Gluconormium Plus - instructions for use, dose, side effects, contraindications

Excipients: microcrystalline cellulose - 61,50 mg or 57,20 mg, giprolase (hydroxypropylcellulose) - 12,00 mg or 13.80 mg, croscarmellose sodium - 18,00 mg, magnesium stearate - 6,00 mg.

Cover for dosing 2.5 mg + 500mg: OPADRY^® 20A230018 Orange [hypromellose (hydroxypropylmethylcellulose 6 cps) - 7.92 mg, giprolose (hydroxypropyl cellulose) - 4.62 mg, talc - 3.78 mg, titanium dioxide - 1.65 mg, dye sunset yellow sunset (E110) - 0.03 mg] - 18.00 mg;

Sheath for dosing 5 mg + 500 mg: VIVACOAT® РМ-2Р-050 [hypromellose (hydroxypropylmethylcellulose 6 cps) - 9.00 mg, giprolose (hydroxypropylcellulose) - 0.90 mg, polyethylene glycol 3350 0.90 mg, gitanium dioxide 4.75 mg, talc 1.80 mg, iron oxide yellow oxide (E172) 0.26 mg, quinoline yellow color (E104) 0, 37 mg, dye solar sunset yellow (E110) - 0.02 mg] - 18.00 mg.

Description:Dosage 2.5 mg + 500 mg: tablets covered with a film shell of pinkish orange color, oval, biconvex. On the cut is white or almost white.

Dosage 5 mg + 500 mg: tablets, covered with a film shell from light yellow to yellow, oval, biconcave. On the cut is white or almost white.

Pharmacotherapeutic group:Hypoglycemic agent for oral administration (derivative of sulfonylurea of the second generation + biguanide)

ATX: & nbsp

A.10.B.D.02 Metformin and sulfonamides

Pharmacodynamics:

The preparation Gluconorm® Plus is a fixed combination of two oral hypoglycemic agents of various pharmacological groups: metformin and glibenclamide.

Metformin belongs to the biguanide group and reduces the content of both basal and postprandial glucose in the blood plasma. Metformin does not stimulate the secretion of insulin, in this regard does not cause hypoglycemia. It has 3 mechanisms of action:

- reduces the production of glucose by the liver by inhibiting gluconeogenesis and glycogenolysis;

- increases the sensitivity of peripheral receptors to insulin, intake and utilization of glucose by cells in muscles;

- delays the absorption of glucose in the gastrointestinal tract.

The drug also has a beneficial effect on the lipid composition of the blood, reducing the concentration of total cholesterol, low density lipoprotein (LDL) and triglycerides.

Glibenclamide belongs to the group of sulfonylurea derivatives II generation. The glucose content of glibenclamide intake decreases as a result of stimulation of insulin secretion by β-cells of the pancreas.

Metformin and glibenclamide have different mechanisms of action, but mutually complement each other's hypoglycemic activity. The combination of two hypoglycemic agents has a synergistic effect in reducing glucose content.

Pharmacokinetics:

Glibenclamide

When ingested, absorption from the gastrointestinal tract is more than 95%. Glibenclamide, which is part of the preparation Gluconorm® Plus, is micronized.The maximum concentration in plasma is reached after about 4 hours, the volume of distribution is about 10 liters. The connection with plasma proteins is 99%. Almost completely metabolized in the liver with the formation of two inactive metabolites, which are excreted by the kidneys (40%) and through the intestine (60%). Half-life is from 4 to 11 hours.

Metformin

Metformin after oral intake is absorbed from the gastrointestinal tract quite fully, the maximum concentration in the plasma is reached within 2.5 hours.

Approximately 20-30% of metformin is excreted through the intestines in an unchanged form. Absolute bioavailability is from 50 to 60%.

Metformin is rapidly distributed in tissues, practically does not bind to plasma proteins. Exposed to a very weak degree of metabolism and excreted by the kidneys. The half-life is 6.5 hours. If the renal function is impaired, the kidney clearance decreases, as does the creatinine clearance, while the half-life increases, which leads to an increase in the concentration of metformin in the blood plasma. The combination of metformin and glibenclamide in one dosage form has the same bioavailability as when taking tablets containing metformin or glibenclamide in isolation.The bioavailability of metformin in combination with glibenclamide is not affected by eating, as well as the bioavailability of glibenclamide. However, the rate of absorption of glibenclamide increases with food intake.

