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

hypromellose (100 mPas *) 16.0 mg, calcium carbonate 14.0 mg, lactose monohydrate 73.5 mg, silicon dioxide colloidal anhydrous 0.5 mg, magnesium stearate 2.0 mg

* The figure represents the nominal viscosity values for 2% aqueous

solution of hypromellose.

Description:Oval, slightly biconvex tablets white or almost white.

Pharmacotherapeutic group:hypoglycemic agent for oral use of the second-generation sulfonylurea group

ATX: & nbsp

A.10.B.B.09 Gliclazide

Pharmacodynamics:

Gliclazide is a hypoglycemic preparation for oral administration, a derivative of sulfonylureas of the second generation. It differs from other derivatives of sulfonylurea in the presence of a nitrogen-containing heterocyclic ring with an endocyclic bond. Gliclazide reduces the concentration of blood glucose, mainly stimulating the secretion and release of insulin from the beta cells of the islets of Langerhans (pancreatic action). The increase in postprandial concentration of insulin and C-peptide persists after two years of therapy.

As with other sulfonylurea derivatives, this effect is based on an increase in the response of the beta cells of the islets of Langerhans to physiological stimulation with glucose. In type 2 diabetes mellitus glycazide restores the first (early) peak of insulin secretion (unlike other sulfonylureas, which primarily affect the second stage of secretion) in response to glucose and enhances the second phase of insulin secretion. A marked increase in the release of insulin is observed in response to stimulation by ingestion of food or glucose.

In addition to hypoglycemic action glycazide affects the microcirculation, reduces adhesion and aggregation thrombocytes, reduces the concentration of markers of platelet activation (beta-thromboglobulin, thromboxane B2), and also restores fibrinolytic activity of vascular endothelium with increased activity tissue activator of plasminogen. Slows the development of diabetic retinopathy in

nephroproliferative stage; with diabetic nephropathy against a background of long applications reliable decreased proteinuria.

Has antiatherogenic properties, lowers the concentration in the blood of total cholesterol.

Intensive glycemic Control based on the use of Gliclazide (mean level of glycosylated hemoglobin (HbAlc) <6.5%) significantly reduces the risk of macrovascular and microvascular complications of type 2 diabetes in comparison with standard glycemic control (standard therapy).

The strategy of intensive glycemic control included the administration of glyclazide (on average 103 mg / day) and an increase in its dose (up to 120 mg / day) with the use (or instead of) standard therapy before adding to it another hypoglycemic drug (eg, metformin, glucosidase, thiazolidinedione or insulin derivative). Intensive glycemic control (mean HbAlc level of 6.5%) significantly reduces the relative risk of combined rate of development of macro and microvascular complications by 10% due to a significant decrease in the relative risk of major microvascular complications by 14%, development and progression of nephropathy by 21% the occurrence and progression of microalbuminuria by 9%, macroalbuminuria by 30% and the development of renal complications by 11%.The benefits of intensive glycemic control in the use of glycazide do not depend on the results of treatment with antihypertensive drugs.

Pharmacokinetics:

Absorption is high, the drug is completely absorbed. Eating does not affect the speed and degree of absorption. Plasma concentrations increase rapidly during the first 6 hours after taking gliclazide inwards, reaching a plateau that is maintained for 6 to 12 hours. Individual variability is low.

The ratio between the dose taken (up to 120 mg) and the area under the concentration-time curve (AUC) is linear. The volume of distribution is approximately 30 liters. Connection with plasma proteins - 95%. Gliclazide mainly metabolized in the liver. Active metabolites in plasma are not found. It is excreted mainly by the kidneys (70%) (less than 1% unchanged). The half-life (T1 / 2) of the glycazide ranges from 12 to 20 hours.

In the elderly, significant changes no pharmacokinetic parameters were detected.

Taking a daily dose of Glyclad® once a day provides effective concentrations of glycazide in the blood plasma for more than 24 hours.

Indications:

Treatment of Type 2 Diabetes Mellitus in Adults with Ineffectiveness diet, exercise and weight loss.

