Glibenfazh pills 5mg + 500mg, 30pcs

Composition

Active ingredients:

glibenclamide 5 mg + metformin hydrochloride 500 mg;

Auxiliary substances:

Core:

hypromellose-16.0 mg,

croscarmellose sodium-18.0 mg,

sodium stearyl fumarate-7.0,

povidone K 30 – 15.0 mg,

povidone (collidone F90) – 19.0 mg;

Composition of the film shell:

hypromellose E 15 – 7.0 mg, macrogol 6000 (polyethylene glycol 6000) – 0.9 mg, titanium dioxide-2.0 mg, polysorbate 80 (Twin 80) – 0.1 mg

Pharmacological action

Pharmacotherapy group: Hypoglycemic agent for oral use (second generation sulfonylurea derivative + biguanide)ATX: A. 10. B. D. 02 Metformin and sulfonamides Pharmacodynamics : Fixed combination of two oral hypoglycemic agents of different pharmacological groups: glibenclamide and metformin. Metformin belongs to the biguanide group and reduces the concentration of both basal and postprandial glucose in blood plasma. Metformin does not stimulate insulin secretion, and therefore 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 insulin receptors, the consumption and utilization of glucose by cells in the muscles; delays the absorption of glucose in the gastrointestinal tract (GIT). The drug also has a beneficial effect on the lipid composition of the blood, reducing the concentration of total cholesterol, low-density lipoproteins (LDL) and triglycerides. Glibenclamide belongs to the group of second-generation sulfonylurea derivatives. The glucose concentration during glibenclamide use decreases as a result of stimulation of insulin secretion by beta cells of the pancreas. Metformin and glibenclamide have different mechanisms of action, but complement each other’s hypoglycemic activity. The combination of two hypoglycemic agents has a synergistic effect in reducing glucose concentrations. Pharmacokinetics: Glibenclamydabsorption When taken orally, absorption from the gastrointestinal tract is more than 95%. The time to reach the maximum concentration is 4 hours, the volume of distribution is about 10 liters. The distribution of binding to plasma proteins is high (99%). Metabolism and excretion 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%). The half-life is from 4 to 11 hours. Metforminabsorption After oral use is absorbed from the gastrointestinal tract quite fully, the maximum concentration in plasma is reached within 2.5 hours. Absolute bioavailability ranges from 50 to 60%. Distribution Metformin is rapidly distributed in tissues, practically does not bind to plasma proteins. Metabolism and excretion It is metabolized to a very low degree and is excreted by the kidneys. Approximately 20-30% of metformin is excreted unchanged through the intestine. The elimination half-life is on average 6.5 hours. Pharmacokinetics in special groups of patients with impaired renal function, the renal clearance of metformin decreases, as well as creatinine clearance, while the half-life increases, which leads to an increase in the concentration of metformin in 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, as is the bioavailability of glibenclamide, but the rate of absorption of glibenclamide increases with food intake.

Indications

Type 2 diabetes mellitus in adults:

• if diet therapy, exercise and previous monotherapy with metformin or sulfonylurea derivatives are ineffective;
• to replace the previous therapy with two drugs (metformin and a sulfonylurea derivative) in patients with stable and adequate glycemic control.

Use during pregnancy and lactation

During pregnancy, the use of a combination of glibenclamide and metformin is contraindicated. The patient should be warned that during treatment with Glibenfazh, it is necessary to inform the doctor about the planned pregnancy and the onset of pregnancy. When planning pregnancy, as well as in the case of pregnancy during the period of taking the drug, it should be canceled and insulin therapy should also be prescribed.

The combination of glibenclamide and metformin is contraindicated in breast-feeding, since there are no data on its ability to enter breast milk. If it is necessary to use the drug during breastfeeding, you should switch to insulin therapy or stop breastfeeding.

Contraindications

Hypersensitivity to metformin, glibenclamide or other sulfonylurea derivatives, as well as to other excipients 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 may lead to changes in renal function: dehydration, severe infection, shock, intravascular use of iodine-containing drugs. contrast agents (see “Special instructions”); acute or chronic diseases that are accompanied by tissue hypoxia: heart or respiratory failure, recent myocardial infarction; liver failure; porphyria; pregnancy, breast-feeding; simultaneous use of miconazole; major surgical interventions, injuries, extensive burns and other conditions requiring insulin therapy; chronic alcoholism, acute alcohol intoxication; lactic acidosis (including in the case of anamnesis); compliance with 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: Febrile syndrome; adrenal insufficiency; hypofunction of the anterior pituitary gland; diseases of the thyroid gland (with uncompensated violation of its function); in the elderly due to the risk of hypoglycemia.

