Diabeton MB, 60 mg 30 pcs

Diabeton MB is an oral hypoglycemic drug from the group of sulfonylurea derivatives of the II generation, which differs from similar drugs by the presence of N-containing heterocyclic ring with endocyclic bond.

Diabeton MB reduces blood glucose levels by stimulating insulin secretion by P-cells of Langerhans islets. After 2 years of treatment, increased postprandial insulin levels and C-peptide secretion persist.

In insulin-independent diabetes mellitus (type II), the drug restores early peak insulin secretion in response to glucose intake and enhances the second phase of insulin secretion. Significant increases in insulin secretion are observed in response to stimulation caused by food intake and glucose administration.

It has been demonstrated that gliclazide increases peripheral tissue sensitivity to insulin. In muscle tissue, the effect of insulin on glucose uptake assessed during the euglycemic hyperinsulin test was significantly increased (+35%), which was due to improved peripheral tissue sensitivity to insulin.

These changes significantly improve the ability to control diabetes. This effect of gliclazide is mainly due to the fact that it promotes the action of insulin on muscle glycogen synthetase. Moreover, studies on muscle tissues have shown that gliclazide induces posttranscriptional changes in GLUT4 relative to glucose. Diabeton MB reduces glucose formation in the liver by normalizing fasting glucose levels.

In addition to affecting carbohydrate metabolism, Diabeton MB has an effect on the microcirculation. Preparation decreases risk of small vessel thrombosis by influence on two mechanisms, which may be involved in development of complications in diabetes: partial inhibition of platelet aggregation and adhesion and decrease of concentration of platelet activating factors (beta-thromboglobulin and thromboxane B2) and restoration of fibulinolytic activity of vascular endothelium and increase of activity of tissue plasminogen activator.

Controlled clinical trials in diabetic patients confirmed antioxidant properties of gliclazide previously demonstrated in clinical pharmacological studies: reduction of plasma lipid peroxide levels and increase of erythrocyte superoxide dismutase activity.

Indications

Active ingredient

Composition

Active ingredient:

Glyclazid – 60.0 mg.

Auxiliary substances:

Lactose monohydrate 71.36 mg,

Maltodextrin 22.0 mg,

Hypromellose 100 cP 160.0 mg,

magnesium stearate 1.6 mg,

colloidal anhydrous silica 5.04 mg.

How to take, the dosage

The drug is intended for adults only. The recommended starting dose is 30 mg (including for patients 65 years and older).
The dose should be adjusted according to blood glucose levels after the start of treatment. Each subsequent dose change can be undertaken after at least a 2-week period.

In maintenance therapy, daily administration of a single dose provides effective control of blood glucose levels. The daily dose of the drug may vary from 30 mg to 120 mg (1-4 tablets) once daily. Maximum daily dose is 120 mg.

The drug is taken orally once daily with breakfast.

If one or more doses of the drug are missed, the higher dose should not be taken at the next dose.

For patients who have not previously been treated, the starting dose is 30 mg. The dose is then adjusted individually until the desired therapeutic effect is achieved.

Diabeton MB can replace diabeton in doses of 1 to 4 tablets/day.

Transitioning from another hypoglycemic drug to Diabeton MB does not require any transition time.

If a patient has previously received therapy with sulfonylurea derivatives with a long T1/2 (e.g., chlorpropamide), close monitoring (glycemic control) is necessary for 1-2 weeks to prevent development of hypoglycemia as a consequence of residual effects of previous therapy.

Patients with mild to moderate renal dysfunction (CKR 15 to 80 ml/min) should use the drug according to the dosing regimen described above.

Interaction

1. Drugs and substances that increase the risk of hypoglycemia (increasing the effect of gliclazide)

.Contraindicated combinations

Miconazole (when administered systemically and when used on the oral mucosa gel): intensifies the hypoglycemic effect of gliclazide (possible development of hypoglycemia up to the state of coma).

Unrecommended combinations

Phenylbutazone (systemic administration): enhances the hypoglycemic effect of sulfonylurea derivatives (displaces them from binding to plasma proteins 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 warned about the need for glycemic control. If necessary, the dose of Diabeton® MV should be adjusted during and after taking phenylbutazone.

Ethanol:increases hypoglycemia by inhibiting compensatory responses and may contribute to hypoglycemic coma. It is necessary to avoid taking drugs that contain ethanol, and alcohol consumption.

Combinations requiring caution

The use of gliclazide in combination with some drugs: other hypoglycemic drugs (insulin, acarbose, metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, GFP-1 agonists); beta-adrenoblockers, fluconazole; ACE inhibitors – captopril, enalapril; Histamine H2-receptor blockers; MAO inhibitors; sulfonamides; clarithromycin and NSAIDs – with increased hypoglycemic effect and risk of hypoglycemia.