Preventing 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 or to any

support component of the preparation, to other

derivatives of sulfonylureas or sulfonamide preparations;

- Type 1 diabetes mellitus;

- diabetic ketoacidosis, diabetic precoma and

diabetic coma;

- Severe violations of the liver and / or kidney function;

- concomitant therapy with miconazole (in dosage forms for systemic use and gels for the oral mucosa);

- pregnancy and lactation;

- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome;

- children and adolescents under 18 years (no data available on efficiency and safety).

Carefully:

patients of advanced age, irregular and / or unbalanced nutrition, heavy or uncompensated endocrine diseases (hypopituitarism, adrenal or pituitary insufficiency, hypothyroidism or thyrotoxicosis), severe cardiovascular diseases (severe ischemic heart disease, carotid disease, systemic vascular disease), renal and / or liver failure; alcoholism; with cancellation of long-term or high-dose glucocorticosteroid therapy (GCS); failure glucose-6-phosphate dehydrogenase; simultaneous use of phenylbutazone, danazol, ethanol or alcohol-containing medicines (it is recommended to avoid simultaneous application).

Pregnancy and lactation:

The experience of using gliclazide during pregnancy in humans is absent. Data on the use of other sulfonyl urea derivatives during pregnancy are limited.

In animal studies glycazide had no teratogenic effect.

If there is insufficient compensation for diabetes, there is a risk of developing congenital anomalies. To reduce this risk, it is necessary to achieve adequate control of diabetes before conception.Oral hypoglycemic agents during pregnancy are not applied. Insulin is the drug of choice for the therapy of diabetes mellitus in pregnant women. In the case of a planned pregnancy or at the onset of pregnancy, a woman should be transferred to insulin therapy.

There is no data on the intake of gliclazide or its metabolites in breast milk. Given the risk of developing hypoglycemia in newborns, the drug is contraindicated during breastfeeding. It is recommended to switch to insulin therapy or stop breastfeeding.

Dosing and Administration:

Inside, 1 time per day during breakfast. Initial and maintenance doses of the drug are set individually based on the results of regular monitoring of blood glucose and the level of HbAlc.

Initial dose and dose selection

At the beginning of the treatment, 30 mg of Gliclada® is prescribed once a day. When optimal therapeutic effect is recommended to take this dose as a supportive. In the absence of glycemic control, the daily dose should be incrementally increased by regular monitoring of blood glucose concentrations (at intervals of not less than 1 month,except for those patients in whom the blood glucose concentration does not decrease within two weeks of therapy; in such cases, the dose of the drug can be increased at the end of the second week of treatment) to 60 mg, 90 mg or 120 mg per day.

The maximum recommended daily dose is 120 mg.

The transition from the treatment with gliclazide tablets 80 mg (with immediate release) on Therapy with prolonged-action tablets of Glyclad®, 30 mg.

One tablet of the Gliclazide (immediate release) of 80 mg is equivalent to one tablet of Glyclad® 30 mg. The transition from one type of tablets to another should be done under careful control of the concentration of glucose in the blood.

Transition from therapy to another hypoglycemic drug for oral administration to tablets with prolonged action of Glyclad®. When transferring a patient from another oral hypoglycemic drug on glycazide the initial daily dose of the latter should be 30 mg (even if the patient is transferred to the preparation of Gliclada ® from the maximum dose of another oral hypoglycemic drug). Any increase in the dose of the drug should be carried out in stages in accordance with the above recommendations.It is necessary to take into account the effectiveness, dose and duration of action of the previously used

hypoglycemic agent.

In some cases, especially when taking hypoglycemic drugs with a longer T1 / 2, there may be a need for a temporary (several days) cessation of treatment to avoid an additive effect that increases risk development of hypoglycemia. In this case, careful monitoring (1-2 weeks) is recommended to avoid hypoglycemia caused by superposition of their effects.

Combination therapy with other hypoglycemic agents The preparation of Glyclad® can be used in combination with biguanides, a-glucosidase inhibitors or insulin.

