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

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.

Gliclazide reduces the concentration of glucose in the blood, stimulating the secretion of insulin βcells 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 mellitus glycazide restores early peak fromthe 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 aggregation and adhesion of platelets and a decrease in the concentration of platelet activating factors (beta-thromboglobulin, thromboxane AT₂), 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 modified-release glycazide (target of glycosylated hemoglobin (HbAlc) <6.5%) significantly reduces the risk of micro- and macrovascular complications of type 2 diabetes mellitus, in comparison with standard glycemic control.

Pharmacokinetics:

Absorption

After oral administration glycazide completely absorbed from the gastrointestinal tract.The concentration of active substance in the blood plasma gradually increases within 6 hours, the plateau level is maintained from 6 to 12 hours after taking the drug. Individual variability is low. The ingestion of food does not affect the absorption of gliclazide.

Distribution

The connection with plasma proteins is approximately 95%. The volume of distribution is about 30 liters. Daily intake of a single dose of the drug 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 unchanged. The half-life of gliclazide is, on average, 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, 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;
miconazole;
pregnancy and the period of breastfeeding;
age to 18 years.

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

Carefully:

Elderly age, irregular and / or unbalanced diet, severe cardiovascular diseases (including IHD, atherosclerosis), hypothyroidism, adrenal or hypophysial insufficiency, hypopituitarism, renal and / or hepatic insufficiency, long-term glucocorticosteroid therapy (GCS), alcoholism, insufficiency of glucose-6-phosphate dehydrogenase.

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.

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, both in the case of a planned pregnancy, and if the pregnancy occurred while taking the drug.

Breastfeeding period

Taking into account the lack of data on the penetration of glycazide into breast milk and the risk of developing neonatal hypoglycemia, during breastfeeding therapy, it is contraindicated.

Dosing and Administration:

The drug is intended only for the treatment of adults.

The recommended dose of the drug should be taken orally, once a day, preferably during breakfast. It is recommended to swallow 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 glycosylated hemoglobin (HbAlc).

Initial dose

The initial recommended dose in adults (including those in the elderly ≥ 65 years) - 30 mg (1 tablet) per day.

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 mg, 90 mg 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.

Supportive therapy

The maintenance daily dose is 30 to 120 mg.

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

Transition from the administration of Glidiab ® tablets 80 mg to the preparation Glidiab ® MB, modified release tablets 30 mg

One tablet of Glidiab®, a tablet of 80 mg, can be replaced with 1 tablet with a modified release of 30 mg of Gliradiab MB. When transferring patients from Gliradiab®, 80 mg tablets, careful glycemic control is recommended for the preparation Gliabetes MB.

Transition from taking another hypoglycemic drug to Gliradab® MB, modified release tablets 30 mg The Glydiab® MB preparation, modified-release tablets of 30 mg, can be used in place of another oral hypoglycemic agent. When translating to Gliwiab® CF patients receiving other oral hypoglycemic drugs should take their dose and half-life into account. As a rule, a transition period is not required. The initial dose of Glidiab® MB should be 30 mg and then should be titrated depending on the concentration of blood glucose.

When transferring a patient from therapy with hypoglycemic drugs with a long half-life,there may be a need for a temporary (within a few days) cessation of treatment in order to avoid an additive effect that increases the risk of developing hypoglycemia. The initial dose of Glidiab® MB is also 30 mg and, if necessary, can be further increased as described above.

Combination with another hypoglycemic drug Glydiab® MB 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.

Special patient groups

Elderly patients

Recommended dosage for elderly people is identical to that for adults up to 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.

Patients at risk of developing hypoglycemia

In patients who are at risk for developing hypoglycemia (inadequate or unbalanced nutrition, severe or poorly compensated endocrine disorders - pituitary and adrenal insufficiency,hypothyroidism; abolition of SCS after their long reception and / or intake in high doses; severe cardiovascular disease (severe ischemic heart disease, severe carotid artery atherosclerosis, widespread atherosclerosis), it is recommended to apply the minimum dose (30 mg) of Glidiab® MB.

