Amaryl - instructions for use, analogs, reviews and release forms (1 mg, 2 mg, 3 mg and 4 mg, M with Metformin 250 mg and 500 mg) medications for the treatment of non-insulin-dependent type 2 diabetes in adults, children and pregnancy . Composition

In this article, you can read the instructions for using the drug Amaryl. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors specialists on the use of Amaril in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Amaril in the presence of existing structural analogues. Use for the treatment of non-insulin-dependent diabetes mellitus type 2 in adults, children, as well as during pregnancy and lactation.Composition of the preparation.

 

Amaryl - oral hypoglycemic drug, derivative of sulfonylureas of the 3rd generation.

 

Glimepiride (the active substance of the drug Amaryl) reduces the concentration of glucose in the blood, mainly by stimulating the release of insulin from the beta cells of the pancreas. Its effect is mainly associated with improving the ability of beta cells of the pancreas to respond to physiological stimulation with glucose. Compared to glibenclamide, Glimepiride in low doses causes the release of less insulin when the blood glucose concentration is approximately the same. This fact testifies in favor of the presence in glimepiride of extrapancreatic hypoglycemic effects (increase of sensitivity of tissues to insulin and insulinomimetic effect).

 

Secretion of insulin. Like all other derivatives of sulfonylurea, glimepiride regulates insulin secretion through interaction with ATP-sensitive potassium channels on beta-cell membranes. Unlike other derivatives of sulfonylurea, glimepiride selectively binds to a protein with a molecular weight of 65 kilodaltons located in the membranes of beta cells of the pancreas.This interaction of glimepiride with the protein binding it regulates the opening or closing of ATP-sensitive potassium channels.

 

Glimepiride covers potassium channels. This causes depolarization of beta cells and leads to the discovery of voltage-sensitive calcium channels and the intake of calcium into the cell. As a result, an increase in the intracellular calcium concentration activates the secretion of insulin by exocytosis.

 

Glimepiride is much faster and accordingly more often comes into contact and is released from the bond with the protein that binds it than glibenclamide. It is suggested that this property of a high rate of exchange of glimepiride with the protein binding to it causes its pronounced effect of sensitizing beta cells to glucose and their protection against desensitization and premature exhaustion.

 

The effect of increasing the sensitivity of tissues to insulin. Amaryl enhances insulin effects on glucose uptake by peripheral tissues.

 

Insulinomimetichesky effect. Glimepiride has effects similar to insulin effects on glucose uptake by peripheral tissues and glucose output from the liver.

 

Absorption of glucose by peripheral tissues is carried out by its transport inside the muscle cells and adipocytes. Glimepiride directly increases the amount of glucose-transporting molecules in the plasma membranes of muscle cells and adipocytes. Increasing the intake of glucose into the cells leads to the activation of glycosylphosphatidylinositol-specific phospholipase C. As a result, the intracellular calcium concentration decreases, causing a decrease in the activity of protein kinase A, which in turn leads to stimulation of glucose metabolism.

 

Glimepiride inhibits glucose output from the liver by increasing the concentration of fructose-2,6-bisphosphate, which inhibits gluconeogenesis.

 

Effect on platelet aggregation. Amaryl reduces the aggregation of platelets. This effect appears to be related to the selective inhibition of COX, which is responsible for the formation of thromboxane A, an important endogenous platelet aggregation factor.

 

Anti-atherogenic action. Glimepiride promotes normalization of lipid content, reduces the level of malonic aldehyde in the blood, which leads to a significant decrease in lipid peroxidation.In animals, glimepiride leads to a significant decrease in the formation of atherosclerotic plaques.

 

Reducing the severity of oxidative stress, which is constantly present in patients with type 2 diabetes mellitus. Glimepiride increases the level of endogenous alpha-tocopherol, the activity of catalase, glutathione peroxidase and superoxide dismutase.

