Gliclazide-teva mr

Ukraine
Brand name Gliclazide-teva mr
Form tablets, modified release
Active substance / Dosage
gliclazide · 30 mg
Prescription type prescription only
ATC code
A10BB09
Registration number UA/16821/01/01
Manufacturer Balkanpharma-Dupnitsa JSC

Table of Contents

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GLICLAZIDE-TEVA MR (GICLAZIDE-TEVA MR)

Composition:

active substance: gliclazide;

1 modified-release tablet contains gliclazide 30 mg or 60 mg;

excipients: lactose monohydrate, hypromellose, microcrystalline cellulose, colloidal anhydrous silicon dioxide, magnesium stearate.

Pharmaceutical form. Modified-release tablets.

Main physicochemical properties:

30 mg modified-release tablets: white, oval, biconvex tablets with the imprint «G» on one side;

60 mg modified-release tablets: white, oval, biconvex tablets with a score line on both sides, with the imprint «G» on one side and «60» on the other side of the score line on both sides.

Pharmacotherapeutic group. Drugs affecting the digestive system and metabolism. Antidiabetic agents. Blood glucose-lowering agents, excluding insulin. Sulfonylureas, urea derivatives. Gliclazide. ATC code A10BB09.

Pharmacological Properties

Pharmacodynamics

Gliclazide is an oral hypoglycemic agent, a derivative of sulfonylurea. It differs from other agents by the presence of a heterocyclic ring containing nitrogen and having endocyclic bonds.

Mechanism of action

Gliclazide reduces plasma glucose levels by stimulating insulin secretion from pancreatic β-cells of the islets of Langerhans. Elevated postprandial insulin levels and C-peptide secretion are maintained even after 2 years of treatment. In addition to these metabolic properties, gliclazide also has hemovascular properties.

Effect on insulin secretion

In patients with type 2 diabetes, gliclazide restores the early peak of insulin secretion in response to glucose intake and enhances the second phase of insulin secretion. Increased insulin release occurs in proportion to food intake or glucose load.

Hemovascular properties

Gliclazide reduces microthrombosis through two mechanisms that may contribute to the development of complications in diabetes mellitus:

  • Partially inhibits platelet aggregation and adhesion, reduces levels of platelet activation markers (β-thromboglobulin, thromboxane B2);
  • Affects endothelial fibrinolytic activity of blood vessels (increases tPA activity).

Pharmacokinetics

Absorption

Plasma concentration of gliclazide progressively increases during the first 6 hours after administration, then reaches a plateau level maintained from 6 to 12 hours after dosing.

Individual variability is minimal.

Gliclazide is completely absorbed in the gastrointestinal tract. Food intake does not affect the rate or extent of absorption.

Distribution

Plasma protein binding of gliclazide is approximately 95%. The volume of distribution is about 30 L. A single daily dose of Gliclazide-Teva MR provides effective plasma concentrations of gliclazide over 24 hours.

Biotransformation

Gliclazide is primarily metabolized in the liver and excreted in urine; less than 1% of the active substance is excreted unchanged in urine. No active metabolites are present in plasma.

Elimination

The elimination half-life of gliclazide is approximately 12–20 hours.

Linearity/Non-linearity

The relationship between administered doses up to 120 mg and the area under the concentration-time curve (AUC) is linear.

Special patient groups

Elderly patients. Clinically significant changes in pharmacokinetics of the drug have not been observed in elderly patients.

Clinical characteristics.

Indications.

Type 2 diabetes mellitus in adults:

  • Reduction and control of blood glucose when normalization of glucose levels cannot be achieved by diet, physical exercise, and weight reduction alone.

Contraindications.

  • Hypersensitivity to gliclazide or to other sulfonylurea drugs, sulfonamides, or to any component of the medicinal product;
  • Type 1 diabetes mellitus;
  • Diabetic precoma and coma, diabetic ketoacidosis;
  • Severe hepatic or renal insufficiency (in such cases insulin therapy is recommended);
  • Concomitant treatment with miconazole;
  • Breastfeeding period.

Interaction with other medicinal products and other forms of interaction.

Medicinal products which, when co-administered, may increase the risk of hypoglycemia

Contraindicated combination

Miconazole (for systemic use, oral gel) enhances the hypoglycemic effect, possibly leading to hypoglycemic symptoms and even coma.

