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

– Diabetes mellitus type 2 with insufficient effectiveness of diet therapy of physical activity and weight reduction.

– Prevention of complications of diabetes: reducing the 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:

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.

How to take, the dosage

GliClazide is indicated for the treatment of adult patients only.

The recommended dose of gliclazide should be taken orally once daily (p/day), preferably during breakfast.

The daily dose can be 30 to 120 mg (in terms of the required number of tablets) at a time.

It is recommended that a tablet or half a tablet be swallowed whole without chewing or crushing.

If one or more doses of the medication are missed, the higher dose should be taken the next day at the usual time.

As with other hypoglycemic medications, the dose of gliclazide must be adjusted in each case according to the blood glucose concentration and HbAlc.

The initial dose

The initial recommended dose (including for elderly patients ≥65 years) is 30 mg 1 p/day.

If adequately controlled, gliclazide at this dose may be used for maintenance therapy. In case of inadequate glycemic control, the daily dose of gliclazide may be sequentially increased to 60 90 or 120 mg (in terms of the required number of tablets).

The dose can be increased no earlier than 1 month of therapy with gliclazide at the previously prescribed dose. Patients in whom blood glucose concentrations have not decreased after 2 weeks of therapy are an exception. In these cases, the dose of gliclazide may be increased after 2 weeks of therapy.

The maximum recommended daily dose of gliclazide is 120 mg (in terms of the required number of tablets).

1 tablet of gliclazide with sustained release 60 mg is equivalent to 2 tablets of gliclazide with sustained release 30 mg.

The risk on the 60 mg tablets allows splitting the tablet and taking the daily dose as 30 mg (1/2 tablet 60 mg) and if necessary 90 mg (1 and 1/2 tablets 60 mg).

Transition from taking gliclazide tablets with normal release to gliclazide tablets with prolonged release

Gliclazide tablets 80 mg (with normal release) can be replaced with gliclazide tablets with prolonged release at a dose of 30 mg (in terms of the required number of tablets). Careful glycemic control is recommended when transferring patients from gliclazide with normal release to gliclazide with prolonged release.

Transfer from another hypoglycemic drug to gliclazide

Gliclazide may be used instead of another GGP. When switching to gliclazide, patients receiving other PHCPs should consider their dose and half-life. As a rule, no transition period is required. The initial dose of sustained-release gliclazide should be 30 mg per day and should then be titrated according to the blood glucose concentration.

When gliclazide is replaced with long half-life sulfonylurea derivatives to avoid hypoglycemia caused by the additive effect of two hypoglycemic agents, their administration may be discontinued for several days. The initial dose of sustained-release gliclazide in this case is also 30 mg 1 p/day and can be further increased as described above, if necessary.

Combination with another hypoglycemic drug

Glicluclazide may be used in combination with α-glucosidase inhibitors biguanidins or insulin.

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

Patients in the elderly

There is no need to adjust the dose of gliclazide for patients over 65 years of age.

Patients with renal impairment

The results of clinical studies have shown that dosage adjustment of gliclazide in patients with mild to moderate renal impairment is not required. Close 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); discontinuation of GCS after long-term use and/or use in high doses; severe cardiovascular diseases – severe coronary heart disease severe carotid atherosclerosis widespread atherosclerosis) a minimum dose of gliklazide of 30 mg of the drug per day is recommended.

Prevention of diabetes complications

To achieve intense glycemic control, the dose of gliclazide may be gradually increased to 120 mg 1 p/day in addition to diet and exercise until the target HbAlc is achieved. It should be remembered about the risk of hypoglycemia development. In addition, other hypoglycemic medications such as metformin α-glucosidase inhibitor thiazolidinedione or insulin may be added to therapy.

Children and adolescents under 18 years of age

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

Interaction

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

Contraindicated combinations

– Miconazole (systemic administration or application of 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 plasma proteins binding 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 administration of phenylbutazone.

– 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 drugs e.g. other hypoglycemic agents (insulin α-glucosidase inhibitor metformin thiazolidinedione dipeptidyl peptidase-4 inhibitors GFP-1 agonists); β-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 weaken the effect of gliclazide:

Unrecommended combinations

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

Combinations requiring precautions

Chlorpromazine: at high doses (over 100 mg daily) increases blood glucose concentration by reducing insulin secretion. It is recommended to monitor blood glucose concentration carefully. If co-administration is necessary, it is recommended that the dose of gliklazide be adjusted both during chlorpromazine administration and after its withdrawal.

– GCS (systemic and local use: intraarticular external and rectal administration) and tetracosactide: 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 administration): β2-adrenomimetics contribute to increased blood glucose concentrations. Special 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. Adjustment of the anticoagulant dose may be required.

Special Instructions

Diabefarm® MB can only be prescribed to patients whose diet is regular and includes breakfast. It is important to maintain an adequate intake of carbohydrates with food, since the risk of hypoglycemia increases with an irregular or insufficient diet and consumption of carbohydrate-poor foods.

Hypoglycemia develops when a low-calorie diet is starved after prolonged or vigorous exercise after drinking alcohol or when taking multiple hypoglycemic medications at the same time.

