Диабетон® MV

General characteristics. Structure:

Active agent: gliclazide – 60,0 mg.
Excipients: lactoses monohydrate of 71,36 mg, maltodextrin of 22,0 mg, gipromelloza 100 Wednesday of 160,0 mg, magnesium stearate of 1,6 mg, silicon dioxide of colloid anhydrous 5,04 mg.
Description
White, biconvex, oval tablets with a notch and an engraving of "DIA" "60" on both parties.

Pharmacological properties:

Pharmacodynamics. Gliclazide is derivative sulphonylurea, hypoglycemic drug for intake which differs from similar drugs in existence of N-of the containing heterocyclic ring with endocyclic communication. Gliclazide reduces concentration of glucose of blood, stimulating insulin secretion with β-cells of islets of Langerhans. Increase in concentration of postprandialny insulin and S-peptide remains after 2 years of therapy. In addition to influence on carbohydrate metabolism gliclazide renders haemo vascular effects.
Influence on insulin secretion
At a diabetes mellitus 2 types drug recovers early peak of secretion of insulin in response to intake of glucose and strengthens the second phase of secretion of insulin. Substantial increase of secretion of insulin is observed in response to the stimulation caused meal or administration of glucose.
Haemo vascular effects
Gliclazide reduces risk of thromboses of small vessels, influencing mechanisms which can cause development of complications at a diabetes mellitus: partial inhibition of aggregation and adhesion of thrombocytes and decrease in concentration of factors of activation of thrombocytes (beta thromboglobulin, B2 thromboxane), and also on recovery of fibrinolitic activity of a vascular endothelium and increase in activity of a fabric plasminogen activator.
The intensive glycemic control based on use of Diabetona® of MV (HbA1c <6,5%) authentically reduces micro and makrososudsity complications of a diabetes mellitus 2 types, in comparison with standard glycemic control (research ADVANCE). The strategy of intensive glycemic control provided purpose of the drug Diabeton® MV and increase in its dose against the background of (or instead of) standard therapy before addition to it of other hypoglycemic medicine (for example, Metforminum, inhibitor of alpha glucosidase, a derivative tiazolidindion or insulin). The average daily dose of the drug Diabeton® MV at patients in group of intensive control made 103 mg, the maximum daily dose made 120 mg.
Against the background of use of the drug Diabeton® MV in group of intensive glycemic control (average duration of observation of 4,8 years, the average level of HbA1c 6,5%) in comparison with group of standard control (the average level of HbA1c 7,3%) significant decrease by 10% of relative risk of the combined frequency macro - and microvascular complications is shown
Advantage was reached due to significant decrease relative riska:osnovny microvascular complications for 14%, emergence and progressing of a nephropathy for 21%, emergence of a microalbuminuria for 9%, macroalbuminurias for 30% and development of renal complications for 11%. Advantages of intensive glycemic control against the background of administration of drug of Diabeton® of MV did not depend on the advantages reached against the background of hypotensive therapy.

Pharmacokinetics. After intake gliclazide is completely absorbed. Concentration of gliclazide increases in a blood plasma gradually, coming to the plateau in 6-12 hours. Individual variability low. Meal does not influence extent of absorption of gliclazide. The interrelation between the accepted dose (to 120 mg) and the area under a pharmacokinetic curve "concentration – time" is linear.
About 95% of gliclazide contact proteins of plasma. Gliclazide is metabolized preferential in a liver and removed, mainly, by kidneys: removal is carried out in the form of metabolites, less than 1% are removed by kidneys in an invariable look. Active metabolites in plasma are absent. The elimination half-life of gliclazide averages from 12 to 20 hours. Distribution volume - about 30 l. At elderly people essential changes of pharmacokinetic parameters are not observed. Administration of drug of Diabeton® of MV in a dose of 60 mg provides maintenance of effective concentration of gliclazide in a blood plasma more than 24 hours once a day.

Indications to use:

• A diabetes mellitus 2 types at insufficient efficiency of a dietotherapy, exercise stresses and decrease in body weight.
• Prevention of complications of a diabetes mellitus: decrease in risk microvascular (a nephropathy, a retinopathy) and macrovascular complications (a myocardial infarction, a stroke) at patients with a diabetes mellitus 2 types by intensive glycemic control.

