Pharmacological properties of the drug Glibomet
Pharmacodynamics. Glibomet is a combination of glibenclamide and metformin. The combined effect of the two components is that the secretion of endogenous insulin caused by glibenclamide is stimulated, and glucose utilization by muscle tissue is significantly increased due to the action of metformin. This leads to a significant synergistic effect, which allows you to reduce the dose of each component of the drug, thus reducing excessive stimulation of pancreatic β-cells and the risk of developing their functional failure, and significantly reduces the risk of side effects. Pharmacokinetics. About 84% of glibenclamide is absorbed in the digestive tract. Metabolized in the liver to form inactive metabolites and excreted in feces and urine. The half-life is 5 hours. The degree of binding to plasma proteins is 97%. Metformin, adsorbed in the digestive tract, is quickly excreted in feces and urine, does not bind to blood plasma proteins, and is not metabolized in the body. The half-life is approximately 2 hours.
Glibomet tab ppo 2.5mg+400mg No. 40
Compound
Active ingredients: glibenclamide 2.5 mg, metformin hydrochloride 400 mg.
Excipients: microcrystalline cellulose - 65 mg, corn starch - 57.5 mg, colloidal silicon dioxide - 20 mg, gelatin - 40 mg, glycerol - 17.5 mg, talc - 15 mg, magnesium stearate - 7.5 mg.
Shell composition: cellulose acetate - 2 mg, diethyl phthalate - 0.5 mg, talc - 2.5 mg.
Pharmacokinetics
Glibenclamide
Suction and distribution
It is quickly and fairly completely (84%) absorbed from the gastrointestinal tract, the time to reach Cmax is 1-2 hours. Plasma protein binding is 97%.
Metabolism and excretion
Almost completely metabolized in the liver to inactive metabolites. Excreted by the kidneys (50%) and bile (50%). T1/2 ranges from 5 to 10 hours.
Metformin
Suction and distribution
It is absorbed quite completely in the gastrointestinal tract, quickly distributed into tissues, and practically does not bind to blood plasma proteins.
Metabolism and excretion
It is not metabolized in the body and is excreted unchanged mainly by the kidneys and, partially, through the intestines. T1/2 is approximately 7 hours.
Indications for use
Type 2 diabetes mellitus with ineffective diet therapy and previous therapy with sulfonylurea derivatives or biguanides, as well as other oral hypoglycemic agents.
Contraindications
- Diabetes mellitus type 1;
- gestational diabetes mellitus;
- diabetic ketoacidosis, diabetic precoma, diabetic coma;
- lactic acidosis (including history);
- conditions accompanied by impaired absorption of food and the development of hypoglycemia;
- liver dysfunction;
- acute conditions that can lead to changes in kidney function (dehydration, severe infection, shock, intravascular administration of iodinated contrast agents);
- renal failure or impaired renal function (creatinine level above 135 mmol/L for men and above 110 mmol/L for women);
- infectious diseases, gangrene, major surgical interventions, trauma, acute massive blood loss, extensive burns and other conditions requiring insulin therapy;
- hypoxic conditions (heart or respiratory failure, recent myocardial infarction, shock, severe respiratory diseases);
- a period of 48 hours before and 48 hours after radioisotope or x-ray studies with the introduction of iodine-containing contrast agent;
- a period of 48 hours before and 48 hours after surgery;
- dystrophic diseases (myotonic dystrophy, lipodystrophy);
- leukopenia;
- porphyria;
- chronic alcoholism, acute alcohol intoxication;
- adherence to a strict hypocaloric diet (less than 1000 kcal/day);
- deficiency of glucose-6-phosphate dehydrogenase;
- pregnancy;
- lactation period (breastfeeding);
- children and adolescents up to 18 years of age;
- hypersensitivity to metformin, glibenclamide or other sulfonylurea derivatives, as well as to other components of the drug.
It is not recommended to use the drug in patients over 60 years of age who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis.
The drug should be used with caution during febrile syndrome; diseases of the thyroid gland (with dysfunction); hypofunction of the anterior pituitary gland and/or adrenal cortex.
Directions for use and doses
The drug is taken orally with meals.
The dosage regimen and duration of treatment are determined by the attending physician depending on the state of carbohydrate metabolism and the concentration of glucose in the blood.
The initial dose is, as a rule, 1-3 tablets/day with further gradual selection of an effective dose until a stable normalization of blood glucose concentration is achieved.
The maximum daily dose of Glibomet® is 6 tablets.
Storage conditions
The drug should be stored out of the reach of children at a temperature not exceeding 30°C.
Best before date
3 years. Do not use after expiration date.
special instructions
During treatment, patients must strictly follow the doctor's recommendations regarding the dosage and method of administration of the drug, as well as diet, exercise regimen and self-monitoring of blood glucose levels.
Lactic acidosis is a rare and life-threatening pathological condition characterized by the accumulation of lactic acid in the blood, which can be caused by the accumulation of metformin. The described cases of the development of lactic acidosis in patients receiving metformin were observed mainly in patients with diabetes mellitus with severe heart and renal failure. Prevention of lactic acidosis involves identifying all associated risk factors, such as decompensated diabetes mellitus, ketosis, prolonged fasting, excessive alcohol consumption, liver failure and any condition associated with hypoxia.
When taking Glibomet®, serum creatinine concentrations should be regularly monitored:
- at least once a year in patients with normal renal function;
- at least 2-4 times a year in patients with serum creatinine concentrations close to ULN, as well as in elderly patients.
Caution should be exercised in cases where there is a risk of impaired renal function, for example, when prescribing antihypertensive or diuretic drugs when initiating NSAID therapy. Treatment with Glibomet® should be stopped 48 hours before an x-ray examination with intravenous administration of iodine-containing contrast agents and replaced with therapy with other hypoglycemic drugs (for example, insulin).
The use of the drug Glibomet® must be stopped 48 hours before a planned operation under general anesthesia, spinal or epidural anesthesia. Therapy should be continued after resumption of oral nutrition or no earlier than 48 hours after surgery, provided that normal renal function is confirmed.
Ethanol can provoke the development of hypoglycemia, as well as a disulfiram-like reaction (nausea, vomiting, abdominal pain, a feeling of heat on the skin of the face and upper body, tachycardia, dizziness, headache), so you should refrain from drinking alcohol during treatment with Glibomet®.
Description
Hypoglycemic agent for oral use (second generation sulfonylurea + biguanide).
Use in children
The use of the drug is contraindicated in children and adolescents under the age of 18 years.
Pharmacodynamics
A combined oral hypoglycemic drug containing a second generation sulfonylurea derivative and a biguanide. It has pancreatic and extrapancreatic effects.
Glibenclamide is a second generation sulfonylurea derivative. Stimulates insulin secretion by lowering the threshold for irritation of pancreatic β-cells by glucose, increases sensitivity to insulin and the degree of its binding to target cells, increases insulin release, enhances the effect of insulin on glucose uptake by muscles and liver, and inhibits lipolysis in adipose tissue. Acts in stage II of insulin secretion.
Metformin belongs to the group of biguanides. Stimulates peripheral tissue sensitivity to the action of insulin (increases the binding of insulin to receptors, enhances the effects of insulin at the post-receptor level), reduces glucose absorption in the intestine, suppresses gluconeogenesis and has a beneficial effect on lipid metabolism, helps reduce excess body weight in patients with diabetes, and also has a fibrinolytic effect due to the suppression of tissue-type plasminogen activator inhibitor.
The hypoglycemic effect of the drug develops after 2 hours and lasts 12 hours.
The synergistic combination of two active components of the drug - the stimulating effect of a sulfonylurea derivative on the production of endogenous insulin (pancreatic effect) and the direct effect of biguanide on muscle and adipose tissue (a significant increase in glucose uptake - extrapancreatic effect) and liver tissue (decreased gluconeogenesis), allows, at a certain ratio doses to reduce the content of each component. This helps to avoid excessive stimulation of pancreatic β-cells, and therefore reduce the risk of impaired pancreatic function, and also ensures increased safety of hypoglycemic drugs and a reduced incidence of side effects.
Side effects
Possible side effects when using the drug Glibomet® are given in descending order depending on the frequency of occurrence: often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10 000, <1/1000), very rare (<1/10,000), including isolated reports.
From the digestive system: rarely - nausea, vomiting, loss of appetite, abdominal pain, diarrhea, metallic taste in the mouth; in some cases - increased activity of liver enzymes.
From the hematopoietic system: rarely - leukopenia, thrombocytopenia, erythrocytopenia; very rarely - agranulocytosis, hemolytic or megaloblastic anemia, pancytopenia.
From the side of the central nervous system: infrequently - headache.
From the skin: rarely - urticaria, erythema, itching, photosensitivity.
Metabolism: rarely - hypoglycemia; very rarely - lactic acidosis.
If symptoms of lactic acidosis appear (vomiting, abdominal pain, general weakness, muscle cramps), you must immediately stop taking the drug and immediately consult a doctor.
Other: disulfiram-like reaction when taking alcohol simultaneously (the most common signs are redness of the skin of the face and upper body, headache, nausea and vomiting, palpitations, increased blood pressure).
Use during pregnancy and breastfeeding
The drug is contraindicated for use during pregnancy and lactation (breastfeeding).
Interaction
The hypoglycemic effect of the drug Glibomet® is enhanced by simultaneous administration of coumarin derivatives (warfarin, syncumar), beta-blockers, cimetidine, oxytetracycline, allopurinol, MAO inhibitors, sulfonamides, phenylbutazone and its derivatives, chloramphenicol, probenecid, salicylates, cyclophosphamide, sulfonamide, perhexiline , pheniramidol , miconazole (oral), sulfinpyrazone and ethanol.
Adrenaline, corticosteroids, oral contraceptives, thyroid hormone preparations, thiazide diuretics and barbiturates reduce the hypoglycemic effect of Glibomet®.
When used simultaneously with the drug Glibomet®, the effect of anticoagulants may be enhanced.
Concomitant use with cimetidine may increase the risk of developing lactic acidosis.
The use of beta-blockers may mask the symptoms of hypoglycemia (with the exception of increased sweating).
The use of iodine-containing X-ray contrast agents (for intravascular administration) can lead to impaired renal function and accumulation of metformin, which increases the risk of developing lactic acidosis.
Overdose
Symptoms: possible lactic acidosis (due to the action of metformin), hypoglycemia (due to the action of glibenclamide).
Symptoms of lactic acidosis: severe weakness, muscle pain, respiratory disorders, drowsiness, nausea, vomiting, diarrhea, abdominal pain, hypothermia, decreased blood pressure, reflex bradyarrhythmia, confusion and loss of consciousness.
Symptoms of hypoglycemia: feeling of hunger, increased sweating, weakness, palpitations, pallor of the skin, paresthesia in the oral cavity, tremor, general anxiety, headache, pathological drowsiness, sleep disorders, feelings of fear, impaired coordination of movements, temporary neurological disorders. As hypoglycemia progresses, loss of self-control and consciousness is possible.
Treatment: if the development of lactic acidosis is suspected, immediate discontinuation of the drug and emergency hospitalization are recommended. The most effective treatment method is hemodialysis.
For mild hypoglycemia, you should take a piece of sugar, food or drinks high in carbohydrates (jam, honey, a glass of sweet tea).
In case of loss of consciousness, it is necessary to administer 40-80 ml of a 40% dextrose (glucose) solution intravenously, followed by an infusion of a 5-10% dextrose solution. Then you can additionally administer 1 mg of glucagon intravenously, intramuscularly or subcutaneously. If the patient does not regain consciousness, it is recommended to repeat these steps. If there is no effect, intensive therapy is indicated.
Impact on the ability to drive vehicles and operate machinery
When taking the drug Glibomet®, hypoglycemia may develop, and, as a result, a decrease in the ability to concentrate attention and the speed of psychomotor reactions, therefore, during treatment with the drug, caution should be exercised when driving vehicles, machinery and engaging in potentially hazardous activities.
Use of the drug Glibomet
The daily dose and duration of use of the drug is determined individually by the doctor according to the patient’s metabolic state. The starting dose for adults is usually 2 tablets per day (take 1 tablet in the morning and evening with meals); the daily dose should not exceed 6 tablets (2 tablets 3 times a day with meals). Prescribed in the minimum effective dose to ensure adequate control of glycemic levels. The daily dose can be gradually reduced over time until the minimum dose sufficient to control blood glucose levels is reached.
Contraindications to the use of the drug Glibomet
Hypersensitivity to glibenclamide, metformin or any of the components of the drug; latent diabetes mellitus, diabetic coma or precoma; serum creatinine level 12 mg/l; history of lactic acidosis; severe liver or kidney dysfunction; treatment with diuretics or antihypertensive drugs that may cause renal impairment; intravenous urography, severe diseases of the cardiovascular system with cardiac decompensation, cardiogenic or toxic shock, impaired peripheral arterial circulation, severe respiratory diseases, chronic alcoholism, following a low-calorie diet or fasting, severe forms of degenerative diseases, acute heavy bleeding; state of shock; gangrene, period 2 days before and 2 days after surgery; During pregnancy and breastfeeding; children.
Side effects of the drug Glibomet
In rare cases, hypoglycemia may develop, especially in weakened patients, elderly people, with unusual physical activity, with irregular diet or alcohol consumption, in case of impaired liver and/or kidney function. Sometimes headaches and gastrointestinal disorders occur: nausea, anorexia, gastralgia, vomiting, diarrhea, requiring cessation of treatment. Occasionally, allergic skin reactions develop; they are usually temporary and disappear on their own with continued treatment. Cases of the possible development of metabolic acidosis described in the literature during treatment with metformin are rare. However, it has been reliably revealed that in patients with risk factors, such as renal and acute cardiovascular failure, this condition can very quickly become severe if treatment with the drug is not stopped immediately and appropriate therapeutic measures are not taken. Cases of increased serum lactic acid levels, increased lactate/pyruvate ratio, decreased blood pH and hyperazotemia have been reported (all cases described in patients with unfavorable diabetes mellitus). The development of metabolic acidosis may result from simultaneous intake of alcohol during treatment with the drug. Hematopoietic disorders are extremely rare and are usually reversible.
Special instructions for the use of the drug Glibomet
In case of concomitant diseases, injuries, surgical interventions, infections, fever, there may be a need to temporarily switch to insulin therapy in order to ensure adequate control of the patient's metabolism. The possibility of developing a disulfiram-like reaction after drinking alcohol should be taken into account. Patients with diabetes mellitus receiving Glibomet should be informed by their doctor about symptoms indicating the development of lactic acidosis, so that they can be recognized and promptly seek medical help. Patients should also inform the doctor about the occurrence of diseases accompanied by fever and/or digestive disorders. Kidney function must be monitored before prescribing Glibomet to a patient, every 8 weeks for the first 6 months of therapy and then once every six months. At the slightest suspicion of the appearance of symptoms of lactic acidosis, treatment should be stopped and the patient should be hospitalized. The use of the drug should be discontinued 48 hours before angiographic or urographic examination; The drug is resumed 48 hours after administration. Use during pregnancy and lactation. The use of the drug is contraindicated. Children. The use of the drug is contraindicated. The ability to influence reaction speed when driving vehicles or working with other mechanisms. The patient should be informed about the possibility of hypoglycemia and, as a result, a decrease in his ability to concentrate and react quickly.
Glibomet®
Patients must strictly follow the doctor's recommendations regarding the dose of Glibomet®, as well as accompanying nutrition, exercise regimen and self-monitoring of plasma glucose concentrations.
Lactic acidosis is a rare and life-threatening pathological condition characterized by the accumulation of lactic acid in the blood, one of the reasons for the development of which may be a high concentration of metformin in the blood.
The reported cases of lactic acidosis in patients receiving metformin were observed mainly in patients with diabetes mellitus with severe heart and/or renal failure.
Prevention of lactic acidosis involves identifying all associated risk factors, such as decompensated diabetes mellitus, ketosis, prolonged fasting, excessive alcohol consumption, liver failure and any condition associated with hypoxia.
Because the drug Glibomet® contains glibenclamide, then taking the drug may be accompanied by a risk of hypoglycemia in the patient.
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; some endocrine disorders: insufficiency of the thyroid gland, pituitary gland and adrenal glands; overdose of the drug Glibomet® (see section “Overdose”); simultaneous use of certain medications (see section “Interaction with other medications”).
In elderly patients and patients receiving beta-blockers, clonidine, reserpine, guanethidine, sympathomimetics, it is possible to mask some symptoms of hypoglycemia, such as palpitations and tachycardia.
This treatment can only be prescribed to a patient who adheres to a regular diet (including breakfast).
When taking Glibomet®, serum creatinine concentrations should be regularly monitored:
- at least once a year in patients with normal renal function;
- at least 2-4 times a year in patients with serum creatinine concentrations close to the upper limit of normal, as well as in elderly patients.
Caution should be exercised in cases where there is a risk of impaired renal function, for example, when prescribing antihypertensive drugs or diuretics, as well as when using non-steroidal anti-inflammatory drugs (NSAIDs), especially at the beginning of therapy.
Patients should be taught to recognize the symptoms of lactic acidosis and hypoglycemia (see Overdose section) so that they can immediately inform the doctor of their occurrence.
When visiting other medical institutions, the patient must notify the doctor about the presence of diabetes mellitus.
The use of Glibomet® should be discontinued 48 hours before and within 48 hours after radioisotope or x-ray examination with intravenous administration of iodine-containing contrast agents (angiography or urography) and replaced with therapy with other hypoglycemic agents (for example, insulin).
In case of injuries, infectious diseases, febrile conditions and surgical interventions, it may be necessary to temporarily use insulin to sufficiently maintain metabolic regulation.
The use of Glibomet® should be discontinued 48 hours before planned surgery with spinal or epidural anesthesia. Therapy should be continued after resumption of oral nutrition, or no earlier than 48 hours after surgery, provided that normal renal function is confirmed.
Ethanol can provoke the development of hypoglycemia, as well as a disulfiram-like reaction (alcohol intolerance, characterized by nausea, vomiting, abdominal pain, a feeling of heat on the face and upper body, tachycardia, dizziness, headache), so you should refrain from drinking alcohol while using the drug Glibomet®.
In patients with glucose-6-phosphate dehydrogenase deficiency, the use of sulfonylurea drugs can lead to the development of hemolytic anemia, so special care should be taken when using the drug Glibomet® in this category of patients and it is better to use hypoglycemic agents that are not sulfonylurea derivatives.
Interactions of the drug Glibomet
The hypoglycemic effect of glibenclamide is potentiated by dicumarol and its derivatives, MAO inhibitors, sulfonamide drugs, phenylbutazone and its derivatives, chloramphenicol, cyclophosphamide, probenecid, pheniramine, salicylates, miconazole for oral use, sulfinpyrazone, perhexillin, and alcohol consumption in high doses. The effect of glibenclamide may be weakened by concomitant use of epinephrine, corticosteroids, oral contraceptives, thiazide diuretics and barbiturates. Caution should be exercised when used concomitantly with beta-adrenergic blockers. It must be taken into account that biguanides can enhance the effect of anticoagulants.
Glibomet n40 film-coated tablets
pharmachologic effect
Oral hypoglycemic drug of combined composition. Glibenclamide, which is part of the drug, enhances the secretion of insulin by beta cells of the pancreas, probably increases the sensitivity of peripheral tissues to insulin by stimulating the activity of tyrosine kinase of insulin receptors, and suppresses gluconeogenesis and glycogenolysis in the liver. Metformin reduces tissue insulin resistance by increasing peripheral glucose utilization and increasing cellular glucose uptake. Reduces hepatic gluconeogenesis. Reduces the absorption and utilization of glucose by the intestinal mucosa. In addition, it reduces body weight and prevents its increase, normalizes lipid metabolism, and enhances fibrinolysis processes. The drug is effective in non-insulin-dependent diabetes mellitus as a primary combination therapy when diet therapy is ineffective, late diagnosis of diabetes mellitus, and initially aggressive diabetes. The drug is also effective in non-insulin-dependent diabetes mellitus as a secondary combination therapy when monotherapy in high doses is ineffective, in individuals with preserved insulin secretion with secondary resistance to sulfonylurea derivatives or metformin. The drug Glibomet, being a rational combination of two active substances, optimally combines their properties. At the same time, this combination makes it possible to achieve the required hypoglycemic effect with a lower dose of each component and reduce the risk of side effects (compared to monotherapy), which allows the drug to be used when there are relative contraindications to oral hypoglycemic therapy.
Pharmacokinetics
Data on the pharmacokinetics of the drug Glibomet are not provided.
Indications
– non-insulin-dependent diabetes mellitus (type II) with ineffective diet therapy or monotherapy with oral hypoglycemic drugs.
Dosage regimen
The dosage regimen and duration of treatment are set individually depending on the state of the patient’s carbohydrate metabolism and the level of glucose in the blood. The initial dose is, as a rule, 1-3 tablets/day with further gradual selection of an effective dose until stable compensation of the disease is achieved. The optimal regimen is to take the drug 2 times a day (morning and evening) with meals. The maximum daily dose is 5 tablets.
Side effect
Metabolism: possible hypoglycemia, increased blood lactate levels. From the digestive system: rarely - nausea, vomiting; in some cases - cholestatic jaundice, hepatitis. From the hematopoietic system: rarely - a decrease in the number of platelets, leukocytes, erythrocytes; in some cases - hemolytic or megaloblastic anemia. From the central nervous system and peripheral nervous system: headache, dizziness, weakness; rarely - paresis, sensory disturbances. Allergic reactions: rarely - urticaria, increased body temperature, joint pain, the appearance of protein in the urine. Dermatological reactions: rarely - photosensitivity.
Contraindications
– insulin-dependent diabetes mellitus (type I); – hypoglycemia; – diabetic ketoacidosis, diabetic precoma, coma; – history of lactic acidosis; – severe diseases accompanied by impaired liver and/or kidney function; – pregnancy; – lactation (breastfeeding); – hypersensitivity to the components of the drug.
Pregnancy and lactation
The drug is contraindicated for use during pregnancy and lactation (breastfeeding).
special instructions
If symptoms of lactic acidosis appear (vomiting, abdominal pain, general weakness, muscle cramps), you should stop taking the drug and carry out appropriate therapy. The patient should be warned that while taking the drug it is very important to follow a diet and self-monitor blood glucose levels.
Overdose
Symptoms: the described side effects may increase. Treatment: if necessary, carry out symptomatic therapy.
Drug interactions
The hypoglycemic effect of Glibomet may be enhanced by concomitant use of dicoumarol and its derivatives, beta-blockers, cimetidine, oxytetracycline, allopurinol, MAO inhibitors, sulfonamides, phenylbutazone and its derivatives, chloramphenicol, probenecid, salicylates, miconazole (for oral administration), sulfinpyrazone and ethanol in large quantities. The effect of Glibomet may be reduced when used simultaneously with adrenaline, corticosteroids, oral contraceptives, thyroid hormones, thiazide diuretics and barbiturates. When used simultaneously with Glibomet, the effect of anticoagulants may be enhanced. Concomitant use of Glibomet with cimetidine may increase the risk of developing lactic acidosis.
Storage conditions and periods
Shelf life: 3 years. Conditions for dispensing from pharmacies The drug is dispensed with a prescription.
