Diabeton MV tablets 60mg, No. 30

• Diabetes mellitus type 2 with insufficient effectiveness of diet therapy, physical activity and weight loss;

• prevention of complications of diabetes mellitus: reducing the risk of microvascular (nephropathy, retinopathy) and macrovascular complications (myocardial infarction, stroke) in patients with type 2 diabetes mellitus by intensive glycemic control.

The drug is intended only for the treatment of adults.

The recommended dose of the drug should be taken orally, 1 time / day, preferably with breakfast.

The daily dose may be 30-120 mg (1 / 2-2 tab.) In 1 reception. It is recommended to swallow the tablet or half of the tablet whole without chewing or crushing.

If you miss one or more doses of the drug, you should not take a higher dose in the next dose, the missed dose should be taken the next day. As with other hypoglycemic drugs, the dose of the drug in each case must be selected individually, depending on the concentration of blood glucose and HbA1c.

The initial recommended dose for adults (including for elderly patients ?65 years old) is 30 mg (1/2 tab.) / Day.

In case of adequate control, the drug at this dose can be used for maintenance therapy. With inadequate glycemic control, the daily dose of the drug can be sequentially increased to 60 mg, 90 mg or 120 mg. Increasing the dose is possible no earlier than 1 month after the drug therapy in the previously prescribed dose The exception is patients in whom the blood glucose concentration did not decrease after 2 weeks of therapy. In such cases, the dose of the drug can be increased 2 weeks after the start of administration.

The maximum recommended daily dose of the drug is 120 mg.

1 tab. the drug DiabetonЃ MV tablets with modified release 60 mg is equivalent to 2 tab. the drug DiabetonЃ MV tablets with modified release 30 mg. The presence of a notch on 60 mg tablets allows you to divide the tablet and take a daily dose of both 30 mg (1/2 tab. 60 mg) and, if necessary, 90 mg (1 tab. 60 mg and 1/2 tab. 60 mg).

Switching from taking DiabetonЃ tablets 80 mg to DiabetonЃ MB tablets with modified release 60 mg

1 tablet of the drug DiabetonЃ 80 mg can be replaced by 1/2 tablet with a modified release of DiabetonЃ MB 60 mg. When transferring patients from DiabetonЃ 80 mg to DiabetonЃ MV, careful glycemic control is recommended.

Switching from another hypoglycemic drug to DiabetonЃ MB modified-release tablets 60 mg

The drug DiabetonЃ MB modified-release tablets 60 mg can be used instead of another hypoglycemic agent for oral administration. When transferring to DiabetonЃ MB patients receiving other hypoglycemic drugs for oral administration, their dose and T1 / 2 should be taken into account. As a rule, there is no need for a transition period. The starting dose should be 30 mg and then titrated against the blood glucose concentration.

If the drug DiabetonЃ MB replaces sulfonylurea derivatives with a long T1 / 2 in order to avoid hypoglycemia caused by the additive effect of two hypoglycemic agents, you can stop taking them for several days. The initial dose of the drug DiabetonЃ MB is also 30 mg (1/2 tab. 60 mg) and, if necessary, can be increased further, as described above.

Combined administration with another hypoglycemic drug

DiabetonЃ MB can be used in combination with biguanidines, alpha-glucosidase inhibitors or insulin.

In case of inadequate glycemic control, additional insulin therapy should be prescribed with careful medical monitoring.

Special patient groups

No dose adjustment is required for patients over 65 years of age.

The results of clinical studies have shown that dose adjustment of the drug in patients with mild to moderate renal insufficiency is not required. Careful medical monitoring is recommended.

In patients at risk of developing hypoglycemia (inadequate or unbalanced nutrition; severe or poorly compensated endocrine disorders - pituitary and adrenal insufficiency, hypothyroidism; cancellation of GCS after long-term administration and / or administration of high doses; severe diseases of the cardiovascular system - severe coronary artery disease, severe atherosclerosis of the carotid arteries, widespread atherosclerosis), it is recommended to use the minimum dose (30 mg) of DiabetonЃ MB.

