration of metformin or glimepiride begins with a low dose, which is then titrated depending on the target level of metabolic control up to the maximum daily dose. Combination therapy should be started under strict medical supervision.

Use in combination with insulin

Patients with insufficiently controlled diabetes mellitus, when taking the maximum daily doses of glimepiride, can be simultaneously administered insulin. In this case, the last dose of glimepiride prescribed to the patient remains unchanged. In this case, insulin treatment begins with low doses, which are gradually increased under the control of the concentration of glucose in the blood. Combination treatment requires close medical supervision.

Use in patients with renal impairment. There is a limited amount of information on the use of the drug in patients with renal insufficiency. Patients with impaired renal function may be more sensitive to the hypoglycemic effect of glimepiride (see sections 'Pharmacokinetics', 'Contraindications').

Use in patients with hepatic impairment. There is a limited amount of information on the use of the drug in liver failure (see section 'Contraindications').

Application in children. There is insufficient data on the use of the drug in children.

Pills

1 tab.

glimepiride 1,2,3 or 4 mg

Excipients: lactose monohydrate, sodium carboxymethyl starch (type A), povidone 25,000, microcrystalline cellulose, magnesium stearate, indigo carmine (E132).

• Hypersensitivity to glimepiride or to any auxiliary substance of the drug, other sulfonylurea derivatives or sulfonamide drugs (risk of developing hypersensitivity reactions);

• type 1 diabetes mellitus;

• diabetic ketoacidosis, diabetic precoma and coma;

• severe liver dysfunction (lack of clinical experience of use);

• severe renal dysfunction, incl. in patients on hemodialysis (lack of clinical experience of use);

• rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption;

• pregnancy;

• lactation;

• children's age (lack of clinical experience of use).

Carefully:

condition in the first weeks of treatment (increased risk of hypoglycemia). In the presence of risk factors for the development of hypoglycemia (see section 'Special instructions'), you may need to adjust the dose of glimepiride or all therapy;

intercurrent diseases during treatment or when changing the lifestyle of patients (changing the diet and time of eating, increasing or decreasing physical activity);

insufficiency of glucose-6-phosphate dehydrogenase;

disorders of absorption of food and drugs in the gastrointestinal tract (intestinal obstruction, intestinal paresis).

pharmachologic effect

Oral hypoglycemic drug - III generation sulfonylurea derivative.

Glimepiride reduces the concentration of glucose in the blood, mainly by stimulating the release of insulin from the ?-cells of the pancreas. Its effect is predominantly associated with an improvement in the ability of pancreatic ? cells to respond to physiological glucose stimulation. Compared to glibenclamide, low doses of glimepiride cause the release of less insulin while achieving approximately the same reduction in blood glucose concentration. This fact testifies in favor of the presence of extrapancreatic hypoglycemic effects in glimepiride (increased tissue sensitivity to insulin and insulinomimetic effect).

Insulin secretion. Like all other sulfonylurea derivatives, glimepiride regulates insulin secretion by interacting with ATP-sensitive potassium channels on the membranes of ?-cells. Unlike other sulfonylurea derivatives, glimepiride selectively binds to a protein with a molecular weight of 65 kilodaltons, which is located in the membranes of pancreatic ?-cells. This interaction of glimepiride with a protein binding to it regulates the opening or closing of ATP-sensitive potassium channels.

Glimepiride closes potassium channels. This causes depolarization of ?-cells and leads to the opening of voltage-sensitive calcium channels and the flow of calcium into the cell. As a result, an increase in intracellular calcium concentration activates insulin secretion by exocytosis.

Glimepiride much faster and, accordingly, more often enters into a bond and is released from a bond with a protein that binds to it than glibenclamide. It is assumed that this property of a high exchange rate of glimepiride with a protein binding to it causes its pronounced effect of sensitizing ? cells to glucose and protecting them from desensitization and premature depletion.

The effect of increasing the sensitivity of tissues to insulin. Glimepiride enhances the effects of insulin on glucose uptake by peripheral tissues.

Insulinomimetic effect. Glimepiride has effects similar to those of insulin on glucose uptake by peripheral tissues and the release of glucose from the liver.

