Glucovans tablets p/o 500mg/2.5mg №15×2

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Glyukovans tabl p / film.ob. 500mg/2.5mg in bl. in pack. No. 15×2
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Main active ingredient Metformin glibenclamide Release form Tablets Dosage 500 mg/2.5 mg Lactic acidosis Lactic acidosis is an extremely rare but serious (high mortality in the absence of emergency treatment) complication that can occur due to the accumulation of metformin. Cases of lactic acidosis in patients treated with metformin occurred mainly in patients with diabetes mellitus with severe renal insufficiency. Other associated 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. The risk of developing lactic acidosis should be taken into account when non-specific signs appear, such as muscle cramps, accompanied by dyspeptic disorders, abdominal pain and severe malaise. In severe cases, acidotic dyspnoea, 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 Glucovance® contains glibenclamide, so taking the drug is accompanied by the risk of hypoglycemia in the patient. Gradual dose titration after the start of treatment may prevent the occurrence of hypoglycemia. This treatment can only be prescribed to a patient who adheres to a regular meal regimen (including breakfast). It is important that carbohydrate intake is regular, because. the risk of developing hypoglycemia increases with late meals, insufficient or unbalanced carbohydrate intake. The development of hypoglycemia is most likely with a low-calorie 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, sweating, anxiety, tachycardia, hypertension, palpitations, angina pectoris and arrhythmia may occur. The latter symptoms may be absent if hypoglycemia develops slowly, in case of autonomic neuropathy, or while taking beta-blockers, clonidine, reserpine, guanethidine, or sympathomimetics. Other symptoms of hypoglycemia in patients with diabetes mellitus may be headache, hunger, nausea, vomiting, severe fatigue, sleep disorders, agitation, aggression, impaired concentration and psychomotor reactions, depression, confusion, speech disturbance, visual impairment, trembling, paralysis and paresthesia, dizziness, delirium, convulsions, somnolence, unconsciousness, shallow breathing, and bradycardia. Careful prescribing, dose titration, and proper patient instructions are important to reduce the risk of hypoglycemia. If the patient has recurring episodes of hypoglycemia that are either severe or associated with unawareness of the symptoms, treatment with other hypoglycemic agents should be considered. Factors contributing to the development of hypoglycemia: the simultaneous use of alcohol, 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 meals, fasting, or changes in diet; imbalance between exercise and carbohydrate intake; kidney failure; severe liver failure; overdose of the drug Glucovans®; individual endocrine disorders: insufficiency of the thyroid gland, pituitary and adrenal glands; concomitant use of certain drugs. Renal and hepatic insufficiency Pharmacokinetics and / or pharmacodynamics may change in patients with hepatic insufficiency or severe renal insufficiency. The hypoglycemia that occurs in such patients can be prolonged, in which case appropriate treatment should be initiated. Instability of blood glucose In the event of surgery or other cause of decompensation of diabetes mellitus, it is recommended to consider a temporary transition to insulin therapy. Symptoms of hyperglycemia are frequent urination, severe thirst, dry skin. 48 hours before a planned surgical intervention or intravenous administration of an iodine-containing radiopaque agent, Glucovance® 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. Renal function Since metformin is excreted by the kidneys, it is necessary to determine CC and / or serum creatinine before starting treatment and regularly thereafter: at least 1 time per year in patients with normal renal function, and 2-4 times per year in elderly patients, as well as in patients with CC on VGN. Particular caution is advised in cases where renal function may be impaired, such as in elderly patients, or if antihypertensive therapy, diuretics or NSAIDs are started. Other Precautions The patient should inform the doctor about the occurrence of a bronchopulmonary infection or an infectious disease of the genitourinary organs. Influence on the ability to drive a car and work with mechanisms Patients should be informed about the risk of hypoglycemia and should take precautions when driving and working with mechanisms that require increased concentration and speed of psychomotor reactions. Pharmacological action Glukovance® is a fixed combination of two oral hypoglycemic agents of different pharmacological groups: metformin and glibenclamide. Metformin belongs to the group of biguanides and reduces the content 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 receptors to insulin, the consumption and utilization of glucose by muscle cells; 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 level of total cholesterol, LDL and TG. Glibenclamide belongs to the group of second generation sulfonylurea derivatives. When taking glibenclamide, the glucose content decreases as a result of stimulation of insulin secretion by pancreatic β-cells. 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. Pharmacokinetics Glibenclamide When taken orally, absorption from the gastrointestinal tract is more than 95%. Glibenclamide, which is part of the Glucovance® preparation, is micronized. Cmax in plasma is reached in about 4 hours. Vd is about 10 liters. Communication 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 bile (60%). T1 / 2 – from 4 to 11 hours. Metformin After oral administration, it is completely absorbed from the gastrointestinal tract. Cmax in plasma is achieved within 2.5 hours. Absolute bioavailability ranges from 50 to 60%. Approximately 20-30% of metformin is excreted through the gastrointestinal tract unchanged. Metformin is rapidly distributed in tissues, practically does not bind to plasma proteins. It is metabolized to a very low degree and excreted by the kidneys. T1 / 2 averages 6.5 hours. 