To achieve intensive glycemic control, the dose of DiabetonЃ MB can be gradually increased to 120 mg / day in addition to diet and exercise until the target HbA1c level is reached. Be aware of the risk of hypoglycemia. In addition, other hypoglycemic drugs such as metformin, an alpha-glucosidase inhibitor, a thiazolidinedione derivative or insulin can be added to the therapy.

There are no data on the efficacy and safety of the drug in children and adolescents under the age of 18 years.

Modified release tablets are white, biconvex, oval with notches and 'DIA' '60' engraving on both sides.

1 tab. gliclazide 60 mg

Excipients: lactose monohydrate - 71.36 mg, maltodextrin - 22 mg, hypromellose 100 cP - 160 mg, magnesium stearate - 1.6 mg, colloidal anhydrous silicon dioxide - 5.04 mg.

• Type 1 diabetes mellitus;

• diabetic ketoacidosis, diabetic precoma, diabetic coma;

• severe renal or hepatic impairment (insulin is recommended in these cases);

• taking miconazole (see the section 'Drug interactions');

• pregnancy and lactation (see section 'Pregnancy and lactation');

• age under 18;

• hypersensitivity to gliclazide, other sulfonylurea derivatives, sulfonamides or to excipients that make up the drug.

Due to the fact that the drug contains lactose, DiabetonЃ MB is not recommended for patients with congenital lactose intolerance, galactosemia, glucose-galactose malabsorption.

It is not recommended to use the drug in combination with phenylbutazone or danazol (see section 'Drug interactions').

The drug should be used with caution in case of irregular and / or unbalanced nutrition, deficiency of glucose-6-phosphate dehydrogenase, severe diseases of the cardiovascular system, hypothyroidism, adrenal or pituitary insufficiency, renal and / or hepatic insufficiency, long-term GCS therapy, alcoholism, in elderly patients age

pharmachologic effect

Gliclazide is a sulfonylurea derivative, a hypoglycemic drug for oral administration, which differs from similar drugs by the presence of an N-containing heterocyclic ring with an endocyclic bond.

Gliclazide reduces the concentration of glucose in the blood by stimulating the secretion of insulin by ?-cells of the islets of Langerhans. The increase in the concentration of postprandial insulin and C-peptide persists after 2 years of therapy. In addition to the effect on carbohydrate metabolism, gliclazide has hemovascular effects.

Influence on insulin secretion

In type 2 diabetes mellitus, the drug restores the early peak of insulin secretion in response to glucose intake and enhances the second phase of insulin secretion. A significant increase in insulin secretion is observed in response to stimulation caused by food intake and glucose administration.

Hemovascular effects

Gliclazide reduces the risk of thrombosis of small vessels, influencing the mechanisms that can cause the development of complications in diabetes mellitus: partial inhibition of platelet aggregation and adhesion and a decrease in the concentration of platelet activating factors (beta-thromboglobulin, thromboxane B2), as well as the restoration of fibrinolytic activity of the vascular endothelium and increased activity of tissue plasminogen activator.

Intensive glycemic control, based on the use of the drug DiabetonЃ MB (glycosylated hemoglobin (HbA1c <6.5%), significantly reduces micro- and macrovascular complications of type 2 diabetes mellitus, in comparison with standard glycemic control (ADVANCE study).

The strategy of intensive glycemic control included the appointment of the drug DiabetonЃ MB and an increase in its dose against the background (or instead of) standard therapy before adding another hypoglycemic drug to it (for example, metformin, an alpha-glucosidase inhibitor, a thiazolidinedione derivative or insulin). The average daily dose of DiabetonЃ MB in patients in the intensive control group was 103 mg, the maximum daily dose was 120 mg.

Against the background of the use of the drug DiabetonЃ MB in the group of intensive glycemic control (average follow-up 4.8 years, average HbA1c level 6.5%) compared with the standard control group (average HbA1c level 7.3%), a significant 10% decrease in the relative risk of the combined frequency of macro- and microvascular complications.

