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 reduction.

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

Prolonged release tablets.

1 tablet contains:

Active substance:

gliclazide 30 mg;

Associates:

Hypromellose (hydroxypropyl methylcellulose) 50 mg,

Silica colloidal dioxide 3.5 mg,

Mannitol 10 mg,

magnesium stearate 1.8 mg,

vegetable oil hydrogenated 3.6 mg,

microcrystalline cellulose 81.1 mg.

How to take, the dosage

The drug is intended for adults only.

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

The daily dose is 30-120 mg (1-4 tablets) at 1 sitting. It is recommended that the tablet be swallowed whole, without chewing or crushing.

If one or more doses of the drug are missed, the higher dose should be taken the next day. As with other hypoglycemic drugs, the dose of the drug must be adjusted individually in each case, depending on the blood glucose concentration and glycosylated hemoglobin (HbAlc).

The starting dose

The initial recommended dose in untreated adults (including elderly people ≥65 years) is 30 mg/day (1 tablet), then the dose is adjusted individually until the desired effect is achieved.

There is no transition time required when replacing Gliclazide Kanon with another hypoglycemic drug.

You should first stop taking this medication and only then take Gliclazide Canon.

Dose adjustment

The dose can be increased after no earlier than 1 month of therapy with the drug at the previously prescribed dose. The dose should be adjusted according to the blood glucose concentration after the start of treatment. Each subsequent dose change can be undertaken after at least a two-week period.

Supportive therapy

The maintenance daily dose is 30 to 90 to 120 mg (1 to 3 to 4 tablets), and should not exceed 120 mg. Gliclazide Canon may be used in combination with biguanidines, alpha-glucosidase inhibitors or insulin.

Patients in the elderly

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

Renal failure

The recommended doses of the drug for mild to moderate renal failure are identical to those for those with normal renal function. Close medical monitoring of patients is recommended.

Patients at risk for hypoglycemia

In patients at risk for hypoglycemia (insufficient or unbalanced nutrition; severe or poorly compensated endocrine disorders – pituitary and adrenal insufficiency, hypothyroidism; discontinuation of GCS after long-term use and/or when taking them in high doses; severe cardiovascular diseases (severe coronary artery disease, severe carotid atherosclerosis, widespread atherosclerosis) the minimum dose (30 mg) of the drug is recommended.

Prevention of diabetes complications

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

Interaction

1) Drugs that increase the effect of gliclazide (increased risk of hypoglycemia):

Contraindicated combinations

Miconazole (systemic administration or oral mucosal gel application): increases the hypoglycemic effects of gliclazide (possible development of hypoglycemia to the point 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). It is preferable to use another anti-inflammatory drug. If administration of phenylbutazone is necessary, the patient should be advised to monitor blood glucose concentrations. If necessary, the dose of gliclazide should be adjusted during and after taking phenylbutazone. Ethanol: intensifies hypoglycemia by inhibiting the compensatory reactions, may contribute to the development of hypoglycemic coma. It is necessary to refrain from taking drugs that contain ethanol, and the use of alcohol.

Combinations requiring precautions

The use of gliclazide in combination with certain drugs, such as other hypoglycemic agents – insulin, acarbose, biguanides; beta-adrenoblockers, 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, accompanied by increased hypoglycemic effect and risk of hypoglycemia.

2) Drugs that weaken the effect of gliclazide:

Unrecommended combinations

Danazol: has a diabetogenic effect. The patient is advised to monitor blood glucose concentrations carefully if this medication is needed. If co-administration is necessary, it is recommended that the dose of gliklazide be adjusted both while taking danazolol and after discontinuation of the drug.

Combinations requiring precautions

Chlorpromazine: In high doses (more than 100 mg per day) increases blood glucose concentration, reducing insulin secretion. It is recommended to monitor blood glucose concentration carefully. If co-administration is necessary, it is recommended that the dose of gliclazide be adjusted both during chlorpromazine administration and after its withdrawal.

HKS (systemic and topical use: intraarticular, external and rectal administration): increase blood glucose concentration with possible development of ketoacidosis (reduced tolerance to carbohydrates). It is recommended to monitor blood glucose concentration carefully, 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-monitoring of blood glucose concentrations. If necessary, it is recommended to transfer the patient to insulin therapy.

Combinations to be considered

Anticoagulants (e.g., warfarin): Sulfonylurea derivatives may increase the effect of anticoagulants when taken together. Correction of anticoagulant dose may be required.

Special Instructions

Hypoglycemia may occur when taking sulfonylurea derivatives, including gliclazide, and in some cases may be severe and prolonged, requiring hospitalization and intravenous administration of dextrose solution for several days.

The drug Gliclazide Canon can only be prescribed to patients whose diet is regular and includes breakfast. It is very important to maintain a sufficient intake of carbohydrates with food, because the risk of hypoglycemia increases with an irregular or insufficient diet, as well as with the consumption of food poor in carbohydrates. Hypoglycemia is more likely to develop with a low-calorie diet, after prolonged or vigorous exercise, after drinking alcohol or when taking several hypoglycemic drugs at the same time.

As a rule, the symptoms of hypoglycemia disappear after eating a food rich in carbohydrates (such as sugar). Note that taking sugar substitutes does not help to eliminate hypoglycemic symptoms.

