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

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

Gliclazide reduces the concentration of blood glucose, stimulating the secretion of insulin beta cells of the islets of Langerhans. The increase in the concentration of postprandial insulin and C-peptide persists after 2 years of therapy. Like other sulfonylurea derivatives, the basis for this effect is the increase in reaction β-cells of Langerhans islets on the physiological stimulation of glucose.

In addition to the effect on carbohydrate metabolism glycazide has hemovascular effects.

Influence on secretion of insulin

In type 2 diabetes mellitus glycazide 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

Gliclazide reduces the risk of thrombosis of small vessels, affecting the mechanisms that can cause the development of 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 with the use of modified-release glycazide (target glycosylated hemoglobin (HbAlc) <6.5%) significantly reduces the risk of micro- and macrovascular complications of type 2 diabetes in comparison with standard glycemic control (study ADVANCE).

The strategy of intensive glycemic control included the appointment of glyclazide (on average 103 mg / day) and an increase in its dose (up to 120 mg / day) when applied against a background (or instead of) standard therapy before adding to it another hypoglycemic drug (eg, metformin, inhibitor alpha-glucosidase, thiazolidinedione derivative or insulin). When gliclazide is used in the group of intensive glycemic control (mean follow-up 4,8 years, mean HbAlc 6.5%) compared to the standard control group (mean values HbAlc 7.3%) shows a significant decrease in the relative risk of the combined frequency of development of macro- and microvascular complications by 10% due to: a significant reduction in the relative risk of major microvascular complications by 14%, development and progression of nephropathy - 21%, the occurrence and progression of microalbuminuria - in 9%, macroalbuminuria by 30% and development of renal complications by 11%.

The advantages of intensive glycemic control in the use of glycazide are not dependent on the results of treatment with antihypertensive drugs.

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

Distribution

About 95% of the drug binds to plasma proteins. The volume of distribution is about 30 liters.

Taking the drug Gliklazid MB at a dose of 60 mg once a day ensures the maintenance of an effective concentration of glycazide in the blood plasma for more than 24 hours.

Metabolism

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

Excretion

Excretion is carried out, basically, by kidneys in the form of metabolites, less than 1% is excreted unchanged. The half-life of gliclazide averages 16 hours (12 to 20).

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, clinically significant changes in pharmacokinetic parameters are not observed.

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:

increased sensitivity to gliclazide or any of the excipients of the drug, other derivatives of sulfonylurea, sulfonamides;
type 1 diabetes mellitus;
Diabetic ketoacidosis, diabetic precoma, diabetic coma;
severe renal or hepatic insufficiency (in these cases, the use of insulin is recommended);
simultaneous administration of miconazole (and dosage forms for systemic use and gels for the oral mucosa) - see the section "Interaction with drugs");
pregnancy and the period of breastfeeding (see the section on "Application during pregnancy and during breastfeeding");
age under 18 years (no data but safety and effectiveness).

It is not recommended to use the drug simultaneously in combination with phenylbutazone or danazol.

Carefully:

Elderly age; inadequate or unbalanced nutrition; severe and decompensated endocrine diseases (hypothyroidism, pituitary and adrenal insufficiency); cancellation of long-term and / or high doses of glucocorticosteroid therapy (GCS); severe cardiovascular diseases (severe ischemic heart disease, severe carotid arteries, widespread atherosclerosis); renal and / or liver failure; alcoholism; insufficiency of glucose-phosphate dehydrogenase.

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.

If there is insufficient compensation for diabetes mellitus, there is a risk of developing congenital anomalies. To reduce this risk, it is necessary to achieve adequate glycemic control.Oral hypoglycemic drugs during pregnancy are not applied. The drug of choice for the treatment of diabetes in pregnant women is insulin. It is recommended to replace gliclazide with insulin therapy, as in the case of a planned pregnancy, and if the pregnancy occurred against the background of taking the drug.

