Instructions Diaglizid MR modified-release tablets 60 mg No. 30
Composition
active ingredient: gliclazide;
1 tablet contains gliclazide 60 mg;
Excipients: hypromellose, lactose monohydrate, copovidone, colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Modified-release tablets.
Main physicochemical properties: round tablets with a flat surface with a score and a bevel, white or white with a slightly yellowish tint. Marbling is allowed on the surface of the tablets.
Pharmacotherapeutic group
Antidiabetic agents. Oral hypoglycemic agents, except insulins. Sulfonamides, urea derivatives. Gliclazide.
ATX code A10V B09.
Pharmacological properties
Pharmacodynamics.
Gliclazide is an oral hypoglycemic drug, a sulfonylurea derivative, which differs from other drugs in the presence of a heterocyclic ring containing nitrogen and having endocyclic bonds.
Gliclazide lowers blood 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. 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. A significant increase in insulin secretion occurs in response to a meal or glucose load.
Hemovascular properties: Gliclazide reduces microthrombosis by 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 the activity of tPA).
Prevention of complications of type 2 diabetes.
The advantages of the strategy of intensive glycemic control with the appointment of Gliclazide MR as the basis of therapy were due to:
– a significant reduction in the relative risk of major macrovascular complications by 14%;
– a significant reduction in the relative risk of new cases or progression of nephropathy by 21%;
– a significant reduction in the relative risk of new-onset microalbuminuria by 8%;
– a significant reduction in the relative risk of renal events by 11%.
At the end of the study, 65% and 81.1% of patients in the intensive control group (28.8% and 50.2% in the standard control group) achieved the goal of HbA1c ≤ 6.5% and ≤ 7%, respectively.
90% of patients in the intensive control group took Gliclazide MR (average daily dose was 103 mg), 70% of them took the maximum daily dose of 120 mg. In the intensive glycemic control group based on Gliclazide MR, the body weight of patients remained stable.
The benefits of the intensive glycemic control strategy based on Gliclazide MR were independent of blood pressure reduction.
Pharmacokinetics.
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.
The binding of gliclazide to plasma proteins is approximately 95%. The volume of distribution is approximately 30 l.
A single daily dose of Diaglizid® MR, 60 mg, provides an effective concentration of gliclazide in blood plasma for 24 hours.
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 plasma.
The half-life of gliclazide is approximately 12-20 hours.
There is a linear relationship between the dose of the drug taken up to 120 mg and the plasma concentration.
In elderly patients, no clinically significant changes in the pharmacokinetics of the drug are noted.
Indication
Type II diabetes:
Ø lowering and controlling blood glucose when it is impossible to normalize glucose levels only through diet, exercise, or weight loss;
Ø prevention of complications of type 2 diabetes mellitus: reducing the risk of macro- and microvascular complications, including new cases or worsening of existing nephropathy, in patients with type 2 diabetes mellitus.
Contraindication
– Hypersensitivity to gliclazide or to other sulfonylureas, sulfonamides or to any component of the drug;
– insulin-dependent diabetes mellitus (type I);
– diabetic precoma and coma, diabetic ketoacidosis;
– severe liver or kidney failure;
– treatment with miconazole.
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, the simultaneous administration of which increases the risk of hypoglycemia.
Concomitant use is contraindicated:
Miconazole (for systemic use, oral gel) enhances the hypoglycemic effect, the development of symptoms of hypoglycemia and even coma is possible.
Concomitant 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);
Alcohol increases the risk of hypoglycemic reactions (due to inhibition of 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, metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists), β-blockers, ACE inhibitors (captopril, enalapril), fluconazole, H2-receptor antagonists, sulfonamides, clarithromycin, nonsteroidal anti-inflammatory drugs, MAO inhibitors.
Drugs, the simultaneous administration of which increases the risk of hyperglycemia.
Concomitant use is not recommended:
Danazol has a diabetogenic effect.
Combinations requiring caution:
chlorpromazine (neuroleptic) when used in high doses (over 100 mg per day) increases blood glucose levels (due to reduced insulin release);
glucocorticoids (for systemic and local use: intra-articular, cutaneous and rectal preparations) and tetracosactide – increase blood glucose levels, possible development of ketoacidosis (reduce carbohydrate tolerance);
Ritodrine, salbutamol, terbutaline (intravenous) may increase blood glucose levels due to β2-agonist effect.
Combinations to consider:
Anticoagulants (e.g. warfarin, etc.): when used simultaneously with anticoagulants, sulfonylurea derivatives may potentiate the anticoagulant effect of the latter. If necessary, the dose of anticoagulants may be adjusted.
Application features
Hypoglycemia. This drug 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 hypoglycemia is increased when meals are taken late, in inadequate quantities, or if the meal is low in carbohydrates. Factors that increase the risk of hypoglycemia include:
– the patient refuses or cannot follow the doctor's recommendations (this especially 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 system disorders: thyroid dysfunction, hypopituitarism, and adrenal insufficiency;
– simultaneous use of certain medications (see section “Interaction with other medicinal products and other types of interactions”).
Renal and hepatic insufficiency: The pharmacokinetics and/or pharmacodynamics of gliclazide may be altered in patients with hepatic and severe renal insufficiency. Episodes of hypoglycemia in such patients may be prolonged and require appropriate treatment.