Not recommended combination

Phenylbutazone (for systemic use) enhances the hypoglycemic effect of sulfonylureas (by displacing them from plasma protein binding sites and/or reducing their excretion). It is advisable to use an alternative anti-inflammatory agent and to inform the patient about the necessity and importance of self-monitoring. If necessary, the dosage of the medicinal product should be adjusted during and after anti-inflammatory therapy.

Alcohol increases the risk of hypoglycemic reactions (due to inhibition of compensatory mechanisms), potentially leading to hypoglycemic coma. Consumption of alcohol and medicinal products containing alcohol should be avoided.

Combinations requiring caution

When used concomitantly with any of the following medicinal products, hypoglycemia may occur in some cases due to enhanced hypoglycemic effect: other antidiabetic agents (insulins, acarbose, biguanides (e.g., metformin), thiazolidinediones, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists),
β-blockers, fluconazole, ACE inhibitors (captopril, enalapril), H2-receptor antagonists, MAO inhibitors, sulfonamides, clarithromycin, and nonsteroidal anti-inflammatory drugs.

Medicinal products which, when co-administered, may increase the risk of hyperglycemia

Not recommended combination

Danazol exerts a diabetogenic effect. If use of this active substance cannot be avoided, the patient should be informed about the necessity and importance of self-monitoring of glucose levels in blood and urine. Adjustment of the antidiabetic agent dosage may be required during and after danazol therapy.

Combinations requiring caution

Chlorpromazine (neuroleptic), when used in high doses (> 100 mg per day), increases blood glucose levels (due to reduced insulin release). The patient should be informed about the necessity and importance of monitoring blood glucose levels. Adjustment of the antidiabetic agent dosage may be required during and after neuroleptic therapy.

Glucocorticoids (for systemic and local use: intra-articular, topical, rectal preparations) and tetracosactide increase blood glucose levels, possibly leading to ketoacidosis (due to reduced carbohydrate tolerance). The patient should be informed about the necessity and importance of monitoring blood glucose levels, especially at the beginning of treatment. Adjustment of the antidiabetic agent dosage may be required during and after glucocorticoid therapy.

Ritodrine, salbutamol, terbutaline (intravenous) increase blood glucose levels due to β2-agonist effects. The patient should be informed about the need for blood glucose monitoring. If necessary, the patient should be switched to insulin therapy.

St. John’s wort (Hypericum perforatum) decreases gliclazide concentrations. Emphasis should be placed on the importance of monitoring blood glucose levels.

Medicinal products that may cause dysglycemia

Combinations requiring caution

Fluoroquinolones. When gliclazide is used concomitantly with a fluoroquinolone, the patient should be informed about the risk of dysglycemia and the importance of monitoring blood glucose levels.

Combinations to be considered

Anticoagulants (e.g., warfarin, etc.). Sulfonylureas may potentiate the anticoagulant effect of anticoagulants when used concomitantly. If necessary, the dosage of anticoagulants may be adjusted.

Special precautions for use.

Hypoglycemia

This medicinal product should be prescribed only to patients who are able to eat regular meals (including breakfast). It is important to regularly consume carbohydrates, as the risk of hypoglycemia increases when meals are delayed, inadequate in quantity, or low in carbohydrates. Hypoglycemia is more likely to occur during low-calorie diets, prolonged or intense physical exertion, alcohol consumption, or when using a combination of hypoglycemic agents.

Hypoglycemia may occur during treatment with sulfonylurea drugs (see section "Adverse reactions"). Sometimes hypoglycemia can be severe and prolonged. In such cases, hospitalization and administration of glucose for several days may be required.

To reduce the risk of hypoglycemic episodes, individual patient characteristics must be considered, clear instructions provided, and the dose carefully selected.

Factors that increase the risk of hypoglycemia:

  • Patient refuses or is unable to follow physician's recommendations (particularly relevant for elderly patients);
  • Inadequate or irregular eating, missed meals, periods of fasting, or dietary changes;
  • Imbalance between physical activity and carbohydrate intake;
  • Renal impairment;
  • Severe hepatic impairment;
  • Overdose of the drug;
  • Certain endocrine disorders: thyroid dysfunction, hypopituitarism, and adrenal insufficiency;
  • Concomitant alcohol consumption or use of certain medicinal products (see section "Interaction with other medicinal products and other forms of interaction").

