Expiration date: 07/2025

The composition and form of issue: 

1 tablet contains gliclazide 30 mg in blister packs of 30 PCs., in box 1 or 2 blisters.

Description pharmaceutical form:

White, biconvex, oval tablet with a notch and engraved "DIA" "60" on both sides.

Pharmacokinetics:

After oral gliclazide is completely absorbed. The concentration of gliclazide in plasma increases gradually, coming to a plateau after 6-12 h. the Individual variability is low.

Eating does not affect the extent of absorption of gliclazide. The relationship between the adopted dose (120 mg) and AUC is linear.

The plasma protein binds about 95% of gliclazide. Gliclazide is metabolized primarily in the liver and excreted mainly by the kidneys: excretion is in the form of metabolites, less than 1% is excreted by the kidneys unchanged. Active metabolites in plasma are absent.

T1/2 of gliclazide is an average of from 12 to 20 h. Vd is approximately 30 L.

In elderly age no significant changes of pharmacokinetic parameters.

The drug gliclazide MR at a dose of 60 mg 1 time per day maintains the effective concentration of gliclazide in plasma more than 24 hours.

Description pharmacological action:

Gliclazide is a derivative of the sulfonylurea hypoglycemic drug for oral administration, which differs from similar products by the presence of N-containing heterocyclic ring with endotoksicski communication.

Gliclazide reduces blood glucose concentrations by stimulating insulin secretion from the beta cells of the islets of Langerhans. Increasing the concentration of postprandial insulin and C-peptide persisted after 2 years of therapy.

In addition to the impact on carbohydrate metabolism gliclazide has hemovascular effects.

Effect on insulin secretion

Diabetes type 2 drug restores early peak of insulin secretion in response to glucose intake and increases second phase insulin secretion. A significant increase in insulin secretion observed in response to stimulation caused by the ingestion or administration of glucose.

Hemovascular effects

Gliclazide reduces the risk of thrombosis of small vessels, affecting the mechanisms that may influence the development of complications in diabetes mellitus: partially inhibits aggregation and adhesion of platelets and reduces the concentration of factors of platelet activation (beta-thromboglobulin, thromboxane B2) and also restores fibrinolytic activity of the vascular endothelium and increases the activity of tissue plasminogen activator.

Intensive glycemic control, based on application of MR Gliclazide (HbA1c <6.5%) have significantly reduces micro - and macrovascular complications of diabetes mellitus type 2 in comparison with the standard glycemic control (the ADVANCE study).

The strategy of intensive glycemic control provided for the appointment of the drug gliclazide MR and increasing the dose in the background (or instead of) standard treatment before adding to it another hypoglycemic drugs (e.g., Metformin, inhibitors of alpha-glucosidase, derived thiazolidinedione or insulin). The average daily dose of the drug gliclazide MR in patients in the intensive control group was 103 mg, the maximum daily dose was 120 mg.

On the background of the drug gliclazide MR in the group of intensive glycemic control (mean duration of observation of 4.8 years, the average HbA1c level of 6.5%) compared to the standard control group (average HbA1c is 7.3%) have shown significant decrease by 10% the relative risk of the combined frequency of macro - and microvascular complications.

The advantage was achieved by a significant reduction in the relative risk of major microvascular complications by 14%, the occurrence and progression of nephropathy by 21%, the risk of microalbuminuria by 9%, macroalbuminuria 30% and development of renal complications in 11%.

The benefits of intensive glycemic control on background drug gliclazide MR did not depend on benefits achieved on the background of antihypertensive therapy.

Indications:

• diabetes mellitus type 2 with the lack of effectiveness of diet, physical activity and reducing body mass
  
• prevention of complications of diabetes: reducing the risk of microvascular (nephropathy, retinopathy) and macrovascular complications (myocardial infarction, stroke) in patients with diabetes type 2 diabetes through intensive glycemic control.
  

