Diabefarm CF, 60 mg 30 pcs

Hypoglycemic oral sulfonylurea group II generation

ATCode

A10BB09

Pharmacodynamics:

Diabefarm® MB is an oral hypoglycemic drug whose active ingredient (gliclazide) is a Generation II sulfonylurea derivative and differs from similar drugs in having an N-containing heterocyclic ring with an endocyclic bond.

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 type 2 diabetes mellitus, the drug restores the early peak of insulin secretion in response to glucose intake and enhances the second phase of insulin secretion. Significant increase of insulin secretion is observed in response to stimulation caused by food intake or glucose administration. In addition to the effect on insulin secretion, the drug has hemovascular effects.

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

Intensive glycemic control based on the use of prolonged-release gliclazide (target glycated hemoglobin (HbA1c)<65%) significantly reduces the risk of 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 Diabefarm® MV at a dose of 60 mg once daily maintains effective plasma concentration of gliclazide for more than 24 hours.

Metabolism

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

Exhaust

Gliclaclazide is excreted mainly 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 with insufficient effectiveness of diet therapy, physical activity 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 mellitus through intensive glycemic control.

Pharmacological effect

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

ATX code

A10BB09

Pharmacodynamics:

Diabepharm® MB is an oral hypoglycemic drug whose active substance (gliclazide) is a second generation sulfonylurea derivative, differs from similar drugs by the presence of an N-containing heterocyclic ring with an endocyclic linkage.

Gliclazide reduces blood glucose concentrations by stimulating insulin secretion by β-cells of the islets of Langerhans. Increases in postprandial insulin and C-peptide concentrations persist after 2 years of therapy.

In type 2 diabetes mellitus, the drug 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. In addition to influencing insulin secretion, the drug has hemovascular effects.

Gliclazide reduces the risk of thrombosis of small vessels by influencing the 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 restoring the fibrinolytic activity of the vascular endothelium and increasing the activity of tissue plasminogen activator.

Intensive glycemic control based on the use of extended-release gliclazide (target glycated hemoglobin (HbA1c) <65%) significantly reduces the risk of micro- and macrovascular complications of type 2 diabetes mellitus compared with standard glycemic control.

Pharmacokinetics:

Suction

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

Food intake does not affect the rate or extent of absorption of gliclazide.

Distribution

Approximately 95% of gliclazide is bound to plasma proteins. Distribution volume – about 30 l. Taking the drug Diabepharm® MB at a dose of 60 mg once a day ensures the maintenance of an effective concentration of gliclazide in the blood plasma for more than 24 hours.

Metabolism

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

Removal

Gliclazide is excreted mainly by the kidneys: excretion occurs in the form of metabolites; less than 1% is excreted unchanged by the kidneys. The half-life of gliclazide averages from 12 to 20 hours. Linearity

The relationship between the dose taken (up to 120 mg) and the area under the concentration-time pharmacokinetic curve is linear.

Special populations

Elderly people

In elderly people, no significant changes in pharmacokinetic parameters are observed.

Special instructions

The drug Diabepharm® MB can be prescribed only to those patients whose meals are regular and include breakfast. It is important to maintain a sufficient intake of carbohydrates from food as the risk of hypoglycemia increases with irregular or insufficient nutrition when consuming foods low in carbohydrates.

Hypoglycemia occurs when following a low-calorie diet, fasting, prolonged or vigorous exercise, drinking alcohol, or when taking multiple hypoglycemic drugs at the same time.

Typically, symptoms of mild to moderate hypoglycemia are relieved by taking easily digestible carbohydrates (such as sugar) or foods high in carbohydrates. It should be noted that taking sweeteners does not help eliminate hypoglycemic symptoms. Experience with the use of sulfonylurea derivatives indicates that hypoglycemia may recur despite effective initial relief of this condition. If hypoglycemic symptoms are pronounced or long-lasting, even in the case of a temporary improvement in the condition after eating a meal rich in carbohydrates, emergency medical care is necessary, including hospitalization.

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 prescriptions 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 Diabepharm® MV;

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

– simultaneous use of certain medications (see section “Interaction with other medications”).

Sulfonylurea derivatives can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency; the possibility of using a different class of hypoglycemic drug in such patients should be assessed.

Kidney and liver failure

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

Insufficient glycemic control

Glycemic control in patients receiving therapy with hypoglycemic agents may be weakened in the following cases: fever, trauma, infectious diseases, major surgical procedures. In these conditions, it is necessary to stop taking Diabepharm® MB and prescribe insulin therapy.

In many patients, the effectiveness of oral hypoglycemic agents, including gliclazide, tends to decrease after prolonged 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 HbAlc concentrations is recommended. In addition, it is advisable to regularly self-monitor blood glucose concentrations.

Patient Information

It is necessary to inform the patient and his family members about the risk of developing hypoglycemia, its symptoms and conditions conducive to its development. The patient should be aware of the potential risks and benefits of the proposed treatment. The patient must be explained the importance of diet, regular exercise and regular monitoring of blood glucose concentrations.

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

Due to the possible development of hypoglycemia when using gliclazide, patients should be aware of the symptoms of hypoglycemia and should exercise caution when driving or performing work that requires concentration and high speed of psychomotor reactions, especially at the beginning of therapy when selecting a dose.

Active ingredient

Gliclazide

Composition

One tablet contains:

active ingredient: gliclazide – 60 mg

excipients: hypromellose – 96.0 mg, microcrystalline cellulose – 157.6 mg, colloidal silicon dioxide – 3.2 mg, magnesium stearate – 3.2 mg.

Pregnancy

There is no experience with the use of gliclazide during pregnancy. Data on the use of other sulfonylureas during pregnancy are limited.