Renal and hepatic impairment

The pharmacokinetics and/or pharmacodynamics of gliclazide may be altered in patients with hepatic impairment or severe renal impairment. Hypoglycemic episodes in such patients may be prolonged and therefore require appropriate treatment.

Patient information

The patient and family members should be informed about risk factors and conditions that may predispose to hypoglycemia, symptoms of hypoglycemia (see section "Adverse reactions"), and methods for their management.

The patient should be informed about the importance of adhering to dietary recommendations, the importance of regular physical activity, and regular monitoring of blood glucose.

Worsening glycemic control

In patients receiving antidiabetic medications, worsening glycemic control may be caused by St. John's wort (Hypericum perforatum), infection, fever, trauma, or surgery. In some cases, insulin therapy may be required.

The hypoglycemic efficacy of any oral antidiabetic agent, including gliclazide, may change over time. This may result from progression of disease severity or reduced response to treatment. This phenomenon is known as secondary failure, which differs from primary failure, where the drugs are ineffective from the beginning of treatment. Before concluding that a patient has developed secondary failure, the appropriateness of the prescribed dose and the patient's adherence to dietary recommendations should be verified.

Disglycemia

Abnormalities in blood glucose levels, including hypoglycemia and hyperglycemia, have been observed in diabetic patients receiving concomitant treatment with fluoroquinolones, particularly in elderly patients. Therefore, careful monitoring of blood glucose levels is recommended in all patients receiving gliclazide together with fluoroquinolones.

Laboratory tests

To assess blood glucose control, measurement of glycated hemoglobin (or fasting plasma glucose) is recommended. Self-monitoring of blood glucose by patients may also be useful.

In patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, treatment with sulfonylurea agents may induce hemolytic anemia. Since gliclazide belongs to the chemical class of sulfonylureas, caution should be exercised, and alternative therapies not containing sulfonylureas should be considered for patients with G6PD deficiency.

Patients with porphyria

Cases of acute porphyria have been reported with the use of certain other sulfonylurea agents in patients with porphyria.

Excipients

This medicinal product contains lactose monohydrate. The modified-release tablet Gliclazide-Teva MR 30 mg contains 54 mg of lactose (as monohydrate), and Gliclazide-Teva MR 60 mg contains 108 mg of lactose (as monohydrate). This product is not recommended for patients with rare hereditary disorders of galactose intolerance, glucose-galactose malabsorption syndrome, or Lapp lactase deficiency.

Use during pregnancy or breastfeeding.

Pregnancy. Data on the use of gliclazide during pregnancy are lacking or limited (fewer than 300 cases of use in pregnant women), as are data on the use of other sulfonylurea agents.

Animal studies have shown that gliclazide has no teratogenic effects.

As a precautionary measure, it is advisable to avoid using gliclazide during pregnancy.

Glycemic control should be achieved before planning pregnancy to reduce the risk of abnormalities associated with uncontrolled diabetes.

Insulin is the treatment of choice for managing diabetes during pregnancy; oral hypoglycemic agents are not suitable.

Women should be switched from oral antidiabetic agents to insulin at the time of planning pregnancy or immediately after pregnancy is confirmed.

Breastfeeding. There are no data on the passage of gliclazide or its metabolites into breast milk. Gliclazide-Teva MR is contraindicated during breastfeeding due to the risk of neonatal hypoglycemia. Risk to newborns and infants cannot be excluded.

Fertility. No effects on fertility or reproductive capacity in male or female rats were observed in preclinical studies.

Ability to affect reaction speed when driving or operating machinery.

Gliclazide-Teva MR may have a negligible influence on the ability to drive vehicles or operate machinery. Patients should be aware of the symptoms of hypoglycemia, be able to recognize them, and exercise caution when driving a car or operating machinery, especially at the beginning of treatment.

Method of Administration and Dosage

For oral use.

Prescribe only to adults.

The daily dose may vary from 30 to 120 mg (from 1 to 4 tablets of 30 mg per day or from half to 2 tablets of 60 mg per day).

The 60 mg tablet may be divided into equal doses.

The daily dose should be taken once daily with breakfast.

