Metglyb Force, 2.5mg+500 mg 30 pcs

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

Indications

Type 2 diabetes mellitus in adults:

– when diet therapy, exercise, and prior monotherapy with metformin or sulfonylurea derivatives are ineffective;

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

Active ingredient

Composition

1 film-coated tablet, 2.5 mg + 500 mg contains:

the active ingredients:

glibenclamide 2.5 mg + metformin hydrochloride 500 mg;

excipients:

corn starch 56.5 mg,

calcium hydrophosphate dihydrate 62.5 mg,

croscarmellose sodium 15 mg,

macrogol (polyethylene glycol 6000) 15 mg,

povidone K-30 50 mg,

sodium stearyl fumarate 4 mg,

microcrystalline cellulose 44.5 mg;

film sheath:

Opadray orange 25 mg, including: [hypromellose (hydroxypropyl methylcellulose) 8.438 mg, hyprolose (hydroxypropyl cellulose) 8.437 mg, talc 5 mg, titanium dioxide 2.795 mg, iron oxide yellow dye 0.275 mg, iron oxide red dye 0.055 mg].

How to take, the dosage

Ingestion.

The dose of the drug is determined by the physician individually for each patient depending on the level of glycemia.

The starting dose is 1 tablet of Metglyb® Force 2.5 mg + 500 mg or Metglyb® Force 5 mg + 500 mg once daily. To avoid hypoglycemia, the starting dose should not exceed the daily dose of glibenclamide (or the equivalent dose of another previously taken sulfonylurea drug) or metformin if used as first-line therapy. It is recommended that the dose be increased by no more than 5 mg of glibenclamide + 500 mg of metformin per day every 2 or more weeks to achieve adequate blood glucose control.

Replacement of prior combination therapy with metformin and glibenclamide: The starting dose should not exceed the daily dose of glibenclamide (or the equivalent dose of another sulfonylurea drug) and metformin taken previously. Every 2 or more weeks after the start of treatment, the dose of the drug is adjusted according to the level of glycemia.

The maximum daily dose is 4 tablets of Metglyb® Force 5 mg + 500 mg or 6 tablets of Metglyb® Force 2.5 mg + 500 mg.

Dosing regimen:

The dosing regimen depends on the individual prescription:

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

– Once daily, in the morning during breakfast, when prescribed 1 tablet per day.

Twice a day, morning and evening, when prescribing 2 or 4 tablets a day.

For dosing 2.5 mg + 500 mg

– Three times daily, morning, afternoon, and evening, when prescribing 3, 5, or 6 tablets per day.

For a dosage of 5 mg + 500 mg

– Three times a day, morning, noon, and evening, when prescribing 3 tablets per day.

The tablets should be taken with meals. Each administration of the drug should be accompanied by a meal that is high enough in carbohydrates to prevent hypoglycemia.

Elderly patients

The dose of the drug is adjusted according to the state of renal function. The initial dose should not exceed 1 tablet of Metglib® Force 2.5 mg + 500 mg. Regular evaluation of renal function should be performed.

In children

Metglib® Force is not recommended for use in children.

Interaction

Contraindicated combinations

Involved with glibenclamide

Miconazole may cause hypoglycemia (up to and including coma).

Associated with metformin use

Iodine contrast agents: Depending on renal function, the drug should be discontinued 48 hours before or after intravenous administration of iodine contrast agents.

Unrecommended combinations

Related to the use of sulfonylurea derivatives

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

Alcohol may increase the hypoglycemic effect (by inhibiting the compensatory reactions or delaying its metabolic inactivation), which may contribute to the development of hypoglycemic coma. During treatment with the drug Metglib® Force, alcohol and medicinal products containing ethanol should be avoided.

Bozentan in combination with glibenclamide increases the risk of hepatotoxic effects. It is recommended to avoid concomitant administration of these drugs. The hypoglycemic effect of glibenclamide may also be reduced.

Phenylbutazone increases the hypoglycemic effect of sulfonylurea derivatives (by replacing sulfonylurea derivatives at protein-bound sites and/or reducing their elimination). It is preferable to use other anti-inflammatory agents that find fewer interactions, or to warn the patient about the need for self-control of glycemic levels; if necessary, the dose should be adjusted when the anti-inflammatory agent is used together and after discontinuation.

Risk of lactoacidosis is increased with acute alcohol intoxication, especially in case of starvation, or poor diet or liver failure. Alcoholic beverages and drugs containing ethanol should be avoided during treatment with Metglib® Force.

