Gliklada - instructions for use, dose, side effects, contraindications

Gliclazide is a sulfonylurea derivative, a hypoglycemic preparation for ingestion, which differs from similar drugs by the presence N-containing heterocyclic ring with an endocyclic bond.

Gliclazide reduces the concentration of blood glucose, stimulating the secretion of insulin beta cells of the islets of Langerhans. The increase in the concentration of postprandial insulin and C-peptide persists after 2 years of therapy.

In addition to the effect on carbohydrate metabolism glycazide has hemovascular effects.

Influence on secretion of insulin

In type 2 diabetes, the drug restores the early peak of insulin secretion in response to the intake of glucose and enhances the second phase of insulin secretion.A significant increase in insulin secretion is observed in response to stimulation due to food intake or the introduction of glucose.

Hemovascular effects

Gliclazide reduces the risk of thrombosis of small vessels, affecting the mechanisms that can cause the development of complications in diabetes mellitus: partial inhibition of platelet aggregation and adhesion and a decrease in the concentration of platelet activating factors (beta-thromboglobulin, thromboxane B2), and restoration of fibrinolytic activity of the vascular endothelium and an increase activity of tissue plasminogen activator.

Intensive glycemic control, based on the use of long-acting glycazide (glycosylated hemoglobin (HbAlc) <6.5%), significantly reduces micro- and macrovascular complications of type 2 diabetes mellitus, in comparison with standard glycemic control.

The strategy of intensive glycemic control included the appointment of a long-acting glyclazide and an increase in its dose against a background (or instead of) standard therapy before adding to it another hypoglycemic drug (eg metformin, alpha-glucosidase inhibitor, thiazolidinedione or insulin derivative).The average daily dose of prolonged-release gliclazide in patients in the intensive control group was 103 mg, the maximum daily dose was 120 mg.

Against the background of the use of long-acting glyclazide in the group of intensive glycemic control (mean follow-up 4,8 years, mean level HbAlc 6.5%) compared to the standard control group (medium level HbAlc 7.3%) shows a significant decrease of 10% relative risk of the combined frequency of macro- and microvascular complications.

The advantage was achieved due to a significant reduction in the relative risk: major microvascular complications by 14%, the onset and progression of nephropathy by 21%, the occurrence of microalbuminuria by 9%, macroalbuminuria by 30% and the development of renal complications by 11%.

The benefits of intensive glycemic control against the background of taking gliclazide prolonged action did not depend on the benefits achieved against the background of antihypertensive therapy.

Pharmacokinetics:

After oral administration glycazide completely absorbed. The concentration of glycazide in the blood plasma increases gradually, leaving the plateau after 6-12 hours. Individual variability is low.

The intake of food does not affect the degree of absorption of gliclazide. The relationship between the dose taken (up to 120 mg) and the area under the pharmacokinetic curve "concentration-time" is linear.

About 95% of the glycazide binds to plasma proteins. Gliclazide is metabolized primarily in the liver and is excreted mainly by the kidneys. Excretion is carried out in the form of metabolites, less than 1% is excreted by the kidneys unchanged. There are no active metabolites in the blood plasma.

The half-life of gliclazide is, on average, 12 to 20 hours. The volume of distribution is about 30 liters.

In elderly people, there are no significant changes in pharmacokinetic parameters.

Taking Gliklada in a dose of 60 mg once a day ensures maintenance of an effective concentration of glycazide in the blood plasma for more than 24 hours.

Indications:

Diabetes mellitus type 2 with insufficient effectiveness of diet therapy, exercise and weight loss.
Prevention of complications of diabetes mellitus: reducing the risk of microvascular (nephropathy, retinopathy) and macrovascular complications (myocardial infarction, stroke) in patients with type 2 diabetes by intensive glycemic control.

Contraindications:

Hypersensitivity to gliclazide, other derivatives of sulfonylurea, sulfonamides or to auxiliary substances included in the preparation;
type 1 diabetes mellitus;
Diabetic ketoacidosis, diabetic precoma, diabetic coma;
severe renal or hepatic insufficiency (in these cases it is recommended to use insulin);
taking miconazole (see section "Interaction with other drugs");
pregnancy and the period of breastfeeding (see the section on "Application during pregnancy and during breastfeeding");
age to 18 years.

