Diadenon

General characteristics. Structure:

Active ingredient: 60 mg of gliclazide.

Excipients: lactoses monohydrate, maltodextrin, gipromelloza, magnesium stearate, silicon dioxide colloid anhydrous.

Peroral antidiabetic hypoglycemic drug

Pharmacological properties:

Pharmacodynamics. Gliclazide is a peroral antidiabetic hypoglycemic drug which differs from similar connections in existence of the N-containing heterocyclic ring with endocyclic communication.

Gliclazide reduces glucose level in blood, stimulating insulin secretion with beta cells of islets of Langerhans. After 2 years of treatment increase in level of postprandialny insulin and secretion of S-peptide remains.

In addition to metabolic properties, gliclazide has haemo vascular activity.

Influence on insulin secretion. At diabetes 2 types, gliclazide are recovered by the first 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 noted in response to the stimulation caused by administration of glucose or meal.

Haemo vascular properties. Gliclazide reduces risk of thromboses of small vessels, influencing two mechanisms which can be involved in development of complications at a diabetes mellitus:
• partial inhibition of aggregation and adhesion of thrombocytes and decrease in markers of activation of thrombocytes (beta thromboglobulin, tromboksanav2).
• recovery of fibrinolitic activity of a vascular endothelium and increase in activity of a fabric plasminogen activator.

Pharmacokinetics. Absorption. Drug level in plasma gradually increases within the first 6 hours after reception and reaches the plateau which remains from the 6th to the 12th hour.

Intra individual variability is low.

Gliclazide is completely absorbed in an organism. Meal does not influence the speed or extent of absorption.

Distribution. Linkng with proteins of plasma makes about 95%. The volume of distribution makes about 30 liters. The single daily dose of Diadeon provides preservation of effective concentration of gliclazide in a blood plasma for more than 24 hours.

Metabolism. Metabolism of gliclazide happens preferential in a liver, drug is emitted in urine: less than 1% are removed with urine in not changed look. Active metabolites in plasma are not revealed.

Removal. The elimination half-life of gliclazide varies from 12 to 20 hours.

Linearity. The interrelation between the accepted dose, up to 120 mg, and the area under the curve describing dependence of concentration on time has linear character.

Pharmacokinetics at separate groups of patients. Patients of advanced age. At elderly patients of clinically significant changes of pharmacokinetic parameters it is not revealed.

Indications to use:

Insulinonezavisimy diabetes (type 2) at adults when observance of a diet, the exercise stress and loss of weight are insufficient adequately to control glucose level in blood.

Route of administration and doses:

Pill is taken внутрьодин once a day during a breakfast, without chewing, washing down with enough water.

The daily dose of Diadeon can vary from 30 to 120 mg, i.e. from 1/2 to 2 tablets. In case of the admission of reception it is impossible to increase a dose next day.

As well as when using any other hypoglycemic medicine, the dose of drug is adjusted depending on individual metabolic reaction of the patient (content of glucose in blood, HbAlc).

Initial dose. The recommended initial dose makes 30 mg a day (a half of a tablet). At effective control of level of glucose in blood this dose can be used as a maintenance therapy.

If glucose level in blood is controlled inadequately, then the daily dose can be gradually increased to 60, 90 or 120 mg. The interval between each increase in a dose has to make not less than 1 month, except patients at whom after two weeks of reception glucose level in blood did not decrease. In such cases the dose can be increased at the end of the second week of reception.

The maximum recommended dose makes 120 mg a day.

One tablet with the modified release by a dosage of 60 mg is equivalent to two tablets with the modified release by a dosage of 30 mg. The tablet Diadeon easily shares with the modified release that allows to adapt a drug dosage.

Transition from gliclazide tablets a dosage of 80 mg on tablets with the modified release Diadeon a dosage of 60 mg: one tablet of gliclazide a dosage of 80 mg is comparable with a formula of 30 mg with the modified release (i.e. and a half a tablet Diadeon a dosage of 60 mg) therefore such transition can be carried out at strict monitoring of indicators of blood.

Transition from one antidiabetic drug on Diadeon. Diadeon can be used for replacement of other peroral antidiabetic drugs. Upon transition to Diadeon it is necessary to consider a dosage and an elimination half-life of the previous antidiabetic drug.

As a rule, observance of a transition period is not required. Reception it is necessary to begin with a dose 30 mg, with the subsequent adjustment depending on reaction of level of glucose in blood as it was described above.