The experience with other sulfonylurea derivatives suggests that hypoglycemia may recur despite effective initial management of this condition.

If hypoglycemic symptoms are severe or prolonged, even if there is temporary relief from carbohydrate-rich foods, an emergency treatment, up to and including hospitalization, is necessary.

In order to avoid hypoglycemia, careful individual choice of medication and dosing regimen is necessary, and the patient must be fully informed about the treatment offered.

An increased risk of hypoglycemia may occur in the following cases:

– the patient’s refusal or inability (especially the elderly) to follow doctor’s orders and monitor their condition:

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

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

– renal failure:

– severe hepatic impairment;

– overdose of Gliclazide Canon;

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

– concomitant administration of certain drugs.

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 evaluated.

Hepatic/renal failure

In patients with severe hepatic and/or renal failure, the pharmacokinetic and/or pharmacodynamic properties of gliklazide may change. Hypoglycemia developing in these patients may be quite prolonged, in such cases, immediate appropriate therapy is necessary.

Patient Information

The patient and family members should be informed of 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, the need for regular exercise and regular blood glucose monitoring.

Lack of glycemic control

Glycemic control in patients treated with hypoglycemic agents may be impaired in the following cases: fever, injury, infectious disease, or major surgery. Under these conditions, it may be necessary to discontinue therapy with Gliclazide Canon and prescribe insulin therapy. In many patients, the efficacy of oral hypoglycemic agents, including gliclazide, tends to decrease after a long period of treatment. This effect may be due to both the 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 drug resistance, in which the drug does not produce the expected clinical effect when first prescribed. Before a patient is diagnosed with secondary drug resistance, the appropriateness of the patient’s dose and adherence to the prescribed diet must be evaluated.

Control of laboratory parameters

To assess glycemic control, regular fasting blood glucose and glycosylated hemoglobin concentrations are recommended.

In addition, regular self-monitoring of blood glucose concentration is advisable.

The effect on the ability to drive:

Patients should be aware of the symptoms of hypoglycemia and exercise caution while driving vehicles or performing work requiring high psychomotor reaction speed, especially at the beginning of therapy.

Contraindications

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

– type 1 diabetes mellitus;

– Diabetic ketoacidosis, diabetic precoma, diabetic coma;

– Severe renal or hepatic failure;

– taking miconazole;

– pregnancy and the period of breastfeeding;

– age under 18 years.

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

With caution:

Elderly age, irregular and/or unbalanced diet, severe cardiovascular disease (including coronary heart disease, atherosclerosis), hypothyroidism, adrenal or pituitary insufficiency, hypopituitarism, renal and/or hepatic insufficiency, long-term therapy with glucocorticosteroids (GCS), alcoholism, glucose-6-phosphate dehydrogenase deficiency.

Side effects

Hypoglycemia in case of irregular meals and especially if meals are missed, may be accompanied by the following symptoms: Headache, intense hunger, nausea, vomiting, increased fatigue, sleep disturbance, irritability, agitation, reduced concentration, delayed reactions, depression, confusion, visual and speech impairment, aphasia, tremors, paresis, perception disturbances, dizziness, weakness, seizures, bradycardia, delirium, breathing disturbances, drowsiness, loss of consciousness with possible development of coma, up to and including death.

Adrenergic reactions may also be noted: increased sweating, “clammy” skin, anxiety, tachycardia, increased blood pressure, palpitations, arrhythmia, and angina.

Other side effects

Gastrointestinal side effects: nausea, vomiting, diarrhea, abdominal pain, constipation (the severity of these symptoms is reduced when taken with meals).

Skin and subcutaneous tissue disorders: rash, pruritus, urticaria, erythema, maculopapular rash, bullous reactions (such as Stevens-Johnson syndrome, toxic epidermal necrolysis).

Hematological and lymphatic system disorders: anemia, thrombocytopenia, leukopenia, granulocytopenia. 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). In case of cholestatic jaundice it is necessary to discontinue therapy.

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

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

Also against the background of taking other sulfonylurea derivatives increased activity of “liver” enzymes, liver dysfunction (e.g., with the development of cholestasis and jaundice) and hepatitis were observed. These manifestations decreased with time after withdrawal of sulfonylurea drugs, but in some cases led to life-threatening liver failure.

Overdose

Overdose of sulfonylurea derivatives, including gliclazide, may lead to the development of hypoglycemia, up to hypoglycemic coma. Moderate symptoms of hypoglycemia without impairment of consciousness or neurological symptoms are corrected by taking carbohydrates, adjusting the dose and/or changing the diet. Careful monitoring of the patient’s condition should continue until it is certain that the patient’s health is not in danger.

The development of severe hypoglycemic states accompanied by coma, seizures or other neurological disorders is possible. If such symptoms occur, emergency medical assistance and immediate hospitalization is necessary. If hypoglycemic coma is suspected or diagnosed, the patient is injected intravenously with 50 ml of 40% dextrose (glucose) solution. Then intravenously drip 5% dextrose solution to maintain the necessary blood glucose concentration of about 1 g/l. Close monitoring of the blood glucose concentration and monitoring of the patient should be done for at least 48 hours afterwards. Subsequently, depending on the patient’s condition, the need for further monitoring of the patient’s vital functions should be decided.

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

Similarities