Due to the fact that lactose is included in the preparation, the drug Gliklada8 is not recommended for patients with congenital lactose intolerance, galactosemia, glucose-galactose malabsorption.

It is not recommended to use in combination with phenylbutazone or danazol (see section "Interaction with other drugs"),

Carefully:

Elderly patients, irregular and / or unbalanced diet, insufficiency of glucose-6-phosphate dehydrogenase, severe diseases of the cardiovascular system, hypothyroidism,adrenal or pituitary insufficiency, renal and / or hepatic insufficiency, long-term therapy with glucocorticosteroids (GCS), alcoholism.

Pregnancy and lactation:

Pregnancy

Experience with glycazide during pregnancy is absent. Data on the use of other derivatives of sulfonylurea during pregnancy are limited.

In studies on laboratory animals teratogenic effects of glycazide were not revealed.

To reduce the risk of developing congenital malformations, optimal control (appropriate therapy) of diabetes mellitus is necessary.

Oral hypoglycemic drugs during pregnancy are not applied. Insulin is the drug of choice for the therapy of diabetes mellitus in pregnant women. It is recommended to replace the intake of oral hypoglycemic drugs with insulin therapy, as in the case of a planned pregnancy, and if the pregnancy occurred while taking the drug.

Breastfeeding period

Taking into account the lack of data on excretion of gliclazide in breast milk and the risk of developing neonatal hypoglycemia during drug therapy,breast-feeding is contraindicated.

Dosing and Administration:

PREPARATION IS INTENDED FOR ADULT TREATMENT.

The recommended dose of Glyclad® should be taken orally, once a day, preferably during breakfast.

The daily dose can be from 30 mg (it is possible to use gliclazide, prolonged-release tablets 30 mg) to 120 mg in a single dose.

If it is necessary to use long-acting glyclazide in a daily dose of 30 mg, prolonged-release tablets of 30 mg gliclazide (Gliclada®, prolonged-release tablets, 30 mg) should be used.

It is recommended to swallow the whole tablet without chewing or grinding.

If you skip one or more doses of Glyclad®, you can not take a higher dose to the next dose, the missed dose should be taken the next day.

As with other hypoglycemic drugs, the dose of the drug in each case must be selected individually, depending on the concentration of glucose and blood HbAlc.

Initial dose

The initial recommended dose (including for elderly patients,> 65 years) of prolonged-release glyclazide is 30 mg per day (1 tablet of long-acting glyclazide 30 mg).

In case of adequate control, the drug in this dose can be used for maintenance therapy. With inadequate glycemic control, the daily dose of gliclazide can be sequentially increased to 60 mg, 90 mg or 120 mg.

Increase in the dose is possible not earlier than after 1 month of therapy with the drug in the previously prescribed dose. Exception is made by patients, in whom the blood glucose concentration did not decrease after 2 weeks of therapy. In such cases, the dose of the drug may be increased 2 weeks after the start of the treatment.

The maximum recommended daily dose of the drug is 120 mg.

1 tablet of the drug Gliklada® 60 mg is equivalent to 2 tablets of the drug Gliklad® 30 mg.

Transition from gliclazide therapy to tablets with immediate release of 80 mg to therapy with Gliclide® sustained-release tablets

2 tablets immediate release glycazide 80 mg are equivalent to 1 tablet of the drug Gliklada® 60 mg. When transferring patients from gliclazide therapy (tablets with immediate release) 80 mg per tablet Gliclade® careful glycemic control is recommended.

Transition from therapy with another hypoglycemic drug to therapy with Gliklad® prolonged action tablets 60 mg

Glyclad preparation® a 60 mg long-acting tablet can be used in place of another hypoglycemic drug for ingestion. When transferring to the drug Gliklada® patients receiving other hypoglycemic drugs for ingestion should take into account their dose and half-life. As a rule, a transition period is not required. The initial dose of prolonged-action gliclazide should be 30 mg (1 tablet of long-acting glyclazide 30 mg) and then should be titrated depending on the concentration of blood glucose.

When replaced with Gliclide® derivatives of sulfonylurea with a long half-life to avoid hypoglycemia caused by the additive effect of two hypoglycemic agents, you can stop taking them for several days. The initial dose of Glyclad®, in addition, is also 30 mg (1 tablet of long-acting glyclazide 30 mg) and, if necessary, can be further increased as described above.

Combination with another hypoglycemic drug

The drug Gliklada can be used in combination with biguanides, inhibitors of alpha-glucosidase or insulin.

With inadequate glycemic control, additional insulin therapy should be prescribed with careful medical supervision.

Elderly patients

Correction of the dose of Glyclad® for patients over 65 years of age is not required.

Patients with renal insufficiency

The results of clinical studies showed that correction of the dose of the drug in patients with mild and moderate renal insufficiency is not required. It is recommended that a thorough medical check is carried out.

Patients at risk of developing hypoglycemia

In patients who are at risk for developing hypoglycemia (insufficient or unbalanced nutrition, severe or poorly compensated endocrine disorders - pituitary and adrenal insufficiency, hypothyroidism, cancellation of GCS after their long reception and / or reception in high doses, severe diseases of the cardiovascular system - severe ischemic heart disease, severe atherosclerosis of the carotid arteries, widespread atherosclerosis), it is recommended to use the minimal dose (30 mg) of gliclazide prolonged de action.

Prevention of complications of diabetes mellitus

To achieve intensive glycemic control, you can gradually increase the dose of Gliclada® to 120 mg / day in addition to diet and exercise before reaching the target level HbAlc. It should be remembered about the risk of developing hypoglycemia. In addition, other hypoglycemic drugs may be added to therapy, for example, metformin, an alpha-glucosidase inhibitor, a thiazolidinedione derivative or insulin.

Children and teenagers under the age of 18

Data on the efficacy and safety of gliclazide in children and adolescents under the age of 18 are not available.

Side effects:

Taking into account the experience of the use of gliclazide and other derivatives of sulfonylureas, one should remember about the possibility of developing the following side effects.

Hypoglycaemia

Like other drugs of the sulfonylurea group, the drug Gliklada can cause hypoglycemia in case of irregular intake of food and especially if the meal is missed. Possible symptoms of hypoglycemia: headache, severe hunger, nausea, vomiting, fatigue, sleep disturbance, irritability,agitation, decreased concentration of attention, delayed reaction, depression, confusion, impaired vision and speech, aphasia, tremor, paresis, impaired perception, dizziness, weakness, convulsions, bradycardia, delirium, respiratory depression, drowsiness, loss of consciousness with possible development of coma, up to a lethal outcome. Also can be marked adrenergic reactions: sweating, "sticky" skin, anxiety, tachycardia, hypertension, palpitations, arrhythmia, and angina pectoris.

As a rule, the symptoms of hypoglycemia are stopped by the intake of carbohydrates (sugar). The intake of sugar substitutes is ineffective. Against the background of other derivatives of sulfonylureas, there were relapses of hypoglycemia after its successful cupping.

With severe or prolonged hypoglycemia, emergency medical care is indicated, possibly with hospitalization, even if there is an effect of taking carbohydrates.

Other side effects

From the gastrointestinal tract: abdominal pain, nausea, vomiting, diarrhea, constipation. Taking the drug during breakfast allows you to avoid these symptoms or minimize them.

Less common are the following side effects:

from the skin and subcutaneous tissue: rash, itching, urticaria, Quincke's edema, erythema, maculopapular rash, bullous reactions (such as Stevens-Johnson syndrome and toxic epidermal necrolysis);
from the blood and lymphatic system, hematological disorders (anemia, leukopenia, thrombocytopenia, granulocytopenia) are rare. As a rule, these phenomena are reversible in the event of discontinuation of therapy;
from the side of baked and bile ducts: increased activity of "hepatic" enzymes (aspartate aminotransferase (ACT), alanine aminotransferase (ALT), alkaline phosphatase), hepatitis (isolated cases). When cholestatic jaundice occurs, therapy should be discontinued.

The following side effects are usually reversible in the event of discontinuation of therapy:

from the side of the organ of vision: can occur transient visual disorders caused by changes in blood glucose concentration, especially at the beginning of therapy;
side effects inherent in derivatives of sulfonylurea. as against the background of taking other sulfonylurea derivatives, the following side effects were noted: erythrocytopenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, hyponatremia.There was an increase in the activity of liver enzymes, a violation of liver function (for example, with the development of cholestasis and jaundice) and hepatitis, the manifestations decreased with time after the withdrawal of sulfonylureas, but in some cases led to life-threatening liver failure.

Side effects noted during clinical trials

In the clinical study, there was a slight difference in the incidence of various serious adverse events between the two groups of patients. No new safety data was received. A small number of patients experienced severe hypoglycemia, but the overall incidence of hypoglycemia was low. The frequency of hypoglycemia in the group of intensive glycemic control was higher than in the group of standard glycemic control. Most episodes of hypoglycemia in the group of intensive glycemic control were noted against the background of concomitant insulin therapy.

Overdose:

When an overdose of sulfonylurea derivatives may develop hypoglycemia.

If mild symptoms of hypoglycemia occur without a loss of consciousness or neurological symptoms, you should increase the intake of carbohydrates with food, reduce the dose of the drug and / or change the diet.Close medical surveillance of the patient's condition should continue until there is no certainty that his health is not threatened.

Possible development of severe hypoglycemic conditions, accompanied by coma, seizures or other neurological disorders. If such symptoms appear, emergency medical care and immediate hospitalization are necessary.

In the case of hypoglycemic coma or if it is suspected, 50 ml of 20-30% solution of dextrose (glucose) is injected intravenously. Then 10% dextrose solution is administered intravenously dropwise to maintain a glucose concentration in the blood above 1 g / l. Careful monitoring of blood glucose concentration and patient monitoring should be carried out for at least 48 consecutive hours. After this period of time, depending on the patient's condition, the attending physician decides on the need for further observation.

Dialysis is ineffective due to the expressed binding of gliclazide to plasma proteins.

Interaction:

Drugs that increase the risk of developing hypoglycemia (enhancing the action of gliclazide)

Contraindications

Miconazole (with systemic administration and with the use of gel on the mucosa of the oral cavity): increases the hypoglycemic effect of glycazide (hypoglycemia may develop 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 more preferable to use another anti-inflammatory drug. If the reception of phenylbutazone is necessary, the patient should be warned about the need for glycemic control. If necessary, the dose of Glyclad should be adjusted during and after phenylbutazone administration.

Ethanol: enhances hypoglycemia by inhibiting compensatory reactions, can

promote the development of hypoglycemic coma. It is necessary to refuse from taking medicines, which include ethanol, and the use of alcohol.

Combinations that require precautions

The use of gliclazide in combination with certain drugs (for example, other hypoglycemic agents (insulin, acarbose, metformin, thiazolidinediones, inhibitors of dipeptidyl peptidase-4, glucagon-like peptide-1 receptor agonists (GLP-1)), beta adrenoblockers, fluconazole, angiotensin converting enzyme inhibitors (captopril, enalapril), H2-histamine receptor blockers , monoamine oxidase inhibitors, sulfonamides, clarithromycin and non-steroidal anti-inflammatory drugs) is accompanied by increased hypoglycemic effect and risk of hypoglycemia.

Drugs that increase blood glucose concentration (weakening effect of Gliclazide)

Unrecommended combinations

Danazol: has a diabetic effect. In case the reception of this drug is necessary, the patient is recommended careful glycemic control. If it is necessary to take medications together, it is recommended that the dosage of the hypoglycemic agent be selected at the time of taking danazol and after its withdrawal.

Combinations that require precautions

Chlorpromazine (antipsychotic): in high doses (more than 100 mg per day) increases the concentration of glucose in the blood, reducing the secretion of insulin. Careful glycemic control is recommended.If it is necessary to take drugs together, it is recommended that a dose of a hypoglycemic agent be chosen, both during the administration of the neuroleptic and after its withdrawal.

GCS (systemic and topical application: intraarticular, external, rectal administration) and tetracosactide: increase the concentration of blood glucose with the possible development of ketoacidosis (reduced tolerance to carbohydrates). Careful glycemic control is recommended, especially at the beginning of treatment. If it is necessary to take medications together, it may be necessary to correct the dose of the hypoglycemic agent both during the administration of the GCS and after their withdrawal.

Ritodrin, salbutamol, terbutaline (intravenous administration): beta-2 adrenomimetics contribute to increased blood glucose concentrations.

It is necessary to pay special attention to the importance of independent glycemic control. If necessary, it is recommended to transfer the patient to insulin therapy. Combinations that need to be taken into account

Anticoagulants (eg, warfarin): sulfonylureas can strengthen the effect of anticoagulants in a joint reception.You may need to adjust the dose of anticoagulant.

Special instructions:

Hypoglycaemia

When taking sulfonylurea derivatives, including glycazide, hypoglycemia may develop, in some cases in severe and prolonged form, requiring hospitalization and intravenous administration of a dextrose solution for several days (see section "Side effect").

The drug can be prescribed only to those patients, whose meals are regular and includes breakfast. It is very important to maintain sufficient intake of carbohydrates with food, since the risk of developing hypoglycemia increases with irregular or inadequate nutrition, as well as when consuming food poor in carbohydrates. Hypoglycemia often develops with a low-calorie diet, after prolonged or vigorous exercise, after drinking alcohol or taking several hypoglycemic drugs at the same time. Typically, the symptoms of hypoglycemia go away after eating a meal rich in carbohydrates (such as sugar). It should be borne in mind that the use of sugar substitutes does not help to eliminate hypoglycemic symptoms.The experience of using other sulfonylurea derivatives suggests that hypoglycemia can recur despite effective initial arrest of this condition. In the event that hypoglycemic symptoms have a pronounced character or are prolonged, even in the case of temporary improvement after a meal rich in carbohydrates, it is necessary to provide emergency medical care right up to hospitalization.

In order to avoid the development of hypoglycemia, careful individual selection of drugs and dosing regimens is necessary, as well as providing the patient with complete information 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 the prescriptions of the doctor and monitor their condition;
insufficient and irregular meals, skipping meals, fasting and changing diets;
an imbalance between exercise and the amount of carbohydrates taken;
kidney failure;
severe hepatic impairment;
an overdose of Glyclad®;
some endocrine disorders: thyroid disease, pituitary and adrenal insufficiency;

simultaneous administration of certain drugs (see section "Interaction with other drugs").

Renal and hepatic impairment

In patients with hepatic and / or severe renal insufficiency, the pharmacokinetic and / or pharmacodynamic properties of the glycazide can vary. The condition of hypoglycemia, developing in such patients, can be quite long, in such cases, immediate appropriate therapy is needed.

Information for patients

It is necessary to inform the patient, as well as members of his family about the risk of developing hypoglycemia, its symptoms and conditions conducive to its development. The patient should be informed of the potential risks and benefits of the proposed treatment.

The patient needs to explain the importance of dieting, the need for regular exercise and control of blood glucose.

Insufficient glycemic control

Glycemic control in patients receiving therapy with hypoglycemic agents,can be weakened in the following cases: fever, trauma, Infectious diseases or large surgical interventions. In these conditions, it may be necessary to stop therapy with Gliclide and prescribe insulin therapy.

In many patients, the effectiveness of oral hypoglycemic agents, including gliclazide, tends to decline after a long treatment period. This effect can be due to both the progression of the disease and the decrease in the therapeutic response to the drug. This phenomenon, known as secondary drug resistance, which must be distinguished from the primary, in which the drug already at the first appointment does not give the expected clinical effect. Before diagnosing the patient's secondary drug resistance, it is necessary to evaluate the adequacy of dose selection and patient compliance with the prescribed diet.

Laboratory Tests

For evaluation of glycemic control, regular determination of fasting blood glucose and HbAlc. In addition, it is advisable to regularly conduct self-monitoring of blood glucose concentration.

Derivatives of sulfonylureas can cause hemolytic anemia in patients with deficiency of glucose-6-phosphate dehydrogenase. Because the glycazide is a derivative of sulfonylureas, caution should be exercised when it is administered to patients with deficiency of glucose-6-phosphate dehydrogenase. One should evaluate the possibility of prescribing a hypoglycemic drug of another group.

Effect on the ability to drive transp. cf. and fur:

In connection with the possible development of hypoglycemia in the use of the drug Gliklad, patients should be aware of the symptoms of hypoglycemia and should be careful when driving vehicles or performing work that requires a high rate of physical and mental reactions, especially at the beginning of therapy.

Form release / dosage:

Long-acting tablets, 60 mg.

Packaging:

For 15 tablets in a blister of the combined material PVC / PVDC - aluminum foil (PVC / PVDC-A1).

For 2, 4, 6 or 8 blisters are placed in a pack of cardboard along with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002725

Date of registration:24.11.2014 / 05.04.2017

Expiration Date:24.11.2019

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, dd, Novo mesto, AO Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp12.01.2016

Illustrated instructions

Instructions

Glyclad® (Gliclada®)