Instructions for use Gliclazide-Teva MR modified-release tablets 60 mg blister No. 90
Composition
active ingredient: gliclazide;
1 modified-release tablet contains gliclazide 30 mg or 60 mg;
Excipients: lactose monohydrate, hypromellose, microcrystalline cellulose, colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Modified-release tablets.
Main physicochemical properties:
30 mg modified-release tablets: white, oval, biconvex tablets with a “G” stamp on one side;
60 mg modified-release tablets: white, oval, biconvex tablets scored on both sides, debossed with “G” on one side and “60” on the other side of the score on both sides.
Pharmacotherapeutic group
Drugs affecting the digestive system and metabolism. Antidiabetic drugs. Hypoglycemic drugs, except insulins. Sulfonamides, urea derivatives. Gliclazide. ATC code A10B B09.
Pharmacological properties
Pharmacodynamics.
Gliclazide is an oral hypoglycemic agent, a sulfonylurea derivative. It differs from other drugs in the presence of a heterocyclic ring containing nitrogen and having endocyclic bonds.
Mechanism of action
Gliclazide reduces plasma glucose levels by stimulating insulin secretion by β-cells of the islets of Langerhans of the pancreas. The increase in postprandial insulin levels and C-peptide secretion persist even after 2 years of use of the drug. In addition to the above 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 and increases the second phase of insulin secretion. The increase in insulin secretion occurs in response to a meal or glucose load.
Hemovascular properties
Gliclazide reduces microthrombosis through two mechanisms that may be involved in the development of complications of diabetes:
partially inhibits platelet aggregation and adhesion, reduces the number of platelet activation markers (β-thromboglobulin, thromboxane B2);
affects the fibrinolytic activity of the vascular endothelium (increases tPA activity).
Pharmacokinetics.
Absorption
The concentration of gliclazide in the blood plasma increases progressively during the first 6 hours after administration, after which it reaches a constant level (plateau), which is maintained from the 6th to the 12th hour after administration.
Individual fluctuations are insignificant.
Gliclazide is completely absorbed from the gastrointestinal tract. Food intake does not affect the rate and extent of absorption.
Distribution
The binding of gliclazide to plasma proteins is approximately 95%. The volume of distribution is approximately 30 l. A single daily dose of Gliclazide-Teva MR provides an effective concentration of gliclazide in the blood plasma for 24 hours.
Biotransformation
Gliclazide is metabolized mainly in the liver and excreted in the urine, less than 1% of the active substance is excreted in the urine unchanged. Active metabolites are absent in the blood plasma.
Breeding
The half-life of gliclazide is approximately 12–20 hours.
Linearity/nonlinearity
The relationship between the dose taken up to 120 mg and the area under the concentration-time curve is linear.
Special patient groups
Elderly patients: No clinically significant changes in the pharmacokinetics of the drug are observed in elderly patients.
Indication
Type II diabetes in adults:
lowering and controlling blood glucose when it is impossible to normalize glucose levels through diet, exercise, and weight loss alone.
Contraindication
Hypersensitivity to gliclazide or to other sulfonylurea drugs, sulfonamides or to any component of the drug;
type I diabetes;
diabetic precoma and coma, diabetic ketoacidosis;
severe hepatic or renal failure (in such cases, the use of insulin is recommended);
treatment with miconazole;
breastfeeding period.
Interaction with other medicinal products and other types of interactions
Drugs that may increase the risk of hypoglycemia when administered concomitantly
Concomitant use contraindicated
Miconazole (for systemic use, oral gel) enhances the hypoglycemic effect with the possible development of symptoms of hypoglycemia and even the development of coma.
Concomitant use not recommended
Phenylbutazone (for systemic use) enhances the hypoglycemic effect of sulfonylurea drugs (replaces their binding to plasma proteins and/or reduces their excretion). It is advisable to use another anti-inflammatory agent and draw the patient's attention to the need and importance of self-monitoring. If necessary, the dosage of the drug is adjusted during and after therapy with the anti-inflammatory agent.
