Diabetes MB - instructions for use, dose, side effects, contraindications

Active substance: gliclazide - 30.0 mg. Excipients: calcium hydrophosphate dihydrate 83.64 mg, hypromellose 100 cp 18.0 mg, hypromellose 4000 cp 16.0 mg, magnesium stearate 0.8 mg, maltodextrin 11.24 mg, silicon dioxide colloidal anhydrous 0.32 mg

Description:

White, biconvex oval tablets with engraving "DIA 30 "on one side and the company logo on the other.

Pharmacotherapeutic group:hypoglycemic agent for oral use of the second-generation sulfonylurea group

ATX: & nbsp

A.10.B.B.09 Gliclazide

Pharmacodynamics:

Gliclazide is a sulfonylurea derivative, a hypoglycemic preparation for ingestion; which differs from similar drugs by the presence of an N-containing heterocyclic ring with an endocyclic linkage.

Gliclazide reduces the concentration of blood glucose, stimulating the secretion of insulin by beta 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 glycazide has hemovascular effects.

Influence on secretion of insulin

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

Hemovascular effects

Gliklazid reduces the risk of thrombosis of small vessels, affecting the mechanisms that can cause 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 restoration of fibrinolytic activity of the vascular endothelium and increase in activity of tissue activator plasminogen.

Intensive glycemic control based on the use of Diabeton ® MV (HbA1c <6.5%) significantly reduces micro- and macrovascular complications of type 2 diabetes, in comparison with standard glycemic control (ADVANCE study).

The strategy of intensive glycemic control included the appointment of Diabeton® MB and an increase in its dose against a background (or instead of) of standard therapy beforeaddition to it of another hypoglycemic medicinal

agents (e.g., metformin, an inhibitor alpha-glucosidase,

a thiazolidinedione derivative or insulin). The average daily dose of Diabeton® 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 Diabeton® MB in the group of intensive glycemic control (mean follow-up of 4.8 years, average HbAlc level of 6.5%) compared to the standard control group (average HbAlc 7.3%), a significant decrease of 10% relative risk of 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 emergence of microalbum Nuria on 9%, macroalbuminuria by 30% and development of renal complications by 11%.

Benefits intensive glycemic control while taking Diabeton® MV did not depend on the benefits achieved against the background of antihypertensive therapy.

Pharmacokinetics:

After oral administration glycazide completely absorbed. The concentration of gliclazide in the plasma increases gradually, leaving the plateau after 6-12 hours. Individual variability is low.

Eating does not affect the degree of absorption of the drug. The relationship between the dose taken (up to 120 mg) and the area under the pharmacokinetic curve "concentration-time" is linear. About 95% of the drug binds to plasma proteins. Gliclazide is metabolized primarily in the liver and is excreted mainly by the kidneys: excretion is carried out in the form of metabolites, less than 1% is excreted by the kidneys in an unchanged form. There are no active metabolites in the plasma. The half-life of gliclazide averages from 12 to 20 hours. The volume of distribution is about 30 liters.

In elderly people, there are no significant changes in pharmacokinetic parameters.

Taking Diabeton® MV 30 mg once daily provides maintenance of an effective concentration of glycazide in the blood plasma for more than 24 hours.

Indications:Diabetes mellitus type 2 with insufficient effectiveness of diet therapy, exercise and weight loss.Preventing complications of diabetes mellitus: reducing the risk of microvascular (nephropathy, retinopathy) and macrovascular complications (myocardial infarction, stroke) in patients with type 2 diabetes by intensive glycemic control.

Contraindications:

hypersensitivity to glycazide, other derivatives of sulfonylurea, sulfonamides or to the auxiliary substances included in the preparation;
diabetes mellitus type 1;
Diabetic ketoacidosis, diabetic precoma, diabetic coma; severe renal or hepatic insufficiency (in these cases it is recommended to use insulin)
concomitant therapy with miconazole (see section "Interaction with other drugs");
pregnancy and the period of breastfeeding (see the section "Pregnancy and the period of lactation");
age to 18 years.

It is not recommended to use in combination with phenylbutazone and danazol (see section "Interaction with other drugs").