The advantage was achieved due to a significant reduction in the relative risk: major microvascular complications by 14%, the onset and progression of nephropathy by 21%, the onset of microalbuminuria by 9%, macroalbuminuria by 30%, and the development of renal complications by 11%.

The advantages of intensive glycemic control while taking DiabetonЃ MB did not depend on the advantages achieved during antihypertensive therapy.

Pharmacokinetics

Suction

After oral administration, gliclazide is completely absorbed. The concentration of gliclazide in blood plasma increases gradually during the first 6 hours, the plateau level is maintained from 6 to 12 hours. Individual variability is low.

Food intake does not affect the rate or extent of absorption of gliclazide.

Distribution

Plasma protein binding is approximately 95% of gliclazide. Vd - about 30 liters. Taking the drug DiabetonЃ MB at a dose of 60 mg 1 time / day ensures the maintenance of the effective concentration of gliclazide in the blood plasma for more than 24 hours.

Metabolism

Gliclazide is metabolized primarily in the liver. There are no active metabolites in plasma.

Withdrawal

T1 / 2 averages from 12 to 20 hours. Gliclazide is excreted mainly by the kidneys, excretion is carried out in the form of metabolites, less than 1% is excreted by the kidneys unchanged.

Linearity

The relationship between the dose taken (up to 120 mg) and the AUC is linear.

Pharmacokinetics in special clinical situations

In the elderly, no significant changes in pharmacokinetic parameters are observed.

Side effect

Taking into account the experience of using gliclazide, one should remember about the possibility of developing the following side effects.

Hypoglycemia

Like other drugs of the sulfonylurea group, DiabetonЃ MB can cause hypoglycemia in case of irregular meals and especially if meals are skipped. Possible symptoms of hypoglycemia: headache, severe hunger, nausea, vomiting, increased fatigue, sleep disturbance, irritability, agitation, decreased concentration, delayed reaction, depression, confusion, blurred vision and speech, aphasia, tremor, paresis, loss of self-control , feeling of helplessness, impaired perception, dizziness, weakness, convulsions, bradycardia, delirium, shallow breathing, drowsiness, loss of consciousness with the possible development of coma, up to death.

Adrenergic reactions may also occur: increased sweating, 'clammy' skin, anxiety, tachycardia, increased blood pressure, palpitations, arrhythmia and angina pectoris.

As a rule, the symptoms of hypoglycemia are relieved by the intake of carbohydrates (sugar). Taking sweeteners is ineffective. Against the background of other sulfonylurea derivatives, relapses of hypoglycemia were noted after successful relief.

For severe or prolonged hypoglycemia, urgent medical attention is indicated, possibly with hospitalization, even if there is an effect of carbohydrate intake.

Other side effects

From the digestive system: abdominal pain, nausea, vomiting, diarrhea, constipation. Taking the drug with breakfast can help avoid or minimize these symptoms.

The following side effects are less common:

Skin and subcutaneous tissue disorders: rash, itching, urticaria, Quincke's edema, erythema, maculopapular rash, bullous reactions (such as Stevens-Johnson syndrome and toxic epidermal necrolysis).

On the part of the hematopoietic and lymphatic system: hematological disorders (anemia, leukopenia, thrombocytopenia, granulocytopenia) rarely develop. As a rule, these phenomena are reversible in the event of discontinuation of therapy.

From the liver and biliary tract: increased activity of liver enzymes (AST, ALT, ALP); in isolated cases - hepatitis. If cholestatic jaundice develops, therapy should be discontinued. These phenomena are usually reversible in the event of discontinuation of therapy.

From the side of the organ of vision: transient visual disturbances caused by changes in the concentration of blood glucose may occur, especially at the beginning of therapy.

Side effects inherent in sulfonylurea derivatives: as with other sulfonylurea derivatives, erythrocytopenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, hyponatremia were noted. There was an increase in the activity of liver enzymes, impaired liver function (for example, with the development of cholestasis and jaundice) and hepatitis. These manifestations diminished over time after discontinuation of sulfonylurea drugs, but in some cases led to life-threatening liver failure.