Half a tablet or a whole tablet (tablets) should be swallowed whole (do not crush or chew).

If a dose is missed, the dose should not be increased the following day.

As with all antidiabetic agents, Glimepiride-Teva MR requires individual dose adjustment based on the patient's response to treatment (blood glucose levels, glycated hemoglobin HbA1c).

Initial Dose and Dose Adjustment. The recommended initial dose is 30 mg once daily. If adequate glucose control is achieved, treatment may be continued at this dose. If enhanced glucose control is required, the daily dose may be gradually increased to 60 mg, 90 mg, or 120 mg. Dose increases should be made gradually, at intervals of 1 month, except when no reduction in blood glucose levels is observed within 2 weeks of treatment. In such cases, the dose may be increased at the end of the second week of treatment.

Maximum Recommended Daily Dose – 120 mg.

One modified-release tablet of Glimepiride-Teva MR 60 mg is equivalent to two modified-release tablets of Glimepiride-Teva MR 30 mg.

The modified-release tablet of Glimepiride-Teva MR 60 mg may be divided, allowing administration of the drug at a dose of 30 mg (0.5 tablet) or 90 mg (1.5 tablets).

Switching Patients from Preparations Containing 80 mg of Gliclazide to the Medicinal Product
Glimepiride-Teva MR, Modified-Release Tablets 30 mg. One tablet containing 80 mg of gliclazide corresponds to one tablet of Glimepiride-Teva MR, modified-release 30 mg. Blood parameters must be carefully monitored when switching to Glimepiride-Teva MR, modified-release 30 mg tablets.

Switching Patients from Preparations Containing 80 mg of Gliclazide to the Medicinal Product
Glimepiride-Teva MR, Modified-Release Tablets 60 mg. One tablet containing 80 mg of gliclazide corresponds to 0.5 tablet of Glimepiride-Teva MR, modified-release 60 mg. Blood parameters must be carefully monitored when switching to Glimepiride-Teva MR, modified-release 60 mg tablets.

Switching Patients from Other Oral Antidiabetic Medicinal Products to Glimepiride-Teva MR. When switching to Glimepiride-Teva MR, the dosage and half-life of the previous oral antidiabetic agent should be taken into account. A transition period is usually not required. Treatment should be initiated at a dose of 30 mg, with subsequent dose adjustment (see "Initial Dose and Dose Adjustment").

When switching from sulfonylurea antidiabetic agents with a long elimination half-life, a treatment break of several days may be necessary to avoid the cumulative effect of both agents and prevent hypoglycemia.

Treatment with Glimepiride-Teva MR should be initiated at a dose of 30 mg daily, with subsequent dose adjustment according to the principles of initial treatment and dose titration (see above).

Concomitant Use with Other Antidiabetic Medicinal Products. Glimepiride-Teva MR may be used in combination with biguanides, alpha-glucosidase inhibitors, or insulin. If adequate blood glucose control is not achieved in patients taking Glimepiride-Teva MR, concomitant insulin therapy may be initiated under close medical supervision.

Special Patient Populations

Elderly Patients (aged 65 years and older). The dosing regimen is the same as in patients under 65 years of age.

Patients with Mild to Moderate Renal Impairment. The dosing regimen for Glimepiride-Teva MR is the same as in patients with normal renal function; however, such patients should be under close monitoring.

Patients at Risk of Hypoglycemia

Risk factors for hypoglycemia:

  • Inadequate or irregular food intake;
  • Severe or poorly compensated endocrine disorders (hypothyroidism, hypopituitarism, and adrenocorticotropic insufficiency);
  • Withdrawal from long-term corticosteroid therapy and/or therapy with high-dose corticosteroids;
  • Severe vascular diseases (severe ischemic heart disease, severe carotid artery pathology, diffuse vascular disorders).

A minimal initial dose of 30 mg daily is recommended.

Children

The safety and efficacy of the drug for the treatment of children and adolescents (under 18 years of age) have not been established. Glimepiride-Teva MR is not recommended for use in children due to lack of data on its use in this patient population.

Overdose

Overdose of sulfonylurea agents may cause hypoglycemia.

