Gliclazide-SZ, 60 mg 30 pcs

Gliclazide is an oral sulfonylurea derivative hypoglycemic drug that differs from similar drugs by the presence of N-containing heterocyclic ring with endocyclic bonding.

Glyclazide reduces blood glucose concentration by stimulating insulin secretion by β-cells of Langerhans islets. Increased concentration of postprandial insulin and C-peptide persists after 2 years of therapy.

In addition to effects on carbohydrate metabolism, gliclazide has hemovascular effects.

The effect on insulin secretion

In type 2 diabetes, the drug restores the early peak of insulin secretion in response to glucose intake and increases the second phase of insulin secretion. Significant increase of insulin secretion is observed in response to stimulation caused by food intake or glucose administration.

Hemovascular effects

Glyclazid reduces the risk of small vessel thrombosis by affecting the mechanisms that can cause complications in diabetes: Partial inhibition of platelet aggregation and adhesion and decreased concentration of platelet activation factors (beta-thromboglobulin thromboxane B2) and on restoration of fibrinolytic activity of the vascular endothelium and increased tissue plasminogen activator activity.

Intensive glycemic control based on the use of prolonged-release gliclazide significantly reduces micro- and macrovascular complications of type 2 diabetes compared to standard glycemic control.

Pharmacokinetics:

Intake

After oral administration, gliclazide is completely absorbed. The plasma concentration of gliclazide increases gradually over the first 6 hours a plateau level is maintained from 6 to 12 hours. Individual variability is low.

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

Distribution

About 95% of gliclazide is bound to blood plasma proteins. The volume of distribution is about 30 liters. Administration of Gliklazid-SZ at a dose of 60 mg once daily maintains the effective plasma concentration of gliklazide for more than 24 hours.

Metabolism

Glyclazide is metabolized predominantly in the liver. There are no active metabolites in blood plasma.

Elimation

Gliclaclazide is mainly excreted by the kidneys: less than 1% is excreted unchanged by the kidneys as metabolites. The elimination 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.

Particular populations

The elderly

There are no significant changes in pharmacokinetic parameters in the elderly.

Indications

Type 2 diabetes mellitus when the effectiveness of diet therapy of physical activity and weight loss is insufficient.

Prevention of diabetes complications: reduction of risk of microvascular (nephropathy retinopathy) and macrovascular complications (myocardial infarction stroke) in patients with type 2 diabetes by intensive glycemic control.

Active ingredient

Composition

One tablet contains:

the active ingredient: gliclazide – 60 mg

excipients:

calcium hydrophosphate dihydrate – 53.5 mg;

maltodextrin – 15.0 mg;

Hypromellose 4 K M (hydroxypropyl methylcellulose) – 4.3 mg;

Hypromellose K 100 LV (hydroxypropyl methylcellulose) – 25.7 mg;

Silica colloidal dioxide anhydrous (aerosil anhydrous) – 0.5 mg;

Magnesium stearate – 1.0 mg.

How to take, the dosage

The drug is indicated for the treatment of adults only.

The recommended dose should be taken orally once daily, preferably during breakfast.

The daily dose can be 30 to 120 mg (1/2 to 2 tablets) in one sitting. It is recommended that a tablet or half a tablet be swallowed whole without chewing or crushing.

If you miss one or more doses, do not take the higher dose at the next appointment, take the missed dose the next day.

As with other hypoglycemic medications, the dose of the drug must be adjusted individually in each case depending on the blood glucose concentration and glycated hemoglobin (HbAlc).

The initial recommended dose

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

If adequately controlled, the drug at this dose may be used for maintenance therapy. In case of inadequate glycemic control, the daily dose of the drug may be sequentially increased to 60 90 or 120 mg.

The dose can be increased not earlier than 1 month of therapy with the drug in the previously prescribed dose. Exceptions are patients in whom blood glucose concentrations have not decreased after 2 weeks of therapy. In such cases, the drug dose may be increased after 2 weeks of therapy.

The maximum recommended daily dose of the drug is 120 mg. The presence of a risk on the 60 mg tablets allows splitting the tablet and taking the daily dose as 30 mg (1/2 tablet of 60 mg) and, if necessary, 90 mg (1 tablet of 60 mg and 7 g tablets of 60 mg).

Transition from another hypoglycemic medication to Gliclazid-SZ 60 mg sustained release tablets

Gliclazid-SZ 60 mg sustained release tablets can be used in place of another oral hypoglycemic medication. When switching to Gliklazid-SZ, patients treated with other oral hypoglycemic agents should take into account their dose and half-life. As a rule, a transitional period is not required.