 

Cardiovascular effects. Through ATP-sensitive potassium channels, the sulfonylureas derivatives also affect the cardiovascular system. Compared with the traditional derivatives of sulfonylureas, glimepiride has a significantly lower effect on the cardiovascular system, which can be explained by the specific nature of its interaction with the ATP-sensitive potassium channel protein binding to it.

 

In healthy volunteers, the minimum effective dose of Amaril is 0.6 mg. The effect of glimepiride is dose-dependent and reproducible. Physiological response to physical activity (reduced secretion of insulin) with the intake of glimepiride is preserved.

 

There are no significant differences in the effect, depending on whether the drug was taken 30 minutes before meals or just before meals.In patients with diabetes mellitus, sufficient metabolic control can be achieved within 24 hours with a single administration of the drug. Moreover, in a clinical trial, sufficient metabolic control was also achieved in 12 of 16 patients with renal insufficiency (CK 4-79 ml / min).

 

Combination therapy with metformin. In patients with insufficient metabolic control with the maximum dose of glimepiride, combined therapy with glimepiride and Metformin may be initiated. In two studies, combined therapy showed improved metabolic control compared with that in the treatment of each of these drugs individually.

 

Combination therapy with insulin. In patients with insufficient metabolic control, concomitant insulin therapy can be initiated with maximum dose glimepiride. Based on the results of two studies using this combination, the same improvement in metabolic control is achieved as with the use of only one insulin. However, combined therapy requires a lower dose of insulin.

 

Composition

 

Glimepiride + auxiliary substances (Amaryl).

 

Glimepiride micronized + Metformin hydrochloride + auxiliary substances (Amaryl M).

 

Pharmacokinetics

 

Glimepiride

 

With repeated administration of the drug inside at a daily dose of 4 mg Cmax in the blood serum is achieved after about 2.5 hours and is 309 ng / ml. There is a linear relationship between the dose and Cmax of glimepiride in blood plasma, as well as between dose and AUC. When ingested glimepiride, its absolute bioavailability is complete. Eating does not have a significant effect on absorption, except for a slight slowing of its speed. Glimepiride is excreted in breast milk and penetrates the placental barrier. Glimepiride poorly penetrates the blood-brain barrier (BBB).

 

Comparison of single and multiple (2 times per day) glimepiride did not reveal significant differences in pharmacokinetic parameters, and their variability in different patients was insignificant. A significant accumulation of glimepiride was absent.

 

Glimepiride is metabolized in the liver with the formation of two metabolites - hydroxylated and carboxylated derivatives, which are found in urine and in stool.

 

After a single oral intake, 58% of glimepiride is excreted by the kidneys (in the form of metabolites) and 35% by the intestine. An unchanged active substance in the urine is not detected.

 

In patients of different sex and different age groups, the pharmacokinetic parameters of glimepiride are the same.

 

Metformin

 

After ingestion, metformin is absorbed from the digestive tract quite full. With simultaneous intake of food, absorption of metformin decreases and slows down. Metformin is rapidly distributed into tissues, practically does not bind to plasma proteins. Exposed to a very weak degree of metabolism. It is excreted by the kidneys.

 

Pharmacokinetics of Amaril M with fixed doses of glimepiride and metformin

 

The Cmax and AUC values ​​for a fixed-dose combination drug (glimepiride tablet 2 mg + metformin 500 mg) meet the bioequivalence criteria when compared to the same indicators when taken in the same combination as separate preparations (glimepiride 2 mg tablet and metformin 500 tablet mg).

 

In addition, a dose-proportional increase in Cmax and AUC of glimepiride was shown with an increase in its dose in fixed-dose combination preparations from 1 mg to 2 mg with a constant dose of metformin (500 mg) in these preparations.

 

In addition, there were no significant differences in safety, including the profile of adverse effects, between patients taking Amaril M 1 mg + 500 mg and patients taking Amaril M 2 mg + 500 mg.