The absorption of glucose by peripheral tissues is carried out by its transport into muscle cells and adipocytes. Glimepiride directly increases the number of glucose-transporting molecules in the plasma membranes of muscle cells and adipocytes. An increase in the intake of glucose into cells leads to the activation of glycosylphosphatidylinositol-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 the stimulation of glucose metabolism.

Glimepiride inhibits the release of glucose from the liver by increasing the concentration of fructose-2,6-bisphosphate, which inhibits gluconeogenesis.

Influence on platelet aggregation. Glimepiride reduces platelet aggregation in vitro and in vivo. This effect appears to be related to the selective inhibition of COX, which is responsible for the formation of thromboxane A, an important endogenous platelet aggregation factor.

Antiatherogenic action. Glimepiride helps to normalize the lipid content, reduces the level of malonic aldehyde in the blood, which leads to a significant decrease in lipid peroxidation. In animals, glimepiride leads to a significant decrease in the formation of atherosclerotic plaques.

Reducing the severity of oxidative stress, which is constantly present in patients with type 2 diabetes. Glimepiride increases the level of endogenous ?-tocopherol, the activity of catalase, glutathione peroxidase and superoxide dismutase.

Cardiovascular Effects. Sulfonylurea derivatives also have an effect on the cardiovascular system through ATP-sensitive potassium channels. Compared with traditional sulfonylurea derivatives, glimepiride has a significantly lower effect on the cardiovascular system, which can be explained by the specific nature of its interaction with the protein ATP-sensitive potassium channels that binds to it.

In healthy volunteers, the minimum effective dose of glimepiride is 0.6 mg. The effect of glimepiride is dose dependent and reproducible. The physiological response to exercise (decreased insulin secretion) persists with glimepiride.

There are no significant differences in the effect depending on whether the drug was taken 30 minutes before a meal or immediately before a meal. In patients with diabetes mellitus, sufficient metabolic control can be achieved within 24 hours with a single dose of the drug. Moreover, in a clinical study, 12 out of 16 patients with renal insufficiency (CC 4-79 ml / min) also achieved sufficient metabolic control.

Combination therapy with metformin. In patients with insufficient metabolic control, when using the maximum dose of glimepiride, combination therapy with glimepiride and metformin may be initiated. In two studies, combination therapy has shown improved metabolic control compared to that with each of these drugs alone.

Combination therapy with insulin. In patients with insufficient metabolic control, while taking glimepiride at maximum doses, concomitant insulin therapy may be initiated. In two studies, this combination achieved the same improvement in metabolic control as with insulin alone. However, with combination therapy, a lower dose of insulin is required.

Pharmacokinetics

When comparing the data obtained with single and multiple (1 time / day) administration of glimepiride, no significant differences in pharmacokinetic parameters were found, and their variability between different patients was very low. There is no significant accumulation of the drug.

Suction

With repeated oral administration of the drug in a daily dose of 4 mg, Cmax in serum is reached after about 2.5 hours and is 309 ng / ml. There is a linear relationship between the dose and Cmax of glimepiride in plasma, as well as between the dose and AUC. When taken orally, the bioavailability of glimepiride is 100%. Food intake has no significant effect on absorption, with the exception of a slight slowdown in its rate.

Distribution

Glimepiride is characterized by a very low Vd (about 8.8 L), approximately equal to the Vd of albumin, a high degree of binding to plasma proteins (more than 99%) and a low clearance (about 48 ml / min).

Glimepiride is excreted in breast milk and crosses the placental barrier.

Metabolism

Glimepiride is metabolized in the liver (mainly with the participation of the isoenzyme CYP2C9) with the formation of 2 metabolites - hydroxylated and carboxylated derivatives, which are found in urine and feces.

Withdrawal

T1 / 2 at plasma concentrations of the drug in serum corresponding to a multiple dosing regimen is approximately 5-8 hours. After taking glimepiride in high doses, T1 / 2 increases slightly.

After a single oral administration, 58% of glimepiride is excreted by the kidneys and 35% through the intestines. The unchanged active substance is not detected in the urine.

T1 / 2 of the hydroxylated and carboxylated metabolites of glimepiride were about 3-5 hours and 5-6 hours, respectively.

Pharmacokinetics in special clinical situations

Pharmacokinetic parameters are similar in patients of different sexes and different age groups.