Deterioration of glycemic control in patients receiving hypoglycemic drugs may be caused by infection, fever, trauma, or surgery. In some cases, insulin may be necessary.
The hypoglycaemic efficacy of any oral antidiabetic agent, including gliclazide, may vary over time. This may be due to progression of the disease or to 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.
Laboratory values: Glycated hemoglobin (or fasting blood glucose) is recommended to assess blood glucose control.
The drug contains lactose, therefore, patients with rare hereditary forms of galactose intolerance, glucose-galactose malabsorption syndrome, or Lapp lactase deficiency are not recommended to take this drug.
Use during pregnancy or breastfeeding
Oral diabetes medications should not be used during pregnancy.
There is no experience with the use of Diaglizid® MR during pregnancy.
When planning or establishing pregnancy, it is necessary to transfer the woman from oral hypoglycemic drugs to insulin.
Diaglizid® MR is contraindicated during breastfeeding due to the possibility of hypoglycemia in the child.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients should be aware of the symptoms of hypoglycemia, be able to recognize them, and if they occur, be careful 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. The daily dose should be taken once during breakfast.
The tablets should be swallowed whole (do not crush or chew).
If the patient forgets to take the tablets, the dose should not be increased the next day.
Like all hypoglycemic agents, Diaglizid® MR requires individual dose adjustment depending on the patient's response to treatment (blood glucose level, glycosylated hemoglobin HbAlc).
Initial dose and dose selection. The recommended initial dose is 30 mg (1 tablet of Diaglizid® MR 30 mg) per day. With effective glucose control, treatment can be continued at this dose. If blood glucose control needs to be improved, the daily dose can be increased sequentially to 60 mg, 90 mg or 120 mg. It is recommended to increase the dose gradually, with an interval of 1 month, unless there is no decrease 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 (2 tablets).
The Diaglizid® MR tablet cannot be divided.
Transferring a patient from other oral hypoglycemic agents to Diaglizid® MR: Diaglizid® MR can be prescribed instead of another oral hypoglycemic agent. The dosage and half-life of the latter should be taken into account. A transition period is usually not required. The dose should be started at 30 mg (Diaglizid® MR tablets 30 mg) with subsequent dose adjustment (see “Initial dose and dose selection”).
When transferring from hypoglycemic sulfonylurea drugs that have a longer half-life than Diaglizid® MR, 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 the drug is started with a dose of 30 mg (Diaglizid® MR tablets 30 mg) per day with subsequent dose adjustment as described above.
Concomitant use with other antidiabetic agents: Diaglizid® MR can be used in combination with biguanides, alpha-glucosidase inhibitors and insulin. If adequate blood glucose control is not achieved in patients taking Diaglizid® MR, concomitant insulin therapy may be initiated under close medical supervision.
For elderly patients (65 years and older), the dosage regimen of Diaglizid® MR is the same as for patients under 65 years of age.
For patients with mild to moderate renal insufficiency, the dosage regimen of Diaglizid® MR is the same as for patients with normal renal function, but the patient should be closely monitored.
For patients at risk of hypoglycemia (see sections "Special warnings and precautions for use" and "Interaction with other medicinal products and other types of interactions"), a minimum initial dose of 30 mg per day (Diaglizid® MR tablets 30 mg) is recommended.
For patients with severe vascular diseases (ischemic heart disease, severe carotid artery disease, diffuse vascular diseases), a minimum initial dose of 30 mg per day (Diaglizid® MR tablets 30 mg) is recommended.
For the prevention of complications of type 2 diabetes. The strategy of intensive glycemic control involves a gradual increase in the dose of Diaglizid® MR to 120 mg per day. The dose increase should be carried out by monitoring the HbA1c level, following the recommendations for diet and exercise, and controlling the risk of hypoglycemia. It is also possible to add other glucose-lowering drugs, such as metformin, acarbose, thiazolidinediones or insulin.
Children.
Diaglizid® 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.
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% to 30%) intravenously, followed by continuous administration 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 monitored continuously. Depending on the patient's condition, the doctor will decide on further tactics.
Gliclazide has a high level of binding to plasma proteins, so dialysis is ineffective.
Adverse reactions.
The following undesirable effects may occur when using gliclazide and other sulfonylurea derivatives.
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, 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 may occur: 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 when the initial measures taken were effective, hypoglycemia can occur again.
If a hypoglycemic episode is severe or prolonged and the patient's condition is temporarily under control only by taking sugar, emergency medical attention or even hospitalization is necessary.
Gastrointestinal: abdominal pain, nausea, vomiting, dyspepsia, diarrhea, and constipation. Taking 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, itching, urticaria, angioedema, erythema, maculopapular rashes, bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis);
• from the blood and lymphatic system (occurs rarely): anemia, thrombocytopenia, leukopenia, granulocytopenia. These phenomena usually disappear after discontinuation of treatment;
• from the 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.
The following undesirable effects usually disappeared 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.
In the group of patients with type 2 diabetes mellitus treated with an intensive glycemic control strategy, no previously undescribed adverse reactions were observed. Several patients experienced severe hypoglycemia. Most episodes of hypoglycemia were observed in patients receiving concomitant insulin therapy.
Expiration date
2 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. 3 or 6 blisters in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Farmak".
Location
Ukraine, 04080, Kyiv, Frunze St., 63.