The starting dose should be 30 mg and then should be titrated according to the blood glucose concentration.

If Gliclazide-CZ is replaced by sulfonylurea derivatives with a long half-life to avoid hypoglycemia caused by the additive effect of the two hypoglycemic agents, their administration may be discontinued for several days. The starting dose of Gliclazide-SZ in this case is also 30 mg (7g tablet 60 mg) and may be subsequently increased as described above, if necessary.

Combination with another hypoglycemic drug

Gliklazide-SZ can be used in combination with biguanidin alpha-glucosidase inhibitors or with insulin.

If glycemic control is inadequate, additional insulin therapy should be prescribed with close medical monitoring.

Prevention of diabetes complications

The dose of Gliclazide-SZ may be gradually increased to 120 mg/day in addition to diet and exercise until target HbAlc levels are achieved to achieve intense glycemic control. The risk of hypoglycemia should be kept in mind. In addition, other hypoglycemic medications such as the thiazolidinedione derivative alpha-alpha-glucosidase inhibitor metformin or insulin may be added to therapy.

Patients in the elderly

There is no need to adjust the dose of the drug in patients over 65 years of age.

Patients with renal impairment

Patients with mild to moderate renal impairment do not require dosage adjustment.

Careful medical monitoring is recommended.

Patients at risk of hypoglycemia

Patients at risk of hypoglycemia (insufficient or unbalanced nutrition; severe or poorly compensated endocrine disorders – pituitary and adrenal insufficiency hypothyroidism; withdrawal of glucocorticosteroids (GCS) after long-term use and/or high doses; severe cardiovascular diseases – severe coronary heart disease severe carotid atherosclerosis widespread atherosclerosis) a minimum dose (30 mg) of Gliclazide-SZ is recommended.

Children and adolescents under 18 years of age.

There are no data on the efficacy and safety of the drug in children and adolescents under 18 years of age.

Interaction

Drugs and substances that increase the risk of hypoglycemia: (increasing the effect of gliclazide)

Contraindicated combinations

Miconazole (when administered systemically and when using the gel on the oral mucosa): Increases the hypoglycemic effect of gliclazide (possible development of hypoglycemia up to the state of coma).

Unrecommended combinations

Phenylbutazone (systemic administration): increases the hypoglycemic effect of sulfonylurea derivatives (displaces them from binding to plasma proteins and/or slows their elimination from the body).

The use of another anti-inflammatory drug is preferable. If administration of phenylbutazone is necessary, the patient should be warned about the need for glycemic control. If necessary, the dose of Gliclazide-SZ should be adjusted during and after phenylbutazone administration

– Ethanol: increases hypoglycemia by inhibiting compensatory responses may contribute to hypoglycemic coma. It is necessary to avoid taking medicines containing ethanol and drinking alcohol.

Combinations requiring precautions

The use of gliclazide in combination with certain medicinal products: Other hypoglycemic agents (insulin acarbose metformin thiazolidinedione dipeptidyl peptidase-4 inhibitors GFP-1 agonists); beta-adrenoblockers fluconazole; angiotensin-converting enzyme inhibitors captopril enalapril; H2-histamine receptor blockers; monoamine oxidase inhibitors; sulfonamides; clarithromycin and non-steroidal anti-inflammatory drugs) are accompanied by increased hypoglycemic effect and risk of hypoglycemia.

Drugs that increase blood glucose: (weakening the effect of gliclazide)

Unrecommended combinations

– Danazol: has a diabetogenic effect. Careful monitoring of blood glucose is recommended if the use of this drug is necessary for the patient. If co-administration is necessary, it is recommended that the dose of the hypoglycemic agent be adjusted both while taking danazolol and after discontinuation of the drug.

Combinations requiring precautions

Chlorpromazine (neuroleptic): in high doses (more than 100 mg per day) increases blood glucose concentration by reducing insulin secretion. Close glycemic control is recommended. If coadministration is necessary, it is recommended to adjust the dose of hypoglycemic agent both during neuroleptic administration and after discontinuation of the drug.

– GCS (systemic and local use: intraarticular dermal rectal administration) and tetracosactide: increase blood glucose concentration with possible development of ketoacidosis (reduced tolerance to carbohydrates). Close glycemic control is recommended, especially at the beginning of treatment. If coadministration of drugs is necessary, it may be necessary to adjust the dose of hypoglycemic agent both during the use of GCS and after their withdrawal.

– Ritodrine salbutamol terbutaline (intravenous): beta-2-adrenomimetics contribute to elevated blood glucose concentrations.