 

Indications

 

Treatment of type 2 diabetes mellitus (in addition to diet, exercise and weight loss):

• non-insulin-dependent diabetes mellitus type 2 (as a monotherapy or as part of a combination therapy with metformin or insulin);
• when glycemic control can not be achieved with monotherapy with glimepiride or metformin (Amaryl M);
• when replacing the combined therapy with glimepiride and metformin for the administration of one combined drug (Amaryl M).

 

Forms of release

 

Tablets 1 mg, 2 mg and 3 mg (Amaryl).

 

Tablets coated with 1 mg + 250 mg, 2 mg + 500 mg (Amaryl M with Metformin).

 

Instructions for use and dosage

 

Amaryl tablets

 

As a rule, the dose of Amaril is determined by the target concentration of glucose in the blood. The drug should be used in a minimum dose sufficient to achieve the necessary metabolic control.

 

During treatment with the drug Amaryl it is necessary to regularly determine the level of glucose in the blood.In addition, regular monitoring of the level of glycosylated hemoglobin is recommended.

 

Violation of the drug, for example, skipping the next dose, should not be replenished by subsequent taking the drug at a higher dose.

 

The doctor should instruct the patient in advance about the actions to be taken when mistakes are made in taking Amaril drug (in particular, if you miss a regular dose or if you miss a meal), or in situations where it is not possible to take the drug.

 

Tablets Amaril should be taken whole, without chewing, squeezed with a sufficient amount of liquid (about 1/2 cup). If necessary, Amaryl tablets can be divided along the risks into two equal parts.

 

The initial dose of Amaril is 1 mg 1 time per day. If necessary, the daily dose can be gradually increased (at intervals of 1-2 weeks) under regular monitoring of blood glucose and in the following order: 1 mg-2 mg-3 mg-4 mg-6 mg (-8 mg) per day .

 

In patients with well-controlled type 2 diabetes mellitus, the daily dose of the drug is usually 1-4 mg.A daily dose of more than 6 mg is more effective only in a small number of patients.

 

The time of taking Amaril and the distribution of doses during the day the doctor determines, taking into account the lifestyle of the patient (meal time, the number of physical exertions). The daily dose is prescribed in a single dose, usually just before a full breakfast or, if the daily dose has not been taken, immediately before the first main meal. It is very important not to skip meals after taking the Amaryl tablets.

 

Because improvement of metabolic control is associated with an increase in insulin sensitivity, during treatment, a decrease in the requirement for glimepiride is possible. In order to avoid the development of hypoglycemia, it is necessary to reduce the dose in a timely manner or stop taking Amaril.

 

Conditions in which glimepiride dose adjustment may also be required:

• decreased body weight;
• changes in lifestyle (changing diet, meal time, amount of exercise);
• the occurrence of other factors that lead to a predisposition to the development of hypoglycemia or hyperglycemia.

 

Treatment with glimepiride is usually carried out for a long time.

 

Transfer of the patient from taking another oral hypoglycemic drug to receive Amaril

 

There is no exact relationship between the doses of Amaril and other oral hypoglycemic drugs. When transferring from such drugs to Amaryl, the recommended initial daily dose of the latter is 1 mg (even if the patient is transferred to Amaril with a maximum dose of another oral hypoglycemic drug). Any increase in the dose should be carried out in stages, taking into account the reaction to glimepiride in accordance with the recommendations given above. It is necessary to take into account the intensity and duration of the effect of the previous hypoglycemic agent. It may be necessary to interrupt treatment to avoid an additive effect that increases the risk of developing hypoglycemia.

 

Use in combination with metformin

 

In patients with insufficiently controlled diabetes mellitus, when taking glimepiride or metformin at the maximum daily doses, a combination of these two drugs can be started.In this case, the previous treatment with either glimepiride or metformin is continued at the same doses, and an additional intake of metformin or glimepiride begins with a low dose, which is then titrated, depending on the target level of metabolic control, up to the maximum daily dose. Combination therapy should be started under strict medical supervision.