Carefully:Elderly age, irregular and / or unbalanced diet, insufficiency of glucose-6-phosphate dehydrogenase, severe diseases of the cardiovascular system,hypothyroidism, adrenal or pituitary insufficiency, renal and / or hepatic insufficiency, long-term therapy with glucocorticosteroids (GCS), alcoholism.

Pregnancy and lactation:

Pregnancy

Experience with glycazide during pregnancy is absent. Data on the use of other derivatives of sulfonylurea during pregnancy are limited.

In studies on laboratory animals teratogenic effects of glycazide were not revealed.

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

Oral hypoglycemic drugs during pregnancy are not applied. Insulin is the drug of choice for the therapy 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 if the pregnancy has occurred while taking the drug.

Lactation

Given the lack of data on the intake of gliclazide in breast milk and the risk of hypoglycemia in a breastfeeding baby, it is contraindicated during therapy with this drug.

Dosing and Administration:

PREPARATION IS INTENDED FOR ADULT TREATMENT.

The recommended dose of the drug (1 to 4 tablets, 30 to 120 mg) should be taken orally, 1 time per day, preferably during breakfast. It is recommended to swallow the whole tablet without chewing or grinding.

If you skip one or more doses of the drug, you can not take a higher dose to 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 glycosylated hemoglobin (HbAlc).

Initial dose

The initial recommended dose (including for elderly patients,> 65 years) is 30 mg per day.

In case of adequate control, the drug in this dose can be used for maintenance therapy. With inadequate glycemic control, the daily dose of the drug can be sequentially increased to 60.90 or 120 mg.

Increase in the dose is possible not earlier than after 1 month of therapy with the drug in the previously prescribed dose. Exception is made by patients, in whom the blood glucose concentration did not decrease after 2 weeks of therapy.In such cases, the dose of the drug may be increased 2 weeks after the start of the treatment.

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

Transition from the administration of the preparation Diabetes ® tablets 80 mg to the preparation Diabeton ® MV tablets with a modified release of 30 mg.

1 tablet of Diabetes 80 mg can be replaced with 1 modified-release tablet of Diabeton® MB 30 mg. When transferring patients from Diabetes 80 mg to Diabeton® MV, careful glycemic control is recommended.

Transition from taking another hypoglycemic drug

funds for Diabeton® MB tablets with modified

release of 30 mg.

The preparation Diabeteston® MV modified-release tablet 30 mg can be used instead of another hypoglycemic drug for ingestion. When transferring to Diabeton® MV patients receiving other hypoglycemic drugs for ingestion, their dose and half-life period should be considered. As a rule, a transition period is not required. The initial dose should be 30 mg and then should be titrated depending on the concentration of blood glucose.When Diabeton® MB is replaced with sulfonylureas with a long half-life 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 Diabeton® MB is also 30 mg and, if necessary, can be further increased as described above.

Combination with another hypoglycemic medicinal

means of

Diabeton® MB can be used in combination with biguanides, alpha-glucosidase inhibitors or insulin.

With inadequate glycemic control, additional insulin therapy should be prescribed with careful medical supervision.

Elderly patients

Correction of dose, drug, for, patients over 65 years is not required.

Patients with renal insufficiency

The results of clinical studies showed that correction of the dose of the drug in patients with mild and moderate renal insufficiency is not required. It is recommended that a thorough medical check is carried out.

Patients at risk of developing hypoglycemia

In patients at risk for development, hypoglycemia (inadequate or unbalanced nutrition, severe or poorly compensated endocrine disorders, pituitary and adrenal insufficiency, hypothyroidism, elimination of glucocorticosteroids (GCS) after long-term use and / or intake in high doses, severe cardiovascular disease, cardiovascular system, severe ischemic heart disease, severe atherosclerosis of the carotid arteries, widespread atherosclerosis),

it is recommended to use the minimum dose (30 mg) of Diabeton® MB.