Simultaneous therapy with insulin should begin in conditions of careful medical observation.

Elderly patients: correction of the dose of Glyclad® for people over 65 is not required.

Kidney failure from mild to moderate severity (creatinine clearance (CC) 15-80 ml / min): according to clinical studies, correction of the dose of gliclazide is not required provided that the patient is closely monitored.

Patients at risk of hypoglycemia: patients who are at risk for developing hypoglycemia (inadequate or unbalanced diet, severe and decompensated endocrine diseases: hypopituitarism, hypothyroidism,

pituitary and adrenal insufficiency; cancellation of long-term and / or high doses of GCS therapy; severe cardiovascular diseases: severe ischemic heart disease, severe carotid atherosclerosis, common atherosclerosis),

It is recommended to use a minimal initial dose of the drug Gliklad ® - 30 mg / day.

Prevention of complications of diabetes mellitus

For achievements intensive glycemic control, you can gradually increase the dose of Gliklad ® to 120 mg / day in addition to diet and exercise until the target level of HbAlc is reached. It should be remembered about the risk of developing hypoglycemia. Also, other hypoglycemic drugs can be added to therapy, for example, metformin, an alpha-glucosidase inhibitor, a thiazolidinedione derivative or insulin.

Side effects:

Disorders from the metabolism and nutrition: in the case of irregular meals, especially when meals are missed, against the background of sulfonylurea derivatives, incl. and a preparation of Glyclad®, perhaps development of hypoglycemic reactions (headache, fatigue, a strong sense of hunger, nausea, vomiting, severe weakness, drowsiness, insomnia, agitation, aggression, irritability, inattention, inability to concentrate and delayed reaction, depression, visual impairment, aphasia, tremor, paresis, sensory disorders, dizziness, helplessness, loss of self-control, delirium, convulsions, shallow breathing, bradycardia, unconsciousness, coma).

Can be observed symptoms of compensatory activation

adrenergic nervous system: increased sweating, "sticky" and cold skin, anxiety, tachycardia, increased blood pressure, sensation palpitation,

angina and heart rhythm disturbances.

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.

In exceptional cases, the development of hyponatremia is also possible. Disorders from the side of the organ of vision: During treatment (especially at the beginning), transient visual impairments can occur changes in glucose concentration in blood.

Disorders from the gastro-intestinal tract: dyspepsia (pain in the stomach, nausea, vomiting, constipation, diarrhea). Taking the drug during breakfast, You can avoid these symptoms or reduce their severity.

Disorders from the liver and bile ducts: in rare cases - increased activity of "liver" transaminase (alanine aminotransferase (ALT) and aspartate aminotransferase (ACT)) and alkaline phosphatase; hepatitis (isolated cases). When cholestatic jaundice therapy the drug must be discontinued.

Violations from the blood and lymphatic system: hematologic disorders (anemia, leukopenia, thrombocytopenia, granulocytopenia) are rare and, As a rule, they are reversible after cancellation preparation.

Disturbances from the skin and subcutaneous tissues: itching, urticaria, skin rash, incl. maculopapular rash and bullous rash, erythema; at exceptional cases may develop late cutaneous porphyria.

Side effects, characteristic for total class of drugs (derivatives sulfonylureas): cases of erythrocytopenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, and hyponatremia have been noted in patients with other sulfonylureas. As against the reception of other drugs of this class, cases increased activity "hepatic" enzymes, impaired liver function (eg, cholestasis and jaundice) and hepatitis that regressed after drug withdrawal, and in some cases led to menacing life hepatic insufficiency.

Side effects noted during clinical trials: was noted a slight difference in the incidence of various serious adverse events between the two groups of patients: intensive and standard glycemic control.No new data on the safety of the use of gliclazide was obtained. Several cases of severe hypoglycemia have been reported. On average, the incidence of severe 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 of the episodes of hypoglycemia were noted against the background of concomitant insulin therapy.