Upon transition from hypoglycemic drugs of group of sulphonylurea with the prolonged period of removal the non-drug period lasting several days, in order to avoid the additive effect of two drugs which can lead to a hypoglycemia can be necessary. Transition to Diadeon has to be carried out according to the procedure described to start treatment, i.e. the initial dosage makes 30 mg/day with the subsequent step-by-step increase in a dose, depending on metabolic reaction.

Use in a combination with other antidiabetic drugs. Diadeon can be appointed combinations with guanyl guanidines, inhibitors of alpha glucosidase or insulin.

To patients at whom glucose level in blood is inadequately controlled by Diadeon's reception an insulin therapy under strict medical observation can be appointed.

Special groups of patients. Patients of advanced age: correction of the mode of a drug dosing for patients is more senior than 65 years it is not required.

Patients with renal failures: to patients with easy and moderate renal failures the same dosage, as to patients with normal renal function, under fixed medical observation can be appointed. Such recommendations were confirmed with clinical trials.

Patients with risk of development of a hypoglycemia:
- at insufficient or improper feeding,
- at the heavy or poorly compensated endocrine frustration (a hypopituitarism, a hypothyroidism, insufficiency of adrenocorticotropic hormone),
- after the termination of long and/or high-dosage corticosteroid therapy,
- at serious vascular diseases (a severe form of a coronary disease, heavy disturbance of passability of carotid arteries, diffusion vascular frustration).

It is recommended to begin treatment with the minimum daily dose of 30 mg.

Use for children. Data on efficiency and safety of use of drug for children and teenagers aged up to 18 years are absent.

Features of use:

Hypoglycemia. It is necessary to appoint this therapy only the patient with guaranteed regular meal (including a breakfast). Importance of regular consumption of carbohydrates is caused by the increased risk of a hypoglycemia at a meal delay, its insufficient quantity or low content of carbohydrates. The risk of emergence of a hypoglycemia increases at a low-calorie diet, after long or excessive exercise stresses, alcohol intake or in case of the combined use of several hypoglycemic drugs.

The hypoglycemia can develop after administration of drugs of group of sulphonylurea. Sometimes it has the difficult and long character demanding hospitalization of the patient and introduction to it glucose for several days.

Careful selection of patients, right choice of a dose and accurate recommendations about its reception are necessary for decrease in risk of hypoglycemic attacks.

The factors increasing risk of development of a hypoglycemia:
• refusal or (especially at elderly patients) inability to follow instructions of the doctor,
• insufficient or improper feeding, irregular reception or admission of meals, periods of starvation or change in food,
• imbalance of exercise stresses and consumption of carbohydrates,
• renal failure,
• heavy liver failure,
• Diadeon's overdose MR,
• some endocrine disturbances: dysfunction of a thyroid gland, hypopituitarism and insufficiency of function of adrenal glands,
• concomitant use of some other medicines.

Insufficiency of function of a liver or kidneys: pharmacokinetic and/or pharmakodinamichesky parameters of gliclazide can change at patients with a liver or heavy renal failure. At such patients episodes of a hypoglycemia can be more long that demands acceptance of adequate measures.

Informing patients. Patients and members of their families need to explain danger of a hypoglycemia, to tell about its symptoms, ways of treatment and factors contributing to development of this complication.

The patient has to be informed on importance of observance of a diet, regular exercise stress and regular control of level of glucose in blood.

Unsatisfactory control of level of glucose in blood: efficiency of control of concentration of glucose in blood of the patient receiving antidiabetic therapy can go down under the influence of the following factors: the increased temperature, an injury, an infection or surgical intervention. In some cases administration of insulin can be required.

Hypoglycemic efficiency of any peroral antidiabetic means, including gliclazide, at many patients decreases over time: it can be caused by progressing of diabetes or weakening of reaction to drug. This phenomenon is known as secondary lack of effect of therapy, unlike its primary absence already at the very beginning of use of drug of primary line of treatment. The conclusion about secondary lack of effect can be done only after adequate dose adjustment and at observance by the patient of a diet.

Laboratory tests: at assessment of control of level of glucose in blood measurement of level of glycated hemoglobin is recommended (or glucose in plasma of a venous blood on an empty stomach). Also independent monitoring of level of glucose in blood can be useful.

Purpose of drugs of group of sulphonylurea to patients with deficit of G6PD can lead to hemolitic anemia. As gliclazide belongs to a chemical class of drugs of group of sulphonylurea, it is necessary to be careful at its appointment to patients with deficit of G6PD and to consider the possibility of alternative treatment by drug of other class.

Special information on excipients. Drug Diadeon contains lactose therefore patients are not recommended to appoint it with a hereditary lactose intolerance, Lapp's galactosemia or a syndrome of the broken glucose galactose absorption.

Children. Safety and efficiency of use of drug of children aged up to 18 years are not established to Diadeon.

Use during pregnancy and feeding by a breast. Experience of use of gliclazide during pregnancy at the person is absent though there are some data on other drugs of group of sulphonylurea. In researches on animals gliclazide did not show teratogenic effect.

It is necessary to achieve control of diabetes before conception to reduce risk of the inborn aberrations connected with noncompensated diabetes.

Peroral hypoglycemic drugs do not approach, drug of the first line of treatment of diabetes during pregnancy is insulin. It is recommended to pass from peroral hypoglycemic therapy to insulin before conception or right after the fact of pregnancy was confirmed.

Lactation. It is unknown whether gliclazide and its metabolites in milk is emitted. Considering risk of a hypoglycemia at the newborn, this drug is contraindicated when feeding by a breast.

Influence on ability to drive the car and potentially dangerous mechanisms. Diadeon does not exert impact on ability to drive the car and potentially dangerous mechanisms. Nevertheless, patients have to be informed on symptoms of a hypoglycemia and have to be careful at control of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions, especially at the beginning of therapy.

Side effects:

At use of gliclazide it was reported about the following undesirable effects.

Hypoglycemia. As well as other drugs of group of sulphonylurea, Diadeon can cause a hypoglycemia in case of irregular meal and especially in case of the admission of its receptions. Treat possible symptoms of a hypoglycemia: the headache, strong feeling of hunger, nausea, vomiting, increased fatigue, sleep disorders, excitement, aggression, decrease in concentration of attention, decline in the ability to estimate a situation, the slowed-down reactions, a depression, opacification of consciousness, a vision disorder and the speech, aphasia, a tremor, paresis, perception disturbance, dizziness, feeling of helplessness, self-checking loss, nonsense, spasms, shallow breathing, bradycardia, drowsiness and a loss of consciousness which can come to the end with a coma and a lethal outcome.

Besides, development of such signs of adrenergic counterregulation as the increased sweating, "sticky" skin, chuvstvotrevog, tachycardia, the increased blood pressure, a cardiopalmus, stenocardia and cardiac arrhythmia is possible.

Usually these clinical manifestations disappear after reception of carbohydrates (sugar). At the same time artificial sweeteners are inefficient. Experience of use of other derivatives of sulphonylurea testifies to a possibility of a recurrence of a hypoglycemia even when the measures taken for its elimination seemed effective in the beginning.

At heavy and long attacks of a hypoglycemia and even if she manages to be eliminated temporarily with sugar reception, the neotlozhnayameditsinsky help or even hospitalization is necessary.

Other undesirable phenomena. Disturbances from a gastrointestinal trakta:bol in a stomach, nausea, vomiting, dyspepsia, diarrhea and locks. Reception of gliclazide during a breakfast allows to avoid such effects or to minimize them.

It was less often reported about the following undesirable phenomena. Disturbances from skin and hypodermic fabrics: rash, itch, urticaria, Quincke's disease, erythema, makulo-papular rashes, violent reactions (such as Stephens-Johnson's syndrome and toxic epidermal necrolysis).

Disturbances from blood and lymphatic system: hematologic changes are rare. Among them: anemia, leukopenia, thrombocytopenia, granulocytopenia. Usually they are reversible after the termination of administration of drug.
Disturbances from a liver and bile-excreting putey:povysheny activities of liver enzymes (nuclear heating plant, ALT, an alkaline phosphatase), hepatitis (isolated cases). To stop treatment in case of developing of cholestatic jaundice.

The following undesirable phenomena usually disappear after the treatment termination. Disturbances from an organ of sight: the passing vision disorders caused by change of concentration of glucose in blood, especially in an initiation of treatment are possible.

Effects inherent in this pharmacological group: against the background of reception of other derivatives of sulphonylurea cases of an erythrocytopenia, an agranulocytosis, hemolitic anemia, a pancytopenia, an allergic vasculitis, a hyponatremia were described. Cases of increase in level of liver enzymes and even an abnormal liver function (for example, a cholestasia and jaundice) and hepatitis which passed after the sulphonylurea reception termination were noted, but in some cases led to a liver failure with threat for life.

Interaction with other medicines:

1) The risk of development of a hypoglycemia increases under the influence of the following drugs.

Contraindicated combinations:
• with Miconazolum (system introduction or drawing on mucous an oral cavity in the form of gel): the hypoglycemic effect amplifies, emergence of symptoms of a hypoglycemia and even approach of a hypoglycemic coma is possible

Not recommended combinations:
• with phenylbutazone (system introduction): strengthens hypoglycemic effect of sulfonilmochevinny drugs (as replaces their bonds with proteins of a blood plasma and/or reduces their removal from an organism). It is preferable to appoint other anti-inflammatory drug, and also to warn the patient and to explain it importance of independent control of glucose level in blood. In case of need it is necessary to adjust a dose during therapy by antiinflammatory drug and after its end.
• with alcohol: alcohol strengthens gipoglikemiziruyushchy action (by suppression of compensatory reactions) that can lead to a hypoglycemic coma.

It is necessary to avoid alcohol intake and reception of the medical supplies containing alcohol.

The combinations demanding respect for care. Strengthening of hypoglycemic effect and, therefore, in certain cases, a hypoglycemia, are possible at reception of one of the following drugs:
other antidiabetic drugs (insulin, acarbose, metformin, tiazolidinidiona, inhibitors dipeptidilpeptidazy-4, GPP-1 agonists), beta-blockers, флуконазол, inhibitors angiotensin - reformative enzyme (kaproprit, enalapril), antagonists of H2 receptors, MAO inhibitors, sulfonamides, кларитромицин and non-steroidal anti-inflammatory drugs.

2) The following products can cause increase in level of glucose of century.

Not recommended combinations:
• with danazoly: даназол possesses diabetogenic action. If reception of this medicinal substance cannot be avoided, warn the patient and explain him importance of control of glucose level in blood and urine. Sometimes it is required to modify a dose of antidiabetic means for therapy time danazoly and after it.

The combinations demanding care:
• with Chlorpromazinum (neuroleptic): in high doses (> 100 mg of Chlorpromazinum a day) it increases glucose level in blood (decrease in secretion of insulin). Warn the patient about it and explain him importance of independent control of glucose level. Dose adjustment of antidiabetic drug for time and after therapy by neuroleptics can be required.
• with glucocorticoids (system and topical administration: vnutrisustavno, under - or nakozhno, rektalno) and with tetrakozaktriny: these drugs increase glucose level in blood and can cause a ketosis (decrease in tolerance to carbohydrates under the influence of glucocorticoids). Warn the patient about it and explain him importance of independent control of glucose level, especially at the beginning of therapy. Dose adjustment of antidiabetic drug for time and after therapy by glucocorticoids can be required.
• with Ritodrinum, salbutamol, terbutaliny: (in/in) increase glucose level in blood. To emphasize importance of independent control of glucose level in blood. If necessary, to transfer the patient to insulin.

3) Combinations which should be considered.
• Antokoagulyanta (for example, warfarin): at the accompanying therapy by drugs of group of sulphonylurea strengthening of anticoagulating effect is possible. Correction of anticoagulating therapy can be required.

Contraindications:

- Hypersensitivity to gliclazide or one of excipients, other drugs of group of sulphonylurea, sulfonamides;
- diabetes of 1 type;
- diabetic ketoacidosis, prekomatozny state and diabetic coma;
- heavy renal or liver failure: in such cases it is recommended to apply insulin;
- therapy by Miconazolum;
- feeding by a breast.

Overdose:

Symptoms: the overdose of drugs of group of sulphonylurea can cause a hypoglycemia, consciousness disturbance, a hypoglycemic coma.

Treatment: symptoms of a hypoglycemia of moderate weight, without loss of consciousness or signs of neurological frustration, have to be eliminated with reception of carbohydrates, correction of a dose and/or change of food. Careful monitoring of a condition of the patient is necessary until the doctor is not convinced that nothing threatens health of the patient.

The heavy hypoglycemic episodes which are followed by a coma, spasms or other neurological disturbances should be considered as the cases demanding acute management with immediate hospitalization of the patient.

At approach of a hypoglycemic coma or suspicion to it, the patient should enter quickly 50 ml of strong solution of glucose (20-30% intravenously), and then to continue infusion with more weak solution of glucose (10%) with a speed which will provide maintenance of concentration of glucose in blood at the level of more than 1 g/l. Careful monitoring of a condition of the patient, and, depending on his state upon termination of an attack is necessary, the doctor makes the decision on need of continuation of monitoring or its cancellation.

Carrying out dialysis is not effective because of strong linkng of gliclazide with blood proteins.

Storage conditions:

To store at a temperature below 30 ºС. To store in the place, unavailable to children. Period of validity 3 years.

Issue conditions:

According to the recipe

Packaging:

Tablets with the modified release of 60 mg. On 15 tablets in a blister strip packaging. 4 blister strip packagings with the instruction on a medical use place in a pack cardboard.