Prevention of complications of diabetes mellitus

To achieve intensive glycemic control, you can gradually increase the dose of Diabeton® MV to 120 mg / day in addition to diet and exercise until the target level of HbAlc is reached. It should be remembered about the risk of developing hypoglycemia. In addition, other hypoglycemic drugs may be added to therapy, for example, metformin, an alpha-glucosidase inhibitor, derivative

thiazolidinedione or insulin.

Children and teenagers under the age of 18.

Data on the efficacy and safety of the drug in children and adolescents under the age of 18 are not available.

Side effects:

Taking into account the experience of the use of gliclazide and other derivatives of sulfonylureas, one should remember about the possibility of developing the following side effects.

Hypoglycaemia

Like other drugs of the sulfonylurea group, Diabeton® CF can cause hypoglycemia in the event of an irregular intake of food and especially if the meal is missed. Possible symptoms of hypoglycemia: headache, a strong sense of hunger, nausea, vomiting, increased fatigue, violation of sleep, irritability, agitation, decreased concentration of attention, delayed reaction, depression, confusion, impaired vision and speech, aphasia, tremor, paresis, violation of perception,

dizziness, weakness, convulsions, bradycardia, delirium, respiratory depression, drowsiness, loss of consciousness with possible development of coma, up to a lethal outcome. Andrnergic reactions can also be noted: increased sweating, "sticky" skin, anxiety, tachycardia, increased blood pressure, palpitations, arrhythmia and angina.

As a rule, the symptoms of hypoglycemia are stopped by the intake of carbohydrates (sugar). The intake of sugar substitutes is ineffective. On the background other derivatives of sulfonylureas, there were relapses of hypoglycemia after its successful cupping.

With severe or prolonged hypoglycemia, emergency medical care is indicated, possibly with hospitalization, even if there is an effect of taking carbohydrates.

Other side effects

- On the part of the gastrointestinal tract: abdominal pain, nausea, vomiting, diarrhea, constipation. Taking the drug during breakfast allows you to avoid these symptoms or minimize them.

Less common are the following side effects:

From the skin and subcutaneous tissue: rash, itching, urticaria, erythema, maculopapular rash, bullous rash.
From the blood and lymphatic system: hematological disorders (anemia, leukopenia, thrombocytopenia, granulocytopenia) develop rarely. As a rule, these phenomena are reversible in the event of discontinuation of therapy.
From the liver and bile ducts: increased activity of "hepatic" enzymes (aspartate aminotransferase (ACT), alanine aminotransferase (ALT), alkaline phosphatase), hepatitis (isolated cases). When cholestatic jaundice occurs, therapy should be discontinued.

The following side effects are usually reversible in the event of discontinuation of therapy.

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

Side effects. inherent derivative sulfonylureas: against the background of taking other sulfonylurea derivatives, the following side effects were noted: erythrocytopenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis and gynonagraemia. There was an increase in the activity of "liver" enzymes, a violation of liver function (for example, with the development of cholestasis and jaundice) and hepatitis, manifestations decreased with time after drug withdrawal sulfonylureas, but in some cases lead to life-threatening hepatic insufficiency.

Side effects noted during clinical trials

In the study ADVANCE There was a slight difference in the incidence of various serious adverse events between the two groups of patients. No new safety data was received. A small number of patients experienced severe hypoglycemia, but the overall incidence of hypoglycemia was low.The frequency of hypoglycemia in the group of intensive glycemic control was higher than in the group of standard glycemic control. Most episodes of hypoglycemia in the group of intensive glycemic control were noted against the background of concomitant insulin therapy.

Overdose:

When an overdose of sulfonylurea derivatives may develop hypoglycemia.

If mild symptoms of hypoglycemia occur without a loss of consciousness or neurological symptoms, you should increase the intake of carbohydrates with food, reduce the dose of the drug and / or change the diet. Close medical surveillance of the patient's condition should continue until there is no certainty that his health is not threatened.

Possible development of severe hypoglycemic conditions, accompanied by coma, seizures or other neurological disorders. If such symptoms appear, emergency medical care and immediate hospitalization are necessary.