Prevention of complications of diabetes mellitus

To achieve intensive glycemic control, you can gradually increase the dose of Glidiab 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. In addition, other hypoglycemic drugs may be added to therapy, for example, metformin, an alpha-glucosidase inhibitor, a thiazolidinedione derivative or insulin.

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 Glioadab ® MB can cause hypoglycemia in the event of an irregular intake of food and especially if the meal is missed.Possible symptoms of hypoglycemia: headache, severe hunger, nausea, vomiting, fatigue, sleep disturbance, irritability, agitation, decreased concentration, slow reaction, depression, confusion, impaired vision and speech, aphasia, tremor, paresis, impaired perception , dizziness, loss of self-control, a feeling of helplessness, weakness, convulsions, bradycardia, delirium, shallow breathing, drowsiness, loss of consciousness with possible development of coma, up to a lethal outcome.

Also can be marked adrenergic reactions: sweating, "sticky" skin, anxiety, tachycardia, hypertension, palpitations, arrhythmia, and angina pectoris.

From the gastrointestinal tract: nausea, vomiting, abdominal pain, diarrhea, constipation. Taking the drug during breakfast allows you to avoid these symptoms or minimize them.

From the skin and subcutaneous tissues: rash, itching, urticaria, angioedema (Quincke's edema), erythema, maculopapular 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, 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. Side Effects of Sulfonylurea Derivations As with other sulfonylurea derivatives, the following side effects were noted: erythropenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, hyponatremia.

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:

Symptoms: hypoglycaemia, up to the development of hypoglycemic coma.

Treatment: Moderate symptoms of hypoglycemia without disturbance of consciousness or Neurological 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

Miconazole (systemic administration or use of the gel on the oral mucosa): enhances the hypoglycemic effect of glycazide (possible development of hypoglycemia 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 plasma proteins and / or slows their elimination from the body). It is preferable to use another anti-inflammatory drug. If taking phenylbutazone is necessary, the patient should be warned about the need to monitor blood glucose concentrations. If necessary, the dose of gliclazide should be adjusted during the administration of phenylbutazone and after its termination.

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

Combinations, requiring precautions

Admission gliclazide in combination with certain drugs, for example, other hypoglycemic agents (insulin, alpha-glucosidase inhibitors, metformin, thiazolidinidiones, inhibitors of dipeptidyl peptidase-4, agonists of glucagon-like peptide-1); beta-adrenoblockers, fluconazole; inhibitors of the angiotensin-converting enzyme - captopril, enalapril; blockers H₂- histamine receptors; monoamine oxidase inhibitors; sulfonamides, clarithromycin and non-steroidal anti-inflammatory drugs is accompanied by increased hypoglycemic effect and risk of hypoglycemia.

2. Drugs that promote the increase in blood glucose (weakening 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 take joint medications, it is recommended that the dose of gliclazide be selected both during and after the 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 blood glucose. 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 hypoglycemic agent both during the administration of GCS or tetracosactide, and after their withdrawal.

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

It is necessary to pay special attention to the importance of self-monitoring of blood glucose concentration. 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 strengthen the effect of anticoagulants in a joint admission. You may need to adjust the dose of anticoagulant.

Special instructions:

Hypoglycaemia

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.

Gliradiab® MB can be given only to those patients who regularly eat breakfast. It is very important to maintain sufficient intake of carbohydrates with food, because 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;
drug overdose Gliradab® MB;
Some endocrine disorders (thyroid gland diseases, pituitary and adrenal insufficiency);
simultaneous intake of certain medicines.

Deficiency of glucose-b-phosphate dehydrogenase

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.

Hepatic / Renal Failure

In patients with hepatic and / or renal insufficiency of a serious degree, a change in the pharmacokinetic and / or pharmaco-dynamic 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. In these conditions, it may be necessary to stop therapy with GliDiab® MB 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, 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 assess the adequacy of dose selection and adherence to the prescribed diet.

Control of laboratory indicators

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

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

In connection with the possible development of hypoglycemia with the use of Glidiab® CF 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 30 mg.

Packaging:10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil. 3 or 6 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In dry, dark place 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 expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000002

Date of registration:25.06.2010 / 22.09.2016

Expiration Date:Unlimited

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp29.04.2017

Illustrated instructions

Instructions

Glidiab® MB (Glidiab MV)