Route of administration and doses:

It is necessary to accept the recommended dose of drug inside, 1 time a day, it is preferable during a breakfast. The daily dose can make 30 - 120 mg (1/2 – 2 tablets) in one step. It is recommended to swallow a tablet or a half of a tablet entirely, without chewing and without crushing. At the admission of one or more administrations of drug it is impossible to accept higher dose in the following reception, the passed dose should be accepted next day. As well as concerning other hypoglycemic medicines, the drug dose in each case needs to be selected individually, depending on concentration of glucose of blood and HbA1c.
Initial dose
The initial recommended dose (including for patients of advanced age, ≥ 65 years) – 30 mg a day (1/2 tablets). In case of adequate control drug in this dose can be used for a maintenance therapy. At inadequate glycemic control the daily dose of drug can be consistently increased to 60, 90 or 120 mg. Increase in a dose is possible not earlier than in 1 month of therapy by drug in earlier appointed dose. The exception is made by patients at whom concentration of glucose of blood did not decrease after 2 weeks of therapy. In such cases the dose of drug can be increased in 2 weeks after the beginning of reception. The maximum recommended daily dose of drug makes 120 mg. 1 tablet of the drug Diabeton® MV of a tablet with the modified release of 60 mg is equivalent to 2 tablets Diabeton® MV of a tablet with the modified release of 30 mg. Existence of a notch on tablets of 60 mg allows to divide a tablet and to accept a daily dose as 30 mg (1/2 tablets of 60 mg), and in need of 90 mg (1 and 1/2 tablets of 60 mg).
Transition from administration of drug of Diabeton® of a tablet of 80 mg to the tablet drug Diabeton® MV with the modified release of 60 mg 1 tablet of the drug Диабетон® 80 of mg can be replaced 1/2 tablets with the modified release of Diabeton® of MV of 60 mg. At transfer of patients from the mg drug Диабетон® 80 on the drug Diabeton® MV careful glycemic control is recommended. Transition from reception of other hypoglycemic medicine to the tablet drug Diabeton® MV with the modified release of 60 mg the tablet Drug Diabeton® MV with the modified release of 60 mg can be applied instead of other hypoglycemic medicine to intake. At transfer into Diabeton® of MV of the patients receiving other hypoglycemic drugs for intake it is necessary to consider their dose and an elimination half-life. As a rule, the transition period at the same time is not required. The initial dose has to make 30 mg and then has to be titrated depending on concentration of glucose of blood. When replacing with the drug Diabeton® MV of derivatives of sulphonylurea with a long elimination half-life for avoidance of the hypoglycemia caused by the additive effect of two hypoglycemic means it is possible to stop their reception for several days. The initial dose of the drug Diabeton® MV at the same time also makes 30 mg (1/2 tablets of 60 mg) and if necessary can be raised further as it is described above. The combined method with other MV hypoglycemic Diabeton® medicine can be used in combination with biguanidina, inhibitors of alpha glucosidase or insulin. At inadequate glycemic control it is necessary to appoint in addition an insulin therapy with carrying out careful medical control.
Patients of advanced age
Dose adjustments of drug for patients are more senior than 65 years it is not required.
Patients with a renal failure
Results of clinical trials showed that dose adjustment of drug with a renal failure of easy and moderate degree of manifestation is not required from patients. Carrying out careful medical control is recommended.
Patients with risk of development of a hypoglycemia
At the patients belonging to risk group of development of a hypoglycemia (insufficient or unbalanced food; the heavy or badly compensated endocrine frustration – pituitary and adrenal insufficiency, a hypothyroidism; cancellation of glucocorticosteroids (GKS) after their long reception and/or reception in high doses; a serious illness of cardiovascular system – heavy coronary heart disease, the heavy atherosclerosis of carotid arteries widespread
atherosclerosis), is recommended to use the minimum dose (30 mg) of the drug Diabeton® MV.
Prevention of complications of a diabetes mellitus
For achievement of intensive glycemic control it is possible to increase gradually a dose of the drug Diabeton® MV to 120 mg/days in addition to a diet and physical exercises before achievement of the target objective of HbA1c. It is necessary to remember risk of development of a hypoglycemia. Besides, it is possible to add other hypoglycemic medicines to therapy, for example, Metforminum, a nigibitor of alpha glucosidase, derivative a tiazolidindiona or insulin.
Children and teenagers aged up to 18 years.
Data on efficiency and safety of use of drug for children and teenagers aged up to 18 years are absent.