In patients with impaired renal function (with low CC), there is a tendency to an increase in the clearance of glimepiride and to a decrease in its average concentrations in the blood serum, which, in all likelihood, is due to a more rapid excretion of the drug due to its lower binding to proteins. Thus, in this category of patients, there is no additional risk of glimepiride cumulation.

Side effect

From the side of metabolism: hypoglycemia is possible, which, as with the use of other sulfonylurea derivatives, can be prolonged. Symptoms of hypoglycemia - headache, hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, anxiety, aggressiveness, impaired concentration, alertness and reaction speed, depression, confusion, speech disorders, aphasia, visual disturbances, tremors, paresis , sensory disturbances, dizziness, loss of self-control, delirium, cerebral cramps, drowsiness or loss of consciousness up to coma, shallow breathing, bradycardia. In addition, manifestations of adrenergic counterregulation in response to hypoglycemia may occur, such as the appearance of cold clammy sweat, anxiety, tachycardia, arterial hypertension, angina pectoris,palpitations and cardiac arrhythmias. The clinical picture of severe hypoglycemia may resemble a stroke. Symptoms of hypoglycemia almost always disappear after its elimination.

From the side of the organ of vision: possible (especially at the beginning of treatment) transient visual disturbances caused by changes in the concentration of glucose in the blood. They are caused by a temporary change in the swelling of the lens, depending on the concentration of glucose in the blood, and due to this change in the refractive index of the lens.

From the digestive system: rarely - nausea, vomiting, feeling of heaviness or fullness in the epigastrium, abdominal pain, diarrhea; in some cases - hepatitis, increased activity of liver enzymes and / or cholestasis and jaundice, which can progress to life-threatening liver failure, but may undergo a regression when the drug is discontinued.

From the hematopoietic system: rarely - thrombocytopenia; in some cases - leukopenia, hemolytic anemia, erythrocytopenia, granulocytopenia, agranulocytosis and pancytopenia. With post-marketing use of the drug, cases of severe thrombocytopenia with a platelet count <10,000 / ?l and thrombocytopenic purpura have been reported (frequency unknown).

Allergic reactions: rarely - allergic and pseudo-allergic reactions such as itching, urticaria, skin rash. Such reactions are almost always mild, but they can turn into severe reactions with shortness of breath, a sharp decrease in blood pressure, which sometimes progress to anaphylactic shock; in some cases - allergic vasculitis.

Others: in some cases - hyponatremia, photosensitivity.

If symptoms of hives develop, see your doctor immediately.

Application during pregnancy and lactation

AmarylЃ is contraindicated for use during pregnancy. In the event of a planned pregnancy or in the event of a pregnancy, a woman should be transferred to insulin therapy.

It has been established that glimepiride is excreted in breast milk. During lactation, the woman should be transferred to insulin or breastfeeding should be stopped.

Application for violations of liver function

Use is contraindicated in severe liver dysfunction.

Application for impaired renal function

Contraindicated for use in severe renal dysfunction (including patients on hemodialysis);

Application in children

Contraindicated in childhood.

special instructions

¬ особых клинических стрессовых состо¤ни¤х, таких как травма, хирургические вмешательства, инфекции, протекающие с фебрильной температурой, возможно ухудшение метаболического контрол¤ у пациентов с сахарным диабетом, поэтому дл¤ поддержани¤ адекватного метаболического контрол¤ может потребоватьс¤ временный перевод на инсулинотерапию.

¬ первые недели лечени¤ возможно повышение риска развити¤ гипогликемии, что требует особенно тщательного контрол¤ концентрации глюкозы в крови.

  факторам, способствующим риску развити¤ гипогликемии относ¤тс¤:

• нежелание или неспособность пациента (более часто наблюдающа¤с¤ у пациентов пожилого возраста) к сотрудничеству с врачом;

• недоедание, нерегул¤рный прием пищи или пропуски приема пищи;

• дисбаланс между физическими нагрузками и потреблением углеводов;

• изменение диеты;

• употребление алкогол¤, особенно в сочетании с пропусками приема пищи;

• т¤желые нарушени¤ функции почек;

• т¤желые нарушени¤ функции печени (у пациентов с т¤желыми нарушени¤ми функции печени показан перевод на инсулинотерапию, по крайней мере, до достижени¤ метаболического контрол¤);

• передозировка глимепирида;

• некоторые декомпенсированные эндокринные расстройства, нарушающие углеводный обмен или адренергическую контррегул¤цию в ответ на гипогликемию (например, некоторые нарушени¤ функции щитовидной железы и переднего отдела гипофиза, недостаточность коры надпочечников);

• одновременный прием некоторых лекарственных средств;

• прием глимепирида при отсутствии показаний к его приему.