Side effects

The following adverse reactions may occur during treatment with Glibenfazh. WHO classification of adverse reaction rates: very common – ≥1/10 prescriptions, common – ≥1/100 to <1/10 prescriptions, uncommon – ≥1/1000 to <1/100 prescriptions, rare – ≥1/10000 to <1/1000 prescriptions, very rare – Classification of undesirable side effects according to the lesion of organs and organ systems (medical Dictionary for regulatory activities Med-DRA). Disorders of the blood and lymphatic system: These adverse events disappear after discontinuation of the drug. Rare: 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”). Rare: 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 prolonged use of metformin. If megaloblastic anemia is detected, it is necessary to consider the possibility of such an etiology. Disulfiram-like reaction when using ethanol. Nervous system disorders: Often: taste disorder (“metallic” taste in the mouth). Visual disturbances: At the beginning of treatment, there may be a temporary visual impairment due to a decrease in the concentration of glucose in the blood. Disorders of the gastrointestinal tract: 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. To prevent the development of these symptoms, it is recommended to take the drug in 2 or 3 doses; a slow increase in the dose of the drug also improves its tolerability. Liver and biliary tract disorders: Very rare: impaired liver function or hepatitis that requires discontinuation of treatment. Skin and subcutaneous tissue disorders: Rare: skin reactions such as pruritus, urticaria, maculopapular rash. Very rare: photosensitivity, cutaneous or visceral allergic vasculitis, erythema multiforme, exfoliative dermatitis. Laboratory and instrumental data: Infrequently: moderate increase in serum urea and creatinine concentrations. Very rare: hyponatremia.

Interaction

Contraindicated combinations associated with the use of glibenclamydamiconazole may provoke the development of hypoglycemia (up to the development of coma). Metformin-related iodine-containing contrast agents: depending on renal function, the drug should be discontinued 48 hours before or after intravenous use of iodine-containing contrast agents. Not recommended combinations associated with the use of sulfonylurea derivatives Alcohol: very rarely, a disulfiram-like reaction (alcohol intolerance) is observed when alcohol and glibenclamide are taken simultaneously. Alcohol can increase the hypoglycemic effect of the drug (by inhibiting compensatory reactions or delaying its metabolic inactivation), which can contribute to the development of hypoglycemic coma. Alcohol and drugs containing ethanol should be avoided during treatment with Glibenfazh. Bosentan in combination with glibenclamide increases the risk of hepatotoxic effects. It is recommended to avoid taking these medications at the same time.The hypoglycemic effect of glibenclamide may also decrease. Phenylbutazone increases the hypoglycemic effect of sulfonylurea derivatives (replacing sulfonylurea derivatives at protein-bound sites and / or reducing their elimination). It is preferable to use other anti-inflammatory drugs that show less interaction, or warn the patient about the need to independently control the concentration of glucose in the blood; if necessary, the dose should be adjusted with the combined use of the anti-inflammatory agent and after its discontinuation. Metformin-related alcohol: The risk of lactic acidosis increases with acute alcohol intoxication, especially in cases of starvation, poor nutrition, or liver failure. Alcohol and drugs containing ethanol should be avoided during treatment with Glibenfazh. Combinations requiring caution Associated with the use of all hypoglycemic agents Chlorpromazine: in high doses (100 mg/day) causes an increase in the concentration of glucose in the blood (reducing the release of insulin). Precautions: the patient should be warned about the need to independently monitor the concentration of glucose in the blood; if necessary, adjust the dose of hypoglycemic agent during the simultaneous use of a neuroleptic and after discontinuation of its use. Glucocorticosteroids (corticosteroids) and tetracosactide: an increase in blood glucose concentrations, sometimes accompanied by ketosis (corticosteroids cause a decrease in glucose tolerance). Precautions: the patient should be warned about the need to independently control the concentration of glucose in the blood; if necessary, the dose of hypoglycemic agent should be adjusted during the simultaneous use of corticosteroids and after discontinuation of their use. Danazol has a hyperglycemic effect. If treatment with danazol is necessary and the latter is discontinued, a dose adjustment of Glibenfazh is required under the control of blood glucose concentration. beta-2-adrenomimetics: by stimulating beta-2-adrenergic receptors, they increase the concentration of glucose in the blood. Precautions: it is necessary to warn the patient and establish control over the concentration of glucose in the blood, it is possible to transfer to insulin therapy. Diuretics: increase the concentration of glucose in the blood. Precautions: the patient should be warned about the need to independently monitor the concentration of glucose in the blood; it may be necessary to adjust 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 to reduce the concentration of glucose in the blood. If necessary, the dose of Glibenfazh should be adjusted during concomitant use with ACE inhibitors and after discontinuation of their use. Metformin-related diuretics: Lactic acidosis that occurs when taking metformin against the background of functional renal failure caused by taking diuretics, especially loop diuretics. Glibenclamide-related beta-2 blockers, clonidine, reserpine, guanethidine, and sympathomimetics mask some of the symptoms of hypoglycemia: palpitation and tachycardia: most non-selective beta-blockers increase the frequency and severity of hypoglycemia. The patient should be warned about the need to independently monitor the concentration of glucose in the blood, especially at the beginning of treatment. Fluconazole: An increase in the half-life of glibenclamide with possible manifestations of hypoglycemia. The patient should be warned about the need for self-monitoring of blood glucose concentrations; it may be necessary to adjust the dose of hypoglycemic drugs during concomitant treatment with fluconazole and after discontinuation of its use. Bile acid sequestrants: Concomitant use with Glibenfazh reduces the concentration of glibenclamide in blood plasma, which may lead to a decrease in the hypoglycemic effect. Glibenfazh should be taken at least 4 hours before taking bile acid sequestrants. Other interactions: combinations to consider:Related to the use of glibenclamideadesmopressin: the combination of glibenclamide and metformin may reduce the antidiuretic effect of desmopressin. Antibacterial drugs (JIC) 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 hypoglycemia with the use of glibenclamide.