2. Drugs that increase blood glucose (which weaken the effect of gliclazide)

No recommended combinations

Danazol: has diabetogenic effects. Careful monitoring of blood glucose is recommended for patients who need to take this medication. If co-administration is necessary, it is recommended that the dose of the hypoglycemic agent be adjusted both during danazol administration and after discontinuation of the drug.

Combinations requiring caution

Chlorpromazine (neuroleptic): At high doses (>100 mg/day), it increases blood glucose concentrations, decreasing insulin secretion. Close glycemic control is recommended. If coadministration is necessary, it is recommended to adjust the dose of hypoglycemic agent, both during neuroleptic administration and after its withdrawal.

HKS (systemic and local administration – intraarticular, cutaneous, rectal administration) and tetracosactide:increase blood glucose concentration with possible development of ketoacidosis (reduced carbohydrate tolerance). Close glycemic control is recommended, especially at the beginning of treatment. If coadministration of drugs is necessary, correction of the dose of hypoglycemic agent may be required, both during the administration of GCS and after their withdrawal.

Ritodrine, salbutamol, terbutaline (intravenous): beta2-adrenomimetics contribute to increased blood glucose concentrations.

Particular attention should be paid to the importance of self-administered glycemic control. If necessary, it is recommended that the patient be switched to insulin therapy.

3. Combinations to be considered

Anticoagulants (e.g., warfarin.Sulfonylurea derivatives may increase the effect of anticoagulants when taken together. Adjustment of anticoagulant dose may be required.

Special Instructions

Hypoglycemia

Hypoglycemia may develop when taking sulfonylurea derivatives, including gliclazide, in some cases in a severe and prolonged form, requiring hospitalization and IV infusion of dextrose solution for several days (see “Side effects”).

The drug can only be prescribed to patients whose diet is regular and includes breakfast. It is very important to maintain sufficient intake of carbohydrates with food, because the risk of hypoglycemia increases with irregular or insufficient diet, as well as with consumption of food poor in carbohydrates. Hypoglycemia is more likely to develop with a low-calorie diet, after prolonged or vigorous exercise, after alcohol consumption or when several hypoglycemic LS are taken at the same time.

As a rule, the symptoms of hypoglycemia disappear after eating a food rich in carbohydrates (e.g. sugar). It should be borne in mind that taking sugar substitutes does not help to eliminate hypoglycemic symptoms. The experience of using other sulfonylurea derivatives suggests that hypoglycemia may recur, despite the effective initial control of this condition. If hypoglycemic symptoms are severe or prolonged, even if there is a temporary improvement after ingestion of carbohydrate-rich foods, emergency medical care, up to and including hospitalization, is necessary.

In order to avoid hypoglycemia, careful individual choice of medications and dosing regimens is necessary, and the patient needs to be fully informed about the treatment.

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

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

– insufficient and irregular meals, skipping meals, starvation, and dietary changes;

– an imbalance between exercise and carbohydrate intake;

– renal impairment;

– severe hepatic impairment;

– overdose of Diabeton® MB;

– some endocrine disorders: thyroid disorders, pituitary and adrenal insufficiency;

– concomitant administration of some drugs (see. “Interactions”).

Hepatic and renal failure

In patients with hepatic and/or severe renal impairment the pharmacokinetic and/or pharmacodynamic properties of gliclazide may change. The state of hypoglycemia that develops in such patients may be quite prolonged, in such cases, immediate appropriate therapy is necessary.

Information for patients

The patient as well as family members should be informed about the risk of hypoglycemia, symptoms and conditions contributing to its development. The patient should be informed about 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 blood glucose monitoring.

Inadequate glycemic control

Glycemic control in patients on hypoglycemic therapy may be impaired in the following conditions: fever, injury, infectious disease, or major surgery. Under these conditions it may be necessary to discontinue therapy with Diabeton® MV and prescribe insulin therapy.

In many patients, the efficacy of oral hypoglycemic agents, including gliclazide, tends to decrease after a long period of 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 produce the expected clinical effect the first time it is prescribed. Before a patient is diagnosed with secondary drug resistance, the appropriateness of the dose and the patient’s compliance with the prescribed diet must be evaluated.

Laboratory tests

To assess glycemic control, regular fasting blood glucose concentration and glycosylated hemoglobin HbA1c levels are recommended. In addition, regular self-monitoring of blood glucose concentration is advisable.

Sulfonylurea derivatives may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency. Since gliclazide is a sulfonylurea derivative, caution should be exercised when prescribing it in patients with glucose-6-phosphate dehydrogenase deficiency. The possibility of prescribing a hypoglycemic drug of another group should be evaluated.

Influence on the ability to drive and operate vehicles

. Because of the possible development of hypoglycemia with Diabeton® MV, patients should be aware of the symptoms of hypoglycemia and exercise caution when driving vehicles or performing work requiring high-speed physical and mental reactions, especially at the beginning of therapy.

