Metglyb Force - instructions for use, dose, side effects, contraindications

Excipients: corn starch 56.5 mg, calcium hydrogen phosphate dihydrate 62.5 mg, croscarmellose sodium 15 mg, macrogol (polyethylene glycol 6000) 15 mg, povidone K-30 50 mg, sodium stearyl fumarate 4 mg, cellulose microcrystalline 44.5 mg;

film sheath: Fill the orange with 25 mg, including: [hypromellose (hydroxypropylmethylcellulose) 8,438 mg, giprolose (hydroxypropylcellulose) 8,437 mg, talc 5 mg, titanium dioxide 2,795 mg, iron oxide dye yellow 0.275 mg, ferric oxide red 0.055 mg].

Dosage of 5 mg + 500 mg:

1 tablet, film-coated, 5 mg + 500 mg contains:

active substance: glibenclamide 5 mg + metformin hydrochloride 500 mg;

Excipients: corn starch 55 mg, calcium hydrophosphate dihydrate 62 mg, croscarmellose sodium 15 mg, macrogol (polyethylene glycol 6000) 15 mg, povidone K-30 50 mg, sodium stearyl fumarate 4 mg, cellulose microcrystalline 44 mg;

film sheath: Fill white with 25 mg, including: [hypromellose (hydroxypropylmethylcellulose) 8,438 mg, giprolose (hydroxypropylcellulose) 8,437 mg, talc 5 mg, titanium dioxide 3,125 mg].

Description:

Oval, biconvex tablets, covered with a film coating of a brownish-orange color (dosage of 2.5 mg + 500 mg), or oval biconvex tablets with a risk, covered with a film membrane of almost white color (dosage of 5 mg + 500 mg). On the cross-section - the core is almost white.

Pharmacotherapeutic group:hypoglycemic agent for oral administration combined (biguanide + sulfonylurea group preparation)

ATX: & nbsp

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

Pharmacodynamics:

A fixed combination of two oral hypoglycemic agents of various pharmacological groups: glibenclamide and metformin.

Metformin belongs to the group of biguanides and reduces the content of both basal and postprandial glucose in blood plasma. Metformin does not stimulate the secretion of insulin, and in this regard does not cause hypoglycemia. Has 3 mechanisms of action: reduces the production of glucose by the liver due to inhibition of 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 (GIT). Stabilizes or reduces body weight in patients with diabetes mellitus.

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

Glibenclamide belongs to the group of derivatives of sulfonylurea of the second generation. The glucose content of glibenclamide is reduced as a result of stimulation of the secretion of insulin by beta cells of the pancreas. Glibenclamide increases the sensitivity to insulin and the degree of its binding to target cells, enhances the effect of insulin on glucose uptake by muscles and liver, inhibits lipolysis in adipose tissue.

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 levels.

Pharmacokinetics:

Glibenclamide. If taken orally, the absorption from the digestive tract is more than 95%. The time to reach the maximum concentration is 4 hours, the volume distribution - 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 after oral intake absorbed from the gastrointestinal tract sufficiently full, the maximum concentration in the plasma is reached within 2.5 hours. Absolute bioavailability is from 50 to 60%. With simultaneous intake of food, absorption of metformin is reduced and delayed. Metformin quickly distributed in tissues, practically does not bind to plasma proteins. Exposed to a very weak degree of metabolism and excreted by the kidneys. The clearance of metformin in healthy subjects is 400 ml / min, which indicates the presence of active tubular secretion. Approximately 20-30% of metformin is excreted through the intestine in unchanged form.The half-life period averages 6.5 hours. If the renal function is impaired, the kidney clearance decreases in the same way as 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 tablet 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 food intake in the same way as globenclamide bioavailability. 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 sulfonylurea derivatives;

- to replace the 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 derivatives of sulfonylureas, as well as to other components of the drug;

- 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, recently transferred myocardial infarction;

- liver failure;

- porphyria;

- pregnancy, the period of breastfeeding;

- simultaneous administration of miconazole;

- infectious diseases, large surgical interventions, traumas, extensive burns and other conditions requiring insulin therapy;

- chronic alcoholism, acute alcohol intoxication;

- lactic acidosis (including in the anamnesis);

- compliance with the hypocaloric diet (less than 1000 kcal / day);

- Children under 18 years.

It is not recommended to use the drug in people over 60 years of age 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;

- diseases of the thyroid gland (with uncompensated violation of its function);

- in the elderly due to the danger of developing hypoglycemia.