As a rule, the symptoms of mild to moderate hypoglycemia are controlled by taking easily absorbable carbohydrates (e.g. sugar) or foods with high carbohydrate content. It should be noted that taking sugar substitutes does not help to eliminate hypoglycemic symptoms. Experience of using sulfonylurea derivatives shows that hypoglycemia may recur in spite of effective initial control of this condition. If hypoglycemic symptoms are pronounced or prolonged, even if there is a temporary improvement after ingestion of carbohydrate-rich food, emergency medical care up to and including hospitalization is required.

The medications and dosing regimens need to be carefully individualized, and the patient needs to be fully informed about the treatment offered.

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

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

– Inadequate or irregular meals, skipping meals, fasting or changing the diet;

– An imbalance between exercise and the amount of carbohydrates taken;

– severe hepatic impairment;

– overdose of DiabepHarm® MB;

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

– concomitant administration of certain medications (see

– concomitant administration of some medicinal products (see section “Interaction with other medicinal products”).

Sulfonylurea derivatives may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency.

Hepatic and renal failure

In patients with severe hepatic and/or renal failure, the pharmacokinetic and/or pharmacodynamic properties of gliklazide may change. Hypoglycemia developing 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 major surgical interventions. In these states the use of Diabefarm® MB should be stopped and insulin therapy should be prescribed.

In many patients, the efficacy of oral hypoglycemic agents, including gliclazide, tends to decrease after prolonged 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 give the expected clinical effect at the first prescription. Before a patient is diagnosed with secondary drug resistance, the adequacy 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 HbAlc concentrations are recommended. In addition, regular self-monitoring of blood glucose concentration is appropriate.

Patient Information

The patient and family members should be informed about the risk of hypoglycemia, its symptoms, and the conditions that contribute to its development. The patient should be made aware of 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 monitoring of blood glucose concentrations.

Patients should be aware of the potential development of hypoglycemia when using gliclazide and should use caution when driving vehicles or performing work that requires concentration and high-speed psychomotor reactions especially at the start of therapy when adjusting the dose.

Contraindications

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

– Diabetes mellitus type 1;

– diabetic ketoacidosis diabetic precoma diabetic coma;

– severe hepatic and/or renal insufficiency (insulin is recommended in these cases);

– pregnancy – breastfeeding period;

– age less than 18 years;

– taking miconazole.

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

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

Side effects

Given the experience with gliclazide and other sulfonylurea derivatives, the following adverse reactions (HP) may occur. The frequency of HP is not specified.

Hypoglycemia

Like other sulfonylurea derivatives, gliclazide 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 convulsions bradycardia delirium shallow breathing sleepiness loss of consciousness with possible development of coma up to death.

Andrenergic 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 easily absorbed carbohydrates (sugar). Administration of sugar substitutes is ineffective. Against the background of using other sulfonylurea derivatives there have been recurrences of hypoglycemia after its cessation.

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

Other HP

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

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

Disorders of the blood and lymphatic system: hematological disorders (anemia leukopenia thrombocytopenia granulocytopenia) are rare and reversible if therapy is stopped.

Hepatic and biliary tract disorders: increased activity of “hepatic” enzymes (aspartate aminotransferase (ACT) alanine aminotransferase (ALT) alkaline phosphatase); liver function disorders (e.g., with the development of cholestasis and jaundice); hepatitis (isolated cases). If cholestatic jaundice occurs, therapy should be discontinued. These HP are usually reversible if therapy is discontinued, but in individual cases have led to life-threatening liver failure.

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

HP inherent to sulfonylurea derivatives:

As with other sulfonylurea derivatives, the following HP have been reported:

Blood and lymphatic system disorders

erythrocytopenia agranulocytosis hemolytic anemia pancytopenia

Immune system disorders

allergic vasculitis

Impact on the results of laboratory and instrumental studies

hyponatremia.

Overdose

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

The symptoms of mild to moderate hypoglycemia without impairment of consciousness are corrected by taking oral carbohydrates by reducing the dose of gliclazide and/or changing the diet. Medical observation 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 conditions is possible

accompanied by coma, seizures or other neurological disorders. If these symptoms occur, emergency medical care and immediate hospitalization are necessary.

In case of suspected or diagnosed hypoglycemic coma, the patient is given 50 ml of 20-30% dextrose (glucose) solution by intravenous shot, then 10% dextrose solution is given by intravenous drip to maintain blood glucose concentration above 1 g/l. The glucose concentration should be monitored and the patient monitored for at least 48 subsequent hours. 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 marked binding of gliclazide to plasma proteins.

Pregnancy use

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

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 (PHGP) are contraindicated during pregnancy. Insulin is the drug of choice for the therapy of diabetes mellitus in pregnant women. It is recommended to transfer a patient from PHGP to insulin therapy both in case of planned pregnancy and in case of pregnancy during taking Diabefarm® MB.

Breastfeeding is contraindicated during therapy with gliclazide, given the lack of data on penetration of gliclazide into breast milk and risk of neonatal hypoglycemia.

Similarities