Particular attention should be paid to the importance of self-administered glycemic control. If necessary, it is recommended that the patient be transferred to insulin therapy.

Combinations to be considered

Anticoagulants (e.g., warfarin)

Sulfonylurea derivatives may increase the effect of anticoagulants when taken together. Adjustment of anticoagulant dose may be necessary.

Special Instructions

Hypoglycemia

Hypoglycemia may develop in some cases when taking sulfonylurea derivatives, including gliclazide, in a severe and prolonged form requiring hospitalization and intravenous administration of dextrose solution for several days (see section “Adverse effects”).

The drug should only be given to patients whose diet is regular and includes breakfast. It is very important to maintain an adequate intake of carbohydrates with food, since the risk of hypoglycemia increases with irregular or insufficient food intake and with consumption of food low in carbohydrates.

Hypoglycemia is more likely to occur with a low-calorie diet after prolonged or vigorous exercise after drinking alcohol or when taking multiple hypoglycemic medications at the same time.

As a rule, the symptoms of hypoglycemia disappear after ingestion of food rich in carbohydrates (such as sugar). It should be borne in mind that taking sugar substitutes does not help to eliminate hypoglycemic symptoms. Experience with other sulfonylurea derivatives suggests that hypoglycemia may recur despite effective initial management of this condition.

If hypoglycemic symptoms are severe or persistent, even if there is a temporary improvement after ingestion of a carbohydrate-rich meal, emergency care up to and including hospitalization is necessary.

In order to avoid hypoglycemia, careful individual selection of drugs and dosing regimens is necessary, as well as providing the patient with complete information about the ongoing treatment. An increased risk of hypoglycemia may occur in the following cases:

– refusal or inability of the patient (especially the elderly) to follow doctor’s orders and control their condition;

– inadequate and irregular meals skipping meals starvation and dietary changes;

– an imbalance between exercise and carbohydrate intake;

– renal impairment;

– severe hepatic impairment;

– overdose of Gliclazide-SZ;

– certain endocrine disorders thyroid diseases pituitary and adrenal insufficiency;

– concomitant administration of some drugs (see.

– concomitant use of certain medicinal products (see section “Interaction with other medicinal products”).

Hepatic and renal failure

In patients with hepatic and/or severe renal impairment the pharmacokinetic and/or pharmacodynamic properties of gliclazide may be altered. The state of hypoglycemia that develops in such patients may be quite prolonged in such cases, immediate appropriate therapy is necessary.

Inadequate glycemic control

Glycemic control in patients receiving therapy with hypoglycemic agents may be impaired in the following cases: fever injury infectious diseases or major surgical interventions. Under these conditions it may be necessary to discontinue therapy with Gliclazid-SZ and initiate insulin therapy.

In many patients, the efficacy of oral hypoglycemic agents, including gliclazide, tends to decrease after a prolonged period of treatment. This effect may be due to both disease progression and decreased therapeutic response to the drug.

This phenomenon is known as secondary drug resistance, which must be distinguished from primary drug resistance in which the drug does not produce the expected clinical effect the first time it is prescribed. Before a patient is diagnosed with secondary drug resistance, the adequacy of the dose and the patient’s compliance with the prescribed diet must be assessed.

Laboratory tests

To evaluate glycemic control, regular fasting blood glucose concentration and glycated hemoglobin HbAlc determination are recommended. In addition, regular self-monitoring of blood glucose concentration is advisable.

Sulfonylurea derivatives may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency. Since gliclazide is a sulfonylurea derivative, caution should be exercised when prescribing it in patients with glucose-6-phosphate dehydrogenase deficiency. The possibility of prescribing a hypoglycemic drug of another group should be assessed.

Patient information

The patient and family members should be informed about the risk of hypoglycemia, its symptoms, and conditions contributing to its development. The patient should be informed about the potential risks and benefits of the proposed treatment.

The patient should be educated about the importance of diet, regular exercise, and blood glucose monitoring.

Contraindications

Hypersensitivity to gliclazide other sulfonylurea derivatives sulfonamides or to excipients in the preparation;

diabetes mellitus type 1;

diabetic ketoacidosis diabetic precoma diabetic coma;

Severe renal or hepatic impairment (insulin is recommended in these cases);

The intake of miconazole (see

Pregnancy and breastfeeding (see section “Interaction with other medicinal products”).

Pregnancy and breastfeeding (see section “Administration during pregnancy and breastfeeding”).

