Gliklazid MB Pharmstandard - instructions for use, dose, side effects, contraindications

Excipients: Hypromellose (hypromellose 100 cps) - 74.00 mg or 138.08 mg, calcium hydrophosphate (calcium hydrophosphate anhydrous) - 25.75 mg or 62.05 mg, lactose monohydrate - 22.54 mg or 45.09 mg, magnesium carbonate (magnesium carbonate basic) - 4.80 mg or 9.60 mg, silicon dioxide colloid - 1.79 mg or 3.58 mg, magnesium stearate - 1.12 mg or 1.60 mg.

Description:

Dosage of 30 mg: White or almost white, biconvex tablets in the form of capsules with bevelled edges.

Dosage of 60 mg: white or almost white, oval biconvex tablets with a risk on both sides.

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 bond.

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 2years 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 (target of glycosylated hemoglobin (HbA1c) <6.5%), significantly reduces the risk of micro- and macrovascular complications of type 2 diabetes, compared with standard glycemic control (study ADVANCE).

Pharmacokinetics:

Absorption

Ingestion glycazide completely absorbed. The concentration of gliclazide in 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 degree of absorption of the drug.

Distribution

About 95% of the glycazide binds to plasma proteins. Admission of the drug Gliklazid MB Pharmstandard (30 mg and 60 mg) once a day ensures the maintenance of an effective concentration of glycazide in the blood plasma for more than 24 hours. Metabolism

Gliklazid is metabolized primarily in the liver. There are no active metabolites in the 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 in an unchanged form. 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

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 (myocardial infarction, stroke) complications 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);

- concomitant therapy with 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;

- congenital lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

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

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:

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.

Gliclazide, like other oral hypoglycemic drugs, is not used in pregnant women.

Insulin is the drug of choice for the therapy of diabetes mellitus in pregnant women. It is recommended to transfer the patient to insulin therapy, as in the case of planned pregnancy, and when pregnancy occurs while taking the drug.

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

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

Dosing and Administration:

The drug is intended only for the treatment of adults.

Initial dose

The recommended initial dose (including for elderly patients ≥ 65 years of age) - 30 mg per day (1 tablet for a dosage of 30 mg or 1/2 tablet for a dosage of 60 mg). The recommended dose of the drug should be taken orally, once a day, preferably during breakfast. 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.

Dose selection and maintenance dose

As with other hypoglycemic drugs, the dose of the drug in each case must be selected individually, depending on the concentration of glucose in the blood and the level of glycosylated hemoglobin (HbA1c).

Increase in the dose is possible not earlier than after 1 month of therapy with the drug at a 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 daily dose of the drug can be 30-120 mg in a single dose (1-4 tablets for a dosage of 30 mg or 1 / 2-2 tablets for a dosage of 60 mg).

When adequate control is achieved, the drug in this dose can be used for maintenance therapy. With inadequate glycemic control, the daily dose of the drug can be gradually increased to 60, 90 or 120 mg.

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

Prevention of complications of diabetes mellitus

To achieve intensive glycemic control, you can gradually increase the dose of Gliklazid MB Pharmstandard to 120 mg per day in addition to diet and exercise to achieve the target level HbA1c. 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, a thiazolidinedione derivative or insulin.

Transition from administration of the immediate-release immediate-release drug, tablets 80 mg per drug Gliklazid MB Pharmstandard, sustained-release tablets, 30 mg and 60 mg

1 tablet immediate-release glycazide 80 mg can be replaced with 1 tablet with prolonged release Gliclazide MB Pharmstandard 30 mg or 1/2 tablet with prolonged release Gliclazide MB Pharmstandard 60 mg. When transferring patients from the immediate-release glycazide preparation 80 mg to the drug Gliklazid MB Pharmstandard, careful glycemic control is recommended.

Transition from taking another hypoglycemic drug to Gliklazid MB Pharmstandard, prolonged release tablets, 30 mg or 60 mg

Preparation Gliklazid MB Pharmstandard, prolonged-release tablets, 30 mg or 60 mg, can be used in place of another hypoglycemic agent for oral administration. When transferring to Gliklazid MB Pharmstandard, patients receiving other hypoglycemic drugs for oral administration should take their dose and half-life into account. As a rule, a transition period is not required.