In the case of hypoglycemic coma or if it is suspected, 50 ml of 20-30% dextrose solution (glucose) is injected intravenously.Then 10% dextrose solution is administered intravenously dropwise to maintain a glucose concentration in the blood above 1 g / l. Careful monitoring of blood glucose and monitoring of the patient should be carried out for at least 48 consecutive hours. After this period of time, depending on the patient's condition, the attending physician decides on the need for further monitoring.

Dialysis is ineffective due to the expressed binding of glycazide to plasma proteins.

Interaction:

1) Drugs that promote increase risk development of hypoglycemia:

(enhancing the action of gliclazide)

Contraindications

Miconazole (with systemic administration and with the use of gel on the mucosa of the oral cavity): increases the hypoglycemic effect of glycazide (hypoglycemia may develop up to the state of coma).

Unrecommended combinations

Phenylbutazone (systemic administration): enhances the hypoglycemic effect of sulfonylurea derivatives (displaces them from the bond with plasma proteins and / or slows their elimination from the body).

It is more preferable to use another anti-inflammatory drug.If the reception of phenylbutazone is necessary, the patient should be warned about the need for glycemic control. If necessary, the dose of Diabeton® CF should be adjusted during and after phenylbutazone administration.

Ethanol: increases hypoglycemia, inhibiting compensatory reactions, can promote the development of hypoglycemic coma. It is necessary to refuse from taking medicines, which include ethanol and drinking alcohol.

Combinations that require precautions

Admission gliclazide in combination with certain drugs (for example, other hypoglycemic agents - insulin, alpha-glucosidase inhibitor, biguanides, beta-adrenoblockers, fluconazole;

inhibitors of the angiotensin-converting enzyme - captopril, enalapril; blockers of H2-histamine receptors; monoamine oxidase inhibitors;

sulfonamides; clarithromycin and non-steroidal anti-inflammatory drugs) is accompanied by increased hypoglycemic effect and risk of hypoglycemia.

2) Drugs that increase blood glucose: (weakening the action of gliclazide)

Unrecommended combinations

- Danazol: has a diabetic effect. In the event that taking this medication is necessary, the patient is recommended careful glycemic control. If it is necessary to take medications together, it is recommended that the dosage of the hypoglycemic agent be selected at the time of taking danazol and after its withdrawal.

Combinations that require precautions

Chlorpromazine (antipsychotic); in high doses (more than 100 mg per day) increases the concentration of glucose in the blood, reducing the secretion of insulin. Careful glycemic control is recommended. If it is necessary to take drugs together, it is recommended that a dose of a hypoglycemic agent be chosen, both during the administration of the neuroleptic and after its withdrawal.

GCS (systemic and topical application: intraarticular, dermal, rectal administration): increase the concentration of blood glucose with the possible development of ketoacidosis (decrease in tolerance to carbohydrates). Careful glycemic control is recommended, especially at the beginning of treatment. If it is necessary to take medications together, it may be necessary to correct the dose of the hypoglycemic agent both during the administration of the GCS and after their withdrawal.
Ritodrin, salbutamol, terbutaline (intravenous administration): beta-2 adrenomimetics contribute to increased blood glucose concentrations.

It is necessary to pay special attention to the importance of independent glycemic control. If necessary, it is recommended to transfer the patient to insulinotherapy.

3) Combinations that must be taken into account

- Anticoagulants (for example, warfarin) Derivatives of sulfonylureas can enhance the effect of anticoagulants when taken together. You may need to adjust the dose of anticoagulant.

Special instructions:

Hypoglycaemia

When taking sulfonylurea derivatives, including glycazide, hypoglycemia may develop, in some cases in severe and prolonged form, requiring hospitalization and intravenous administration of a dextrose solution for several days (see the "Side effect" section).

The drug can be prescribed only to those patients, whose meals are regular and includes breakfast. It is very important to maintain sufficient intake of carbohydrates with food, since the risk of developing hypoglycemia increases with irregular or inadequate nutrition, as well as when consuming food poor in carbohydrates.Hypoglycemia often develops with a low-calorie diet, after prolonged or vigorous exercise, after taking ethanol or ethanol-containing medicines or when taking several hypoglycemic drugs at the same time.

Typically, the symptoms of hypoglycemia go away after eating a meal rich in carbohydrates (such as sugar). It should be borne in mind that the use of sugar substitutes does not help to eliminate hypoglycemic symptoms. The experience of using other sulfonylurea derivatives suggests that hypoglycemia can recur despite effective initial arrest of this condition. In the event that hypoglycemic symptoms have a pronounced character or are prolonged, even in the case of temporary improvement after 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 dosing regimens is necessary, as well as providing the patient with complete information about the treatment.

An increased risk of hypoglycemia can occur in the following cases:

refusal or inability of the patient (especially the elderly) to follow the prescriptions of the doctor and monitor their condition;
insufficient and irregular meals, skipping meals, fasting and changing diets;
an imbalance between exercise and the amount of carbohydrates taken;
kidney failure;
severe hepatic impairment;
overdose of Diabeton® MV;
some endocrine disorders: thyroid disease, pituitary and adrenal insufficiency;
simultaneous administration of certain medications (see section "Interaction with other drugs").

Clinical manifestations of hypoglycemia can be masked when taking beta-blockers, clonidine, reserpine, guanetidine.

Renal and hepatic impairment

In patients with hepatic and / or severe renal insufficiency, the pharmacokinetic and / or pharmacodynamic properties of the glycazide can vary. The condition of hypoglycemia, developing in such patients, can be quite long, in such cases, immediate appropriate therapy is necessary.

Information for patients

It is necessary to inform the patient, as well as members of his family about the risk of developing hypoglycemia, its symptoms and conditions conducive to its development. The patient should be informed of the potential risks and benefits of the proposed treatment.

The patient needs to explain the importance of dieting, the need for regular exercise and control of blood glucose.

Insufficient blood glucose control

Glycemic control in patients receiving therapy with hypoglycemic agents may be weakened in the following cases: large surgical interventions and trauma, extensive burns, infectious diseases with febrile syndrome. In these conditions, it may be necessary to discontinue therapy with Diabeton® MV and prescribe insulin therapy.

In some patients, the effectiveness of oral hypoglycemic agents, including glyclazvoda, tends to decrease after a long treatment period. This effect can be due to both the progression of the disease and the decrease in the therapeutic response to the drug.This effect is known as secondary drug resistance, which must be distinguished from the primary, in which the drug already at the first appointment does not give the expected clinical effect. Before diagnosing the patient for secondary drug resistance, it is necessary to evaluate the adequacy of dose selection and adherence to prescribed diet.

Laboratory Tests

To assess the glycemic control, it is recommended that the fasting blood glucose concentration and the level of glycosylated hemoglobin HbAlc. In addition, it is advisable to regularly conduct self-monitoring of blood glucose concentration.

Derivatives of sulfonylureas can cause hemolytic anemia in patients with deficiency of glucose-6-phosphate dehydrogenase. Because the glycazide is a derivative of sulfonylureas, caution should be exercised when it is administered to patients with deficiency of glucose-6-phosphate dehydrogenase. One should evaluate the possibility of prescribing a hypoglycemic drug of another group.

Effect on the ability to drive transp. cf. and fur:

Patients should be aware of the symptoms of hypoglycemia and should be careful while driving or doing work that requires a high rate of physical and mental reactions, especially at the beginning of therapy.

Form release / dosage:

Modified release tablets 30 mg.

Packaging:

30 tablets per blister (PVC / Al), 1 or 2 blisters with instructions for medical use in a cardboard box.

When packaging (packaging) in the Russian company LLC "Serdiks": 30 tablets per blister (PVC / Al), 2 blisters with instructions for use in a cardboard package.

Storage conditions:

Special storage conditions are not required.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N011940 / 01

Date of registration:03.11.2009 / 25.02.2013

The owner of the registration certificate:Servier LaboratoriesServier Laboratories France

Manufacturer: & nbsp

Laboratories Servier France

Representation: & nbspServier Laboratories Servier Laboratories France

Information update date: & nbsp15.01.2016

Illustrated instructions

Instructions

Diabeton® MB (Diabeton® MR)