Gliclazide Canon, 30 mg 60 pcs

oral hypoglycemic agent of the sulfonylurea group II generation

ICD-10:

IV.E10-E14.E11 insulin-independent diabetes mellitus

ATC:

A.10.B.B.09 Gliclazide

Pharmacodynamics:

Gliclazide is a sulfonylurea derivative, an oral hypoglycemic drug that differs from similar drugs in having an N-bearing heterocyclic ring with an endocyclic bond.

Glyclazide reduces blood glucose concentration by stimulating insulin secretion by beta cells of Langerhans islets. Increase of post-prandial insulin and C-peptide concentration is maintained after 2 years of therapy. In addition to the effect on carbohydrate metabolism, gliclazide has hemovascular effects.

Impacts on insulin secretion

In type 2 diabetes mellitus, gliclazide restores the early peak of insulin secretion in response to glucose intake and increases the second phase of insulin secretion. Significant increases in insulin secretion are seen in response to stimulation from food intake or glucose administration.

Hemovascular effects

Glyclazid reduces the risk of small vessel thrombosis by affecting mechanisms that may cause complications in diabetes: Partial inhibition of platelet aggregation and adhesion and decreased concentration of platelet activation factors (beta-thromboglobulin, thromboxane B2), as well as on restoration of fibrinolytic activity of vascular endothelium and increased activity of tissue plasminogen activator. Intensive glycemic control based on the use of prolonged-release gliclazide (target glycosylated hemoglobin (HbAlc) < 6.5%) significantly reduces the risk of micro- and macrovascular complications of type 2 diabetes compared to standard glycemic control (ADVANCE study).

Pharmacokinetics:

Absorption

After oral administration, gliclazide is completely absorbed. Food intake has no effect on the degree of absorption. The plasma concentration of gliclazide increases gradually, reaching a maximum and reaching a plateau after 6-12 hours. Individual variability is relatively low. The relationship between the dose taken and the plasma concentration curve of the drug is a linear relationship with time.

Distribution

About 95% of the drug is bound to plasma proteins. Gliclazide is metabolized mainly in the liver and excreted mainly by the kidneys. The volume of distribution is about 30 liters.

The drug at a dose of 30 mg once daily maintains the effective plasma concentration of gliclazide for more than 24 hours.

Metabolism

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

Elimation

Elimation is mainly by the kidneys as metabolites, less than 1% is excreted unchanged. The elimination half-life of gliclazide is on average 16 hours (12 to 20).

Particular populations

In the elderly there are no clinically significant changes in pharmacokinetic parameters.

Indications

Type 2 diabetes mellitus with insufficient effectiveness of diet therapy, physical activity and weight loss.

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

Pharmacological effect

hypoglycemic agent for oral use of the sulfonylurea group of the second generation

ICD-10:

IV.E10-E14.E11 Non-insulin-dependent diabetes mellitus

ATX:

A.10.B.B.09 Gliclazide

Pharmacodynamics:

Gliclazide is a sulfonylurea derivative, a hypoglycemic drug for oral administration, which differs from similar drugs in the presence of an N-containing heterocyclic ring with an endocyclic bond.

Gliclazide reduces blood glucose concentrations by stimulating insulin secretion by beta cells of the islets of Langerhans. Increases in postirandial insulin and C-peptide concentrations persist after 2 years of therapy. In addition to its effect on carbohydrate metabolism, gliclazide has hemovascular effects.

Effect on insulin secretion

In type 2 diabetes mellitus, gliclazide restores the early peak of insulin secretion in response to 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 glucose administration.

Hemovascular effects

Gliclazide reduces the risk of thrombosis of small vessels by influencing 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 restoration of fibrinolytic activity of the vascular endothelium and increased activity of tissue plasminogen activator. Intensive glycemic control based on the use of extended-release gliclazide (target glycosylated hemoglobin (HbAlc) < 6.5%) significantly reduces the risk of micro- and macrovascular complications of type 2 diabetes, compared with standard glycemic control (ADVANCE study).

Pharmacokinetics:

Suction

After oral administration, gliclazide is completely absorbed. Food intake does not affect the degree of absorption. The concentration of gliclazide in plasma increases gradually, reaching a maximum and reaching a plateau after 6-12 hours. Individual variability is relatively low. The relationship between the dose taken and the plasma drug concentration curve is a linear function of time.

Distribution

Approximately 95% of the drug is bound to plasma proteins. Gliclazide is metabolized primarily in the liver and excreted mainly by the kidneys. The distribution volume is approximately 30 l.

Taking the drug at a dose of 30 mg once a day ensures that the effective concentration of gliclazide in the blood plasma is maintained for more than 24 hours.

Metabolism

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

Removal

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

Special populations

In elderly people, clinically significant changes in pharmacokinetic parameters are not observed.