The initial dose should be 30 mg (1 tablet for a dosage of 30 mg or 1/2 tablet for a dosage of 60 mg) and then titrated depending on the concentration of glucose in the blood. When replacing sulfonylureas with a long half-life with Gliclazide MB Pharmstandard, to prevent the risk of 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 MB Pharmstandard is also 30 mg (1 tablet for a dosage of 30 mg or 1/2 tablet for a dosage of 60 mg) and, if necessary, can be further increased as described above.

Combination with another hypoglycemic drug

Gliklazid MB Pharmstandard can be used in combination with biguanides, alpha-glucosidase inhibitors or insulin. In case of inadequate glycemic control, additional insulin therapy (insulin preparations of medium duration or long-acting insulin analogues) should be prescribed with careful medical control.

Special patient groups

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.

Elderly people

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

Patients at risk for developing hypoglycemia (insufficient or unbalanced nutrition, severe or poorly compensated endocrine disorders - pituitary or adrenal insufficiency, hypothyroidism, long-term use of high doses of glucocorticosteroids (SCS) or against their withdrawal, 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 MB Pharmstandard.

Side effects:

Taking into account the experience of the use of glycazide and other sulfonylurea derivatives, one should remember about the possibility of developing the following side effects:

Hypoglycaemia

Like other sulfonylureas, Gliklazid MB Pharmstandard can cause hypoglycemia in the event of an occasional meal and, especially, if the meal is missed.

Possible symptoms of hypoglycemia: headache, a strong feeling of hunger, nausea, vomiting, fatigue, sleep disturbance, irritability, agitation, decreased concentration of attention, delayed reaction, depression, impaired vision and speech, incl. aphasia, paresis, tremor, loss of self-control, feelings of helplessness, impaired perception, dizziness, weakness, convulsions, bradycardia, delirium, shallow breathing, drowsiness, confusion or loss with possible coma development up to death. Adrenergic reactions (activation of the sympathetic adrenal system in response to hypoglycemia) can also be noted: increased sweating, sticky skin, anxiety, tachycardia, increased blood pressure, palpitations, arrhythmias 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.

Attacks of severe or prolonged hypoglycemia can endanger the lives of patients, which provides emergency medical treatment and, if necessary, immediate hospitalization of the patient, even with the effect of taking carbohydrates (see section "Overdose", section "Special instructions").

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

- From the blood 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 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 reception of other sulfonylurea derivatives, cases of erythrocytopenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, hyponatremia were noted. Also on the background of taking sulfonylurea derivatives 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. These 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 symptoms of mild 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. Episodes of severe hypoglycemia, manifested neurological disorders (convulsions) with the development of coma (or without it), require urgent medical care and, if necessary, hospitalization of the patient. In the case of hypoglycemic coma, or if it is suspected, 50 ml of 20-40 are injected intravenously% solution of dextrose. If consciousness is not restored, then intravenously drip 5-10% a solution of dextrose 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. You may need an additional intake of carbohydrates, because after a visible clinical improvement, a relapse of hypoglycemia is possible.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:

Drugs and substances that increase the risk of developing hypoglycemia (enhancing the action of gliclazide):

Contraindicated combinations

Miconazole (with systemic administration and with the use of 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 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 the drug Gliklazid MB Pharmstandard should be adjusted during the administration of phenylbutazone and after its termination.

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

Combinations, requiring precautions

The use of gliclazide in combination with certain drugs (for example, other hypoglycemic agents - insulin, acarbose, metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, GLP-1 agonists, beta adrenoblockers, fluconazole, angiotensin-converting enzyme inhibitors - captopril, enalapril, H blockers₂-gistaminovyh receptors; monoamine oxidase inhibitors; sulfonamides; clarithromycin and non-steroidal anti-inflammatory drugs) is accompanied by increased hypoglycemic effect and risk of hypoglycemia.

Drugs that increase blood glucose (weakening action of glycazide):

Unrecommended combinations

Danazol: has a diabetic effect. AT If it is necessary to take joint medications, it is recommended that a dose of hypoglycemic agent be selected and blood glucose is carefully monitored, both during and after danazol administration.