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 food intake, as is the bioavailability of glibenclamide. However, the rate of absorption of glibenclamide increases with food intake. Indications for use Type 2 diabetes mellitus in adults: with the ineffectiveness of diet therapy, exercise and previous monotherapy with metformin or a sulfonylurea derivative; to replace previous therapy with two drugs (metformin and a sulfonylurea derivative) in patients with stable and well-controlled glycemic levels. Method of administration and doses 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 Glucovance® 2.5 mg + 500 mg or Glyukovance® 5 mg + 500 mg 1 time / 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 used as first-line therapy. It is recommended to increase the dose by no more than 5 mg glibenclamide + 500 mg metformin daily 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 drug) and metformin taken previously. 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 Glucovance® 5 mg + 500 mg or 6 tablets of Glucovance® 2.5 mg + 500 mg. Dosing regimen Dosing regimen depends on the individual appointment: 1 time per day, in the morning during breakfast – when prescribing 1 tablet per day; 2 times a day, morning and evening – with the appointment of 2 or 4 tablets per day. The tablets should be taken with meals. 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 Glucovans® 2.5 mg + 500 mg. It is necessary to conduct regular evaluation of kidney function. Children Glucovance® is not recommended for use in children. Use during pregnancy and lactation The use of the drug is contraindicated during pregnancy. The patient should be warned that during the period of treatment with Glucovans® it is necessary to inform the doctor about the planned pregnancy and the onset of pregnancy. When planning a pregnancy, as well as in the event of pregnancy during the period of taking Glucovans®, the drug should be canceled and insulin treatment prescribed. Glucovance® is contraindicated in breastfeeding, as there is no data on its ability to pass into breast milk. Interaction with other drugs Contraindicated combinations Associated with the use of glibenclamide Miconazole can provoke the development of hypoglycemia (up to the development of coma). Associated with the use of metformin Iodine-containing contrast agents: depending on the function of the kidneys, the drug should be discontinued 48 hours before or after the IV administration of iodine-containing contrast agents. Combinations that are not recommended Associated with the use of sulfonylurea derivatives Alcohol. Very rarely, disulfiram-like reactions (alcohol intolerance) are observed while taking alcohol and glibenclamide. Alcohol intake may increase the hypoglycemic effect (by inhibiting compensatory reactions or delaying its metabolic inactivation), which may contribute to the development of hypoglycemic coma. During treatment with Glucovance®, alcohol and medicines containing ethanol should be avoided. Phenylbutazone increases the hypoglycemic effect of sulfonylurea derivatives (replacing sulfonylurea derivatives at protein binding sites and / or reducing their elimination). It is preferable to use other anti-inflammatory drugs that show less interactions, or to warn the patient about the need for self-monitoring of glycemic levels. If necessary, the dose should be adjusted when the anti-inflammatory agent is used together and after its termination. Related to the use of glibenclamide Bosentan in combination with glibenclamide increases the risk of hepatotoxicity. It is recommended to avoid the simultaneous use of these drugs. The hypoglycemic effect of glibenclamide may also be reduced. Associated with 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 treatment with Glucovance®, alcohol and medicines containing ethanol should be avoided. Combinations requiring caution Associated with the use of all hypoglycemic agents Chlorpromazine in high doses (100 mg / day) causes an increase in glycemia (reducing insulin release). Precautions: the patient should be warned about the need for self-monitoring of blood glucose; if necessary, the dose of the hypoglycemic drug should be adjusted during the simultaneous use of an antipsychotic and after stopping its use. GCS and tetracosactide: an increase in blood glucose, sometimes accompanied by ketosis (GCS cause a decrease in glucose tolerance). Precautions: the patient should be warned about the need for self-monitoring of blood glucose; if necessary, the dose of the hypoglycemic agent should be adjusted during the simultaneous use of GCS and after stopping their use. Danazol has a hyperglycemic effect. If treatment with danazol is necessary and when the latter is discontinued, a dose adjustment of the drug Glucovans® is required under the control of glycemic levels. Beta2-agonists by stimulating β2-adrenergic receptors 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 in blood glucose. Precautions: the patient should be warned about the need for self-monitoring of blood glucose; dose adjustment of the hypoglycemic agent may be required during concomitant use with diuretics and after discontinuation of their use. ACE inhibitors: the use of ACE inhibitors (captopril, enalapril) helps to reduce blood glucose levels. If necessary, the dose of Glucovance® should be adjusted during concomitant use with ACE inhibitors and after discontinuation of their use. Associated with the use of metformin 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 Beta-blockers, 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. The patient should be warned about the need for self-monitoring of blood glucose, especially at the beginning of treatment. Fluconazole: an increase in T1 / 2 of glibenclamide with the possible occurrence of manifestations of hypoglycemia. The patient should be warned about the need for self-monitoring of blood glucose; dose adjustment of hypoglycemic drugs may be required during concomitant treatment with fluconazole and after discontinuation of its use. Bile acid sequestrants: Simultaneous use with Glucovance® reduces the concentration of glibenclamide in the blood plasma, which may lead to a decrease in the hypoglycemic effect. Glucovans® should be taken at least 4 hours before taking a bile acid sequestrant. Combinations to be considered Associated with the use of glibenclamide Desmopressin: Glucovance® may reduce the antidiuretic effect of desmopressin. Antibacterial drugs (drugs) from the sulfanilamide group, fluoroquinolones, anticoagulants (coumarin derivatives), MAO inhibitors, chloramphenicol, pentoxifylline, lipid-lowering drugs from the fibrate group, disopyramide – the risk of developing hypoglycemia during the use of glibenclamide. Contraindications hypersensitivity to metformin, glibenclamide or other sulfonylurea derivatives, as well as to excipients; type 1 diabetes; diabetic ketoacidosis; diabetic precoma, diabetic coma; renal failure or impaired renal function (CC <60 ml / min); acute conditions that can lead to a change in kidney function: dehydration, severe infection, shock, intravascular administration of iodine-containing contrast agents; acute or chronic diseases that are accompanied by tissue hypoxia: heart or respiratory failure, recent myocardial infarction, shock; liver failure; porphyria; pregnancy, breastfeeding period; concomitant use of miconazole; extensive surgical operations; chronic alcoholism, acute alcohol intoxication; lactic acidosis (including history); adherence to a hypocaloric diet (less than 1000 cal / day); It is not recommended to use the drug in patients over the age of 60 who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis in them. Glucovance® contains lactose, therefore its use is not recommended in patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome. With caution: febrile syndrome, adrenal insufficiency, hypofunction of the anterior pituitary gland, thyroid disease with uncompensated dysfunction. Composition glibenclamide 2.5 mg Metformin hydrochloride 500 mg Excipients: croscarmellose sodium - 14 mg, povidone K30 - 20 mg, microcrystalline cellulose - 56.5 mg, magnesium stearate - 7 mg Shell composition: Opadry OY-L-24808 pink - 12 mg (lactose monohydrate - 36%, hypromellose 15cP - 28%, titanium dioxide - 24.39%, macrogol - 10%, yellow iron oxide - 1.3%, red iron oxide - 0.3% , iron oxide black - 0.01%), purified water - qs Overdose In case of overdose, hypoglycemia may develop due to the presence of a sulfonylurea derivative in the preparation. Mild to moderate symptoms of hypoglycemia without loss of consciousness and neurological manifestations can be corrected by immediate consumption of sugar. It is necessary to perform dose adjustment and / or change the diet. The occurrence of severe hypoglycemic reactions in patients with diabetes mellitus, accompanied by coma, paroxysm or other neurological disorders, requires emergency medical care. It is necessary to / in the introduction of a solution of dextrose immediately after the diagnosis or suspicion of hypoglycemia, before hospitalization of the patient. 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). Lactic acidosis is a medical emergency; treatment of lactic acidosis should be carried out in the clinic. The most effective treatment for removing lactate and metformin is hemodialysis. Plasma clearance of glibenclamide may be increased in patients with liver disease. Since glibenclamide actively binds to blood proteins, the drug is not eliminated during dialysis. Long-term overdose or the presence of associated risk factors can provoke the development of lactic acidosis, tk. The drug contains metformin. Side effects During treatment with Glucovans®, the following side effects may occur. The frequency of side effects of the drug is regarded as follows: very common: (≥1/10) frequent: (≥1/100, <1/10) infrequent: (≥1/1000, <1/100) rare: (≥1/10 0, <1/1000) very rare: (≤1/10,000) isolated cases (cannot be assessed with available data). Metabolic disorders Hypoglycemia; rarely - attacks of hepatic porphyria and skin porphyria; very rarely - lactic acidosis. Decreased absorption of vitamin B12, accompanied by a decrease in its concentration in the blood serum with prolonged use of metformin. When megaloblastic anemia is detected, the possibility of such an etiology must be considered. Disulfiram-like reaction when drinking alcohol. Circulatory and lymphatic systems These adverse events disappear after discontinuation of the drug. Rarely - leukopenia and thrombocytopenia; very rarely - agranulocytosis, hemolytic anemia, bone marrow aplasia and pancytopenia. 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. 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. Hepatobiliary disorders Very rarely - a violation of liver function tests or hepatitis, requiring discontinuation of treatment. Nervous system Often - a violation of taste (metallic taste in the mouth). Vision At the beginning of treatment, temporary visual impairment may occur due to a decrease in blood glucose. Skin and subcutaneous tissue Rarely - skin reactions such as itching, urticaria, maculopapular rash. Very rarely - skin or visceral allergic vasculitis, erythema multiforme, exfoliative dermatitis, photosensitivity. Immunological reactions Very rarely - anaphylactic shock. Cross-hypersensitivity reactions to sulfonamides and their derivatives may occur. Laboratory indicators: infrequently - an increase in the concentration of urea and creatinine in the blood serum from an average to moderate degree; very rarely - hyponatremia. Storage conditions The drug should be stored out of the reach of children at a temperature not exceeding 30 ° C. Buy Glucovance tablets p/o 500mg/2.5mg №15x2