Special instructions

When taking sulfonylurea derivatives, including gliclazide, hypoglycemia may develop, and in some cases in a severe and prolonged form, requiring hospitalization and intravenous administration of a dextrose solution for several days.

The drug Gliclazide Canon can be prescribed only to those patients whose meals are regular and include breakfast. It is very important to maintain a sufficient intake of carbohydrates from food, because… The risk of developing hypoglycemia increases with irregular or insufficient nutrition, as well as with consumption of foods low in carbohydrates. Hypoglycemia is more likely to occur during a low-calorie diet, after prolonged or vigorous exercise, after drinking alcohol, or when taking multiple hypoglycemic medications at the same time.

Typically, symptoms of hypoglycemia go away after eating a meal rich in carbohydrates (such as sugar). It should be borne in mind that taking sweeteners does not help eliminate hypoglycemic symptoms.

Experience with other sulfonylureas suggests that hypoglycemia may recur despite initial effective management of the condition.

If hypoglycemic symptoms are pronounced or prolonged, even if the condition improves temporarily after eating a meal rich in carbohydrates, emergency medical care is necessary, including hospitalization.

To avoid the development of hypoglycemia, careful individual selection of drugs and dosage regimen is necessary, 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 doctor’s orders and control their condition:

– insufficient and irregular nutrition, skipping meals, fasting and changes in diet;

– imbalance between physical activity and the amount of carbohydrates taken;

– renal failure:

– severe liver failure;

– overdose of the drug Gliclazide Canon;

– some endocrine disorders (thyroid disease, pituitary and adrenal insufficiency);

– simultaneous use of certain medications.

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

Liver/renal failure

In patients with severe hepatic and/or renal insufficiency, the pharmacokinetic and/or pharmacodynamic properties of gliclazide may change. Hypoglycemia developing in these patients can be quite long-lasting; in such cases, immediate appropriate therapy is necessary.

Patient Information

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 must be informed of the potential risks and benefits of the proposed treatment. The patient should be taught the importance of diet, the need for regular exercise, and regular monitoring of blood glucose concentrations.

Insufficient glycemic control

Glycemic control in patients treated with hypoglycemic agents may be impaired in the following situations: fever, trauma, infectious diseases, or major surgery. In these conditions, it may be necessary to stop therapy with Gliclazide Canon and prescribe insulin therapy. In many patients, the effectiveness of oral hypoglycemic agents, incl. gliclazide tends to decrease after a long period of treatment. This effect may be due to both progression of the disease and a decrease in the therapeutic response to the drug. This phenomenon is known as secondary drug resistance, which must be distinguished from primary resistance, in which the drug does not give the expected clinical effect even at the first prescription. Before diagnosing secondary drug resistance in a patient, it is necessary to assess the adequacy of dose selection and compliance with the prescribed diet.

Control of laboratory parameters

To assess glycemic control, regular determination of fasting blood glucose and glycosylated hemoglobin concentrations is recommended.

In addition, it is advisable to regularly self-monitor blood glucose concentrations.

Impact on the ability to drive vehicles. Wed and fur.:

Patients should be aware of the symptoms of hypoglycemia and exercise caution when driving or performing work that requires high psychomotor speed, especially at the beginning of therapy.

Active ingredient

Gliclazide

Composition

Extended release tablets.

1 tablet contains:

Active ingredient:

gliclazide 30 mg;

Excipients:

hypromellose (hydroxypropyl methylcellulose) 50 mg,

colloidal silicon dioxide 3.5 mg,

mannitol 10 mg,

magnesium stearate 1.8 mg,

hydrogenated vegetable oil 3.6 mg,

microcrystalline cellulose 81.1 mg.

Contraindications

– Hypersensitivity to gliclazide or any of the excipients of the drug, other sulfonylurea derivatives, sulfonamides;

– diabetes mellitus type 1;

– diabetic ketoacidosis, diabetic precoma, diabetic coma;

– severe renal or liver failure;

– taking miconazole;

– pregnancy and breastfeeding;

– age up to 18 years.

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

With caution:

Old age, irregular and/or unbalanced diet, severe diseases of the cardiovascular system (including coronary heart disease, atherosclerosis), hypothyroidism, adrenal or pituitary insufficiency, hypopituitarism, renal and/or liver failure, long-term therapy with glucocorticosteroids (GCS), alcoholism, failure glucose-6-phosphate dehydrogenase.

Side Effects

Hypoglycemia in case of irregular meals and especially if meals are missed, may be accompanied by the following symptoms: headache, strong feeling of hunger, nausea, vomiting, increased fatigue, sleep disturbance, irritability, agitation, decreased concentration, slow reaction, depression, confusion, visual and speech impairment, aphasia, tremor, paresis, impaired perception, dizziness, weakness, convulsions, bradycardia, delirium, breathing difficulties, drowsiness, loss of consciousness with the possible development of coma, even death.

Adrenergic reactions may also occur: increased sweating, clammy skin, anxiety, tachycardia, increased blood pressure, palpitations, arrhythmia and angina.