Combinations requiring caution

All hypoglycemic agents related to use

Chlorpromazine: at high doses (100 mg/day) causes increased glycemia (decreasing insulin release).

Precautionary measures: advise patient to monitor blood glucose on their own; if necessary, adjust the dose of hypoglycemic agent during concomitant use of neuroleptic and after discontinuation of the drug.

Glucocorticosteroids (GCS) and tetracosactide: Increased blood glucose, sometimes accompanied by ketosis (GCS cause decreased glucose tolerance).

Precautionary measures: the patient should be advised to self-monitor blood glucose; if necessary, the dose of hypoglycemic agent should be adjusted during concomitant use of GCS and after stopping their use.

Danazolol has a hyperglycemic effect. Metglib® Force requires dosage adjustment under glycemic control if treatment with danazolol is necessary and after discontinuation of danazol.

β2-adrenomimetics: due to stimulation of β2-adrenoreceptors increase blood glucose concentration.

Precautionary measures: the patient should be warned and blood glucose control should be established; transfer to insulin therapy is possible.

Diuretics: increase blood glucose levels.

Precautionary measures: the patient should be warned about the need for self-control of blood glucose; correction of the hypoclycemic agent dose may be required during concomitant use with diuretics and after stopping their use.

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

Associated use of metformin

Diuretics: Lactoacidosis resulting from metformin administration with functional renal failure caused by taking diuretics, especially loop diuretics.

Associated with glibenclamide

The β2-adrenoblockers, clonidine, reserpine, guanethidine, and sympathomimetics mask some symptoms of hypoglycemia: palpitation and tachycardia; most non-selective beta-adrenoblockers increase the frequency and severity of hypoglycemia. Patients should be warned about the need for self-monitoring of blood glucose, especially at the beginning of treatment.

Fluconazole: Increased elimination half-life of glibenclamide with possible occurrence of hypoglycemia. Patients should be cautioned about the need for self-monitoring of blood glucose; adjustment of the dose of hypoglycemic drugs may be required during concomitant treatment with fluconazole and after discontinuation of its use.

Other interactions: combinations to be considered:

Involved with glibenclamide

Desmopressin: Metglib® Force may decrease the antidiuretic effect of desmopressin.

Antibacterial drugs from the group of sulfonamides, fluoroquinolones, anticoagulants (coumarin derivatives), MAO inhibitors, chloramphenicol, pentoxifylline, hypolipidemic drugs from the group of fibrates, disopyramide – risk of hypoglycemia with glibenclamide.

Special Instructions

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

Lactoacidosis

Lactoacidosis is an extremely rare but serious (high mortality if not treated urgently) complication that can occur due to metformin cumulation. Cases of lactoacidosis 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 lactoacidosis should be considered if nonspecific signs occur, such as muscle cramps accompanied by dyspeptic disorders, abdominal pain, and severe malaise. In severe cases, acidotic dyspnea, hypoxia, hypothermia and coma may occur.

The diagnostic laboratory indicators are: low blood pH, plasma lactate concentration above 5 mmol/L, elevated anion interval and lactate/pyruvate ratio.

Hypoglycemia

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

Because of the compensatory reactions caused by hypoglycemia, there may be increased sweating, anxiety, tachycardia, increased blood pressure, palpitations, angina, and arrhythmia. The latter symptoms may be absent if hypoglycemia develops slowly, in cases of autonomic neuropathy, or with concomitant administration of beta-adrenoblockers, clonidine, reserpine, guanethidine, or sympathomimetics.

. Other symptoms of hypoglycemia in diabetic patients may include headache, hunger, nausea, vomiting, marked fatigue, sleep disturbances, agitation, aggression, impaired concentration and psychomotor reactions, depression, confusion, impaired speech, visual disturbances, tremor, paralysis and paresthesias, dizziness, delirium, seizures, somnolence, unconsciousness, shallow breathing and bradycardia.

Cautious use of the drug, dosage selection, and proper patient instructions are important to reduce the risk of hypoglycemia. If a patient has repeated episodes of hypoglycemia that are either severe or due to lack of knowledge of symptoms, treatment with other hypoglycemic agents should be considered. Factors contributing to hypoglycemia: concomitant consumption of alcohol, especially when fasting; refusal or (especially in elderly patients) inability of the patient to interact with the physician and follow the recommendations set forth in the instructions for use; poor diet, irregular meals, fasting or changes in diet; imbalance between physical activity and carbohydrate intake; renal failure; severe liver failure; overdose of Metglib® Force; certain endocrine disorders: not

Hepatic and renal failure

Pharmacokinetics and/or pharmacodynamics may be altered in patients with hepatic failure or severe renal impairment. Hypoglycemia occurring in such patients may be prolonged, in which case appropriate treatment should be initiated.

