Metglyb Force, 5 mg+500 mg 30 pcs

Hypoglycemic agent for oral use (sulfonylurea derivative of the II generation + biguanide).

Indications

Type 2 diabetes mellitus in adults:

– if diet therapy, physical exercise and previous monotherapy with metformin or sulfonylurea derivatives are ineffective;

– to replace previous therapy with two drugs (metformin and a sulfonylurea derivative) in patients with stable and well-controlled glycemic levels.

Pharmacological effect

Hypoglycemic agent for oral use (second generation sulfonylurea derivative + biguanide).

Special instructions

Treatment with Metglib® Force is carried out only under the supervision of a doctor! When taking the drug, you must strictly follow your doctor’s recommendations regarding diet and self-monitoring of blood glucose concentrations. It is necessary to regularly monitor the level of glycemia on an empty stomach and after meals.

Lactic acidosis

Lactic acidosis is an extremely rare but serious (high mortality rate if not treated urgently) complication that can occur due to the accumulation of metformin. Cases of lactic acidosis when using metformin occurred mainly in patients with diabetes mellitus and severe renal failure. Other associated risk factors should be considered, such as poorly controlled diabetes mellitus, ketosis, prolonged fasting, excessive alcohol consumption, liver failure and any condition associated with severe hypoxia.

The risk of developing lactic acidosis should be taken into account when nonspecific signs appear, such as muscle cramps accompanied by dyspeptic disorders, abdominal pain and severe malaise. In severe cases, acidotic dyspnea, hypoxia, hypothermia and coma may occur.

Diagnostic laboratory parameters are: low blood pH, plasma lactate concentration above 5 mmol/L, increased anion gap and lactate/pyruvate ratio.

Hypoglycemia

Since Metglib® Force contains glibenclamide, taking the drug is accompanied by a risk of hypoglycemia in the patient. Gradual dose titration after initiation of treatment may prevent the occurrence of hypoglycemia. This treatment can only be prescribed to a patient who adheres to a regular diet (including breakfast). It is important that your carbohydrate intake is regular; since the risk of developing hypoglycemia increases with late meals, insufficient or unbalanced carbohydrate intake. The development of hypoglycemia is most likely during a hypocaloric diet, after intense or prolonged physical activity, when drinking alcohol, or when taking a combination of hypoglycemic agents.

Due to compensatory reactions caused by hypoglycemia, increased sweating, fear, tachycardia, increased blood pressure, palpitations, angina pectoris and arrhythmia may occur. The latter symptoms may be absent if hypoglycemia develops slowly, in the case of autonomic neuropathy, or while taking 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 disturbances, restlessness, aggression, impaired concentration and psychomotor reactions, depression, confusion, speech impairment, visual impairment, trembling, paralysis and paresthesia, dizziness, delirium, convulsions, somnolence, unconsciousness, shallow breathing and bradycardia.

Careful use of the drug, dose selection, and appropriate patient instructions are important to reduce the risk of hypoglycemia. If the patient has recurrent episodes of hypoglycemia that are either severe or due to unawareness of symptoms, treatment with other hypoglycemic agents should be considered. Factors contributing to the development of hypoglycemia: simultaneous consumption of alcoholic beverages, especially during fasting; refusal or (especially for older patients) inability of the patient to interact with the doctor and follow the recommendations set out in the instructions for use; poor nutrition, irregular eating, fasting, or changes in diet; imbalance between physical activity and carbohydrate intake; renal failure; severe liver failure; overdose of the drug Metglib® Force; certain endocrine disorders: insufficiency of the thyroid gland, pituitary gland and adrenal glands; simultaneous use of individual medications.

Kidney and liver failure

Pharmacokinetics and/or pharmacodynamics may vary in patients with hepatic impairment or severe renal impairment. The hypoglycemia that occurs in such patients can be prolonged, in which case appropriate treatment should be started.

Instability of blood glucose levels

In case of surgery or other cause of decompensation of diabetes mellitus, it is recommended to consider a temporary transition to insulin therapy. Symptoms of hyperglycemia include frequent urination, severe thirst, and dry skin. 48 hours before planned surgery or intravenous administration of an iodinated radiocontrast agent, Metglib® Force should be discontinued. Treatment is recommended to be resumed after 48 hours, and only after renal function has been assessed and found to be normal.

Kidney function

Since metformin is eliminated by the kidneys, before starting treatment and regularly thereafter, it is necessary to determine creatinine clearance and/or serum creatinine levels: at least once a year in patients with normal renal function, and 2-4 times a year in elderly patients, as well as in patients with creatinine clearance at the upper limit of normal.

Particular caution is recommended in cases where renal function may be impaired, for example in elderly patients, or when initiating antihypertensive therapy, diuretics or non-steroidal anti-inflammatory drugs (NSAIDs).

Other Precautions

The patient should inform the doctor about the occurrence of a bronchopulmonary infection or an infectious disease of the genitourinary organs.

Impact on the ability to drive vehicles and operate machinery

Patients should be informed about the risk of hypoglycemia and should take precautions when driving a vehicle and operating machinery that requires increased concentration and speed of psychomotor reactions.

Active ingredient

Glibenclamide, Metformin

Composition

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

Active substance:

glibenclamide 5 mg + metformin hydrochloride 500 mg;

Excipients:

corn starch 55 mg,

calcium hydrogen phosphate dihydrate 62 mg,

croscarmellose sodium 15 mg,

macrogol (polyethylene glycol 6000) 15 mg,

povidone K-30 50 mg,

sodium stearyl fumarate 4 mg,

microcrystalline cellulose 44 mg;

Film casing:

Opadry white 25 mg, including: [hypromellose (hydroxypropyl methylcellulose) 8.438 mg, hyprolose (hydroxypropyl cellulose) 8.437 mg, talc 5 mg, titanium dioxide 3.125 mg].

Contraindications

Hypersensitivity to metformin, glibenclamide or other sulfonylurea derivatives, 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 changes in kidney function: dehydration, severe infection, shock, intravascular administration 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; liver failure; porphyria; pregnancy, breastfeeding period; simultaneous use of miconazole; infectious diseases, major surgical interventions, injuries, extensive burns and other conditions requiring insulin therapy; chronic alcoholism, acute alcohol intoxication; lactic acidosis (including history); following a hypocaloric diet (less than 1000 kcal/day); children under 18 years of age.

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.

With caution

Fever syndrome; adrenal insufficiency; hypofunction of the anterior pituitary gland; diseases of the thyroid gland (with uncompensated impairment of its function); in elderly people due to the risk of developing hypoglycemia.

Use during pregnancy and breastfeeding

During pregnancy, the use of Metglib® Force is contraindicated. The patient should be warned that during treatment with Metglib® Force it is necessary to inform the doctor about the planned pregnancy and the occurrence of pregnancy. When planning a pregnancy, as well as in the event of pregnancy occurring while taking the drug, it should be discontinued and insulin therapy prescribed.

Metglib® Force is contraindicated during breastfeeding, as there is no data on its ability to pass into breast milk. If it is necessary to use the drug during breastfeeding, you should switch to insulin therapy or stop breastfeeding.

Side Effects

During treatment with Metglib® Force, the following adverse reactions may occur.

WHO classification of the incidence of adverse reactions:

very often – ≥1/10 appointments

often – from ≥1/100 to <1/10 prescriptions

uncommon – from ≥1/1000 to <1/100 prescriptions

rarely – from ≥1/10000 to <1/1000 prescriptions

very rare – < 1/10000 prescriptions

Classification of undesirable side reactions in accordance with damage to organs and organ systems (medical dictionary for regulatory activities Med-DRA).

Blood and lymphatic system disorders:

These adverse events disappear after discontinuation of the drug.

Rarely: leukopenia and thrombocytopenia.

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

Immune system disorders:

Very rare: anaphylactic shock.

Cross-hypersensitivity reactions to sulfonamides and their derivatives may occur.

Metabolic and nutritional disorders:

Hypoglycemia (See “Overdose”, “Special instructions”).

Rarely: attacks of porphyria (hepatic or cutaneous).

Very rare: lactic acidosis (See “Special Instructions”).

Decreased absorption of vitamin B12, accompanied by a decrease in its concentration in the blood serum with long-term use of metformin. When megaloblastic anemia is detected, the possibility of such an etiology must be taken into account. Disulfiram-like reaction when drinking ethanol.

Nervous system disorders:

Common: taste disturbance (“metallic” taste in the mouth).

Visual disorders:

At the beginning of treatment, temporary visual impairment may occur due to a decrease in blood glucose.

Gastrointestinal disorders:

Very common: nausea, vomiting, diarrhea, abdominal pain and lack of appetite. These symptoms are more common at the beginning of treatment and in most cases go away on their own.

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

To prevent the development of these symptoms, it is recommended to take the drug in 2 or 3 doses; Slowly increasing the dose of the drug also improves its tolerability.

Disorders of the liver and biliary tract:

Very rare: abnormal liver function tests or hepatitis requiring discontinuation of treatment.

Disorders of the skin and subcutaneous tissues:

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

Very rare: photosensitivity, cutaneous or visceral allergic vasculitis, erythema multiforme, exfoliative dermatitis.

Laboratory and instrumental data:

Uncommon: moderate increase in serum urea and creatinine concentrations

Very rare: hyponatremia.

Interaction

Contraindicated combinations

Associated with the use of glibenclamide

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

Associated with metformin use

Iodinated contrast media: Depending on renal function, the drug should be discontinued 48 hours before or after intravenous administration of iodinated contrast media.