How to take, course of use and dosage

Inside. The dose of the drug is determined by the doctor individually for each patient, depending on the concentration of glucose in the blood. The initial dose is: 1 tablet of Glibenfazh 2.5 mg + 500 mg or 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) or metformin, if they were used as first-line therapy. It is recommended to increase the dose by no more than 5 mg of glibenclamide and 500 mg of metformin per day every 2 or more weeks to achieve adequate blood glucose control. Replacement of previous combination therapy with metformin and glibenclamide: the initial dose should not exceed the daily dose of glibenclamide (or an equivalent dose of another sulfonylurea) and metformin taken earlier. Every 2 or more weeks after starting treatment, the dose of the drug is adjusted depending on the concentration of glucose in the blood. The maximum daily dose is 4 tablets of Glibenfazh 5 mg + 500 mg or 6 tablets of Glibenfazh 2.5 mg + 500 mg. Dosage regimen:The dosage regimen depends on the individual appointment: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 per day. Twice a day, in the morning and in the evening, with the appointment of 2 or 4 tablets per day. For a dosage of 2.5 mg + 500 mg 3 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 3 times a day, morning, afternoon and evening, with the appointment of 3 tablets per day. Tablets should be taken with a meal. Each dose 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 renal function. The initial dose should not exceed 1 tablet of Glibenfazh 2.5 mg + 500 mg. Regular assessment of renal function should be performed. Glibenfazh is not recommended for use in children.

Overdose

In case of overdose, hypoglycemia may develop due to the presence of a sulfonylurea derivative in the drug (see “Special instructions”). Symptoms of mild to moderate hypoglycemia without loss of consciousness and neurological symptoms can be stopped by immediate intake of easily digestible carbohydrates. It is necessary to adjust the dose of the drug 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 urgent medical attention. Intravenous use of dextrose solution is necessary immediately after diagnosis or suspicion of hypoglycemia, before the patient is hospitalized. After regaining consciousness, it is necessary to take food rich in easily digestible carbohydrates (in order to avoid the re-development of hypoglycemia). Plasma clearance of glibenclamide may increase in patients with liver disease. Since glibenclamide actively binds to blood proteins, the drug is not excreted during dialysis. Overdose or the presence of associated risk factors can trigger the development of lactic acidosis, since the drug contains metformin (see “Special Instructions”). Lactic acidosis is a condition that requires urgent medical attention; lactic acidosis should be treated in a hospital setting. Hemodialysis is the most effective treatment method for removing lactate and metformin.