Indications:

Diabetes mellitus type 2 in adults:

- with ineffectiveness of diet therapy, exercise and previous monotherapy with metformin or a sulfonylurea derivative;

- for the replacement of previous therapy with two drugs (metformin and sulfonylureas) in patients with a stable and well-controlled level of glycemia.

Contraindications:

- Hypersensitivity to metformin, glibenclamide or other sulfonylurea derivatives, as well as to auxiliary substances;

- type 1 diabetes mellitus;

- Diabetic ketoacidosis, diabetic precoma, diabetic coma;

- renal failure or impaired renal function (creatinine clearance less than 60 ml / min);

- acute conditions that can lead to a change in kidney function: dehydration, severe infection, shock, intravascular injection of iodine-containing contrast agents (see "Special instructions");

- acute or chronic diseases that are accompanied by tissue hypoxia: cardiac or respiratory failure, recent myocardial infarction, shock;

- liver failure;

- porphyria;

- pregnancy, the period of breastfeeding;

- simultaneous administration of miconazole;

- extensive surgical operations;

- chronic alcoholism, acute alcohol intoxication;

- lactoacidosis (including in the anamnesis);

- adherence to a hypocaloric diet (less than 1000 calories / day).

It is not recommended to use the drug for people over 60 who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis.

Carefully:

Feverish syndrome, adrenal insufficiency, hypofunction of the anterior lobe of the pituitary gland, thyroid gland diseases with uncompensated disturbance of its function.

Pregnancy and lactation:

The use of the drug is contraindicated during pregnancy. The patient should be warned that during the treatment with Gluconorm® Plus, the doctor should be informed about the planned pregnancy and about the onset of pregnancy. When planning pregnancy, as well as in the case of pregnancy during the reception of Gluconorm® Plus, the drug must be canceled and insulin treatment is prescribed.

The drug Gluconorm® Plus is contraindicated in breastfeeding, as there is no evidence of its ability to penetrate breast milk.

Dosing and Administration:

The dose of the drug is determined by the doctor individually for each patient, depending on the level of glycemia. The initial dose is 1 tablet of the drug Gluconorm® Plus 2.5 mg + 500 mg or Gluconorm® Plus 5 mg + 500 mg once a day. To avoid hypoglycemia, the initial dose should not exceed the daily dose of glibenclamide (or the equivalent dose of another previously taken sulfonylurea drug) or metformin if they were used as first-line therapy. It is recommended to increase the dose by no more than 5 mg glibenclamide + 500 mg metformin per day every 2 or more weeks to achieve adequate control of blood glucose.

Replacement of previous combination therapy with metformin and glibenclamide: the initial dose should not exceed the daily dose of glibenclamide (or the equivalent dose of another sulfonylurea drug) and metformin taken earlier. Every 2 or more weeks after the start of treatment, the dose of the drug is adjusted depending on the level of glycemia.

The maximum daily dose is 4 tablets of the drug Gluconorm® Plus 5 mg + 500 mg or 6 tablets Gluconorm® Plus 2.5 mg + 500 mg.

Dosing regimen

The dosage regimen depends on the individual purpose:

For dosages of 2.5 mg + 500 mg and 5 mg + 500 mg

- once a day, in the morning during breakfast, with the appointment of 1 tablet a day;

- twice a day, morning and evening, with the appointment of 2 or 4 tablets per day.

For a dosage of 2.5 mg + 500 mg

- three times a day, morning, afternoon and evening, with the appointment of 3, 5 or 6 tablets per day.

For a dosage of 5 mg + 500 mg

- three times a day, morning, afternoon and evening, with the appointment of 3 tablets a day.

Tablets should be taken with meals. Each intake of the drug should be accompanied by a meal with a sufficiently high carbohydrate content to prevent the occurrence of hypoglycemia.

Elderly patients

The dose of the drug is selected based on the state of kidney function. The initial dose should not exceed 1 tablet of the drug Gluconorm® Plus 2.5 mg + 500 mg. It is necessary to conduct a regular assessment of kidney function.

Children

The drug Gluconorm® Plus is not recommended for use in children.

Side effects:

In the course of treatment with Gluconorm® Plus, the following side effects may occur.

Side effects are presented depending on the effect on organs and organ systems.

The following undesirable phenomena noted with Gluconorm® Plus are distributed according to the frequency of occurrence according to the following gradation: very often (≥ 1/10), often (≥ 1/100 to 1/10), infrequently (≥ 1/1000 to <1/100), rarely (≥ 1/10000 to <1/1000), very rarely (<1/10000).