Instability of blood glucose content

In case of surgical intervention or other cause of decompensation of diabetes mellitus, it is recommended to provide for temporary transition to insulin therapy. Symptoms of hyperglycemia are rapid urination, marked thirst, dry skin. Metglib® Force should be discontinued 48 hours before elective surgery or intravenous injection of iodine containing radiopaque contrast agent. It is recommended that treatment be resumed after 48 hours and only after renal function has been evaluated and found to be normal.

Renal function

Because metformin is excreted by the kidneys, creatinine clearance and/or serum creatinine content should be determined before starting treatment and regularly thereafter: at least once a year in patients with normal renal function, and 2-4 times a year in older patients, and in patients with creatinine clearance at the upper limit of normal.

Particular caution is recommended in cases where renal function may be impaired, such as in elderly patients, or if antihypertensive therapy, diuretics or non-steroidal anti-inflammatory drugs (NSAIDs) are started.

Other precautions

The patient should inform the physician if there is a bronchopulmonary infection or urinary tract infection.

Influence on driving and operating machinery

Patients should be informed of the risk of hypoglycemia and should take precautions when driving and operating machinery that require increased concentration and quick psychomotor reactions.

Contraindications

Hypersensitivity to metformin, glibenclamide or other sulfonylurea derivatives or other drug components; type 1 diabetes mellitus; diabetic ketoacidosis, diabetic precoma, diabetic coma; renal failure or impaired renal function (creatinine clearance

Side effects

The following adverse reactions may occur during treatment with Metglib® Force.

WHO Classification of the frequency of adverse reactions:

very common – ≥1/10 appointments

often – ≥1/100 to < 1/10 appointments

infrequent – ≥1/1000 to < 1/100 appointments

rarely – ≥1/10000 to < 1/1000 appointments

very rare – < 1/10000 appointments

Classification of adverse adverse reactions according to organ and organ system involvement (Med-DRA Regulatory Medical Dictionary).

Blood and lymphatic system disorders:

These adverse events disappear after discontinuation of the drug.

Rarely: leukopenia and thrombocytopenia.

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

Disorders of the immune system:

Very rare: anaphylactic shock.

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

Metabolic and nutritional disorders:

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

Rarely: episodes of porphyria (hepatic or cutaneous).

Very rarely: lactoacidosis (See “Special Indications”).

Decreased absorption of vitamin B12, accompanied by a decrease in its serum concentrations with long-term use of metformin. If megaloblastic anemia is detected, the possibility of this etiology must be considered. Disulfiram-like reaction with ethanol use.

Nervous system disorders:

Often: impaired taste (“metallic” taste in the mouth).

Visual organ disorders:

In the beginning of treatment, temporary visual impairment may occur due to decreased blood glucose levels.

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.

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

To prevent these symptoms, it is recommended that the drug be taken in 2 or 3 doses; increasing the dose slowly also improves tolerability.

Hepatic and biliary tract disorders:

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

Skin and subcutaneous tissue disorders:

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

Very rare: photosensitization, cutaneous or visceral allergic vasculitis, erythema polymorphicum, exfoliative dermatitis.

Laboratory and instrumental findings:

Infrequent: moderate increase in serum urea and creatinine concentrations

Very rare: hyponatremia.

Overdose

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

Mild to moderate symptoms of hypoglycemia without loss of consciousness and neurological manifestations may be corrected by immediate consumption of sugar. It is necessary to perform a dose adjustment and/or change the diet. The occurrence of severe hypoglycemic reactions in patients with diabetes mellitus, accompanied by coma, seizures or other neurological disorders, requires emergency medical care. It is necessary to administer intravenous dextrose solution immediately after establishing the diagnosis or suspicion of hypoglycemia, before hospitalization of the patient. After recovery of consciousness, it is necessary to take a meal rich in easily digestible carbohydrates (to avoid recurrence of hypoglycemia).

The plasma clearance of glibenclamide may be increased in patients with liver disease. Since glibenclamide is actively bound to blood proteins, the drug is not excreted by dialysis.

Overdose or the presence of associated risk factors may provoke lactoacidosis because the drug contains metformin (see “Cautions”).

Lactoacidosis is a condition requiring emergency medical care; treatment of lactoacidosis should be performed in a hospital. Hemodialysis is the most effective treatment to eliminate lactate and metformin.

Similarities