Breastfeeding period

Given the lack of data on the intake of glycazide in breast milk and the risk of developing neonatal hypoglycemia, during drug therapy, breast-feeding is contraindicated.

Dosing and Administration:

PREPARATION IS INTENDED FOR ADULTS ONLY IN ADULTS

The recommended dose of the drug should be taken orally, 1 time / day, preferably during breakfast.

The daily dose is 30-120 mg (½-2 tablets) in 1 reception. It is recommended to swallow the entire dose of the drug entirely, without chewing or grinding.

If you skip one or more doses of the drug, you can not take a higher dose to the next dose, the missed dose should be taken the next day. As with other hypoglycemic drugs, the dose of the drug in each case must be selected individually, depending on the concentration of blood glucose and glycosylated hemoglobin (HbAlc).

Initial dose

The initial recommended dose in adults who had not previously received treatment (including in elderly patients ≥65 years) is 30 mg / day (½ tablets), then the dose is selected individually until the desired result is achieved.

Dose selection

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, whose blood glucose concentration did not decrease within two weeks of therapy. In such cases, the dose of the drug can be increased at the end of the second week of treatment, and each subsequent dose change can be undertaken after at least a two-week period.

Supportive therapy

The maintenance daily dose is from 30 mg to 90-120 mg. The maximum recommended daily dose is 120 mg. The presence of a notch on the 60 mg tablet allows you to divide the tablet and take a daily dose equal to 30 mg (½ tablets 60 mg) and, if necessary, 90 mg (1 ½ tablets 60 mg).

Transition from the reception of gliclazide, tablets 80 mg

1 tablet of gliclazide 80 mg is equivalent ½ modified release tablets 60 mg of Gliclazide MB. When transferring a patient from taking gliclazide tablets 80 mg to therapy with Gliclazide CF, careful glycemiccontrol.

Transition from therapy to another oral hypoglycemic drug

The drug Gliklazid MB can be used in place of another oral hypoglycemic agent. When transferring patients from therapy with another oral hypoglycemic preiarate to long-acting gliclazide therapy, consideration should be given to effectiveness, dose and duration of action of the previously used hypoglycemic agent. Usually a transition period is not required. The initial dose of long-acting glyclazide should be 30 mg per day, then the dose is selected by titration under control of blood glucose concentration.

When transferring a patient from therapy with hypoglycemic drugs with a longer T_1/2, there may be a need for a temporary (within a few days) cessation of treatment to avoid an additive effect that increases the risk of developing hypoglycemia. The initial dose of prolonged-action gliclazide in this case should also be 30 mg per day. If necessary, the dose can be further increased by titration under control of blood glucose concentration.

Combination therapy with other hypoglycemic agents

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

Elderly people

The recommended doses to elderly people are identical to those for adults under 65 years of age.

Renal insufficiency

The recommended doses of the drug for renal failure of mild to moderate severity are identical to those for persons with normal renal function. It is recommended that careful medical supervision of the patient is carried out.

Patients at risk of developing hypoglycemia

In patients at risk of hypoglycaemia (poor diet, severe or poorly compensated endocrine disorders - pituitary and adrenal insufficiency, hypothyroidism; abolition of corticosteroids after long-term use and / or receiving high doses, severe diseases of the cardiovascular system ( severe ischemic heart disease, severe atherosclerosis of the carotid arteries, widespread atherosclerosis) it is recommended to apply a minimal dose (30 mg) to the drug Gliklazid MB.

Prevention of complications of diabetes mellitus

To achieve intensive glycemic control, you can gradually increase the dose of Gliclazide MB to 120 mg / day in addition to diet and exercise until the target HbAlc. It should be remembered about the risk of developing hypoglycemia. Besides, To the therapy, other hypoglycemic drugs can be added, for example, metformin, an alpha-glucosidase inhibitor, a hyazolidinedione derivative or insulin.