In each group, undesirable effects are presented in order of decreasing severity.

From the side of metabolism and nutrition:

Hypoglycemia (see "Overdose", "Special instructions").

Rarely: attacks of hepatic porphyria and cutaneous porphyria.

Very rarely: lactic acidosis (see "Special instructions").

Decreased absorption of vitamin B12, accompanied by a decrease in its concentration in the blood serum with prolonged use of metformin. When detecting megaloblastic anemia, it is necessary to consider the possibility of such etiology. Disulfiram-like reaction with alcohol.

Laboratory indicators:

Infrequent: an increase in the concentrations of urea and creatinine in the blood serum from moderate to moderate.

Very rarely: hyponatremia.

From the side of the blood and lymphatic system:

Rarely: leukopenia, thrombocytopenia.

Rarely: agranulocytosis, hemolytic anemia, bone marrow aplasia and pancytopenia.

These undesirable effects disappear after the drug is discontinued.

From the nervous system:

Often: a taste disorder (metallic taste in the mouth).

From the side of the organ of vision: at the beginning of treatment there may be a temporary visual impairment due to a decrease in the glucose level in the blood.

From the gastrointestinal tract:

Very often: nausea, vomiting, diarrhea, abdominal pain and lack of appetite. These symptoms are more common at the beginning of treatment and in most cases go by themselves. To prevent the development of these symptoms, it is recommended to take the drug in 2 or 3 admission; A slow increase in the dose of the drug also improves its tolerability.

From the side of the rut and subcutaneous tissues:

Rarely: skin reactions, such as: itching, hives, maculopapular rash.

Very rarely: cutaneous or visceral allergic vasculitis, polymorphic erythema, exfoliative dermatitis, photosensitivity.

From the immune system:

Very rarely: anaphylactic shock.

There may be cross-reactivity reactions to sulfonamides and their derivatives.

From the liver and bile ducts:

Rarely: impaired liver function or hepatitis, requiring discontinuation of treatment.

Overdose:

In case of an overdose it is possible to develop hypoglycemia due to the presence of a sulfonylurea derivative in the formulation (see "Special instructions").

Light and moderate symptoms of hypoglycemia without loss of consciousness and neurological manifestations can be corrected by immediate consumption of sugar. Dose adjustments and / or changes in diet should be performed. The occurrence of severe hypoglycemic reactions in patients with diabetes mellitus, accompanied by coma, paroxysm or other neurological disorders, requires the provision of emergency medical care. An intravenous dextrose solution should be administered immediately after the diagnosis is established or hypoglycemia is suspected before the patient is hospitalized. After the restoration of consciousness, it is necessary to give the patient food rich in easily digestible carbohydrates (in order to avoid the re-development of hypoglycemia).

Long-term overdose or the presence of conjugated risk factors can provoke the development of lactic acidosis, since the formulation includes metformin (cm."Special instructions").

Lactic acidosis is a condition requiring urgent medical attention; treatment of lactic acidosis should be performed at the clinic. The most effective method of treatment, allowing to withdraw lactate and metformin, is hemodialysis.

Glibenclamide clearance in the blood plasma can increase in patients with liver disease. Because the glibenclamide actively binds to blood proteins, the drug is not eliminated during dialysis.

Interaction:

Contraindicated combinations

Associated with the use of glibenclamide

Miconazole can provoke the development of hypoglycemia (up to the development of coma).

Related to the use of metformin

Iodine-containing contrast media: Depending on the function of the kidneys, the drug should be discontinued 48 hours before or after intravenous iodine-containing contrast agents.

Unrecommended combinations

Related to the use of sulfonylureas derivatives

Alcohol: very rarely observed disulfiramoid-like reaction (alcohol intolerance) with simultaneous intake of alcohol and glibenclamide. Alcohol intake can increase hypoglycemic action (by inhibiting compensatory reactions or delaying its metabolic inactivation),which can contribute to the development of hypoglycemic coma. During the period of treatment with the drug Gluconorm® Plus, alcohol and drugs containing alcohol should be avoided. Phenylbutazone increases the hypoglycemic effect of sulfonylurea derivatives (replacing the sulfonylurea derivatives at the sites of binding them to the protein and / or reducing their elimination). It is preferable to use other anti-inflammatory drugs that show lesser effects, or to warn the patient about the need for self-monitoring of the level of glycemia; if necessary, the dose should be adjusted when the anti-inflammatory agent is used together and after it is discontinued.