Other side effects

From the gastrointestinal tract: nausea, vomiting, diarrhea, abdominal pain, constipation (the severity of these symptoms decreases when taken with food).

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

From the circulatory and lymphatic system: anemia, thrombocytopenia, leukopenia, granulocytopenia. As a rule, these phenomena are reversible if therapy is discontinued.

From the liver and biliary tract: increased activity of liver enzymes (aspartate aminotransferase (ACT), alanine aminotransferase (ALT), alkaline phosphatase), hepatitis (isolated cases). If cholestatic jaundice appears, therapy should be discontinued.

On the part of the organ of vision: transient visual disturbances may occur caused by changes in blood glucose concentrations, especially at the beginning of therapy.

Common side effects of sulfonylurea derivatives: erythropenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, hyponatremia.

Also, while taking other sulfonylurea derivatives, there was an increase in the activity of liver enzymes, impaired liver function (for example, with the development of cholestasis and jaundice) and hepatitis. These manifestations decreased over time after discontinuation of sulfonylurea drugs, but in some cases led to life-threatening liver failure.

Interaction

1) Drugs that enhance the effect of gliclazide (increasing the risk of hypoglycemia):

Contraindicated combinations

Miconazole (systemic administration or use of gel on the oral mucosa): enhances the hypoglycemic effect of gliclazide (possible development of hypoglycemia up to the state of coma).

Not recommended combinations

Phenylbutazone (systemic administration) enhances the hypoglycemic effect of sulfonylurea derivatives (displaces them from association with plasma proteins and/or slows down 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 while taking phenylbutazone and after it is stopped. Ethanol: increases hypoglycemia by inhibiting compensatory reactions and can contribute to the development of hypoglycemic coma. It is necessary to stop taking medications that contain ethanol and drinking alcohol.

Combinations requiring precautions

Taking gliclazide in combination with certain medications, for example, other hypoglycemic agents – insulin, acarbose, biguanides; beta-blockers, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, fluconazole; angiotensin-converting enzyme inhibitors – captopril, enalapril; H2-histamine receptor blockers; monoamine oxidase inhibitors; sulfonamides, clarithromycin and non-steroidal anti-inflammatory drugs, is accompanied by an increased hypoglycemic effect and the risk of hypoglycemia.

2) Drugs that weaken the effect of gliclazide:

Not recommended combinations

Danazol: has a diabetogenic effect. If taking this drug is necessary, the patient is advised to carefully monitor blood glucose concentrations. If it is necessary to take drugs together, it is recommended to adjust the dose of gliclazide both while taking danazol and after its discontinuation.

Combinations requiring precautions

Chlorpromazine: in high doses (more than 100 mg per day) increases the concentration of glucose in the blood, reducing insulin secretion. It is recommended to carefully monitor blood glucose concentrations. If it is necessary to take drugs together, it is recommended to adjust the dose of gliclazide both while taking chlorpromazine and after its discontinuation.

GCS (systemic and local use: intra-articular, external and rectal administration): increase the concentration of glucose in the blood with the possible development of ketoacidosis (decreased tolerance to carbohydrates). It is recommended to carefully monitor blood glucose concentrations, especially at the beginning of treatment. If it is necessary to take drugs together, it may be necessary to adjust the dose of the hypoglycemic agent both while taking GCS and after their withdrawal.

Ritodrine, salbutamol, terbutaline (intravenous administration):

Beta-2 adrenergic agonists help increase blood glucose concentrations.

Particular attention should be paid to the importance of self-monitoring of blood glucose concentrations. If necessary, it is recommended to transfer the patient to insulin therapy.

Combinations to be taken into account

Anticoagulants (for example, warfarin): sulfonylureas may enhance the effect of anticoagulants when taken together. Anticoagulant dose adjustment may be required.

Overdose

An overdose of sulfonylurea derivatives, including gliclazide, can lead to the development of hypoglycemia, including hypoglycemic coma. Moderate symptoms of hypoglycemia without impairment of consciousness or neurological symptoms are corrected by carbohydrate intake, dose adjustment and/or dietary changes. Careful monitoring of the patient’s condition should continue until it is certain that the patient’s health is not in danger.

Severe hypoglycemic conditions may develop, accompanied by coma, convulsions or other neurological disorders. If such symptoms appear, emergency medical care and immediate hospitalization are necessary. If a hypoglycemic coma is suspected or diagnosed, the patient is injected intravenously with 50 ml of a 40% dextrose (glucose) solution. Then a 5% dextrose solution is injected intravenously to maintain the required blood glucose concentration of about 1 g/l. Careful monitoring of blood glucose concentrations and monitoring of the patient should be carried out for at least the next 48 hours. Subsequently, depending on the patient’s condition, the issue of the need for further monitoring of the patient’s vital functions should be decided.

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

Manufacturer

Kanonpharma production CJSC, Russia