Symptoms of moderate hypoglycemia (without loss of consciousness and without neurological symptoms) should be managed by ingestion of carbohydrates (sugar), adjustment of the antidiabetic agent dose, and/or dietary correction. Close monitoring of the patient should be continued until the physician is confident that the patient is safe.

Severe hypoglycemia leading to coma, seizures, or other neurological disturbances requires immediate medical intervention and urgent hospitalization.

In cases of diagnosed hypoglycemic coma or suspected coma, the patient should receive a rapid intravenous injection of 50 mL of concentrated glucose solution (20% to 30%), followed by continuous infusion of a less concentrated glucose solution (10%) at a rate sufficient to maintain blood glucose levels above 1 g/L. Continuous monitoring of the patient is required. The physician will decide on further monitoring based on the patient's condition.

Glimepiride is highly protein-bound in plasma; therefore, dialysis is ineffective.

Adverse Reactions

When using gliclazide and other sulfonylurea derivatives, the undesirable effects listed below may occur.

Hypoglycemia

The most common adverse reaction associated with gliclazide is hypoglycemia. As with other sulfonylurea drugs, gliclazide may cause hypoglycemia, especially in cases of irregular eating habits or particularly when meals are skipped. Hypoglycemia may be accompanied by characteristic symptoms such as: headache, intense feeling of hunger, nausea, vomiting, fatigue, sleep disturbances, agitation, aggression, decreased concentration and attention, slowed reactions, depression, confusion, visual and speech disturbances, aphasia, tremor, paralysis, sensory disturbances, dizziness, weakness, loss of self-control, delirium, seizures, shallow breathing, bradycardia, drowsiness, and loss of consciousness, which may progress to coma and potentially result in death.

Additionally, symptoms related to the adrenergic system may occur: sweating, clammy skin, anxiety, tachycardia, arterial hypertension, palpitations, chest pain, and arrhythmia.

Typically, symptoms of hypoglycemia resolve after carbohydrate intake (sugar). However, sugar substitutes will not be effective in this case. Clinical experience with other sulfonylurea drugs indicates that even after effective intervention, hypoglycemia may recur.

If a hypoglycemic episode is severe or prolonged and the patient's condition is temporarily controlled by sugar intake, urgent medical attention or even hospitalization is required.

Other Adverse Reactions

Gastrointestinal system: gastrointestinal disturbances, including abdominal pain, nausea, vomiting, dyspepsia, diarrhea, and constipation. Adhering to the recommendation of taking the medication during breakfast may help prevent or minimize these effects.

The following adverse reactions are observed less frequently.

Skin and subcutaneous tissue: rash, pruritus, urticaria, angioneurotic edema, erythema, maculopapular eruptions, bullous reactions (such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and autoimmune bullous disorders), and very rarely, drug reaction with eosinophilia and systemic symptoms (DRESS).

Blood and lymphatic system: hematological disorders are rare and may include anemia, thrombocytopenia, leukopenia, and granulocytopenia. These effects usually resolve after discontinuation of treatment.

Hepatobiliary system: increased levels of liver enzymes (ALT, AST, alkaline phosphatase), hepatitis (isolated cases). If cholestatic jaundice occurs, treatment with the drug should be discontinued. These adverse reactions usually resolve after stopping the medication.

Eye disorders: transient visual disturbances may occur due to changes in blood glucose levels, especially at the beginning of treatment.

Reactions typical of the sulfonylurea class: cases of erythropenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, hyponatremia, increased liver enzyme levels, and even liver function impairment (e.g., with cholestasis and jaundice), hepatitis with regression after discontinuation of sulfonylurea drugs, or in isolated cases, subsequent life-threatening liver failure.

Reporting suspected adverse reactions. All suspected adverse reactions and cases of lack of efficacy should be reported via the following link: https://aisf.dec.gov.ua/.

Shelf life.

2 years.

Storage conditions.

The medicinal product does not require special storage conditions. Keep out of reach of children.

Packaging.

Modified-release tablets 30 mg: 10 tablets in a blister; 6 blisters in a carton.

Modified-release tablets 60 mg: 10 tablets in a blister; 3 or 9 blisters in a carton.

Prescription category.

Prescription only.

Manufacturer.

Balkanpharma-Dupnitsa AD.

Manufacturer's address and location of business activity.

3 Samokovsko Shose Str., Dupnitsa, 2600, Bulgaria.