Features of use:

Hypoglycemia
At reception of derivatives of sulphonylurea including gliclazide, the hypoglycemia, in certain cases – in the severe and long form demanding hospitalization and intravenous administration of solution of a dextrose within several days can develop (see the section "Side effect"). Drug can be appointed only to those patients whose food is regular and
includes a breakfast. It is very important to support sufficient intake of carbohydrates with food as the risk of development of a hypoglycemia increases at irregular or a hyponutrient, and also at consumption of the food poor in carbohydrates. The hypoglycemia develops at a low-calorie diet, after long or vigorous physical exercises, after alcohol intake or at reception of several hypoglycemic medicines at the same time more often. As a rule, symptoms of a hypoglycemia pass after meal, carbohydrate-rich (for example, sugar). It must be kept in mind that reception of sweeteners does not promote elimination of hypoglycemic symptoms. Experience of use of other derivatives of sulphonylurea demonstrates to what the hypoglycemia can recur despite effective initial stopping of this state. If hypoglycemic symptoms have pronounced character or are long, even in case of temporary improvement of a state after meal, carbohydrate-rich, rendering emergency medical service is necessary, up to hospitalization. In order to avoid development of a hypoglycemia careful individual selection of drugs and the mode of dosing, and also providing the complete information to the patient about the carried-out treatment is necessary. The increased risk of development of a hypoglycemia can be noted in the following cases:
- refusal or inability of the patient (especially advanced age) to follow appointments of the doctor and to control the state;
- insufficient and irregular food, admission of meals, starvation and change of a diet;
- an imbalance between an exercise stress and amount of the accepted carbohydrates;
- renal failure;
- heavy liver failure;
- overdose of the drug Diabeton® MV;
- some endocrine frustration: diseases of a thyroid gland, pituitary and adrenal insufficiency;
- a concomitant use of some medicines (see the section "Interaction with Other Medicines").
Renal and liver failure
At patients with a liver and/or heavy renal failure pharmacokinetic and/or pharmakodinamichesky properties of gliclazide can change. The condition of a hypoglycemia developing at such patients can be rather long, in such cases immediate performing the corresponding therapy is necessary.
Information for patients
It is necessary to inform the patient, and also members of his family on the risk of development of a hypoglycemia, its symptoms and conditions promoting its development. The patient needs to be informed on potential risk and advantages of the offered treatment. The patient needs to explain importance of observance of a diet, need of regular physical exercises and control of concentration of glucose of blood.
Insufficient glycemic control
Glycemic control at the patients receiving therapy by hypoglycemic means can be weakened in the following cases: fever, injuries, infectious diseases or big surgical interventions. At these states there can be a need to stop therapy by the drug Diabeton® MV and to appoint an insulin therapy. Many patients have an efficiency of peroral hypoglycemic means, including gliclazide, tends to decrease after the long period of treatment. This effect can be caused both by progressing of a disease, and decrease in the therapeutic answer to drug. This phenomenon is known as secondary medicinal resistance which needs to be distinguished from primary, at which medicine already at the first appointment does not give the expected clinical effect. Before diagnosing secondary medicinal resistance for the patient, it is necessary to estimate adequacy of selection of a dose and observance by the patient of the ordered diet.
Laboratory tests
For assessment of glycemic control regular definition of concentration of glucose of blood on an empty stomach and glikozilirovanny HbA1c hemoglobin is recommended. Besides, reasonablly regularly to carry out self-checking of concentration of glucose of blood.
Derivatives of sulphonylurea can cause hemolitic anemia in patients with deficit glyukozo-6-fosfatdegidrogenazy. As gliclazide is derivative sulphonylurea, it is necessary to be careful at its appointment to patients with deficit glyukozo-6-fosfatdegidrogenazy. It is necessary to estimate a possibility of purpose of hypoglycemic drug another
groups.
INFLUENCE ON ABILITY OF DRIVING OF THE CAR AND PERFORMANCE OF WORK, THE MENTAL AND PHYSICAL REACTIONS DEMANDING HIGH SPEED
Patients have to be informed on symptoms of a hypoglycemia and have to
to be careful during driving or performance of the work demanding the high speed of physical and mental reactions, especially at the beginning of therapy.

Side effects:

Considering experience of use of gliclazide and other derivatives of sulphonylurea, it is necessary to remember a possibility of development of the following side effects.
Hypoglycemia
As well as other drugs of group of sulphonylurea, Diabeton® of MV can cause a hypoglycemia in case of irregular meal and especially if meal is missed. Possible symptoms of a hypoglycemia: a headache, strong feeling of hunger, nausea, vomiting, increased fatigue, a sleep disorder, irritability, excitement, decrease in concentration of attention, the slowed-down reaction, a depression, confusion of consciousness, a vision disorder and speeches, aphasia, a tremor, paresis, perception disturbance, dizziness, weakness, spasms, bradycardia, nonsense, breath disturbance, drowsiness, a loss of consciousness with possible development of a coma, up to a lethal outcome. Also andrenergichesky reactions can be noted: the increased sweating, "sticky" skin, concern, tachycardia, increase in arterial pressure, a heart consciousness, arrhythmia and stenocardia. As a rule, symptoms of a hypoglycemia are stopped by reception of carbohydrates (sugar). Reception of sweeteners is inefficient. Against the background of other derivatives of sulphonylurea a hypoglycemia recurrence after its successful stopping was celebrated.
At a heavy or long hypoglycemia emergency medical service, perhaps, with hospitalization, even with effect of reception of carbohydrates is shown.
Other side effects
• From digestive tract: abdominal pain, nausea, vomiting, diarrhea, locks. Administration of drug during a breakfast allows to avoid these symptoms or to minimize them.
The following side effects are less often noted:
• From skin and hypodermic cellulose: rash, itch, urticaria, erythema, makulopapullezny rash, violent rash.
• From circulatory and lymphatic system: hematologic disturbances (anemia, a leukopenia, thrombocytopenia, a granulocytopenia) develop seldom. As a rule, these phenomena are reversible in case of the therapy termination.
• From a liver and biliary tract: increase in activity of "hepatic" enzymes (aspartate aminotransferase (nuclear heating plant), alaninaminotranspherase (ALT), alkaline phosphatase), hepatitis (isolated cases). At emergence of cholestatic jaundice it is necessary to stop therapy.
The following side effects are usually reversible in case of the therapy termination.
• From an organ of sight: there can be passing visual frustration caused by change of concentration of glucose of blood, especially at the beginning of therapy.
• Side effects inherent in sulphonylurea derivatives: as well as against the background of reception of other derivatives of sulphonylurea the following side effects were noted: erythrocytopenia, agranulocytosis, hemolitic anemia, pancytopenia, allergic vasculitis, hyponatremia. Increase in activity of "hepatic" enzymes, an abnormal liver function was noted (for example, with
development of a cholestasia and jaundice) and hepatitis; manifestations decreased after cancellation of drugs of sulphonylurea over time, but in some cases led to a zhizneugrozhayushchy liver failure. The side effects noted during clinical trials. In the research ADVANCE the insignificant difference of frequency of various serious undesirable phenomena between two groups of patients was noted. New data on safety were not received. At a small number of patients the heavy hypoglycemia was noted, however the general frequency of a hypoglycemia was low. Hypoglycemia frequency in group of intensive glycemic control was higher, than in group of standard glycemic control. The majority of episodes of a hypoglycemia in group of intensive glycemic control was noted against the background of the accompanying insulin therapy.

Interaction with other medicines:

1) The drugs promoting increase in risk of development of a hypoglycemia: (strengthening effect of gliclazide)
Contraindicated combinations
- Miconazolum (at system introduction and when using gel on a mucous membrane of an oral cavity): strengthens hypoglycemic effect of gliclazide (possibly development of a hypoglycemia up to coma).
Not recommended combinations
- Phenylbutazone (system introduction): strengthens hypoglycemic effect of derivatives of sulphonylurea (forces out them from communication with proteins of plasma and/or slows down their removal from an organism).
It is more preferable to use other antiinflammatory drug. If reception of phenylbutazone is necessary, the patient has to be warned about need of glycemic control. If necessary the dose of the drug Diabeton® MV should be adjusted during reception of phenylbutazone and after its termination.
- Ethanol: strengthens a hypoglycemia, inhibiting compensatory reactions, can promote development of a hypoglycemic coma. It is necessary to refuse reception of medicines which part ethanol and alcohol intake is.
The combinations demanding precautions
Reception of gliclazide in a combination with some medicines (for example, other hypoglycemic means – insulin, alpha glucosidase inhibitor, guanyl guanidines; beta adrenoblockers, flukonazoly; inhibitors of an angiotensin-converting enzyme – captopril, enalapril; blockers of H2-histamine receptors; monoaminooxidase inhibitors; streptocides; klaritromitsiny and non-steroidal anti-inflammatory drugs) is followed by strengthening of hypoglycemic effect and risk of a hypoglycemia.
2) The drugs promoting increase in content of glucose in blood: (weakening effect of gliclazide)
Not recommended combinations
- Danazol: has diabetogenic effect. If reception of this drug is necessary, careful glycemic control is recommended to the patient. In need of joint administration of drugs, selection of a dose of hypoglycemic means is recommended both during reception of a danazol, and after its cancellation.
The combinations demanding precautions
- Chlorpromazinum (neuroleptic): in high doses (more than 100 mg a day) increases concentration of glucose in blood, reducing insulin secretion.
Careful glycemic control is recommended. In need of joint administration of drugs, selection of a dose of hypoglycemic means is recommended, both during reception of a neuroleptic, and after its cancellation.
- GKS (system and topical administration: intra joint, skin, rectal administration): increase concentration of glucose of blood with possible development of ketoacidosis (decrease in tolerance to carbohydrates). Careful glycemic control, especially in an initiation of treatment is recommended. In need of joint administration of drugs, dose adjustment of hypoglycemic means can be required both during reception of GKS, and after their cancellation.
- Ritodrinum, salbutamol, тербуталин (intravenous administration): beta-2 adrenomimetik promote increase in concentration of glucose of blood.
It is necessary to pay special attention to importance of independent glycemic control. If necessary, it is recommended to transfer the patient to an insulin therapy.
3) Combinations which have to be taken into account
- Anticoagulants (for example, warfarin)
Derivatives of sulphonylurea can strengthen effect of anticoagulants at joint reception. Anticoagulant dose adjustment can be required.