Contraindications

– hypersensitivity;

– type 1 diabetes mellitus;

– diabetic ketoacidosis, diabetic precoma, diabetic coma;

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

– taking miconazole;

– pregnancy and lactation;

– under 18 years of age.

Because the drug contains lactose, Diabeton® MV is not recommended for patients with congenital lactose intolerance, galactosemia, and glucose-galactose malabsorption.

The use in combination with phenylbutazone or danazol is not recommended. Caution. Elderly age, irregular and/or unbalanced diet, glucose-6-phosphate dehydrogenase deficiency, severe cardiovascular disease, hypothyroidism, adrenal or pituitary insufficiency, renal and/or hepatic insufficiency, long-term glucocorticosteroid (GCS) therapy, alcoholism.

Side effects

Given the experience with gliclazide and other sulfonylurea derivatives, the following side effects should be kept in mind. Hypoglycemia Like other drugs of the sulfonylurea group, Diabeton® MV may cause hypoglycemia in case of irregular meal intake and especially if meal intake is missed.

Possible symptoms of hypoglycemia: Headache, intense hunger, nausea, vomiting, increased fatigue, sleep disturbance, irritability, agitation, reduced concentration, delayed reactions, depression, confusion, visual and speech impairment, aphasia, tremors, paresis, perception disturbance, dizziness, weakness, seizures, bradycardia, delirium, respiratory disturbance, drowsiness, 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, palpitations, arrhythmias and angina.

In general, the symptoms of hypoglycemia are controlled by taking carbohydrates (sugar). Administration of sugar substitutes is ineffective. Against the background of other sulfonylurea derivatives, there have been recurrences of hypoglycemia after its successful resolution. In severe or prolonged hypoglycemia, emergency medical care is indicated, possibly with hospitalization, even if the effect of carbohydrate intake is present. Other side effects

– Gastrointestinal tract: abdominal pain, nausea, vomiting, diarrhea, constipation. Taking the drug during breakfast can avoid or minimize these symptoms. The following side effects are less common:

– Skin and subcutaneous tissue: rash, itching, urticaria, erythema, maculopapular rash, bullous rash.

– Blood and lymphatic system disorders: hematological disorders (anemia, leukopenia, thrombocytopenia, granulocytopenia) are rare. As a rule, these phenomena are reversible in case of discontinuation of therapy.

– Liver and biliary tract: increased activity of “liver” enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase), hepatitis (single cases). If cholestatic jaundice occurs, therapy should be discontinued. The following side effects are usually reversible in case of discontinuation of therapy.

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

Sulfonylurea derivative side effects: as with other sulfonylurea derivatives, the following side effects have been reported: erythrocytopenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, and hyponatremia.

Elevated liver enzymes, impaired liver function (e.g., with the development of cholestasis and jaundice) and hepatitis have been noted; manifestations decreased with time after discontinuation of sulfonylureas, but in individual cases have led to life-threatening liver failure.

In the ADVANCE study, there was little difference in the incidence of various serious adverse events between the two patient groups. No new safety data were obtained. A small number of patients experienced severe hypoglycemia, but the overall incidence of hypoglycemia was low. The frequency of hypoglycemia in the intensive glycemic control group was higher than in the standard glycemic control group. Most episodes of hypoglycemia in the intensive glycemic control group occurred on concomitant insulin therapy.

Overdose

Symptoms: hypoglycemia, in severe cases – accompanied by coma, seizures and other neurological disorders.

Treatment: moderate symptoms of hypoglycemia are corrected by taking carbohydrates, adjusting the dose and/or changing the diet. Close monitoring of the patient’s condition should be continued until the attending physician is confident that the patient’s health is not threatened. If the condition is severe, an ambulance should be called for and the patient should be hospitalized immediately.

If a hypoglycemic coma is suspected or diagnosed, the patient is quickly given 50 ml of concentrated glucose solution (40%) by IV. A more diluted glucose solution (5%) is then administered by IV drip to maintain the necessary blood glucose levels. Close monitoring should be done for at least the next 48 h. Thereafter, depending on the condition of the patient, the need for further monitoring of the patient’s vital functions should be decided.

In patients with liver disease, plasma clearance of gliclazide may be delayed. Dialysis is not usually performed in these patients due to the pronounced 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. Optimal control (appropriate therapy) of diabetes mellitus is necessary to reduce the risk of birth defects. Oral hypoglycemic drugs are not used during pregnancy. Insulin is the drug of choice for the therapy of diabetes mellitus in pregnant women.

The use of oral hypoglycemic drugs is recommended to be replaced with insulin therapy both if pregnancy is planned and if pregnancy has occurred while taking the drug.

With due consideration of the lack of data on absorption of gliclazide in breast milk and the risk of neonatal hypoglycemia, breastfeeding is contraindicated during therapy with Diabeton MB.

Similarities