 

Use in combination with insulin

 

Patients with insufficiently controlled diabetes mellitus while taking glimepiride in the maximum daily dose can be simultaneously assigned to insulin. In this case, the last dose of glimepiride prescribed to the patient remains unchanged. In this case, treatment with insulin begins with low doses, which gradually increase the concentration of glucose in the blood under control. Combined treatment is conducted under close medical supervision.

 

Amaryl M Tablets

 

Typically, the dose of Amaril M is determined by the target glucose concentration in the patient's blood. Use the smallest dose sufficient to achieve the necessary metabolic control.

 

During treatment with Amaril M it is necessary to regularly determine the concentration of glucose inblood. In addition, regular monitoring of the percentage of glycosylated hemoglobin in the blood is recommended.

 

Incorrect drug intake, for example, skipping the next dose, should never be replenished by the subsequent administration of a higher dose.

 

The patient's actions in case of mistakes in taking the drug (in particular, if the next dose is missed or when meals are skipped), or in situations where there is no possibility to take the drug, should be discussed by the patient and the doctor in advance.

 

Because improved metabolic control is associated with an increase in the sensitivity of tissues to insulin, then during treatment with Amaril M, the demand for glimepiride may decrease. In order to avoid the development of hypoglycemia, it is necessary to reduce the dose in a timely manner or stop taking the drug Amaril M.

 

Amaryl M should be taken 1 or 2 times a day during meals.

 

The maximum dose of metformin per dose is 1000 mg. The maximum daily dose: for glimepiride - 8 mg, for metformin - 2000 mg.

 

Only a small number of patients have a more effective daily glimepiride dose of more than 6 mg.

 

In order to avoid the development of hypoglycemia, the initial dose of Amaril M should not exceed the daily doses of glimepiride and metformin, which the patient is already taking. When transferring patients from taking a combination of certain preparations of glimepiride and metformin to Amaryl M, its dose is determined based on the already taken doses of glimepiride and metformin in the form of separate preparations. If it is necessary to increase the dose, the daily dose of Amaril M should be titrated in steps of only 1 tablet of Amaril M 1 mg + 250 mg or 1/2 tablet of Amaril M 2 mg + 500 mg.

 

Usually treatment with Amaril M is carried out for a long time.

 

It is known that metformin is excreted primarily by the kidneys, and since the risk of developing severe adverse reactions to metformin in patients with impaired renal function is higher, it can be used only in patients with normal renal function. Due to the fact that with age, the kidney function decreases, in elderly patients, metformin should be used with caution. Care should be taken to select the dose and ensure thorough and regular monitoring of kidney function.

 

Side effect

• the development of hypoglycemia, which can be protracted;
• headache;
• an acute sense of hunger;
• nausea, vomiting;
• diarrhea;
• flatulence;
• anorexia;
• metallic taste in the mouth;
• weakness;
• lethargy;
• sleep disorders;
• anxiety;
• aggressiveness;
• decreased concentration of attention;
• decrease in vigilance and slowing of psychomotor reactions;
• depression;
• confusion of consciousness;
• speech disorders;
• aphasia;
• visual impairment;
• tremor;
• paresis;
• impaired sensitivity;
• dizziness;
• helplessness;
• loss of self-control;
• delirium;
• convulsions;
• Drowsiness and loss of consciousness until the development of coma;
• shallow breathing and bradycardia;
• increased sweating;
• stickiness of skin;
• increased anxiety;
• tachycardia;
• increased blood pressure;
• a feeling of intense heartbeat;
• angina pectoris;
• heart rhythm disturbances;
• temporary visual impairment, especially at the beginning of treatment, due to fluctuations in blood glucose concentration;
• hepatitis;
• thrombocytopenia, leukopenia or hemolytic anemia, erythrocytopenia, granulocytopenia, agranulocytosis, or pancytopenia;
• decrease of vitamin B12 concentration in blood serum due to reduction of its intestinalabsorption;
• allergic or pseudo-allergic reactions (eg, itching, hives, or rashes);
• anaphylactic shock;
• allergic vasculitis;
• photosensitization;
• lactic acidosis.