Side effects:

Hypoglycemia (in case of dysregulation and inadequate diet): headache a feeling of hunger, nausea, vomiting, fatigue, sleep disturbance, irritability, agitation, decreased concentration of attention, delayed reaction, depression, confusion, impaired vision and speech, aphasia, tremor, paresis, loss of self-control, feelings of helplessness, impaired perception , dizziness, weakness, convulsions, bradycardia, delirium, respiratory depression, drowsiness, loss of consciousness with possible development of coma, up to a lethal outcome.

Symptoms of compensatory activation of adrenergicnervous system: increased sweating, "sticky" skin, anxiety, tachycardia, increased blood pressure, palpitations, arrhythmia and angina.

From the gastrointestinal tract: nausea, vomiting, diarrhea, abdominal pain, constipation (the severity of these symptoms decreases with admission during meals).

Less common are the following side effects:

From the skin and subcutaneous tissue: skin rash, itching, urticaria, Quincke edema, erythema) maculopapulletic rash, bullous reactions (such as Stevens-Johnson syndrome and toxic epidermal necrolysis).

From the side of the blood and lymphatic system: anemia, thrombocytopenia, leukopenia, granulocytopenia. 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 (aspartame aminotransferase (ACT), alanine aminotransferase (ALT), alkaline phosphatase), hepatitis (isolated cases). When cholestatic jaundice occurs, therapy should be discontinued.

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

Common side effects of sulfonylurea derivatives: erythropenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, hyponatremia. Also on the background of taking other sulfonylureas, 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.

Side effects noted during clinical trials

There was a slight difference in the incidence of various serious adverse events between the two groups of patients: intensive and standard glycemic control. No new data on the safety of the use of gliclazide was obtained. Several cases of severe hypoglycemia have been reported. On average, the incidence of severe hypoglycemia was low. The frequency of hypoglycemia in the group of intensive glycemic control was higher than in the group of standard glycemic control; at the same time, most episodes of hypoglycemia were noted against the background of concomitant insulin therapy.

Overdose:

Overdose of sulfonylurea derivatives, including glycazide, can lead to the development of hypoglycemia up to hypoglycemic coma.

Treatment

Moderate symptoms of hypoglycemia without disturbance of consciousness or neurologic symptoms are corrected by taking carbohydrates, choosing a dose and / or changing the diet. Careful monitoring of the patient's condition should continue until there is no certainty that the patient's 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. If a hypoglycemic coma is suspected or diagnosed, 50 ml of a 40% solution of dextrose (glucose) is injected intravenously. Then, 5% dextrose solution is dripped intravenously to maintain the necessary blood glucose concentration of about 1 g / l. Careful monitoring of blood glucose concentrations and patient monitoring should be done for at least 48 consecutive hours.In the future, depending on the patient's condition, it is necessary to decide the need for further monitoring of the patient's vital functions.

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

Interaction:

1) Drugs that enhance the effect of glycazide (increased risk of hypoglycemia):

Contraindications

Miconazil (systemic administration or use of the gel on the oral mucosa): we strengthen the hypoglycemic effect of glycazide (hypoglycemia can be developed up to the states of coma).

Unrecommended combinations

Phenylbutazone (systemic administration) enhances the hypoglycemic effect of derivatives of sulfonylureas (displaces them from the bond with plasma proteins and / or slows their elimination from the body). It is preferable to use another anti-inflammatory drug. If the use of phenylbutazone is necessary, the patient should be warned of the need, controlling the concentration of blood glucose. If necessary, the dose of gliclazide during the administration of phenylbutazone and after its termination.

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

Combinations, requiring precautions

The use of gliclazide in combination with certain drugs, for example, other hypoglycemic agents - insulin, inhibitors of alpha-glucosidase (acarbose), biguanides (metformin), thiazolidinediones, inhibitors of dipeptidyl-eptidase-4, agonists of the glucagon-like-p53 receptid (GLP-1) receptors; beta-address blockers, fluconazole; inhibitors of the angiotensin-converting enzyme - captopril, enalapril; blockers H₂-cystamine receptors (cimetidine); monoamine oxidase inhibitors; sulfonamides, clarithromycin and non-steroidal anti-inflammatory drugs, is accompanied by increased hypoglycemic effect and risk of hypoglycemia.