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

Older age irregular and/or unbalanced diet glucose-6-phosphate dehydrogenase deficiency severe cardiovascular disease hypothyroidism adrenal or pituitary insufficiency renal and/or liver failure long-term therapy with glucocorticosteroids (GCS) alcoholism.

Side effects

Considering the experience of using gliclazide, be aware of the possibility of the following side effects.

Hypoglycemia

Like other drugs of the sulfonylurea group, Gliclazide-SZ may cause hypoglycemia if meals are not taken regularly and especially if meals are missed. Possible symptoms of hypoglycemia: headache severe hunger nausea vomiting increased fatigue sleep disturbance irritability agitation decreased concentration of attention delayed reaction depression confusion mental confusion visual and speech aphasia tremor paresis loss of self-control feeling of helplessness perception disturbance dizziness weakness convulsion bradycardia delirium shallow breathing sleepiness loss of consciousness with possible development of coma up to death.

Adrenergic reactions may also be noted: increased sweating “clammy” skin anxiety tachycardia increased blood pressure feeling heart palpitations arrhythmia and angina. As a rule, the symptoms of hypoglycemia are stopped by taking carbohydrates (sugar). Taking sugar substitutes is ineffective. Against the background of other sulfonylurea derivatives, relapses of hypoglycemia have been noted after successful resolution of hypoglycemia.

In severe or prolonged hypoglycemia, emergency medical care is indicated, possibly with hospitalization, even with the effect of carbohydrate intake.

Other side effects

Gastrointestinal side effects: abdominal pain nausea vomiting diarrhea constipation. Taking the drug with breakfast can avoid or minimize these symptoms.

The following side effects are less common:

Skin and subcutaneous tissue side effects: rash pruritus urticaria Quincke’s edema erythema maculopapular rash bullous reactions (such as Stevens-Jones syndrome and toxic epidermal necrolysis).

Hematological disorders (anemia leukopenia thrombocytopenia granulocytopenia) rarely develop. As a rule, these phenomena are reversible in case of discontinuation of therapy.

Hepatic and biliary tract disorders: increased activity of “hepatic” enzymes (aspartate aminotransferase (ACT) alanine aminotransferase (ALT) alkaline phosphatase) hepatitis (single cases). If cholestatic jaundice occurs, therapy should be discontinued.

These phenomena are usually reversible if therapy is discontinued.

VIight: there may be transient visual disturbances caused by changes in blood glucose concentration especially at the beginning of therapy.

Sulphonylurea derivative side effects: as with other sulfonylurea derivatives the following side effects have been observed: erythrocytopenia agranulocytosis hemolytic anemia pancytopenia allergic vasculitis hyponatremia. Increased activity of “liver” enzymes liver dysfunction (e.g., with the development of cholestasis and jaundice) and hepatitis have been noted; the manifestations decreased with time after withdrawal of sulfonylurea drugs but in individual cases led to life-threatening liver failure.

Overdose

Hypoglycemia may develop in case of overdose with sulfonylurea derivatives.

In case of moderate symptoms of hypoglycemia without impairment of consciousness or neurological symptoms, the intake of carbohydrates with food should be increased, the dose of the drug reduced and/or the diet changed. Close medical observation of the patient’s condition should continue until it is certain that his or her health is not in danger.

The development of severe hypoglycemic states accompanied by coma, seizures or other neurological disorders is possible. If these symptoms occur, emergency medical care and immediate hospitalization are necessary.

In case of hypoglycemic coma or if it is suspected, the patient is given 50 ml of 20-40% solution of dextrose (glucose) by intravenous drip. Then 5-10% dextrose solution is given intravenously by drip to maintain blood glucose concentrations above 1 g/L. Close monitoring of blood glucose levels and observation of the patient should be done for at least 48 hours afterwards. After this period of time, depending on the patient’s condition, the attending physician will decide whether further monitoring is necessary.

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

Pregnancy use

Pregnancy

There is no experience with the use of gliclazide during pregnancy. There are limited data on the use of other sulfonylurea derivatives during pregnancy.

There have been no teratogenic effects of gliclazide in studies on laboratory animals.

The optimal control (appropriate therapy) of diabetes mellitus is necessary to reduce the risk of congenital malformations. Oral hypoglycemic drugs are not used during pregnancy. Insulin is the drug of choice for the therapy of diabetes mellitus in pregnant women. It is recommended to replace taking oral hypoglycemic agents with insulin therapy both if pregnancy is planned and if pregnancy occurs while taking the drug.

Breastfeeding

Because of the lack of data on the absorption of gliclazide into the breast milk and the risk of neonatal hypoglycemia during therapy with the drug, breastfeeding is contraindicated.

Similarities