 

Contraindications

• type 1 diabetes mellitus;
• diabetic ketoacidosis (including in the anamnesis), diabetic coma and precoma;
• acute or chronic metabolic acidosis;
• severe impairment of liver function (no experience of use, insulin therapy is necessary to ensure adequate glycemic control);
• patients who are on hemodialysis (lack of experience of use);
• renal failure and impaired renal function;
• acute conditions in which the kidney function may be impaired (dehydration, severe infections, shock, intravascular injection of iodine-containing contrast agents);
• acute and chronic diseases that can cause tissue hypoxia (cardiac or respiratory failure, acute and subacute myocardial infarction, shock);
• propensity to develop lactic acidosis, lactic acidosis in the anamnesis;
• stressful situations (severe injuries, burns, surgical operations, severe infections with fever, septicemia);
• starvation, compliance with the hypocaloric diet (less than 1000 calories per day);
• a violation of absorption of food and drugs in the digestive tract (with intestinal obstruction, intestinal paresis, diarrhea, vomiting);
• chronic alcoholism, acute alcohol intoxication;
• deficiency of lactase, galactose intolerance, glucose-galactose malabsorption;
• pregnancy, pregnancy planning;
• the period of breastfeeding;
• children and adolescents under 18 years of age (inadequate clinical experience);
• hypersensitivity to the components of the drug;
• hypersensitivity to sulfonylurea derivatives, sulfanilamide preparations or biguanides.

 

Application in pregnancy and lactation

 

Amaryl and Amaryl M are contraindicated in pregnancy. In the case of a planned pregnancy or at the onset of pregnancy, a woman should be transferred to insulin therapy.

 

It has been established that glimepiride is excreted in breast milk. During lactation, a woman should be transferred to insulin or to stop breastfeeding.

 

Use in children

 

A study of the safety and efficacy of the drug in children and adolescents under the age of 18 withType 2 diabetes mellitus was not performed. Use of the drug is contraindicated in this age group of patients.

 

Application in elderly patients

 

Caution should be used in elderly patients (they often have an asymptomatic decrease in kidney function), in situations where kidney function may worsen, such as the onset of taking antihypertensive drugs or diuretics, as well as non-steroid anti-inflammatory drugs (NSAIDs) (increased risk development of lactic acidosis and other side effects of metformin).

 

special instructions

 

In special clinical stress conditions such as trauma, surgery, infection with febrile temperature, metabolic control may be impaired in patients with diabetes mellitus, therefore, a temporary transfer to insulin therapy may be required to maintain adequate metabolic control.

 

In the first weeks of treatment, there may be an increased risk of developing hypoglycemia, which requires a particularly careful control of the concentration of glucose in the blood.

 

Factors that contribute to the risk of developing hypoglycemia include:

• unwillingness or inability of the patient (more often observed in elderly patients) to cooperate with a doctor;
• malnutrition, irregular eating or skipping meals;
• an imbalance between exercise and carbohydrate intake;
• changing diet;
• alcohol consumption, especially when combined with meals;
• severe renal dysfunction;
• severe violations of liver function (in patients with severe impairment of liver function, a transfer to insulin therapy is indicated, at least until metabolic control is achieved);
• an overdose of glimepiride;
• some decompensated endocrine disorders that disrupt carbohydrate metabolism or adrenergic counterregulation in response to hypoglycemia (for example, certain disorders of the thyroid gland and anterior pituitary gland, insufficiency of the adrenal cortex);
• simultaneous intake of certain medicines;
• reception glimepirida in the absence of indications for its reception.

 

Treatment with sulfonylurea derivatives, including glimepiride, can lead to the development of hemolytic anemia,Therefore, in patients with glucose-6-phosphate dehydrogenase deficiency, special care should be taken when administering glimepiride, preferably hypoglycemic agents that are not sulfonylurea derivatives.

