Instructions Diaglizid tablets 80 mg blister No. 60
Composition
active ingredient: gliclazide;
1 tablet contains 80 mg of gliclazide in terms of 100% substance;
excipients: lactose monohydrate, microcrystalline cellulose, povidone, calcium stearate, talc.
Dosage form
Pills.
Main physicochemical properties: white or white with a cream tint tablets with a flat surface, a score and a bevel.
Pharmacotherapeutic group
Hypoglycemic drugs, except insulins. Sulfonamides, urea derivatives. Gliclazide. ATC code A10B B09.
Pharmacological properties
Pharmacodynamics
Gliclazide is a sulfonylurea derivative and belongs to the second-generation synthetic oral hypoglycemic drugs. The drug restores the early peak of insulin secretion, affects calcium transport in pancreatic β-cells. The peculiarity of the chemical structure of second-generation drugs determines their greater affinity for the sulfonylurea receptor on the β-cell membrane. This action is implemented by the following mechanism: reduction of the permeability of the β-cell membrane to potassium ions ® membrane depolarization ® influx of calcium ions through channels, the opening of which depends on changes in the electrical potential of the membrane ® increase in the concentration of intracellular calcium ® release of insulin from cytoplasmic granules. Gliclazide selectively, with high affinity and reversibly binds to the regulatory subunit of the β-cell tubules of the pancreas. Gliclazide increases the effectiveness of insulin action, reduces insulin resistance by increasing glucose utilization and accumulation in muscles and reducing its synthesis in the liver. The drug enhances insulin-stimulated glucose metabolism, accelerating its transport to tissues, and also activating muscle glycogen synthetase. The hypoglycemic effect of gliclazide causes stimulation of endogenous insulin secretion. The hypoglycemic effect is mild.
Gliclazide prevents the development of diabetic vascular complications, including microangiopathy and atheromatous macroangiopathy. This effect is realized by reducing platelet adhesion and aggregation, normalizing prostaglandin metabolism (the balance of which is disturbed in diabetes mellitus), increasing vascular fibrinolytic activity. In addition, the drug is a powerful free radical scavenger (in diabetes mellitus, a significant increase in their production is observed), normalizes vascular permeability, prevents the development of microthrombosis and atherogenesis. Gliclazide reduces the severity of oxidative stress. Gliclazide reduces lipid deposition with the formation of atherosclerotic plaques. The drug contributes to weight loss, normalizes lipid metabolism (reduces the concentration of cholesterol, triglycerides, free fatty acids in blood plasma).
Pharmacokinetics
Gliclazide is rapidly absorbed from the gastrointestinal tract. Food intake and its nature do not affect the rate and extent of its absorption. After oral administration of 80 mg of gliclazide to patients with non-insulin-dependent diabetes mellitus who received this drug for a week at the same dose, the maximum concentration in the blood plasma of 6-8 μg/ml was reached after 2-3 hours. In a healthy person, the maximum level of the drug content - 2-4 μg/ml - is reached after 4 hours after its single administration at a dose of 80 mg. 87-95% of gliclazide binds to blood plasma proteins. The drug is almost completely metabolized, mainly in the liver. The half-life of gliclazide from the body is from 10 to 12 hours. 3-6 hours after taking the drug, its metabolites are detected in the intestine. Blood plasma clearance is approximately 13 ml/min, 60-70% of the drug is excreted in the urine, 10-20% in the feces.
Indication
Type II diabetes mellitus (non-insulin-dependent) in adults when blood glucose levels cannot be controlled by diet, exercise, or weight loss alone.
Contraindication
Hypersensitivity to gliclazide, other sulfonylurea derivatives and to inactive components of the drug; type I diabetes mellitus (insulin-dependent); severe ketoacidosis, precomatose state and diabetic coma; severe renal failure; severe hepatic failure; miconazole therapy; quinolone treatment; breastfeeding period.
Interaction with other medicinal products and other types of interactions
When using drugs that may cause hypo- or hyperglycemia, the patient should be warned about the need for careful monitoring of blood glucose levels during treatment. It may be necessary to adjust the dose of the hypoglycemic drug during and after treatment with these drugs.
Drugs, concomitant administration of which may increase the risk of hypoglycemia:
Concomitant use is 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.
Simultaneous use is not recommended.
Phenylbutazone (for systemic use) enhances the hypoglycemic effect of sulfonylurea derivatives (replaces their binding to plasma proteins and/or reduces their excretion). It is recommended to use other nonsteroidal anti-inflammatory drugs or warn the patient and emphasize the importance of self-monitoring of blood glucose. If necessary, the dose of the hypoglycemic drug can be adjusted during and after treatment with phenylbutazone.
Alcohol increases the risk of hypoglycemic reactions (by inhibiting compensatory reactions), which can lead to hypoglycemic coma. Alcohol and drugs containing alcohol should be avoided.
Combinations requiring caution
When used simultaneously with one of the following drugs, hypoglycemia may occur in some cases due to an increase in the hypoglycemic effect: other glucose-lowering drugs (insulin, acarbose, biguanides, 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, nonsteroidal anti-inflammatory drugs, clarithromycin.
Drugs, concomitant administration of which may increase the risk of hyperglycemia:
Simultaneous use is not recommended.
Danazol has a diabetogenic effect. If the use of this drug cannot be avoided, the patient should be warned and the importance of self-monitoring of blood and urine glucose should be emphasized. If necessary, the dose of the hypoglycemic drug may be adjusted during and after treatment with danazol.
Combinations requiring caution
Chlorpromazine (neuroleptic) when used in high doses (more than 100 mg per day) increases blood glucose levels (due to reduced insulin release). The patient should be warned and the importance of self-monitoring of blood glucose should be emphasized. If necessary, the dose of the hypoglycemic drug can be adjusted during and after treatment with the neuroleptic.
Glucocorticoids (for systemic and local use: intra-articular, cutaneous and rectal preparations) and tetracosactide - increase blood glucose levels with possible development of ketoacidosis (reduce carbohydrate tolerance). The patient should be warned and the importance of self-monitoring of blood glucose should be emphasized, especially at the beginning of treatment. If necessary, the dose of the hypoglycemic drug can be adjusted during and after treatment with glucocorticoids.
Ritodrine, salbutamol, terbutaline (intravenous) – may increase blood glucose levels due to β2-agonist effect.
St. John's wort (Hypericum perforatum) preparations reduce gliclazide concentrations. The importance of blood glucose control should be emphasized.
Combinations to consider
Anticoagulants (e.g. warfarin): When used concomitantly with anticoagulants, sulfonylureas may potentiate the anticoagulant effect of the latter. If necessary, the dose of the anticoagulant may be adjusted.
Application features
Hypoglycemia. This drug should only be prescribed if the patient is able to maintain a regular meal schedule (including breakfast). Regular carbohydrate intake is very important. Delayed meals, insufficient amounts of food, or low carbohydrate intake increase the risk of hypoglycemia.
Hypoglycemia is more likely to occur with a low-calorie or irregular diet, prolonged or intense physical exertion, alcohol consumption, or concomitant use of other hypoglycemic drugs.
Hypoglycemia can occur when taking sulfonylureas. In some cases, hypoglycemia can 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.
Risk factors that increase the risk of hypoglycemia:
the patient refuses or cannot follow the doctor's recommendations (especially this applies to elderly patients); unsatisfactory, irregular nutrition, periods of fasting and changes in diet; imbalance between physical activity and carbohydrate intake; alcohol consumption; renal failure; severe liver failure; drug overdose; certain endocrine disorders: thyroid dysfunction, hypopituitarism and adrenal insufficiency; simultaneous use of certain medications (see the section "Drug Interactions").
Patient information. The patient and family members should be informed about the risk factors and conditions that may predispose to hypoglycemia, the symptoms of hypoglycemia, and how to manage them. The patient should be informed about the importance of following the physician's dietary recommendations, the importance of regular exercise, and regular blood glucose monitoring.
Deterioration of glycemic control in patients receiving hypoglycemic drugs may be caused by: St. John's wort (Hypericum perforatum) or any concomitant treatment that may affect the metabolism of gliclazide, infection, fever, trauma or surgery. In some cases, insulin may be necessary. The hypoglycemic efficacy of any oral hypoglycemic agent, including gliclazide, may vary over time. This may be due to the progression of the severity of the disease or due to a decrease in the 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.
Blood glucose disturbances, including hypo- and hyperglycemia, have been observed in diabetic patients, especially the elderly, receiving concomitant treatment with fluoroquinolones. Close monitoring of blood glucose levels is recommended in all patients receiving Diaglizid® and fluoroquinolones concurrently.
Laboratory values: Glycated hemoglobin (or fasting blood glucose) is recommended to assess blood glucose control.
In patients with glucose-6-phosphate dehydrogenase deficiency, the use of sulfonylureas may cause hemolytic anemia. Gliclazide should be administered with caution to such patients and alternative therapy should be considered.
The drug contains lactose, so patients with congenital galactose intolerance, glucose-galactose malabsorption syndrome, or Lapp lactase deficiency are not recommended to prescribe this drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
Diaglizid® may have a minor influence on the ability to drive vehicles or operate other automated systems.
Patients need to know the symptoms of hypoglycemia, be able to recognize them, and if they occur, refrain from driving or operating other machinery.
Use during pregnancy or breastfeeding
Pregnancy. Oral hypoglycemic agents (including Diaglizid®) should not be used during pregnancy. Experience with gliclazide during pregnancy is limited (less than 300 exposed pregnancies), and there are limited data on the use of other sulfonylureas. Animal studies have shown that gliclazide is not teratogenic.
It is advisable to avoid taking gliclazide during pregnancy.
Glucose control should be achieved before pregnancy is planned to reduce the risk of abnormalities associated with uncontrolled diabetes. When planning or immediately after pregnancy, the woman should be transferred from oral hypoglycemic drugs to insulin.
Breastfeeding. There is no data on the penetration of gliclazide or its metabolites into breast milk. Diaglizid® is contraindicated during breastfeeding due to the possibility of neonatal hypoglycemia. A risk to newborns and infants cannot be excluded.
Fertility: In nonclinical studies, no effects on fertility or reproductive performance were observed in male or female rats.
Method of administration and doses
Administer orally to adults.
As with all hypoglycemic agents, Diaglizid® requires individual dose adjustment depending on the individual patient's response to treatment. For patients whose glucose levels are usually well controlled by diet, Diaglizid® can be prescribed for a short period in case of temporary impaired glucose control.
Initial dose: Patients under 65 years of age – 1 tablet (80 mg of gliclazide) per day.
Patients over 65 years of age should start with 40 mg of the drug once a day (use gliclazide preparations with the possibility of such a dosage).
It is recommended to increase the dose at intervals of at least 14 days with careful monitoring of blood sugar levels.
The average daily dose is 1-3 tablets of Diaglizid® (80 mg tablets) in two divided doses.
The standard dose is 2 tablets of the drug per day in two divided doses.
The maximum daily dose is 4 tablets of the drug in two doses.
Other high-risk patients
Patients with insufficient or irregular nutrition, or with a significant impairment of the general condition, as well as patients with renal or hepatic insufficiency, treatment should be started with the minimum dose and recommendations for increasing the dose should be strictly followed in order to avoid the possibility of developing hypoglycemic reactions.
As with other sulfonylureas, this drug can be substituted for another hypoglycemic drug without any transition period. When switching from another sulfonylurea with a longer half-life (e.g. chlorpropamide) to this drug, the patient should be closely monitored (more than a few weeks) to avoid an additive effect of the two drugs and the development of hypoglycemia.
Children
The safety and efficacy of Diaglizid® in children have not been studied, therefore the drug should not be used 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 the use of carbohydrates (sugar), correction of 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.
When a diagnosis of hypoglycemic coma is made or when a coma is suspected, the patient should be given 50 ml of a concentrated glucose solution (20-30%) intravenously quickly, followed by continuous administration of a less concentrated glucose solution (10%) at a frequency that will maintain the blood glucose level above 1 g/l. The patient should be constantly monitored. Depending on the patient's condition, the doctor will decide on further tactics.
Gliclazide has a high level of binding to blood plasma proteins, so dialysis is ineffective.
Adverse reactions
Based on experience with gliclazide and other sulfonylurea derivatives, the following undesirable effects may occur.
Hypoglycemia. As with other sulfonylureas, gliclazide may cause hypoglycemia with irregular meals and especially if meals are missed. The occurrence of hypoglycemia may be accompanied by characteristic symptoms, including: headache, intense hunger, nausea, vomiting, fatigue, sleep disturbances, agitation, aggression, impaired concentration and reaction, depression, confusion, visual and speech disturbances, 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, signs of adrenergic counterregulation may occur, such as increased sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris, and arrhythmia.
Symptoms of hypoglycemia usually disappear after ingestion of carbohydrates (sugar). However, sugar substitutes are ineffective. Experience with other sulfonylureas suggests that hypoglycemia may recur, even if the initial measures were effective.
If a hypoglycemic episode is severe or prolonged, the patient requires emergency medical attention or hospitalization, even if their condition is temporarily controlled by taking sugar.
Other undesirable effects
Gastrointestinal: abdominal pain, nausea, vomiting, dyspepsia, diarrhea, and constipation. Following the recommendation to take the drug with breakfast will help avoid or minimize the occurrence of these manifestations.
The following undesirable effects are less common:
Skin and subcutaneous tissue disorders: rash, pruritus, urticaria, erythema, macropapular rash, bullous rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema; in rare cases - drug rash with eosinophilia and systemic symptoms (DRESS).
From the blood and lymphatic system (occurs rarely): 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 jaundice, treatment with the drug should be discontinued.
These undesirable effects usually disappear after discontinuation of the drug.
On the part of the organs of vision: temporary visual disturbances may occur, especially at the beginning of treatment, due to changes in blood glucose levels.
Metabolic disorders: hyponatremia.
Disorders that may occur with any sulfonylurea: cases of erythrocytopenia, agranulocytosis, hemolytic anemia, pancytopenia and allergic vasculitis. Cases of increased liver enzymes and even liver dysfunction (e.g. with cholestasis and jaundice) and hepatitis have also been described with sulfonylureas, which resolved after discontinuation of these drugs or, in rare cases, led to life-threatening liver failure.
Expiration date
3 years.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
10 tablets in a blister. 6 blisters in a pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak".
Location of the manufacturer and its business address
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