Contraindications:

- hypersensitivity to gliclazide, other derivatives of sulphonylurea, streptocides or to the excipients which are a part of drug
- diabetes mellitus of type 1;
- diabetic ketoacidosis, diabetic prekoma, diabetic coma;
- a heavy renal or liver failure (in these cases it is recommended to apply insulin);
- reception of Miconazolum (see the section "Interaction with Other Medicines");
- pregnancy and the period of feeding by a breast (see the section "Pregnancy and Period of Feeding by a Breast");
- age up to 18 years.
Because lactose is a part of drug, Diabeton® of MV is not recommended to patients with an inborn lactose intolerance, a galactosemia, glyukozo-galaktozny malabsorption.
It is not recommended to apply in a combination with phenylbutazone or danazoly (see the section "Interaction with Other Medicines").
With care
Advanced age, irregular and/or unbalanced food, insufficiency glyukozo-6-fosfatdegidrogenazy, serious illness of cardiovascular system, hypothyroidism, adrenal or pituitary insufficiency, renal and/or liver failure, long therapy by glucocorticosteroids (GKS), alcoholism.
PREGNANCY AND PERIOD OF FEEDING BY THE BREAST
Pregnancy
Experience of use of gliclazide during pregnancy is absent. Data on use of other derivatives of sulphonylurea during pregnancy are limited. In researches on laboratory animals teratogenic effects of gliclazide were not revealed. Optimum control (performing the corresponding therapy) of a diabetes mellitus is necessary for decrease in risk of development of inborn defects. Peroral hypoglycemic drugs during pregnancy are not used. Insulin is choice drug for therapy of a diabetes mellitus at pregnant women. It is recommended to replace reception of peroral hypoglycemic drugs with an insulin therapy as in case of the planned pregnancy and if pregnancy occurred against the background of administration of drug.
Feeding by a breast
In view of lack of data on intake of gliclazide in breast milk and risk of development of a neonatal hypoglycemia, during therapy by drug feeding by a breast contraindicated.

Overdose:

At overdose by derivatives of sulphonylurea the hypoglycemia can develop. At emergence of moderate symptoms of a hypoglycemia without disturbance of consciousness or neurologic symptoms it is necessary to increase reception of carbohydrates with food, to reduce a dose of drug and/or to change a diet. Fixed medical observation of a condition of the patient has to continue until is confidence that nothing threatens his health. Development of the serious hypoglycemic conditions which are followed by a coma, spasms or other neurologic disturbances is possible. At emergence of such symptoms rendering emergency medical service and immediate is necessary
hospitalization. In case of a hypoglycemic coma or at suspicion on it to the patient intravenously struyno enter 50 ml of 20 - 30% of solution of a dextrose (glucose). Then intravenously kapelno enter 10% dextrose solution for maintenance of concentration of glucose into blood higher than 1 g/l. It is necessary to make careful control of level of glucose of blood and observation of the patient at least within 48 next hours. After this span depending on a condition of the patient the attending physician resolves an issue of need of further observation. Dialysis is inefficient in view of the expressed linkng of gliclazide with proteins of plasma.

Storage conditions:

Special storage conditions are not required. To store in the place, unavailable to children. List B. Period of validity 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets with the modified release of 60 mg.
On 30 tablets in the blister (PVC / Is scarlet), on 1 or 2 blisters with the instruction on a medical use in a pack cardboard.
When packaging (packaging) at the Russian enterprise LLC Serdiks:
On 30 tablets in the blister (PVC / Is scarlet), on 1 or 2 blisters with the instruction on a medical use in a pack cardboard.
On 15 tablets in the blister (PVC / Is scarlet), on 2 or 4 blisters with the instruction on a medical use in a pack cardboard.
By production at the Russian enterprise LLC Serdiks
On 15 tablets in the blister from the PVC/ave. On 2 or 4 blisters with the instruction on a medical use in a pack cardboard.