In studies on laboratory animals, teratogenic effects of gliclazide were not detected.

To reduce the risk of developing congenital defects, optimal control (appropriate therapy) of diabetes mellitus is necessary. Oral hypoglycemic agents (OGDs) are contraindicated during pregnancy. Insulin is the drug of choice for the treatment of diabetes mellitus in pregnant women. It is recommended to transfer the patient from taking PHGP to insulin therapy both in the case of a planned pregnancy and in the event of pregnancy while taking the drug Diabepharm® MB.

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

Contraindications

– Hypersensitivity to gliclazide, other sulfonylurea derivatives, sulfonamides and/or to excipients in the drug;

– diabetes mellitus type 1;

– diabetic ketoacidosis, diabetic precoma, diabetic coma;

– severe liver and/or renal failure (in these cases it is recommended to use insulin);

– pregnancy, breastfeeding period;

– age up to 18 years;

– taking miconazole.

It is not recommended to take the drug in combination with danazol or phenylbutazone (see section “Interaction with other drugs”).

With caution:

Irregular and/or unbalanced diet deficiency of glucose-6-phosphate dehydrogenase severe diseases of the cardiovascular system (including coronary heart disease atherosclerosis) adrenal or pituitary insufficiency hypopituitarism renal and/or liver failure of mild to moderate severity long-term therapy with glucocorticosteroids (GCS) diseases of the thyroid gland (with impaired function) alcoholism in old age.

Side Effects

Taking into account the experience with the use of gliclazide and other sulfonylurea derivatives, the following adverse reactions (AP) may develop. The incidence of HP is not specified.

Hypoglycemia

Like other sulfonylureas, gliclazide can cause hypoglycemia if meals are not taken regularly and especially if meals are skipped. Possible symptoms of hypoglycemia: headache, severe hunger, nausea, vomiting, increased fatigue, sleep disturbance, irritability, decreased concentration, slow reaction time, depression, confusion, blurred vision and speech, aphasia, tremors, paresis, loss of self-control, a feeling of helplessness, impaired perception, dizziness, weakness, convulsions, bradycardia, delirium, shallow breathing, drowsiness, loss of consciousness with the possible development of coma, even death.

Andrenergic reactions may also be observed: increased sweating, “sticky” skin, anxiety, tachycardia, increased blood pressure, palpitations, arrhythmia and angina. As a rule, the symptoms of hypoglycemia are relieved by taking easily digestible carbohydrates (sugar). Taking sweeteners is ineffective. With the use of other sulfonylurea derivatives, relapses of hypoglycemia were observed after its relief.

In case of severe or prolonged hypoglycemia, emergency medical care is indicated, possibly with hospitalization, even if there is an effect from taking carbohydrates.

Other HP

Gastrointestinal disorders: abdominal pain, nausea, vomiting, diarrhea, constipation. Taking the drug during breakfast can avoid or minimize these symptoms.

Immune system disorders: skin rash itching erythema urticaria maculopapular rash bullous reactions (such as Stevens-Jones syndrome and toxic epidermal necrolysis).

Blood and lymphatic system disorders: Hematological disorders (anemia, leukopenia, thrombocytopenia, granulocytopenia) are rare and are reversible if therapy is discontinued.

Disorders of the liver and biliary tract: increased activity of liver enzymes (aspartate aminotransferase (ACT), alanine aminotransferase (ALT), alkaline phosphatase); liver dysfunction (for example, with the development of cholestasis and jaundice); hepatitis (isolated cases). If cholestatic jaundice appears, therapy should be discontinued. These HPs are usually reversible if therapy is discontinued but have in isolated cases resulted in life-threatening liver failure.

Visual disturbances: Transient visual disturbances may occur caused by changes in blood glucose concentrations, especially at the beginning of therapy.

HP inherent in sulfonylurea derivatives:

As with the use of other sulfonylurea derivatives, the following HP were noted:

Blood and lymphatic system disorders

erythrocytopenia agranulocytosis hemolytic anemia pancytopenia

Immune system disorders

allergic vasculitis

Influence on the results of laboratory and instrumental studies

hyponatremia.

Interaction

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: enhances hypoglycemia by inhibiting compensatory reactions and may 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, such as other hypoglycemic agents (insulin, α-glucosidase inhibitor, metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, GLP-1 agonists); β-adrenergic blockers; 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 an increased hypoglycemic effect and the risk of hypoglycemia.

Drugs that weaken the effect of gliclazide:

Not recommended combinations

– Danazol: has a diabetogenic effect. If the patient needs to take this drug, 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 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) and tetracosactide: increase the concentration of blood glucose 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): β2-agonists 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 (eg warfarin): sulfonylureas may enhance the effect of anticoagulants when taken together. Anticoagulant dose adjustment may be required.

Overdose

In case of an overdose of sulfonylurea derivatives, including gliclazide, hypoglycemia may develop, including hypoglycemic coma.

Symptoms of mild or moderate hypoglycemia without impairment of consciousness are corrected by ingesting carbohydrates, reducing the dose of gliclazide and/or changing the diet. Medical monitoring of the patient’s condition should continue until it is certain that nothing threatens his health.

Severe hypoglycemic conditions may develop

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, the patient is injected intravenously with 50 ml of a 20-30% dextrose (glucose) solution, then a 10% dextrose solution is injected intravenously to maintain the blood glucose concentration above 1 g/l. Monitoring glucose concentrations and monitoring the patient must be carried out for at least the next 48 hours. After this period of time, depending on the patient’s condition, the attending physician decides on the need for further observation.

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

Storage conditions

At a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf life

2 years.

Do not use after expiration date.

Manufacturer

Pharmacor Production, Russia