Overdose:

After ingestion of a large dose of glycazide, hypoglycemia may develop. Treatment: moderately expressed symptoms of hypoglycemia without loss of consciousness or neurological manifestations should be stopped by the intake of carbohydrates (eg, sugar). Sweet substitutes have no therapeutic effect. The experience of using other sulfonylurea derivatives suggests that hypoglycemia can develop repeatedly despite effective initial cupping. If severe manifestations (hypoglycemic coma, convulsions or other neurological disorders) or long episodes of hypoglycemia, even if they are temporarily controlled by sugar intake, emergency medical care is required, and in some cases, hospitalization.

In case of hypoglycemic coma or in case of hypoglycemic coma, 50 ml of 20-30% dextrose solution should be injected intravenously, then intravenously dropwise 10% dextrose solution until the blood glucose concentration is 5.55 mol / l, 1-2 mg glucagon intramuscularly. The patient should be under continuous medical supervision; it is necessary to carefully monitor blood glucose levels every 15 minutes, as well as the determination of pH, urea, creatinine and electrolytes in the blood. After the restoration of consciousness, it is necessary to give the patient food that is rich in easily digestible carbohydrates (in order to avoid the re-development of hypoglycemia). With edema of the brain - mannitol and dexamethasone. Dialysis is ineffective.

Interaction:

1. Drugs that increase the risk development of hypoglycemia

Contraindicated combinations

Miconazole (with systemic administration and with the use of gel on the mucosa oral cavity): enhances hypoglycemic effect with the possibility of development hypoglycemia up to the state of coma.

Unwanted combinations

Phenylbutazone (with systemic administration): intensifies hypoglycemic action sulfonylurea derivatives (displaces them from the connection with plasma proteins blood and / or slows their excretion).

It is preferable to use other anti-inflammatory drugs, and so It is also necessary to inform the patient about need for more frequent self-monitoring concentration of blood glucose. By opportunities need to be adjusted dose of gliclazide at the time of admission phenylbutazone and after its cancellation.

Ethanol increases hypoglycemic action (suppressing compensatory protective mechanisms), which can lead to to the development of hypoglycemic coma.

Do not use ethanol or ethanol-containing medicinal preparations.

Combinations that require additional precautionary measures

With the simultaneous use of certain drugs (other hypoglycemic agents: insulin, acarbose, biguanides; beta-blockers, fluconazole, angiotensin converting enzyme (ACE) inhibitors: captopril, enalapril; blockers of histamine H2 receptors (cimetidine), monoamine oxidase (MAO) inhibitors, sulfonamides and non-steroidal anti-inflammatory drugs drugs (NSAIDs), clarithromycin), hypoglycemic action of glycazide can be potentiated, and hypoglycemia may develop in some cases.

2. Drugs that increase the concentration of glucose in the blood

Unwanted combinations

Danazol has a diabetic effect.

If you can not avoid the use of this drug, you need to warn the patient about the need for more careful monitoring of blood glucose. If necessary, the dose of hypoglycemic agent should be adjusted both during the administration of danazol and after its cancellation.

Combinations that require precautions during use Chlorpromazine (antipsychotic): high doses of chlorpromazine (more than 100 mg per day) increase the concentration of blood glucose, reducing the secretion of insulin. It is recommended to carefully monitor the concentration of blood glucose. If necessary, the dose of hypoglycemic agent should be adjusted during the intake of chlorpromazine, and after its withdrawal.

Glucocorticosteroids (GCS) (with systemic and intraarticular, external and rectal application) and tetracosactide: increase the concentration glucose blood from possible development of ketoacidosis (decrease in tolerance to carbohydrates). If necessary, the dose of the hypoglycemic agent should be adjusted both during the administration of GCS, and after their withdrawal.

Ritodrin, salbutamol, terbutaline (with intravenous administered): increase the blood glucose concentration due to beta2-adrenomimetic activity.

Required regular control concentration of blood glucose. If necessary, the patient should be transferred to insulin therapy.

3. Combinations that should be considered

Anticoagulants (for example, warfarin): derivatives of sulfonylureas with simultaneous admission may potentsirovat effect of anticoagulants.

You may need to change the dose of anticoagulant.

Special instructions:

Hypoglycaemia

The drug should be given only to patients with a regular diet (including breakfast). It is important to regularly consume carbohydrates, because with a late intake of food, its insufficient amount, or insufficient maintenance of carbohydrates in it, the risk of developing hypoglycemia increases. The likelihood of developing hypoglycemia is higher with a low-calorie diet, after prolonged or intensive physical exertion, alcohol consumption or simultaneous administration of other hypoglycemic agents.

After taking the derivatives sulfonylureas may develop hypoglycemia. In some cases, it can be severe and prolonged, requiring hospitalization of the patient and intravenous administration of glucose for several days.

Factors that increase the risk of hypoglycemia:

refusal or inability of the patient to follow the prescriptions of the doctor and control his condition (especially among the elderly);
insufficient and irregular meals, skipping meals, dieting or a dramatic change in diet;
a balance between physical loads, emotional stress and the amount consumed carbohydrates;

kidney failure;
severe hepatic failure;

drug overdose Glyclad®;

Some endocrine diseases (thyroid gland diseases, hypopituitarism and pituitary-adrenal insufficiency);
simultaneous administration of certain drugs (see section "Interaction with other drugs")

Renal and hepatic impairment

Patients with hepatic or severe renal insufficiency may change the pharmacokinetic and / or pharmacodynamic properties of the glycazide. Such patients may have longer episodes of hypoglycemia.

Information for Patient

The patient and his family members need inform about the risk of development hypoglycemia, its symptoms, treatment, and conditions that promote development conditions that promote the development of hypoglycemia. The patient also needs to explain the importance of adherence to dietary advice, the need for regular exercise and regular monitoring of blood glucose concentrations.

Insufficient glycemic control

Glycemic control in patients receiving hypoglycemic therapy is difficult in the following conditions: febrile syndrome, trauma, extensive burns, infectious diseases or surgical interventions. With these states may arise the need to transfer the patient to insulin therapy.

Clinical manifestations of hypoglycemia can be masked by simultaneous administration of beta-blockers, clonidine, reserpine,guanethidine.

In some patients, the effectiveness of oral hypoglycemic the drug may decrease after prolonged therapy. This may be due to the progression of the severity of diabetes and the decrease in response to treatment. This phenomenon is known as the "secondary drug resistance of the drug", which differs from the primary resistance (ie, when the drug already at the first appointment does not give the expected clinical effect). Before making a decision about secondary resistance of therapy, you need to make sure that the patient complies with the diet and the adequacy of the doses used.

Laboratory parameters

To assess the quality of glycemic control, it is necessary to regularly determine HbAlc or the fasting plasma glucose concentration. It is also advisable to use self-monitoring of glucose concentration in blood plasma. Therapy with sulfonylureas in patients with glucose-6-phosphate dehydrogenase deficiency can lead to the development of hemolytic anemia. The preparation of Glyclad® is a derivative of sulfonylurea, therefore it should be used with caution in patients with insufficiency glucose-6-phosphate dehydrogenase.In these cases, it is advisable to prescribe alternative drugs that are not related to the sulfonylurea derivatives.

The drug Gliklada® contains lactose, therefore, it should not be taken to patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

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

During the treatment period, care must be taken when driving vehicles and other potentially hazardous

activities that require increased concentration and

the speed of psychomotor reactions.

Form release / dosage:

Long-acting tablets 30 mg.

Packaging:

For 10 or 15 tablets in a blister pack.

- blister for 10 tablets: 3, 6 or 9 blisters are placed in a pack of cardboard along with instructions for use;

- blister for 15 tablets: 2, 4, or 6 blisters are placed in a pack of cardboard along with instructions for use.

Storage conditions:At a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:3 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005824/09

Date of registration:17.07.2009 / 09.09.2015

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: & nbsp18.01.2016

Illustrated instructions

Instructions

Glyclad® (Gliclada®)