Contraindications:

• hypersensitivity to gliclazide, other sulfonylureas, sulfonamides or auxiliary substances within the drug
  
• diabetes mellitus type 1
  
• diabetic ketoacidosis, diabetic precoma, diabetic coma
  
• severe renal or hepatic insufficiency (in these cases it is recommended to use insulin)
  
• the use of miconazole (see "Interactions")
  
• pregnancy and breast-feeding (see "pregnancy and breastfeeding")
  
• the age of 18
  
• patients with congenital lactose intolerance, galactosemia, glucose-galactose malabsorption (not recommended gliclazide MR due to the fact that the preparation includes lactose)
  
• use in combination with phenylbutazone or danazol (see "Interactions").
  

With caution: advanced age, irregular and/or unbalanced nutrition, deficiency of glucose-6-phosphate dehydrogenase, severe diseases of the cardiovascular system, hypothyroidism, adrenal or pituitary insufficiency, renal and/or hepatic insufficiency, long-term therapy of corticosteroids, alcoholism.

Application of pregnancy and breast-feeding:

Pregnancy

Experience with the use of gliclazide during pregnancy is absent. Data on the use of other derivatives of sulfonylureas during pregnancy is limited.

In studies on laboratory animals teratogenic effects of gliclazide were identified.

To reduce the risk of development of congenital defects requires optimal control (an appropriate treatment) of diabetes.

Oral hypoglycemic drugs during pregnancy is not applied. Insulin is the drug of choice for treatment of diabetes in pregnant women. It is recommended to change oral hypoglycemic drugs to insulin as in the case of planned pregnancy, and if pregnancy occurred while taking the drug.

Breast-feeding

Taking into account the lack of data on the flow of gliclazide into breast milk and the risk of neonatal hypoglycemia during drug therapy breast-feeding is contraindicated.

Side effects:

Considering experience of application of gliclazide and other sulfonylureas derivatives, it is necessary to remember about possibility of development of side effects.

Hypoglycemia

As with other drugs group sulfonylureas, gliclazide MR can cause hypoglycemia in the case of irregular intake of meals, especially if meal is skipped. Possible symptoms of hypoglycemia: headache, intense hunger, nausea, vomiting, fatigue, sleep disturbance, irritability, agitation, decreased concentration, slowed reaction time, depression, confusion, impaired vision and speech, aphasia, tremor, paresis, violation of perception, dizziness, weakness, convulsion, bradycardia, delirium, respiratory failure, drowsiness, loss of consciousness, possible coma, and even death.

Also may include the adrenergic response: sweating, clammy skin, anxiety, tachycardia, increased blood pressure, palpitations, arrhythmia, and angina.

Generally, symptoms of hypoglycemia are reduced by the intake of carbohydrates (sugar). The reception of substitutes ineffective. Compared to other sulfonylurea derivatives it was observed the recurrence of hypoglycemia after a successful cupping.

In severe or prolonged hypoglycaemia is shown a medical emergency, possible hospitalization, even in the presence of the effect from carbohydrates.

Other side effects

Gastrointestinal: abdominal pain, nausea, vomiting, diarrhea, constipation. The drug is during Breakfast allows you to avoid these symptoms or to minimize them.

Rarely observed side effects.

The skin and subcutaneous tissue: rash, itching, urticaria, erythema, makulopapuleznaya rash, bullous rash.

From the blood and lymphatic system: hematologic disorders (anemia, leukopenia, thrombocytopenia, granulocytopenia) are rare. As a rule, these phenomena are reversible in the event of termination of therapy.

The liver and biliary tract: increased activity of liver enzymes (AST, ALT, alkaline phosphatase), hepatitis (isolated cases). The appearance of cholestatic jaundice should discontinue therapy.

The following side effects are usually reversible in the event of termination of therapy.

On the part of the organ of vision: you may experience temporary visual disturbances caused by changes in the concentration of blood glucose, especially at the beginning of therapy.

Side effects similar to sulfonylureas: as in patients receiving other sulfonylurea derivatives, noted the following side effects: erythropenia, agranulocytosis, haemolytic anaemia, pancytopenia, allergic vasculitis, hyponatremia. There was an increase in liver enzymes, abnormal liver function (e.g. with the development of cholestasis and jaundice) and hepatitis symptoms decreased with time after discontinuation of the sulphonylurea, but in some cases led to ginepraia liver failure.