Associated with the use of glibenclamide

Boszentan in combination with glibenclamide increases the risk of hepatotoxic effects. It is recommended to avoid simultaneous administration of these drugs. Also hypoglycemic effect of glibenclamide may decrease.

Related to the use of metformin

Alcohol: the risk of developing lactic acidosis increases with acute alcohol intoxication, especially in case of fasting or poor nutrition, or liver failure.During the treatment with Gluconorm® Plus, avoid drinking alcohol and medications containing ethanol.

Combinations that require caution

Associated with the use of all hypoglycemic agents

Chlorpromazine: in high doses (100 mg / day) causes an increase in the level of glycemia (reducing the release of insulin).

Precautions: should warn the patient about the need self-monitoring of glucose in the blood; if necessary, the dose of the hypoglycemic agent should be adjusted during the simultaneous use of the antipsychotic and after discontinuation of its use.

Glucocorticosteroids (GCS) and tetracosactide: increase in blood glucose, sometimes accompanied by ketosis (GCS cause a decrease in tolerance to glucose).

Precautions: should warn the patient about the need self-monitoring of glucose in the blood; if necessary, adjust the dose of hypoglycemic agent during simultaneous application of GCS and after the termination of their use.

Danazol has a hyperglycemic effect.If you need treatment with danazol, and when you stop taking the latter, you need to adjust the dose of the drug Gluconorm® Plus under the control of the level of glycemia.

β2-adrenomimetics: by stimulating β2-adrenergic receptors, the concentration of glucose in the blood is increased.

Precautions: it is necessary to warn the patient and establish a control of the glucose content in the blood, a transfer to insulin therapy is possible.

Diuretics: increase in blood glucose.

Precautionary measures: should warn the patient about the need for self-monitoring of glucose in the blood; it may be necessary to correct the dose of hypoglycemic agent during simultaneous use with diuretics and after discontinuation of their use.

Angiotensin-converting enzyme (ACE) inhibitors (captopril, enalapril): the use of ACE inhibitors helps reduce blood glucose. If necessary, the dose of Gluconorm® Plus should be adjusted during simultaneous use with ACE inhibitors and after discontinuation of their use.

Related to the use of metformin

Diuretics: lactic acidosis, which occurs when taking metformin on the background of functional renal failure caused by the intake of diuretics, especially "loop".

Associated with the use of glibenclamide

β-adrenoblockers, clonidine, reserpine, guanethidine and sympathomimetics mask some of the symptoms of hypoglycemia: palpitations and tachycardia; most nonselective β- adrenoblokatorov increase the incidence and severity of hypoglycemia.

It is necessary to warn the patient about the need for self-monitoring of blood glucose, especially at the beginning of treatment.

Fluconazole: an increase in the half-life of glibenclamide with the possible occurrence of hypoglycemia. It is necessary to warn the patient about the need for self-monitoring of glucose in the blood; may need to adjust the dose of hypoglycemic drugs during the simultaneous treatment with fluconazole and after discontinuation of its use.

Sequestants of bile acids: Simultaneous use with Gluconorm®Plus reduces the concentration of glibenclamide in the blood plasma, which can lead to a decrease in hypoglycemic effect.Gluconorm® Plus should be taken at least 4 hours before bile acid sequestrants are taken.

Other interactions: combinations that should be taken into account

Associated with the use of glibenclamide

Desmopressin: glibenclamide can reduce the antidiuretic effect of desmopressin.

Antibacterial drugs from the group of sulfonamides, fluoroquinolones, anticoagulants (coumarin derivatives), monoamine oxidase (MAO) inhibitors, chloramphenicol, pentoxifylline, hypolipidermic drugs from the group of fibrates, disopyramide - the risk of developing hypoglycemia against the background of glibenclamide.

Special instructions:

Against the background of treatment with Gluconorm® Plus, you need to regularly monitor the level of glycemia on an empty stomach after eating.

Lactic acidosis

Lactic acidosis is extremely rare, but serious (high mortality in the absence of emergency treatment) complication, which can occur due to the cumulation of metformin. Cases of lactic acidosis in patients who received metformin, arose mainly in patients with diabetes mellitus with severe renal failure. Other related risk factors should be considered,such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol consumption, liver failure and any condition associated with severe hypoxia. Consider the risk of developing lactic acidosis when non-specific signs appear, such as muscle cramps accompanied by dyspeptic disorders, abdominal pain and severe malaise. In severe cases, there may be acid dyspnea, hypoxia, hypothermia, and coma. Diagnostic laboratory indicators are: low blood pH, plasma lactate concentration above 5 mmol / l, increased anion interval and lactate / pyruvate ratio.