Ћечение производными сульфонилмочевины, к которым относитс¤ и глимепирид, может привести к развитию гемолитической анемии, поэтому у пациентов с недостаточностью глюкозо-6-фосфатдегидрогеназы следует соблюдать особую осторожность при назначении глимепирида, предпочтительно примен¤ть гипогликемические средства, не ¤вл¤ющиес¤ производными сульфонилмочевины.

¬ случае наличи¤ вышеперечисленных факторов риска развити¤ гипогликемии, а также при возникновении интеркуррентных заболеваний во врем¤ лечени¤ или изменении образа жизни пациента может потребоватьс¤ коррекци¤ дозы глимепирида или всей терапии.

—имптомы гипогликемии, возникающие вследствие адренергической контррегул¤ции организма в ответ на гипогликемию, могут быть слабо выраженными или отсутствовать при постепенном развитии гипогликемии, у пациентов пожилого возраста, у пациентов с нарушени¤ми со стороны вегетативной нервной системы или у пациентов, получающих бета-адреноблокаторы, клонидин, резерпин, гуанетидин и другие симпатолитические средства.

vипогликеми¤ может быть быстро устранена при немедленном приеме быстро усваивающихс¤ углеводов (глюкозы или сахарозы).  ак и при приеме других производных сульфонилмочевины, несмотр¤ на первоначальное успешное купирование гипогликемии, гипогликеми¤ может возобновитьс¤. ѕоэтому пациенты должны оставатьс¤ под посто¤нным наблюдением. ѕри т¤желой гипогликемии дополнительно требуетс¤ немедленное лечение и наблюдение врача, а в некоторых случа¤х - госпитализаци¤ пациента.

¬о врем¤ лечени¤ глимепиридом требуетс¤ проведение регул¤рного контрол¤ функции печени и картины периферической крови (особенно количества лейкоцитов и тромбоцитов).

“акие побочные эффекты как т¤жела¤ гипогликеми¤, серьезные изменени¤ картины крови, т¤желые аллергические реакции, печеночна¤ недостаточность могут представл¤ть угрозу дл¤ жизни, поэтому в случае развити¤ подобных реакций пациент должен сразу же информировать о них лечащего врача, прекратить прием препарата и не возобновл¤ть прием без рекомендации врача.

»спользование в педиатрии

?анные по долгосрочной эффективности и безопасности применени¤ препарата у детей отсутствуют.

¬ли¤ние на способность к управлению транспортными средствами и механизмами

¬ начале лечени¤, после изменени¤ лечени¤ или при нерегул¤рном приеме глимепирида может отмечатьс¤ обусловленное гипо- или гипергликемией снижение концентрации внимани¤ и скорости психомоторных реакций. Ёто может отрицательно сказатьс¤ на способности к вождению автотранспорта или к управлению различными машинами и механизмами.

ѕередозировка

—имптомы: при острой передозировке, а также длительном лечении глимепиридом в чрезмерно высоких дозах возможно развитие т¤желой угрожающей жизни гипогликемии.

Ћечение: гипогликеми¤ почти всегда может быть быстро купирована немедленным приемом углеводов (глюкозы или кусочка сахара, сладкого фруктового сока или ча¤). ¬ св¤зи с этим пациент должен всегда иметь при себе не менее 20 г глюкозы (4 кусочка сахара). —ахарозаменители неэффективны при лечении гипогликемии.

?о того момента, пока врач не решит, что пациент находитс¤ вне опасности, пациенту необходимо тщательное медицинское наблюдение. —ледует иметь в виду, что гипогликеми¤ может возобновитьс¤ после первоначального восстановлени¤ концентрации глюкозы в крови.

?сли больного, страдающего сахарным диабетом, лечат разные врачи (например, во врем¤ пребывани¤ в больнице после несчастного случа¤, при заболевании в выходные дни), он должен об¤зательно сообщить им о своем заболевании и о предшествующем лечении.