Side effects noted during clinical trials

In the ADVANCE study showed a slight difference in the frequency of various serious adverse events between the two patient groups (intensive and standard glycemic control). New safety data has been received. A small number of patients had severe hypoglycemia, however, the overall incidence of hypoglycemia was low. The frequency of hypoglycemia in the group of intensive glycemic control were higher than in the group of standard glycemic control. Most episodes of hypoglycemia in a group of intensive glycemic control was observed on the background of concomitant insulin therapy.

Drug interactions:

1. Drugs that increase the risk of hypoglycemia (increases the effect of gliclazide)

Contraindicated combinations

Miconazole (with systemic administration and the use of the gel on the mucous membrane of the oral cavity): increases the hypoglycaemic effect of gliclazide (may develop hypoglycemia up to coma).

Deprecated combination

Phenylbutazone (systemic): increases the hypoglycaemic effect of sulfonylureas (displaces from its Association with plasma proteins and/or slows down their elimination from the body).

It is preferable to use a different anti-inflammatory drug. If the reception of phenylbutazone necessary, the patient should be warned of the need for glycemic control. If necessary, the dose of the drug gliclazide MR should be adjusted during the reception of phenylbutazone and after it.

Ethanol: increases hypoglycaemia by inhibiting compensatory reactions, may contribute to the development of hypoglycemic coma. You need to stop taking drugs, including ethanol, and alcohol consumption.

Combinations requiring precautions

Receiving gliclazide in combination with some drugs (for example, other hypoglycemic drugs — insulin, inhibitors of alpha-glucosidase, biguanides, beta-blockers, fluconazole, ACE inhibitors — captopril, enalapril histamine H2 receptors, MAO inhibitors, sulfonamides, clarithromycin and NSAIDs) is accompanied by increased hypoglycemic effect and risk of hypoglycemia.

2. Drugs that increase glucose in the blood (weaken the effect of gliclazide)

Deprecated combination

The danazol: diabetogenic effect has. If this drug is necessary, the patient it is recommended that careful glycemic control. If necessary, the joint supplementation is recommended dose as hypoglycemic drugs while taking the danazol, and after its cancellation.

Combinations requiring precautions

Chlorpromazine (Thorazine) in high doses (>100 mg/day) increases the concentration of glucose in the blood, reducing insulin secretion. It is recommended that careful glycemic control. When you need to share medication recommended dose hypoglycemic drugs as while receiving neuroleptic and after its withdrawal.

Corticosteroids (systemic and local use — intra-articular, cutaneous, rectal): increase the concentration of blood glucose, with possible development of ketoacidosis (reduced tolerance to carbohydrates). It is recommended that careful glycemic control, especially at the beginning of treatment. If necessary, co-administration of drugs may require correction doses of hypoglycemic drugs as while taking corticosteroids and after their withdrawal.

Ritodrin, salbutamol, terbutaline (in/in the introduction): beta2-agonists help to increase the concentration of blood glucose.

Need to pay special attention to the importance of an independent glycemic control. If necessary, it is recommended to transfer the patient to insulin therapy.

3. Combinations to be taken into account

Anticoagulants (e.g. warfarin). Sulfonylureas may potentiate the effects of anticoagulants when co-administered. You may need to adjust dose of anticoagulant.

Method of application and dose:

Inside, the preparation is intended only for the treatment of adults, swallow tablet or half tablet whole without chewing or crushing, preferably during Breakfast, 1 time a day.

The daily dose may be 30-120 mg (1/2–2 table.) in one go.

When skipping one or more doses of the drug should not take a higher dose next dose, the missed dose should be taken the next day.

As with other hypoglycemic drugs, the dose in each case must be individualized, depending on the concentration of blood glucose and level HbA1c.

The initial dose

The initial recommended dose (including elderly patients, &ge65 years) — 30 mg/day (1/2 tab.).