Side effects reported in clinical trials

In the ADVANCE study, there was little difference in the incidence of various serious adverse events between the two patient groups. No new safety data were received. A small number of patients had severe hypoglycemia, but the overall incidence of hypoglycemia was low. The incidence of hypoglycemia in the intensive glycemic control group was higher than in the standard glycemic control group. Most of the episodes of hypoglycemia in the intensive glycemic control group were observed with concomitant insulin therapy.

Application during pregnancy and lactation

Pregnancy

There is no experience with gliclazide during pregnancy. Data on the use of other sulfonylurea derivatives during pregnancy are limited.

In studies on laboratory animals, the teratogenic effects of gliclazide have not been identified.

To reduce the risk of developing congenital malformations, optimal control (appropriate therapy) of diabetes mellitus is required.

Oral hypoglycemic drugs are not used during pregnancy. Insulin is the drug of choice for the treatment of diabetes mellitus in pregnant women. It is recommended to replace the intake of oral hypoglycemic drugs with insulin therapy both in the case of a planned pregnancy and in the event that the pregnancy occurred while taking the drug.

Lactation

Taking into account the lack of data on the intake of gliclazide in breast milk and the risk of developing neonatal hypoglycemia, breastfeeding is contraindicated during drug therapy.

Application for violations of liver function

The use of the drug is contraindicated in severe hepatic insufficiency.

Application for impaired renal function

The use of the drug is contraindicated in severe renal failure.

The results of clinical studies have shown that dose adjustment of the drug in patients with mild to moderate renal insufficiency is not required.

Application in children

Contraindicated in children and adolescents under 18 years of age.

Use in elderly patients

The drug should be used with caution in elderly patients.

special instructions

Hypoglycemia

When taking sulfonylurea derivatives, incl. and gliclazide, hypoglycemia may develop, and in some cases - in a severe and prolonged form, requiring hospitalization and intravenous administration of a dextrose solution for several days (see the section 'Side effects').

The drug can be prescribed only to those patients whose meals are regular and include breakfast. It is very important to maintain an adequate intake of carbohydrates from the diet, because the risk of developing hypoglycemia increases with irregular or inadequate nutrition, as well as with the consumption of foods poor in carbohydrates. Hypoglycemia is more likely to develop with a low-calorie diet, after prolonged or vigorous exercise, after drinking alcohol, or when taking several hypoglycemic drugs at the same time.

Typically, symptoms of hypoglycemia resolve after eating foods rich in carbohydrates (such as sugar). It should be borne in mind that taking sugar substitutes does not help to eliminate hypoglycemic symptoms. Experience with other sulfonylurea derivatives suggests that hypoglycemia can recur despite effective initial relief of this condition. If the hypoglycemic symptoms are pronounced or prolonged, even in the case of a temporary improvement in the condition after eating a meal rich in carbohydrates, it is necessary to provide emergency medical care, up to hospitalization.

In order to avoid the development of hypoglycemia, careful individual selection of drugs and dosage regimen is required, as well as providing the patient with complete information about the treatment being performed.

ѕовышенный риск развити¤ гипогликемии может отмечатьс¤ в следующих случа¤х:

• отказ или неспособность пациента (особенно пожилого возраста) следовать назначени¤м врача и контролировать свое состо¤ние;

• недостаточное и нерегул¤рное питание, пропуск приемов пищи, голодание и изменение рациона;

• дисбаланс между физической нагрузкой и количеством принимаемых углеводов;

• почечна¤ недостаточность;

• т¤жела¤ печеночна¤ недостаточность;

• передозировка препарата ?иабетонЃ MB;

• некоторые эндокринные расстройства (заболевани¤ щитовидной железы, гипофизарна¤ и надпочечникова¤ недостаточность);

• одновременный прием некоторых лекарственных средств (см. раздел 'Ћекарственное взаимодействие').

ѕеченочна¤/почечна¤ недостаточность

” пациентов с печеночной и/или т¤желой почечной недостаточностью возможно изменение фармакокинетических и/или фармакодинамических свойств гликлазида. vипогликеми¤, развивающа¤с¤ у таких пациентов, может быть достаточно длительной, в таких случа¤х необходимо немедленное проведение соответствующей терапии.