Pregnancy and lactation:

During pregnancy the use of MetgliB® Force is contraindicated. The patient should be warned that during the treatment with MetgliB® Force, the doctor should be informed of the planned pregnancy and the onset of pregnancy. When planning pregnancy, as well as in case of pregnancy during the period of taking the drug, it should be canceled and insulin therapy prescribed.

Metglib® Force is contraindicated when breastfeeding, since there is no evidence of its ability to penetrate breast milk. If it is necessary to use the medication during breastfeeding, you should switch to insulin therapy or stop breastfeeding.

Dosing and Administration:

Inside.

Dose of the drug determines the doctor individually for each patient, depending on the level of glycemia.

Initial dose is 1 tablet of the drug MetgliB® Force 2.5 mg + 500 mg or MetgliB® Force 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 drug sulfonylureas) 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 equivalent dose of another drug sulfonylureas) and metformin, previously taken.

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 MetgliB® Force 5 mg + 500 mg or 6 tablets of the drug MetgliB® Force 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 MetgliB® Force 2.5 mg + 500 mg.

It is necessary to conduct a regular assessment of kidney function.

Children

The drug MetgliB® Force is not recommended for use in children.

Side effects:

The following side reactions may occur during treatment with MetgliB® Force.

WHO classification of incidence of adverse reactions:

Often	- ≥1/10 appointments
often	- from ≥1 / 100 to <1/10 of assignments
infrequently	- from ≥1 / 1000 to <1/100 of the assignments
rarely	- from ≥1 / 10000 to <1/1000 assignments
rarely	- <1/10000 assignments

Classification of undesirable adverse reactions in accordance with the defeat of organs and organ systems (medical dictionary for regulatory legal activities Med-DRA).

Violations of the blood and lymphatic system:

These undesirable effects disappear after the drug is discontinued.

Rarely: leukopenia and thrombocytopenia.

Very rarely: agranulocytosis, hemolytic anemia, bone marrow aplasia and pancytopenia.

Immune system disorders:

Very rarely: anaphylactic shock.

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

Disorders from the metabolism and nutrition:

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

Rarely: attacks of porphyria (hepatic or cutaneous).

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

Decreased absorption of the 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 ethanol.

Disturbances from the nervous system:

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

Disturbances on the part of the organ of sight:

Initially, a temporary visual impairment may occur due to a decrease in blood glucose.

Disorders 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.

Uncommon: a feeling of heaviness and overflow in the stomach, belching.

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.

Disturbances from the liver and bile ducts:

Very rarely: a violation of liver function or hepatitis, requiring discontinuation of treatment.

Disturbances from the skin and subcutaneous tissues:

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

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

Laboratory and instrumental data:

Infrequent: moderate increase in urea and creatinine concentrations in blood serum

Very rarely: hyponatremia.

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, convulsions or other neurological disorders, requires the provision of emergency medical care. An intravenous dextrose solution should be administered immediately after diagnosis is established or suspected hypoglycaemia, prior to hospitalization of the patient. After restoration of consciousness it is necessary to take food rich easily digestible carbohydrates (to avoid the re-development of hypoglycemia).

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

Overdose or presence of conjugated risk factors can provoke the development of lactic acidosis, since the composition of the drug includes metformin (see "Special instructions").

Lactic acidosis is a condition requiring urgent medical attention; treatment of lactic acidosis should be carried out in a hospital. The most effective method of treatment, allowing to withdraw lactate and metformin, is hemodialysis.

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 administration of iodine-containing contrast media.

Unrecommended combinations

Related to the use of sulfonylureas derivatives

Alcohol: a disulfiram-like reaction is very rarely observed (alcohol intolerance) with simultaneous intake of alcohol and glibenclamide.

Alcohol can increase hypoglycemic action (by inhibiting compensatory reactions or delaying its metabolic inactivation), which can contribute to the development of hypoglycemic coma. During the treatment with MetgliB® Force, alcoholic beverages and medications containing ethanol.

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.

Phenylbutazone increases the hypoglycemic effect of sulfonylurea derivatives (replacing the sulfonylurea derivatives in places associated with the protein and / or reducing their elimination). It is preferable to use other anti-inflammatory drugs that show lesser interactions, or to warn the patient about the need for self-monitoring of the level of glycemia; if necessary, the dose should be adjusted by the joint use of the anti-inflammatory agent and after its termination.

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 MetgliB® Force, alcoholic beverages 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 glycemia (reducing the release of insulin).

Precautions: should warn the patient about the need for self-monitoring of glucose in the blood; if necessary, adjust the dose of hypoglycemic agent in the course of simultaneous application of neuroleptic and after discontinuation of its use.