Special instructions

Treatment with Glibenfazh is carried out only under the supervision of a doctor! 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 regularly monitor the concentration of glucose in the blood on an empty stomach and after meals. Lactic acidosis Lactic acidosis is an extremely rare but serious complication (high mortality in the absence of urgent treatment) that can occur due to the accumulation of metformin. Cases of lactic acidosis with metformin use occurred mainly in patients with diabetes mellitus and severe renal insufficiency. Other associated risk factors should also 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 considered if there are non-specific signs, 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 interval, and the lactate/pyruvate ratio. Hypoglycemia Since Glibenfazh contains glibenclamide, taking the drug is associated with the risk of hypoglycemia in the patient. Gradual titration of the dose after starting treatment can prevent the occurrence of hypoglycemia.This treatment can only be prescribed to a patient who adheres to a regular food intake (including breakfast). It is important that carbohydrate intake is regular, as the risk of hypoglycemia increases with late meals, insufficient or unbalanced carbohydrate intake. The development of hypoglycemia is most likely with a hypocaloric diet, after intense or prolonged physical activity, with the use of alcoholic beverages or when taking a combination of hypoglycemic agents. Due to compensatory reactions caused by hypoglycemia, increased sweating, fear, tachycardia, increased blood pressure, palpitation, angina pectoris and arrhythmia may occur. The latter symptoms may be absent if hypoglycemia develops slowly, in the case of autonomic neuropathy, or when taking beta-blockers, clonidine, reserpine, guanethidine, or sympathomimetics at the same time. Other symptoms of hypoglycemia in diabetic patients may include headache, hunger, nausea, vomiting, severe fatigue, sleep disorders, agitation, aggression, impaired concentration and psychomotor reactions, depression, confusion, speech disorders, visual disturbances, trembling, paralysis and paresthesia, dizziness, delirium, convulsions, somnolence, unconsciousness, shallow breathing and bradycardia. Careful use of the drug, dose selection and proper instructions for the patient are important to reduce the risk of hypoglycemia. If a patient has recurrent episodes of hypoglycemia that are either severe or associated with ignorance of symptoms, treatment with other hypoglycemic agents should be considered. Factors contributing to the development of hypoglycemia: concomitant use of alcoholic beverages, especially during fasting; refusal or (especially for elderly patients) inability of the patient to interact with the doctor and follow the recommendations set out in the instructions for use; poor nutrition, irregular food intake, fasting or changes in diet; an imbalance between physical activity and carbohydrate intake: renal failure; severe liver failure; overdose of Glibenfazh; individual endocrine disorders: thyroid, pituitary, etc. adrenal glands; simultaneous use of individual medications. Renal and hepatic insufficiency The 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 initiated. Instability of blood glucose in the event of surgical intervention or other cause of decompensation of diabetes mellitus, it is recommended to provide for a temporary transition to insulin therapy. Symptoms of hyperglycemia include frequent urination, extreme thirst, and dry skin. Glibenfazh should be discontinued 48 hours before elective surgery or intravenous use of an iodine-containing radiopaque agent. Treatment is recommended to resume after 48 hours, and only after kidney function has been evaluated and found to be normal. Renal function Since metformin is excreted by the kidneys, before starting treatment and regularly thereafter, it is necessary to determine the creatinine clearance and / or serum creatinine concentration: 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. Special caution is recommended in cases where renal function may be impaired, such as in elderly patients, or when starting antihypertensive therapy, diuretics, or nonsteroidal anti-inflammatory drugs (NSAIDs). Other precautions The patient should inform the doctor in case of infectious diseases of the lower respiratory tract, genitals, kidneys and urinary tract. Influence on the ability to drive vehicles and mechanisms:Patients should be informed about the risk of hypoglycemia and should take precautions when driving a vehicle and working with mechanisms that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

Store in the original manufacturer’s packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 3 years.

Active ingredient

Glibenclamide, Metformin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets