Gliclazide-SZ - instructions for use, dose, side effects, contraindications

Excipients: calcium hydrophosphate dihydrate - 53.5 mg; maltodextrin 15.0 mg; hypromellose 4 K M (hydroxypropylmethylcellulose) 4.3 mg; hypromellose K 100 LV (hydroxypropylmethylcellulose) 25.7 mg; silicon dioxide colloidal anhydrous (aerosil anhydrous) - 0.5 mg; magnesium stearate 1.0 mg.

Description:

Tablets are white or almost white, round, flat-cylindrical with a facet and a risk on one side.

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

Gliklazid reduces the concentration of blood glucose, stimulating the secretion of insulin β-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 to restore the fibrinolytic activity of the vascular endothelium and increase the activity of the tissue activator of plasminogen.

Intensive glycemic control, based on the use of glyclazide with prolonged release, significantly reduces micro- and macrovascular complications of type 2 diabetes mellitus, in comparison with standard glycemic control.

Pharmacokinetics:

Suction

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

Eating does not affect the rate or degree of absorption of the glycazide.

Distribution

About 95% of the glycazide binds to plasma proteins. The volume of distribution is about 30 liters. Taking Gliklazid-SZ in a dose of 60 mg once a day ensures the maintenance of an effective concentration of gliclazide in the blood plasma for more than 24 hours.

Metabolism

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

Excretion

Gliklazid is excreted mainly by the kidneys: excretion is carried out in the form of metabolites, less than 1% is excreted by the kidneys unchanged. The half-life of gliclazide averages from 12 to 20 hours.

Linearity

The relationship between the dose taken (up to 120 mg) and the area under the pharmacokinetic curve "concentration-time" is linear.

Special Populations

Aged people

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

Indications:

- Diabetes mellitus type 2 with insufficient effectiveness of diet therapy, exercise 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 by intensive glycemic control.

Contraindications:

- Hypersensitivity to gliclazide, other derivatives of sulfonylurea, sulfonamides or to auxiliary substances included in the preparation;

- type 1 diabetes mellitus;

- Diabetic ketoacidosis, diabetic precoma, diabetic coma;

- severe renal or hepatic insufficiency (in these cases it is recommended to use insulin);

- taking miconazole (see section "Interaction with other drugs");

- pregnancy and the period of breastfeeding (see the section on "Application during pregnancy and during breastfeeding");

- age to 18 years.

It is not recommended to use in combination with phenylbutazone or danazol (see section "Interaction with other medicinal products").

Carefully:

Elderly age, irregular and / or unbalanced diet, insufficiency of glucose-6-phosphate dehydrogenase, severe cardiovascular disease, hypothyroidism, adrenal or pituitary insufficiency, renal and / or hepatic insufficiency, long-term glucocorticosteroid (GCS) therapy, 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 sugar diabetes 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.

Breastfeeding period

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

Dosing and Administration:

PREPARATION IS INTENDED FOR ADULT TREATMENT.

The recommended dose of the drug should be taken orally, once a day, preferably during breakfast.

The daily dose can be 30 - 120 mg (1/2 - 2 tablets) in one dose. It is recommended to swallow a pill or half of 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 glycated hemoglobin (HbAlc).

Initial dose

The initial recommended dose (including for elderly patients, ≥ 65 years) is 30 mg per day (1/2 tablet).

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. Presence of risks on 60 mg tablets allows you to divide the pill and take a daily dose like 30 mg (1/2 tablets 60 mg) and, if necessary, 90 mg (1 tablet 60 mg and 7 g tablets 60 mg).

Transition from taking another hypoglycemic drug to the drug Gliklazid-SZ, sustained release tablets 60 mg

The drug Gliclazide-SZ, sustained-release tablets of 60 mg can be used in place of another oral hypoglycemic drug. When transferring to the drug Gliklazid-SZ patients receiving other oral hypoglycemic drugs should take into account their dose and half-life.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 replacing the drug Gliclazide-SZ derivatives of sulfonylureas with a long half-life 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 Gliklazid-SZ is also 30 mg (7 g tablets 60 mg) and, if necessary, can be increased later, as described above.

Combination with another hypoglycemic drug

The drug Gliclazide-SZ 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.

Prevention of complications of diabetes mellitus

To achieve intensive glycemic control, you can gradually increase the dose of Gliclazide-SZ to 120 mg / day in addition to diet and exercise before reaching the target level HbAlc. 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-alpha-glucosidase inhibitor, a thiazolidinedione derivative or insulin.

Elderly patients

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

Patients with renal insufficiency

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 who are at risk for developing hypoglycemia (inadequate or unbalanced diet, severe or poorly compensated endocrine disorders - pituitary and adrenal insufficiency, hypothyroidism; glucocorticosteroids (GCS) after long-term administration and / or use in high doses; severe cardiovascular disease - severe ischemic heart disease, severe atherosclerosis of carotid arteries, widespread atherosclerosis) it is recommended to apply the minimum dose (30 mg) of the drug Gliklazid-SZ.

Children and adolescents 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:

Considering the experience of using glycazide, one should remember about the possibility of developing the following side effects.

Hypoglycaemia

Like other drugs of the sulfonylurea group, the drug Gliclazide-C3 can cause hypoglycemia in the event of an occasional meal and especially if the meal is missed. Possible symptoms of hypoglycemia include headache, severe hunger, nausea, vomiting, fatigue, sleep disturbance, irritability, agitation, decreased concentration, slowed reactions, depression, confusion, impaired vision and speech, aphasia, tremor, paresis, self-loss , helplessness, impaired perception, dizziness, weakness, convulsions, bradycardia, lightheadedness, shortness of breath, drowsiness, loss of consciousness with the possible development of coma, or death.

Adrenergic reactions can also be noted: increased perspiration, "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. Against the background of 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

From 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, hives, Quincke's edema, erythema, maculopapular rash, bullous reactions (such as Stevens-Jones syndrome and toxic epidermal necrolysis).

On the part of the organs of hematopoiesis and lymphatic system: hematological disorders (anemia, leukopenia, thrombocytopenia, granulocytopenia) are rare. 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.

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

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 a 20-40% solution of dextrose (glucose) is injected intravenously. Then, 5-10% dextrose solution is administered intravenously dropwise to maintain blood glucose concentration 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 observation.

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

Interaction:

Preparations and substances, contributing to an increased risk of hypoglycemia: (enhancing the action of gliclazide)

Contraindications

- Miconazole (with systemic administration and with the application of the gel on the oral mucosa): 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 derivatives of sulfonylureas (displaces them from the bond with proteins plasma and / or slows their removal from the body).

It is 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 the drug Gliklazid-SZ should be adjusted during the reception of phenylbutazone and after its completion

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

Combinations, requiring precautions

Admission gliclazide in combination with certain drugs: other hypoglycemic agents (insulin,acarbose, metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, GLP-1 agonists); 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.

Preparations, contributing to increased blood glucose: (weakening action of Glyclazide)

Unrecommended combinations

- Danazol: has a diabetic effect. In case this drug is needed, the patient is recommended to carefully monitor blood glucose. If it is necessary to take joint medications, it is recommended that a dose of a hypoglycemic agent be selected at the time of taking danazol and after its withdrawal.

Combinations, requiring precautions

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

- SCS (systemic and topical application: intraarticular, dermal, rectal administration) and tetracosactide: increase the concentration of glucose blood with the possible development of ketoacidosis (a 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 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 insulin therapy.

Combinations, which must be taken into account

Anticoagulants (eg, 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 drinking alcohol or 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 may 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;

- an overdose of the drug Gliklazid-SZ;

- some endocrine disorders: thyroid disease, pituitary and adrenal insufficiency;

- simultaneous reception of certain medicines (see the section "Interaction with other medicinal products").

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 needed.

Insufficient glycemic control

Glycemic control in patients receiving therapy with hypoglycemic agents may be weakened in the following cases: fever, trauma, infectious diseases or large surgical interventions. With these conditions, it may be necessary to stop therapy with Gliclazide-SZ and prescribe insulin therapy.

In many patients, the effectiveness of oral hypoglycemic agents, including gliclazide, tends to decline 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 phenomenon 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

For evaluation of glycemic control, regular determination of fasting blood glucose and glycated 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.

Information for patients

It is necessary to inform the patient, as well as his family members about the risk of developing hypoglycemia, its symptoms and conditions that contribute 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.

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

In connection with the possible development of hypoglycemia in the use of the drug Gliklazid-SZ, patients should be aware of the symptoms of hypoglycemia and should be careful when driving vehicles or performing work that requires a high rate of physical and mental reactions, especially at the beginning of therapy.

Form release / dosage:

Tablets with prolonged release, 60 mg.

Packaging:

For 10 or 30 tablets in a planar cell package.

For 30 tablets in a plastic can or in a polymer bottle.

Each bank, vial or 3, 6 contour cell packs of 10 tablets or 1, 2, 3 contourcell packs per 30 tablets together with instructions for use in a cardboard pack.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004551

Date of registration:20.11.2017

Expiration Date:20.11.2022

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp18.12.2017

Illustrated instructions

Instructions

Gliklazid-SZ (Gliclazide-SZ)