Combinations not recommended

Related to the use of sulfonylurea derivatives

Alcohol: a disulfiram-like reaction (alcohol intolerance) is very rarely observed when taking alcohol and glibenclamide simultaneously.

Alcohol may increase its hypoglycemic effects (by inhibiting compensatory responses or delaying its metabolic inactivation), which may contribute to the development of hypoglycemic coma. During treatment with Metglib® Force, you should avoid drinking alcoholic beverages and medications containing ethanol.

Bosentan in combination with glibenclamide increases the risk of hepatotoxicity. It is recommended to avoid taking these drugs together. The hypoglycemic effect of glibenclamide may also be reduced.

Phenylbutazone increases the hypoglycemic effect of sulfonylureas (by replacing sulfonylureas at protein-bound sites and/or reducing their elimination). It is preferable to use other anti-inflammatory drugs that exhibit fewer interactions, or to warn the patient about the need to self-monitor glycemic levels; If necessary, the dose should be adjusted when using an anti-inflammatory drug together and after its discontinuation.

Associated with metformin use

Alcohol: The risk of developing lactic acidosis increases with acute alcohol intoxication, especially in the case of fasting, or poor nutrition, or liver failure. During treatment with Metglib® Force, you should avoid drinking alcoholic beverages and medications containing ethanol.

Combinations requiring caution

Associated with the use of all hypoglycemic agents

Chlorpromazine: in high doses (100 mg/day) causes an increase in glycemic levels (reducing insulin release).

Precautions: the patient should be warned about the need to independently monitor blood glucose levels; If necessary, adjust the dose of the hypoglycemic agent during concurrent use of the antipsychotic and after discontinuation of its use.

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

Precautions: the patient should be warned about the need to independently monitor blood glucose levels; if necessary, the dose of the hypoglycemic agent should be adjusted during the simultaneous use of GCS and after discontinuation of their use.

Danazol has a hyperglycemic effect. If treatment with danazol is necessary and when taking the latter, a dose adjustment of Metglib® Force is required under the control of glycemic levels.

β2-adrenergic agonists: by stimulating β2-adrenergic receptors, they increase the concentration of glucose in the blood.

Precautions: it is necessary to warn the patient and establish control of blood glucose levels; transfer to insulin therapy is possible.

Diuretics: increase blood glucose levels.

Precautions: the patient should be warned about the need to independently monitor blood glucose levels; It may be necessary to adjust the dose of the hypoglycemic agent during simultaneous use with diuretics and after stopping their use.

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

Associated with metformin use

Diuretics: Lactic acidosis that occurs when taking metformin against the background of functional renal failure caused by taking diuretics, especially loop diuretics.

Associated with the use of glibenclamide

β2-blockers, clonidine, reserpine, guanethidine and sympathomimetics mask some symptoms of hypoglycemia: palpitations and tachycardia; Most non-selective beta-blockers increase the incidence and severity of hypoglycemia. The patient should be warned about the need to independently monitor blood glucose levels, especially at the beginning of treatment.

Fluconazole: Increased half-life of glibenclamide with the possible occurrence of hypoglycemia. The patient should be warned about the need to self-monitor blood glucose levels; It may be necessary to adjust the dose of hypoglycemic drugs during concomitant treatment with fluconazole and after discontinuation of its use.

Other interactions: combinations to consider:

Associated with the use of glibenclamide

Desmopressin: Metglib® Force may 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 – the risk of developing hypoglycemia during the use of glibenclamide.

Overdose

In case of overdose, hypoglycemia may develop due to the presence of a sulfonylurea derivative in the drug (see “Special Instructions”).

Mild to moderate symptoms of hypoglycemia without loss of consciousness or neurological manifestations can be corrected by immediate consumption of sugar. It is necessary to adjust the dose and/or change the diet. The occurrence of severe hypoglycemic reactions in patients with diabetes mellitus, accompanied by coma, convulsions or other neurological disorders, requires emergency medical care. Intravenous administration of dextrose solution is necessary immediately after diagnosis or suspicion of hypoglycemia, before hospitalization of the patient. After regaining consciousness, it is necessary to take food rich in easily digestible carbohydrates (to avoid the re-development of hypoglycemia).

Plasma clearance of glibenclamide may be increased in patients with liver disease. Since glibenclamide actively binds to blood proteins, the drug is not excreted during dialysis.

An overdose or the presence of associated risk factors can provoke the development of lactic acidosis, since the drug contains metformin (see “Special Instructions”).

Lactic acidosis is a medical emergency; Treatment of lactic acidosis should be carried out in a hospital. The most effective treatment method for removing lactate and metformin is hemodialysis.

Manufacturer

Kanonpharma production CJSC, Russia