»нформаци¤ дл¤ пациентов

Ќеобходимо проинформировать пациента и членов его семьи о риске развити¤ гипогликемии, ее симптомах и услови¤х, способствующих ее развитию. ѕациента необходимо проинформировать о потенциальном риске и преимуществах предлагаемого лечени¤. ѕациенту необходимо разъ¤снить важность соблюдени¤ диеты, необходимость регул¤рных физических упражнений и контрол¤ концентрации глюкозы крови.

Ќедостаточный гликемический контроль

vликемический контроль у пациентов, получающих терапию гипогликемическими средствами, может быть ослаблен в следующих случа¤х: лихорадка, травмы, инфекционные заболевани¤ или большие хирургические вмешательства. ѕри данных состо¤ни¤х может возникнуть необходимость прекратить терапию препаратом ?иабетонЃ MB и назначить инсулинотерапию.

” многих пациентов эффективность пероральных гипогликемических средств, в т.ч. гликлазида, имеет тенденцию снижатьс¤ после продолжительного периода лечени¤. Ётот эффект может быть обусловлен как прогрессированием заболевани¤, так и снижением терапевтического ответа на препарат. ?анный феномен известен как вторична¤ лекарственна¤ резистентность, которую необходимо отличать от первичной, при которой лекарственный препарат уже при первом назначении не дает ожидаемого клинического эффекта. ѕрежде чем диагностировать у больного вторичную лекарственную резистентность, необходимо оценить адекватность подбора дозы и соблюдение пациентом предписанной диеты.

Ћабораторные тесты

?л¤ оценки гликемического контрол¤ рекомендуетс¤ регул¤рное определение концентрации глюкозы крови натощак и гликозилированного гемоглобина HbA1c.  роме того, целесообразно регул¤рно проводить самоконтроль концентрации глюкозы крови.

ѕроизводные сульфонилмочевины могут вызвать гемолитическую анемию у пациентов с дефицитом глюкозо-6-фосфатдегидрогеназы. ѕоскольку гликлазид ¤вл¤етс¤ производным сульфонилмочевины, необходимо соблюдать осторожность при его назначении пациентам с дефицитом глюкозо-6-фосфатдегидрогеназы. —ледует оценить возможность назначени¤ гипогликемического препарата другой группы.

¬ли¤ние на способность к вождению автотранспорта и управлению механизмами

¬ св¤зи с возможным развитием гипогликемии при применении препарата ?иабетонЃ MB, пациенты должны быть осведомлены о симптомах гипогликемии и должны соблюдать осторожность во врем¤ управлени¤ транспортными средствами или выполнени¤ работы, требующей высокой скорости физических и психических реакций, особенно в начале терапии.

ѕередозировка

ѕри передозировке производными сульфонилмочевины может развитьс¤ гипогликеми¤.

ѕри возникновении умеренных симптомов гипогликемии без нарушени¤ сознани¤ или неврологических симптомов следует увеличить прием углеводов с пищей, уменьшить дозу препарата и/или изменить диету. ѕристальное медицинское наблюдение за состо¤нием пациента необходимо продолжать до тех пор, пока лечащий врач не будет уверен, что здоровью больного ничего не угрожает.

¬озможно развитие т¤желых гипогликемических состо¤ний, сопровождающихс¤ комой, судорогами или другими неврологическими нарушени¤ми. ѕри по¤влении таких симптомов необходимо оказание скорой медицинской помощи и немедленна¤ госпитализаци¤.

¬ случае гипогликемической комы или при подозрении на нее больному в/в струйно ввод¤т 50 мл 20-30% раствора декстрозы (глюкозы). «атем в/в капельно 10% раствор декстрозы дл¤ поддержани¤ концентрации глюкозы в крови выше 1 г/л. “щательный контроль уровн¤ глюкозы в крови и наблюдение за пациентом необходимо проводить как минимум в течение последующих 48 ч. «атем, в зависимости от состо¤ни¤ больного, следует решить вопрос о необходимости дальнейшего наблюдени¤.