In case adequate control of the drug at this dose may be used for maintenance therapy. With inadequate glycemic control daily dose can be incrementally increased to 60, 90 or 120 mg.

Increasing the dose is possible not earlier than after 1 month of drug therapy in the previously prescribed dose. The exception is patients in whom the concentration of blood glucose was not reduced after 2 weeks of therapy. In such cases, the dose may be increased after 2 weeks after starting.

The maximum recommended daily dose is 120 mg.

1 table. drug gliclazide MR of the modified-release tablet 60 mg equivalent of 2 tabl. Gliclazide MR of the modified-release tablet 30 mg. the Presence of a notch on tablets 60 mg allows you to divide the tablet and take the daily dose as 30 mg (1/2 table. 60 mg) and if needed, 90 mg (1 and 1/2 table. 60 mg).

The transition from drug gliclazide tablets 80 mg gliclazide drug MR tablets modified-release 60 mg

1 table. drug gliclazide 80 mg can be replaced with 1/2 table. drug MR gliclazide modified-release 60 mg. When transferring patients with drug gliclazide 80 mg to the drug gliclazide MR it is recommended that careful glycemic control.

The transition from receiving other hypoglycemic drugs on the drug gliclazide MR tablets modified-release 60 mg

Drug gliclazide MR tablets modified-release 60 mg can be used instead of the other hypoglycemic drugs for oral administration. When transferring to gliclazide CF patients receiving other hypoglycemic drugs for oral administration, should take into account their dose and T1/2. As a rule, the transition period is not required. The initial dose should be 30 mg and then should Mitrovitsa depending on the concentration of blood glucose.

The replacement drug gliclazide MR of sulfonylureas with prolonged T1/2 to avoid hypoglycemia caused by the additive effect of two hypoglycemic agents, you can stop them for a few days. The initial dose gliclazide MR also is 30 mg (1/2 table. 60 mg) and, if necessary, can be increased further, as described above.

Combined intake with other hypoglycemic drugs

Gliclazide MR can be used in combination with biguanides, inhibitors of alpha-glucosidase or insulin.

With inadequate glycemic control should be assigned additional insulin therapy with a thorough medical supervision.

Elderly patients

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

Patients with renal insufficiency

Results of clinical studies have shown that a dosage adjustment in patients with renal insufficiency mild to moderate severity is not required. It is recommended to conduct a thorough medical control.

Patients with risk of hypoglycemia

In patients at risk of hypoglycemia (inadequate or unbalanced diet severe or poorly compensated endocrine disorders — pituitary and adrenal insufficiency, hypothyroidism cancellation of corticosteroids after long-term use and/or taken in high doses for severe disease, severe coronary artery disease, severe atherosclerosis of the carotid arteries, common atherosclerosis), it is recommended to use the minimum dose (30 mg) of the drug gliclazide MR.

Prevention of complications of diabetes

To achieve intensive glycemic control can gradually increase the dose of the drug gliclazide MR to 120 mg/day in addition to diet and exercise to achieve the target HbA1c level. Remember about the risk of hypoglycemia. In addition, to therapy can be added to other hypoglycemic drugs, such as Metformin, an inhibitor of alpha glucosidase, a derivative of thiazolidinedione or insulin.

Children and adolescents under 18 years

Data on the efficacy and safety of the drug in children and adolescents under the age of 18 years do not exist.

Overdose:

If overdose of sulfonylureas may develop hypoglycemia.

If you experience moderate symptoms of hypoglycemia without impairment of consciousness or neurological symptoms should increase the intake of carbohydrates with food, to decrease the dose and/or change your diet. Careful medical monitoring of patients should continue until, until assured that his health is not in danger.

Perhaps the development of severe hypoglycemic States, accompanied by coma, convulsions or other neurological disorders. When you see these symptoms need emergency medical assistance and immediate hospitalization.

In the case of hypoglycemic coma or suspected her patient in/in struino injected 50 ml of 20-30% solution of dextrose (glucose). Then b/drip to impose 10% dextrose to maintain glucose concentration in the blood above 1 g/l Careful monitoring of blood glucose level and monitoring of the patient must be carried out at least within 48 hours. After this period of time, depending on the condition of the patient the attending physician decides on the need for further observation.