2) drugs that reduce the effect of gliclazide:

Unrecommended combinations

Danazol: has a diabetic effect. If the drug is needed, the patient should carefully monitor the blood glucose concentration.If it is necessary to jointly take medications, it is recommended that the dose of gliclazide be selected both during and after danazol administration.

Combinations that require precautions

Chlorpromazine: in high doses (more than 100 mg per day) increases the concentration of glucose in the blood, reducing the secretion of insulin. It is recommended to carefully monitor the concentration of glucose (blood.) If it is necessary to take joint medications, it is recommended that the dose of gliclazide be selected both during the intake of chlorpromazine and after its withdrawal.

SCS (systemic and topical application: intraarticular, external and rectal administration) and tetracosactide: increase the concentration of glucose in the blood with the possible development of ketoacidosis (a decrease in tolerance to carbohydrates). It is recommended that blood glucose concentration be carefully monitored, especially at the beginning of treatment. If it is necessary to take medications together, it may be necessary to correct the dose of the hypoglycemic agent both during the administration of the GCS and after their withdrawal.

PuTodreen, salbutamol, terbutaline (intravenous): β2-adrenomimetics increase blood glucose concentration.

Regular self-monitoring of blood glucose concentration is necessary. If necessary, it is recommended to transfer the patient to insulin therapy.

Combinations that need to be taken into account

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

Special instructions:

When taking sulfonylurea derivatives, including glycazide, hypoglycemia may develop, and in some cases - in severe and prolonged form, requiring hospitalization and intravenous administration of a dextrose solution for several days. The drug Gliklazid MB can be prescribed only to those patients whose diet is regular and includes breakfast. It is very important to maintain sufficient intake of carbohydrates with food. 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 required, as well as providing the patient with complete information about the proposed 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 MB;
Some endocrine disorders (thyroid gland diseases, pituitary and adrenal insufficiency);
simultaneous reception of certain medicines.

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

Hepatic / Renal Failure

In patients with hepatic and / or renal insufficiency, a change in the pharmacokinetic and / or pharmacodynamic properties of the glycazide is possible. Hypoglycemia, developing in these patients, can be quite long, in such cases, immediate appropriate therapy is needed.

Information for patients

It is necessary to inform the patient and his family 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 clarify the importance of dieting, the need for regular exercise and regular monitoring of blood glucose concentrations.

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 CF and prescribe insulin therapy.

In many patients, the effectiveness of oral hypoglycemic agents, incl. glyclazide, 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,at 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 assess the adequacy of dose selection and adherence to the prescribed diet.

Kocontrol laboratory indicators

For evaluation of glycemic control, regular determination of fasting blood glucose and HbAlc. In addition, it is advisable to regularly conduct self-monitoring of blood glucose concentration.

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

Patients should be aware of the symptoms of hypoglycemia and take care when driving vehicles or performing work that requires a high rate of psychomotor reactions, especially at the beginning of therapy.

Form release / dosage:

Modified release tablets 60 mg.

Packaging:

For 10, 14, 25, 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10, 20, 30, 40, 50, 60 or 100 tablets in cans of polyethylene terephthalate or cans of polypropylene for medicines.

One banky or 1, 2, 3, 4, 5, 6 or 10 contour mesh packages together with the instructions for use are placed in a cardboard package.

Storage conditions:

In a dark place at a temperature of no higher than 25 ° C. Store in a place inaccessible to children.

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003109

Date of registration:21.07.2015

Expiration Date:21.07.2020

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp29.04.2017

Illustrated instructions

Instructions

Gliklazid MB (Gliclazide)