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

Precautions: should warn the patient about the need for self-monitoring of glucose in the blood; if necessary, the dose of the hypoglycemic agent should be adjusted during simultaneous application of GCS and after discontinuation 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 MetgliB®Fors under the control of the level of glycemia.

β2-adrenomimetics: through stimulation β₂-adrenoreceptors increase the concentration of glucose in the blood.

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.

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

Angiotensin converting enzyme (ACE) inhibitors (captopril, enalapril): use of ACE inhibitors reduces the content of glucose in the blood. If necessary, the dose of MetgliB® Force 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 against a background of functional renal failure caused by the intake of diuretics, especially loop ones.

Associated with the use of glibenclamide

β₂- adrenoblockers, clonidine, reserpine, guanethidine and sympathomimetics mask some of the symptoms of hypoglycemia: palpitations and tachycardia; most non-selective beta-blockers 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 possible occurrence of hypoglycemia. It is necessary to warn the patient about the need for self-monitoring of glucose in the blood; it may be necessary to adjust the dose of hypoglycemic drugs during simultaneous treatment with fluconazole and after discontinuation of its use.

Other interactions: combinations that should be taken into account:

Associated with the use of glibenclamide

Desmopressin: Metglyb® Force can reduce the antidiuretic effect of desmopressin.

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

Special instructions:

Treatment with MetgliB® Force is done only under medical supervision!

When taking the drug, you must strictly observe recommendations of a doctor on diet compliance and self-monitoring of blood glucose. It is necessary 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 may occur due to the cumulation of metformin. The cases of lactic acidosis with the use of metformin appeared mainly in patients with diabetes mellitus and expressed renal insufficiency. Other associated risk factors, such as poorly controlled diabetes mellitus, ketosis, prolonged fasting, excessive alcohol consumption, liver failure and any condition associated with severe hypoxia, should be considered.

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 the pH value of the blood, the plasma lactate concentration above 5 mmol / l, the increased anion interval and the lactate / pyruvate ratio.

Hypoglycaemia

Since Metglib® Force contains glibenclamide, then taking the drug is accompanied by a risk of hypoglycemia in the patient. Gradual titration of the dose after the start of treatment can prevent the occurrence 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 intake of food, inadequate or unbalanced carbohydrate intake. The development of hypoglycemia is most likely with a hypocaloric diet, after intense or prolonged physical exertion, with the use of alcoholic beverages or when taking a combination of hypoglycemic agents. Due to compensatory reactions caused by hypoglycemia, there may be increased sweating, a sense of fear,tachycardia, increased blood pressure, palpitations, angina and arrhythmia. The last symptoms may be absent if hypoglycemia develops slowly, in the case of vegetative neuropathy or with the simultaneous administration of beta-blockers, clonidine, reserpine, guanethidine or sympathomimetics.

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

Careful use of the drug, dose selection and appropriate instructions for the patient are important to reduce the risk of developing hypoglycemia. If a patient experiences repeated hypoglycemia, which is either severe or associated with ignorance of the symptoms, consideration should be given to the possibility of treatment with other hypoglycemic agents.

Factors contributing to the development of hypoglycaemia: simultaneous consumption of alcoholic beverages, especially when fasting; failure or (especially in elderly patients) the inability of the patient to interact with a doctor and follow the recommendations in the instructions for use; poor diet, irregular eating, fasting, or changes in diet; an imbalance between exercise and carbohydrate intake; kidney failure; severe hepatic impairment; overdose of MetgliB® Force; 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 hyperglycemia are frequent urination, severe thirst, dry skin. 48 hours before planned surgery or intravenous iodine-containing radiopaque, Metglig® Force 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 the serum creatinine content 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 a broncho-pulmonary 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 a vehicle and working with mechanisms that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets, film-coated, 2.5 mg + 500 mg and 5 mg + 500 mg.

Packaging:

Packing at "Canonfarma Production" CJSC

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

By 3, 4, 6, 9 contour cell packs of 10 tablets or 2, 4, 6 contour cell packs of 15 tablets together with instructions for use in a pack of cardboard.

Packing at OOO NPO FarmVILAR

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

By 3, 6, 9 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, the dark place 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 expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003571

Date of registration:14.04.2016

Expiration Date:14.04.2021

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

NGO Farmvilar, OOO Russia

Representation: & nbspCANONFARMA PRODUCTION CJSC CANONFARMA PRODUCTION CJSC Russia

Information update date: & nbsp29.06.2016

Illustrated instructions

Instructions

Metglybe® Force (Metglib® Force)