»ногда может потребоватьс¤ госпитализаци¤ пациента, хот¤ бы даже в качестве меры предосторожности. «начительна¤ передозировка и т¤жела¤ реакци¤ с такими про¤влени¤ми, как потер¤ сознани¤ или другие серьезные неврологические нарушени¤ ¤вл¤ютс¤ неотложными медицинскими состо¤ни¤ми и требуют немедленного лечени¤ и госпитализации.

ѕри потере сознани¤ необходимо в/в введение концентрированного раствора декстрозы (глюкозы) (дл¤ взрослых, начина¤ с 40 мл 20% раствора). ¬ качестве альтернативы взрослым возможно ввести в/в, п/к или в/м глюкагон, например, в дозе 0.5-1 мг.

ѕри лечении гипогликемии вследствие случайного приема препарата јмарилЃ младенцами или детьми младшего возраста следует тщательно корректировать дозу декстрозы во избежание возможности возникновени¤ опасной гипергликемии; введение декстрозы следует проводить под посто¤нным контролем концентрации глюкозы в крови.

ѕри передозировке препарата јмарилЃ может потребоватьс¤ проведение промывани¤ желудка и прием активированного угл¤.

ѕосле быстрого восстановлени¤ концентрации глюкозы в крови об¤зательно необходимо проведение в/в инфузии раствора декстрозы в более низкой концентрации дл¤ предотвращени¤ возобновлени¤ гипогликемии.  онцентрацию глюкозы в крови у таких пациентов следует посто¤нно контролировать в течение 24 ч. ¬ т¤желых случа¤х с зат¤жным течением гипогликемии опасность снижени¤ уровн¤ глюкозы в крови может сохран¤тьс¤ в течение нескольких дней

 ак только обнаружена передозировка, необходимо срочно сообщить об этом врачу.

Ћекарственное взаимодействие

vлимепирид метаболизируетс¤ при участии изофермента CYP2C9, что следует учитывать при одновременном применении препарата с индукторами (например, рифампицин) или ингибиторами (например, флуконазол) CYP2C9.

ѕотенцирование гипогликемического действи¤ и в некоторых случа¤х св¤занное с этим возможное развитие гипогликемии может наблюдатьс¤ при сочетании препарата јмарилЃ с одним из следующих препаратов: инсулин, другие гипогликемические средства дл¤ приема внутрь, ингибиторы јѕ‘, анаболические стероиды и мужские половые гормоны, хлорамфеникол, производные кумарина, циклофосфамид, дизопирамид, фенфлурамин, фенирамидол, фибраты, флуоксетин, гуанетидин, ифосфамид, ингибиторы ћјќ, флуконазол, ѕј— , пентоксифиллин (высокие парентеральные дозы), фенилбутазон, азапропазон, оксифенбутазон, пробенецид, хинолоны, салицилаты, сульфинпиразон, кларитромицин, сульфаниламиды, тетрациклины, тритоквалин, трофосфамид.

”меньшение гипогликемического действи¤ и св¤занное с этим повышение концентрации глюкозы в крови возможно при сочетании с одним из следующих препаратов: ацетазоламид, барбитураты, v —, диазоксид, диуретики, симпатомиметические средства (в т.ч. эпинефрин), глюкагон, слабительные средства (при длительном применении), никотинова¤ кислота (в высоких дозах), эстрогены и прогестагены, фенотиазины, фенитоин, рифампицин, йодсодержащие гормоны щитовидной железы.

Ѕлокаторы гистаминовых Ќ2-рецепторов, бета-адреноблокаторы, клонидин и резерпин способны как усиливать, так и уменьшать гипогликемическое действие глимепирида.

ѕод вли¤нием симпатолитических средств, таких как бета-адреноблокаторы, клонидин, гуанетидин и резерпин, признаки адренергической контррегул¤ции в ответ на гипогликемию могут уменьшатьс¤ или отсутствовать.

While taking glimepiride, it is possible to increase or decrease the effect of coumarin derivatives.

Single or chronic alcohol consumption can both enhance and weaken the hypoglycemic effect of glimepiride.

Bile acid sequestrants: colesevelam binds to glimepiride and reduces the absorption of glimepiride from the gastrointestinal tract. In the case of the use of glimepiride, at least 4 hours before the ingestion of colesevelam, no interaction is observed. Therefore, glimepiride must be taken at least 4 hours before taking colesevelam.