Combinations requiring precautions

Chlorpromazine (neuroleptic): in high doses (more than 100 mg per day) increases the concentration of glucose in the blood, reducing the secretion of insulin. If it is necessary to co-administer the drugs, it is recommended that a dose of a hypoglycemic agent be selected and a careful glycemic control, both during the administration of the neuroleptic, and after its withdrawal.

GCS (systemic and topical application: intraarticular, cutaneous, rectal administration) and tetracosactide: increase the concentration of glucose in the blood with the possible development of ketoacidosis (reduced 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 reception of the GCS, and after their withdrawal.

Ritodrin, salbutamol, terbutaline (intravenous administration): beta₂-adrenomimetiki contribute to increasing the concentration of glucose in the blood. 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 that need to 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:

Against the background of drug therapy, regular monitoring of blood glucose concentration is necessary.

Correction of the dose of the drug may be required if the patient increases the intensity of physical activity or changes the habitual diet. For evaluation of glycemic control, it is recommended to regularly conduct self-monitoring of fasting blood glucose and after meals and glycosylated hemoglobin HbA1c.

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 section "Side effects").

It is very important to have regular meals without missing enough carbohydrates. The drug can be prescribed only to those patients whose meals include breakfast.Hypoglycemia frequently develops with irregular feeding, the power limitation for weight reduction (without a corresponding change hypoglycemic drug dose) after prolonged or vigorous exercise after ingestion of ethanol or ethanol-containing drugs or while receiving multiple hypoglycemic drugs.

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 reception of sugar substitutes is not conducive to the elimination of hypoglycemia. The experience of using other sulfonylurea derivatives suggests that hypoglycemia can recur despite effective initial arrest of this condition. If a hypoglycaemic episode is characterized by a protracted course with pronounced symptoms, despite a temporary improvement after meals rich in carbohydrates, it is necessary to provide emergency medical services, up to the patient's hospitalization.

In order to avoid or to reduce the risk of hypoglycemia, careful individual selection of drugs,dosing and nutrition regimen, patient compliance with the recommendations of the attending physician, as well as providing the patient and his family members with complete information about the treatment, symptoms-precursors of hypoglycemia and conditions conducive to its development.

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;

- drug overdose;

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

- simultaneous intake of certain drugs (see section "Interaction with other drugs").

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

In many patients, the effectiveness of oral hypoglycemic agents, including glycazide, 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's secondary drug resistance, it is necessary to evaluate the adequacy of dose selection and patient compliance with the prescribed diet.

In intercurrent diseases, the need for insulin increases, which implies a more intensive control of the glucose concentration in the blood and, possibly, correction of the therapy.

In patients receiving oral hypoglycemic therapy,when planning large surgical interventions, injuries, extensive burns, infectious diseases with febrile syndrome, there may be a need for transfer to insulin therapy.

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:

In connection with the possible development of hypoglycemia with the use of the drug Gliklazid MB Pharmstandard, patients should be aware of the symptoms of hypoglycemia and Care must be taken 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, 30 mg and 60 mg.

Packaging:

Dosage of 30 mg: 30 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil printed lacquered.

1 or 2 contour packs of 30 tablets together with the instructions for use are placed in a pack of cardboard.

For 30 tablets in a polymer tube with a cap-compensator.

Tubu together with instructions for use are placed in a pack of cardboard.

Dosage of 60 mg: on 15 tablets in a contour cellular packing from a film of polyvinylchloride and a foil of the aluminum printed varnished.

2 or 4 contour packs of 15 tablets together with the instructions for use are placed in a pack of cardboard.

For 30 tablets in a polymer tube with a cap-compensator.

Tubu together with instructions for use are placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-003625

Date of registration:13.05.2016

Expiration Date:13.05.2021

The owner of the registration certificate:PHARMSTANDART-TOMSKHIMFARM, OJSC PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Representation: & nbspPHARMSTANDART-TOMSKHIMFARM, OJSCPHARMSTANDART-TOMSKHIMFARM, OJSCRussia

Information update date: & nbsp29.04.2017

Illustrated instructions

Instructions

Gliklazid MB Pharmstandard (Gliclazide)