Alcohol increases the risk of hypoglycemic reactions (due to inhibition of compensatory reactions), which can lead to hypoglycemic coma. Alcohol and alcohol-containing medications should be avoided.
When used simultaneously with one of the following drugs, hypoglycemia may occur in some cases due to an increase in the hypoglycemic effect: other sugar-lowering drugs (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 non-steroidal anti-inflammatory drugs.
Drugs that may increase the risk of hyperglycemia when administered concomitantly
Concomitant use not recommended
Danazol has a diabetogenic effect. If the use of this active substance cannot be avoided, the patient should be warned about the need and importance of self-monitoring of glucose levels in the urine and blood. It may be necessary to adjust the dose of the antidiabetic agent during and after treatment with danazol.
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 warned about the need and importance of monitoring blood glucose levels. It may be necessary to adjust the dose of the antidiabetic active substance during and after treatment with the neuroleptic.
Glucocorticoids (systemic and local: intra-articular, cutaneous and rectal preparations) and tetracosactrin increase blood glucose levels with possible development of ketoacidosis (reduce carbohydrate tolerance). The patient should be warned about the need and importance of blood glucose monitoring, especially at the beginning of treatment. It may be necessary to adjust the dose of the antidiabetic agent during and after treatment with glucocorticoids.
Ritodrine, salbutamol, terbutaline (intravenously) increase blood glucose levels due to β2-agonist effect. Blood glucose monitoring should be advised. If necessary, the patient should be switched to insulin.
St. John's wort (Hypericum perforatum) preparations reduce the concentration of gliclazide. The importance of blood glucose control should be emphasized.
Medications that can cause dysglycemia
Combinations requiring caution
Fluoroquinolones. In the case of concomitant use of gliclazide and a fluoroquinolone, the patient should be warned about the risk of dysglycemia and the importance of blood glucose control should be emphasized.
Combinations to consider
Anticoagulants (e.g. warfarin, etc.). When used simultaneously with anticoagulants, sulfonylureas may potentiate the anticoagulant effect of the latter. If necessary, the dose of anticoagulants may be adjusted.
Application features
Hypoglycemia
This medicinal product should only be prescribed to patients who are able to eat regularly (including breakfast). It is important to take carbohydrates regularly, as the risk of hypoglycaemia is increased when meals are eaten late, in inadequate quantities or when the meal is low in carbohydrates. Hypoglycaemia is more likely to occur with a low-calorie diet, prolonged or intense exercise, alcohol consumption or when a combination of hypoglycaemic agents is used.
Hypoglycemia may occur with sulfonylureas (see section 4.8). Hypoglycemia may sometimes be severe and prolonged. In such cases, hospitalization and administration of glucose for several days may be necessary.
To reduce the risk of hypoglycemic episodes, it is necessary to take into account the individual characteristics of patients, provide them with clear explanations, and carefully select the dose.
Factors that increase the risk of hypoglycemia:
the patient refuses or cannot follow the doctor's recommendations (this especially applies to elderly patients);
unsatisfactory, irregular nutrition, missed meals, periods of fasting or changes in diet;
imbalance between physical activity and carbohydrate intake;
renal failure;
severe liver failure;
drug overdose;
certain endocrine system disorders: thyroid dysfunction, hypopituitarism, and adrenal insufficiency;
simultaneous use of alcohol or certain medicines (see section "Interaction with other medicines and other types of interactions").
Renal and hepatic failure
The pharmacokinetics and/or pharmacodynamics of gliclazide may be altered in patients with hepatic and severe renal impairment. Hypoglycaemic episodes in such patients may be prolonged and require appropriate treatment.
Patient information
The patient and his family members should be informed about the risk factors and conditions that may contribute to the occurrence of hypoglycemia, about the symptoms of hypoglycemia (see section "Adverse reactions") and how to eliminate them.