Dialysis is ineffective due to pronounced binding of gliclazide to proteins of plasma.

Special instructions:

Hypoglycemia

When the intake of sulfonylureas, including gliclazide, can develop hypoglycemia, in some cases, in severe and prolonged form, requiring hospitalization and I/V administration of dextrose within a few days (see "Side effects").

The drug can be prescribed only to those patients fed regularly and includes Breakfast. It is important to maintain adequate intake of carbohydrates c food, because the risk of hypoglycemia increases when irregular or insufficient meals, and when consumption of foods poor in carbohydrates. Hypoglycemia often develops in a low-calorie diet, following prolonged or strenuous physical exercise, after drinking alcohol or when taking multiple hypoglycemic drugs at the same time.

Generally, symptoms of hypoglycemia are after a meal rich in carbohydrates (e.g. sugar). It should be borne in mind that the intake of sweeteners is not conducive to the elimination of hypoglycemic symptoms. The use of other derivatives sulfonylureas shows that hypoglycaemia can recur despite effective initial relief of this condition. If hypoglycemic symptoms have a strong character or are long-lasting, even in the case of a temporary improvement the condition after a meal rich in carbohydrates, necessary medical care until hospitalization.

To avoid the development of hypoglycemia requires careful individual selection of drugs and dosing regimen, as well as providing the patient full information about the ongoing treatment.

Increased risk of hypoglycemia can be observed in the following cases:

• refusal or inability of the patient (particularly the elderly) to follow the doctor's orders and monitor their status
  
• insufficient and irregular meals, skipping meals, fasting and change of diet
  
• imbalance between physical exercise and intake of carbohydrates
  
• renal failure
  
• severe hepatic insufficiency
  
• an overdose of the drug gliclazide MR
  
• certain endocrine disorders: thyroid disease, pituitary and adrenal insufficiency
  
• concomitant use of certain drugs (see "Interactions").
  

Kidney and liver failure

In patients with hepatic and/or severe renal failure may change the pharmacokinetic and/or pharmacodynamic properties of gliclazide. The condition of hypoglycemia that develops in these patients may be prolonged, in such cases, immediate appropriate therapy.

Information for patients

You must inform the patient and family members about the risks of hypoglycemia, symptoms and conditions conducive to its development. The patient must be informed of the potential risks and benefits of the proposed treatment.

The patient needs to explain the importance of diet, need for regular physical exercise and control of glucose concentration of blood.

Inadequate glycemic control

Glycemic control in patients receiving therapy with hypoglycemic agents, may be weakened in the following cases: fever, trauma, infectious disease or big surgery. In these States, you may need to stop treatment with the drug gliclazide MR, and insulin therapy is recommended.

In many patients, the effectiveness of oral hypoglycemic agents, including gliclazide, has a tendency to decline after a long period of treatment. This effect may be due to progression of the disease, and decrease of the therapeutic response to the drug. This phenomenon is known as secondary drug resistance, which is necessary to distinguish from primary at which the drug at the first appointment does not give the expected clinical effect. Before diagnosing the patient secondary drug resistance, it is necessary to assess the adequacy of dose selection and patient compliance to the prescribed diet.

Laboratory tests

For the evaluation of glycemic control is recommended regular determination of the concentration of fasting blood glucose and glycated hemoglobin HbA1c. It is also advisable to conduct regular self-monitoring glucose concentration of blood.

Sulfonylureas can cause hemolytic anemia in patients with a deficit glukozo-6-fosfatdegidrogenaza. As gliclazide is a derivative of sulfonylurea, use caution when administered to patients with a deficit glukozo-6-fosfatdegidrogenaza. To evaluate the possibility of appointing a hypoglycemic drug of the other group.

Effect on ability to drive and perform work requiring high speed mental and physical reactions

Patients should be aware of the symptoms of hypoglycemia and take caution while driving or performing work requiring high speed physical and mental reactions, especially at the beginning of therapy.