 

In the case of the above risk factors for hypoglycemia, as well as when intercurrent illness occurs during treatment or lifestyle changes, the patient may need to adjust the dose of Amaril or the whole therapy.

 

Symptoms of hypoglycemia arising from adrenergic counter-regulating of the organism in response to hypoglycemia may be mild or absent with gradual development of hypoglycemia, in elderly patients, in patients with autonomic nervous system disorders or in patients receiving beta-blockers, clonidine, reserpine , guanethidine and other sympatholytic agents.

 

Hypoglycemia can be quickly eliminated by immediate intake of rapidly digesting carbohydrates (glucose or sucrose). As with the administration of other sulfonylureas, despite initial successful reduction of hypoglycemia, hypoglycemia may resume.Therefore, patients should remain under constant supervision. In severe hypoglycemia, immediate treatment and supervision of the physician, and in some cases, hospitalization of the patient, are required.

 

During treatment, Amaril requires regular monitoring of liver function and peripheral blood pattern (especially the number of leukocytes and platelets).

 

Such side effects as severe hypoglycemia, severe changes in the blood picture, severe allergic reactions, liver failure may pose a threat to life, therefore, if such reactions develop, the patient should immediately inform the attending physician about them, stop taking the medication and not resume the appointment without the doctor's advice .

 

Impact on the ability to drive vehicles and manage mechanisms

 

At the beginning of treatment, after a change in treatment or with an irregular intake of glimepiride, there may be a decrease in the concentration of attention and speed of psychomotor reactions caused by hypo- or hyperglycemia. This can adversely affect the ability to drive vehicles or to manage various machines and mechanisms.

 

Drug Interactions

 

Interaction of glimepiride with other drugs

 

When the patient taking glimepiride simultaneously prescribes or abolishes other medications, undesirable reactions are possible: an increase or decrease in the hypoglycemic effect of glimepiride. Based on the clinical experience with glimepiride and other sulfonylureas, the following drug interactions should be considered.

 

With drugs that are inducers and inhibitors of the CYP2C9 isoenzyme: glimepiride is metabolized with the participation of the CYP2C9 isoenzyme. Its metabolism is influenced by the simultaneous use of inducers of the isoenzyme CYP2C9, for example, rifampicin (the risk of a decrease in the hypoglycemic effect of glimepiride when used simultaneously with inducers of the isoenzyme CYP2C9 and an increased risk of hypoglycemia if it is abolished without correction of the glimepiride dose) and inhibitors of the CYP2C9 isoenzyme, for example, Fluconazole increased risk of developing hypoglycemia and side effects of glimepiride when taken concomitantly with inhibitors of the isoenzyme CYP2C9 and the risk of its reduction by hypoglycemia and their effect on cancellation without correction of glimepiride dose).

 

With drugs that enhance the hypoglycemic effect of glimepiride: insulin and hypoglycemic drugs for oral administration, ACE inhibitors, anabolic steroids, male sex hormones, chloramphenicol, indirect anticoagulants, coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine, pheniramidol, fibrates, fluoxetine, guanethidine, ifosfamide, MAO inhibitors, miconazole, fluconazole, aminosalicylic acid, Pentoxifylline (high doses parenterally), phenylbutazone, azapropezone, oxyphenbutazone, probenecid, antimi detail drugs quinolone derivatives, salicylates, sulfinpyrazone, clarithromycin, sulfa antimicrobials, tetracyclines, tritokvalin, trofosfamide: increased risk of hypoglycemia, while the use of these drugs with glimepiride and the risk of deterioration of glycemic control at their cancellation without correction dose of glimepiride.

 

With drugs that reduce hypoglycemic effects: acetazolamide, barbiturates, glucocorticosteroids (GCS), diazoxide, diuretics, epinephrine (adrenaline) or other sympathomimetics, glucagon, laxatives (long-term use),nicotinic acid (high doses), estrogens, progestogens, phenothiazines, phenytoin, rifampicin, thyroid hormones: the risk of worsening glycemic control when combined with these drugs and increasing the risk of hypoglycemia if they are canceled without correction of the dose of glimepiride.