The patient should be informed about the importance of following the doctor's dietary recommendations, the importance of regular physical exercise, and regular blood glucose monitoring.
In patients receiving antidiabetic drugs, worsening of glycemic control may be caused by: St. John's wort (Hypericum perforatum), infection, fever, trauma, or surgery. In some cases, insulin may be necessary.
The hypoglycaemic efficacy of any oral hypoglycaemic agent, including gliclazide, may vary over time. This may be due to progression of the disease or a decrease in response to treatment. This phenomenon is known as secondary insufficiency, which is different from primary insufficiency, when the drugs are ineffective from the very beginning of treatment. Before concluding that a patient has developed secondary insufficiency, it is necessary to check the correctness of the prescribed dose and the patient's adherence to the diet.
Dysglycemia
Abnormalities in blood glucose levels, including hypoglycemia and hyperglycemia, have been observed in diabetic patients receiving concomitant treatment with fluoroquinolones, especially in elderly patients. Therefore, careful monitoring of blood glucose levels is recommended in all patients receiving gliclazide concomitantly with fluoroquinolones.
Laboratory indicators
Glycated hemoglobin (or fasting venous plasma glucose) is recommended to assess blood glucose control. Self-monitoring of blood glucose levels by patients may also be useful.
In patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, the use of sulfonylureas may cause hemolytic anemia. Since gliclazide belongs to the chemical class of sulfonylureas, caution should be exercised and consideration should be given to prescribing alternative therapy with non-sulfonylurea-containing drugs to patients with G6PD deficiency.
Patients with porphyria
Cases of acute porphyria have been described with the use of some other sulfonylureas in patients with porphyria.
Excipients
This medicinal product contains lactose monohydrate. Gliclazide-Teva MR 30 mg modified-release tablet contains 54 mg lactose (as monohydrate), and Gliclazide-Teva MR 60 mg contains 108 mg lactose (as monohydrate). Patients with rare hereditary problems of galactose intolerance, glucose-galactose malabsorption or the Lapp lactase deficiency should not take this medicinal product.
Use during pregnancy or breastfeeding
Pregnancy: There are no or limited amount of data from the use of gliclazide in pregnant women (less than 300 exposed pregnancies), and there are limited data from the use of other sulfonylureas.
Animal studies have shown that gliclazide does not have a teratogenic effect.
As a precautionary measure, it is preferable to avoid taking gliclazide during pregnancy.
Glucose control should be achieved before planning pregnancy to reduce the risk of abnormalities associated with uncontrolled diabetes.
For the treatment of diabetes during pregnancy, the drug of first choice is insulin, and oral hypoglycemic drugs are not acceptable.
When planning or immediately after pregnancy, it is necessary to transfer a woman from oral hypoglycemic drugs to insulin.
Breastfeeding. There is no data on the excretion of gliclazide or its metabolites into breast milk. Gliclazide-Teva MR is contraindicated during breast-feeding due to the risk of neonatal hypoglycaemia. A risk to the newborn and infant cannot be excluded.
Fertility: In nonclinical studies, no effects on fertility or reproductive performance were observed in male or female rats.
Ability to influence reaction speed when driving vehicles or other mechanisms
Gliclazide-Teva MR may have a minor influence on the ability to drive or use machines. Patients should be aware of the symptoms of hypoglycemia, be able to recognize them and, if they occur, exercise caution when driving or operating machinery, especially at the beginning of treatment.
Method of administration and doses
For oral use.
For adults only.
The daily dose can vary from 30 to 120 mg per day (1 to 4 tablets of 30 mg per day or half to 2 tablets of 60 mg per day).
The 60 mg tablet can be divided into equal doses.
The daily dose should be taken once during breakfast.
Half a tablet or whole tablet(s) should be swallowed whole (do not crush or chew).
If you miss a pill, do not increase the dose the next day.
Initial dose and dose selection. The recommended initial dose is 30 mg per day. If effective glucose control is achieved, treatment can be continued at this dose. If blood glucose control is required, the daily dose can be increased sequentially to 60 mg, 90 mg or 120 mg. It is recommended to increase the dose gradually, at intervals of 1 month, unless there is no reduction in blood glucose levels within 2 weeks of treatment. In this case, the dose can be increased at the end of the second week of treatment.
The maximum recommended daily dose is 120 mg.
1 modified-release tablet of Gliclazide-Teva MR 60 mg is equivalent to 2 modified-release tablets of Gliclazide-Teva MR 30 mg.
The modified-release tablet of Gliclazide-Teva MR 60 mg can be divided, which allows the drug to be used in a dose of 30 mg (0.5 tablet) and in a dose of 90 mg (1.5 tablets).
Transferring a patient from preparations containing gliclazide 80 mg to the drug Gliclazide-Teva MR, modified-release tablets 30 mg. 1 tablet containing gliclazide 80 mg corresponds to 1 tablet of the drug Gliclazide-Teva MR, modified-release tablets 30 mg. It is necessary to carefully monitor blood parameters during the transfer to the drug Gliclazide-Teva MR, modified-release tablets 30 mg.
Transferring a patient from preparations containing gliclazide 80 mg to the drug Gliclazide-Teva MR, modified-release tablets 60 mg. 1 tablet containing gliclazide 80 mg corresponds to 0.5 tablets of the drug Gliclazide-Teva MR, modified-release tablets 60 mg. It is necessary to carefully monitor blood parameters during the transfer to the drug Gliclazide-Teva MR, modified-release tablets 60 mg.
Transferring a patient from other oral hypoglycemic drugs to Gliclazide-Teva MR. When transferring to Gliclazide-Teva MR, the dosage and half-life of the previous oral hypoglycemic drug should be taken into account. A transition period is usually not required. The dose should be started at 30 mg with subsequent dose adjustment (see "Initial dose and dose selection").
When transferring from sulfonylurea antidiabetic drugs with a long half-life, a break in treatment for several days may be necessary to avoid the cumulative effect of the two drugs and the development of hypoglycemia.
Treatment with Gliclazide-Teva MR should be started at a dose of 30 mg per day with subsequent dose adjustment in accordance with the rules for initiating treatment and selecting the dose (see above).
Concomitant use with other antidiabetic agents. Gliclazide-Teva MR can be used in combination with biguanides, alpha-glucosidase inhibitors or insulin. If adequate blood glucose control is not achieved in patients taking Gliclazide-Teva MR, concomitant insulin therapy can be initiated under close medical supervision.
Special patient groups
Elderly patients (65 years and older): The dosage regimen is the same as for patients under 65 years of age.
Patients with mild to moderate renal impairment: The dosage regimen of Gliclazide MR is the same as for patients with normal renal function, but the patient should be closely monitored.
Patients at risk of hypoglycemia
Risk factors for hypoglycemia:
insufficient or poor nutrition;
severe or insufficiently compensated endocrine system disorders (hypothyroidism, hypopituitarism and adrenocorticotropic insufficiency);
discontinuation of long-term corticosteroid therapy and/or high-dose corticosteroid therapy;
severe vascular diseases (severe ischemic heart disease, severe carotid vascular pathology, diffuse vascular diseases).
A minimum starting dose of 30 mg per day is recommended.
Children.
The safety and efficacy of the drug in children and adolescents (under 18 years of age) have not been established. Gliclazide-Teva MR is not recommended for use in children due to the lack of data on the use of the drug in this category of patients.
Overdose
Overdose of sulfonylureas can cause hypoglycemia.
Symptoms of moderate hypoglycemia (without loss of consciousness and without neurological symptoms) should be corrected by taking carbohydrates (sugar), adjusting the dose of the hypoglycemic drug and/or diet. Close monitoring of the patient should continue until the doctor is sure that the patient is safe.
Severe hypoglycemia with the development of coma, convulsions, or other neurological disorders requires emergency medical care with immediate hospitalization.
If a diagnosis of hypoglycemic coma is made or if coma is suspected, the patient should be given 50 ml of a concentrated glucose solution (20% to 30%) intravenously rapidly, followed by continuous infusion of a less concentrated glucose solution (10%) at a frequency that will maintain a blood glucose level above 1 g/l. The patient should be kept under constant observation. Depending on the patient's condition, the physician will decide on further monitoring.
Gliclazide has a high level of binding to blood plasma proteins, so dialysis is ineffective.
Side effects
The following undesirable effects may occur when using gliclazide and other sulfonylurea derivatives.
Hypoglycemia
The most common adverse reaction with gliclazide is hypoglycemia. As with other sulfonylureas, gliclazide can cause hypoglycemia with irregular meals and especially if meals are missed. The occurrence of hypoglycemia may be accompanied by characteristic symptoms such as: headache, intense hunger, nausea, vomiting, fatigue, sleep disturbances, agitation, aggression, decreased concentration and attention, slowed reactions, depression, confusion, visual and speech disorders, aphasia, tremor, paresis, sensory disturbances, dizziness, feeling of weakness, loss of self-control, delirium, convulsions, shallow breathing, bradycardia, drowsiness and loss of consciousness, which can lead to coma and death.
In addition, disorders of the adrenergic system are possible: sweating, clammy skin, anxiety, tachycardia, arterial hypertension, palpitations, chest pain, arrhythmia.
Usually, the symptoms of hypoglycemia disappear after taking carbohydrates (sugar). However, taking sugar substitutes will not be effective in this case. Experience with other sulfonylureas shows that even if the measures taken are effective, hypoglycemia may occur again.
If the hypoglycemic episode is severe or prolonged and the patient's condition is temporarily under control by taking sugar, emergency medical attention or even hospitalization is necessary.
Other adverse reactions
Gastrointestinal: Gastrointestinal disorders, including abdominal pain, nausea, vomiting, dyspepsia, diarrhea, and constipation. Following the recommendations for taking the drug with breakfast will help avoid or minimize the occurrence of these manifestations.
The following adverse reactions are less common.
Skin and subcutaneous tissue disorders: rash, pruritus, urticaria, angioedema, erythema, maculopapular rashes, bullous reactions (such as Stevens-Johnson syndrome, toxic epidermal necrolysis and autoimmune bullous disorders) and very rarely - drug rash with eosinophilia and systemic symptoms (DRESS).
Blood and lymphatic system disorders: Hematological disorders are rare and may include anemia, thrombocytopenia, leukopenia, granulocytopenia. These phenomena usually disappear after discontinuation of treatment.
Hepatobiliary system: increased levels of liver enzymes (ALT, AST, alkaline phosphatase), hepatitis (isolated cases). In case of cholestatic jaundice, treatment with the drug should be discontinued. These adverse reactions usually disappear after discontinuation of the drug.
On the part of the organs of vision: temporary 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 erythrocytopenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, hyponatremia, increased liver enzymes and even liver dysfunction (e.g. with cholestasis and jaundice), hepatitis with regression after discontinuation of sulfonylurea drugs or in isolated cases with subsequent life-threatening liver failure.
Reporting of suspected adverse reactions. All cases of suspected adverse reactions and lack of efficacy of the drug should be reported via the link: https://aisf.dec.gov.ua/.
Expiration date
2 years.
Storage conditions
The medicine does not require any special storage conditions. Keep out of the reach of children.
Packaging
Modified-release tablets 30 mg: 10 tablets per blister; 6 blisters per box.
Modified-release tablets 60 mg: 10 tablets in a blister; 3 or 9 blisters in a box.
Vacation category
According to the recipe.
Producer
Balkanfarma-Dupnytsia JSC.
Location of the manufacturer and address of its place of business.
3 Samokovskoe Shose St., Dupnitsa, 2600, Bulgaria.