Hypoglycaemia

Since the preparation Gluconorm® Plus contains glibenclamide, then taking the drug is accompanied by a risk of hypoglycemia in the patient. Gradual titration of the dose after initiation of treatment can prevent the onset of hypoglycemia. This treatment can be prescribed only to a patient who adheres to a regular meal regimen (including breakfast). It is important that the intake of carbohydrates is regular, since the risk of developing hypoglycemia increases with late eating, inadequate or unbalanced consumption of carbohydrates.The development of hypoglycemia is most likely with a hypocaloric diet, after intense or prolonged physical exertion, with alcohol consumption or when taking a combination of hypoglycemic agents.

Due to compensatory reactions caused by hypoglycemia, sweating, fear, tachycardia, hypertension, palpitations, angina and arrhythmia may occur. The latter symptoms may be absent if hypoglycemia develops slowly, in the case of vegetative neuropathy or with the simultaneous administration of β-blockers, clonidine, reserpine, guanethidine or sympathomimetics.

Other symptoms of hypoglycemia in diabetic patients may include headache, hunger, nausea, vomiting, severe fatigue, sleep disorder, nervous state, aggression, impaired concentration and psychomotor reactions, depression, confusion, speech impairment, visual impairment, tremor, paralysis and paresthesia, dizziness, delirium, convulsions, doubt, unconsciousness, shallow breathing and bradycardia.

Careful prescription of the drug, dose selection and appropriate instructions for the patient are important to reduce the risk of developing hypoglycemia.If the patient is experiencing episodes of hypoglycemia that are either severe or associated with unknowing of the symptoms, consideration should be given to the possibility of treatment with other hypoglycemic agents.

Factors contributing to the development of hypoglycemia:

- simultaneous use of alcohol, especially when fasting;

- refusal or inability of the patient to interact with a doctor and follow the recommendations in the instructions for use (especially for elderly patients);

- poor diet, irregular eating, starvation or change in diet;

- an imbalance between exercise and carbohydrate intake;

- kidney failure;

- severe hepatic impairment;

- an overdose of Gluconorm® Plus;

- individual endocrine disorders: insufficiency of thyroid gland function, pituitary gland and adrenal glands;

- simultaneous reception of individual medications.

Renal and hepatic impairment

Pharmacokinetics and / or pharmacodynamics may vary in patients with hepatic insufficiency or severe renal insufficiency.

The hypoglycemia that occurs in such patients may be prolonged, in which case appropriate treatment should be started.

Instability of blood glucose

In the case of surgery or other cause of decompensation of diabetes, it is recommended to provide a temporary transition to insulin therapy. Symptoms of hypoglycemia are frequent urination, severe thirst, dry skin.

48 hours before planned surgery or intravenous iodine-containing radiopaque, Gluconorm® Plus should be discontinued. Treatment is recommended to resume after 48 hours, and only after the kidney function has been evaluated and recognized normal.

Kidney function

Because the metformin it is necessary to determine the creatinine clearance and / or creatinine content in the blood serum before the beginning of treatment, and regularly afterwards, at least once a year in patients with normal renal function, and 2-4 times a year in elderly patients, and also in patients with creatinine clearance at the upper limit of the norm.

Exercise caution is recommended in cases where renal function may be compromised, for example, elderly patients, or in case of antihypertensive therapy, diuretics or non-steroidal anti-inflammatory drugs (NSAIDs).

Other Precautions

The patient should inform the doctor about the appearance of bronchopulmonary infection or an infectious disease of the genito-urinary organs.

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

Patients should be informed of the risk of hypoglycemia and should take precautions when driving vehicles and working with mechanisms that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 2.5 mg + 500 mg, 5 mg + 500 mg.

Packaging:

For 10 or 15 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

3 contour packs of 10 tablets or 2 contour packs of 15 tablets together with instructions for use are placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004249

Date of registration:17.04.2017

Expiration Date:17.04.2022

The owner of the registration certificate:PHARMSTANDART-TOMSKHIMFARM, OJSC PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Information update date: & nbsp12.05.2017

Illustrated instructions

Instructions

Gluconorm® Plus (Gluconorm Plus)