?иализ неэффективен ввиду выраженного св¤зывани¤ гликлазида с белками плазмы.

Ћекарственное взаимодействие

ѕрепараты и вещества, способствующие увеличению риска развити¤ гипогликемии (усиливающие действие гликлазида)

—очетани¤ противопоказаны

ћиконазол (при системном введении и при использовании гел¤ на слизистой оболочке полости рта): усиливает гипогликемическое действие гликлазида (возможно развитие гипогликемии вплоть до состо¤ни¤ комы).

—очетани¤ не рекомендуютс¤

‘енилбутазон (системное введение): усиливает гипогликемический эффект производных сульфонилмочевины, т.к. вытесн¤ет их из св¤зи с белками плазмы и/или замедл¤ет их выведение из организма. ѕредпочтительнее использовать другой противовоспалительный препарат. ?сли прием фенилбутазона необходим, пациент должен быть предупрежден о необходимости гликемического контрол¤. ѕри необходимости дозу препарата ?иабетонЃ MB следует корректировать во врем¤ приема фенилбутазона и после его окончани¤.

Ётанол: усиливает гипогликемию, ингибиру¤ компенсаторные реакции, может способствовать развитию гипогликемической комы. Ќеобходимо отказатьс¤ от приема лекарственных средств, в состав которых входит этанол, и употреблени¤ алкогол¤.

—очетани¤, требующие предосторожностей

ѕрием гликлазида в комбинации с некоторыми лекарственными средствами (например, другими гипогликемическими средствами - инсулином, акарбозой, метформином, тиазолидиндионами, ингибиторами дипептидилпептидазы-4, агонистами vѕѕ-1); бета-адреноблокаторами, флуконазолом; ингибиторами јѕ‘ - каптоприлом, эналаприлом; блокаторами гистаминовых Ќ2-рецепторов; ингибиторами ћјќ; сульфаниламидами, кларитромицином, Ќѕ¬ѕ) сопровождаетс¤ усилением гипогликемического эффекта и риском гипогликемии.

ѕрепараты, способствующие увеличению содержани¤ глюкозы в крови (ослабл¤ющие действие гликлазида)

—очетани¤ не рекомендуютс¤

?аназол обладает диабетогенным эффектом. ¬ случае если прием данного препарата необходим, пациенту рекомендуетс¤ тщательный контроль глюкозы в крови. ѕри необходимости совместного приема препаратов, рекомендуетс¤ подбор дозы гипогликемического средства как во врем¤ приема даназола, так и после его отмены.

—очетани¤, требующие предосторожностей

’лорпромазин (нейролептик): в высоких дозах (более 100 мг/сут) увеличивает концентрацию глюкозы в крови, снижа¤ секрецию инсулина. –екомендуетс¤ тщательный гликемический контроль. ѕри необходимости совместного приема препаратов, рекомендуетс¤ подбор дозы гипогликемического средства как во врем¤ приема нейролептика, так и после его отмены.

ѕри одновременном применении v — (дл¤ системного и местного применени¤ - внутрисуставное, накожное, ректальное введение) и тетракозактид повышают концентрацию глюкозы в крови с возможным развитием кетоацидоза (снижение толерантности к углеводам). –екомендуетс¤ тщательный гликемический контроль, особенно в начале лечени¤. ѕри необходимости совместного приема препаратов может потребоватьс¤ коррекци¤ дозы гипогликемического средства как во врем¤ приема v —, так и после их отмены.

ѕри совместном применении бета2-адреномиметики (ритодрин, сальбутамол, тербуталин в/в введение) способствуют повышению концентрации глюкозы в крови.

Ќеобходимо удел¤ть особое внимание важности самосто¤тельного гликемического контрол¤. ѕри необходимости рекомендуетс¤ перевести пациента на инсулинотерапию.

—очетани¤, которые следует принимать во внимание

Sulfonylurea derivatives can enhance the effect of anticoagulants (eg, warfarin) when taken together. Dose adjustment of the anticoagulant may be required.