 

With blockers of histamine H2 receptors, beta adrenoblockers, clonidine, reserpine, guanethidine: it is possible both to increase and decrease the hypoglycemic effect of glimepiride. A careful monitoring of the concentration of glucose in the blood is necessary. Beta-blockers, clonidine, guanethidine and reserpine as a result of blocking the reactions of the sympathetic nervous system in response to hypoglycemia can make the development of hypoglycemia more inconspicuous for the patient and the doctor and thereby increase the risk of its occurrence.

 

With ethanol: Acute and chronic use of ethanol may unpredictably either weaken or enhance the hypoglycemic effect of glimepiride.

 

With indirect anticoagulants, coumarin derivatives: glimepiride can both enhance and reduce the effects of indirect anticoagulants, coumarin derivatives.

 

With sequestrants of bile acids: kolesevelam binds with glimepiride and reduces the absorption of glimepiride from the digestive tract. In the case of the use of glimepiride, no interaction is observed at least 4 hours before the administration of colesevelam. Therefore, glimepiride must be taken at least 4 hours prior to taking kolesevelam.

 

Interaction of metformin with other drugs

 

Unrecommended combinations

 

With ethanol (alcohol): with acute alcohol intoxication, the risk of lactic acidosis increases, especially in case of missing or insufficient food intake, the presence of liver failure. Avoiding alcohol (ethanol) and ethanol-containing drugs should be avoided.

 

With iodine-containing contrast agents: intravascular injection of iodine-containing contrast agents may lead to the development of renal failure, which in turn can lead to the accumulation of metformin and an increased risk of lactic acidosis. Metformin should be discontinued before or during the study and not resumed within 48 hours after it; resumption of metformin is possible only after research and obtaining normal indicators of kidney function.

 

With antibiotics that have a pronounced nephrotoxic effect (gentamicin): an increased risk of developing lactic acidosis.

 

Combinations of metformin preparations that require caution

 

With GCS (systemic and topical administration), beta2-adrenostimulants and diuretics with internal hyperglycemic activity: the patient should be informed of the need for more frequent monitoring of morning blood glucose concentration, especially at the onset of combination therapy. You may need to adjust the dosage of hypoglycemic therapy during or after the withdrawal of the above drugs.

 

With ACE inhibitors: ACE inhibitors can reduce the concentration of glucose in the blood. It may be necessary to adjust the dosage of hypoglycemic therapy during or after the withdrawal of ACE inhibitors.

 

With drugs that enhance the hypoglycemic effect of metformin: insulin, sulfonylurea drugs, anabolic steroids, guanethidine, salicylates (including acetylsalicylic acid), beta-adrenoblockers (including propranolol), MAO inhibitors: in the case of simultaneous use of these drugs with metformin requires close monitoring of the patientand control the concentration of glucose in the blood, since it is possible to increase the hypoglycemic effect of metformin.

 

With drugs that reduce the hypoglycemic effect of metformin: epinephrine, GCS, thyroid hormones, estrogens, pyrazinamide, isoniazid, nicotinic acid, phenothiazines, thiazide diuretics and diuretics of other groups, oral contraceptives, phenytoin, sympathomimetics, slow calcium channel blockers: in case of simultaneous application These preparations with metformin require close monitoring of the patient and monitoring of blood glucose concentration, possibly weakening hypoglycemic action.

 

Interaction, which should be taken into account

 

With furosemide: in a clinical study on the interaction of metformin and Furosemide with their single administration in healthy volunteers, it was shown that the simultaneous use of these drugs affects their pharmacokinetic indices. Furosemide increased Cmax of metformin in blood plasma by 22%, and AUC by 15% without any significant changes in renal clearance of metformin. When used with metformin Cmax and AUC furosemide decreased by 31% and 12%, respectively,compared with furosemide monotherapy, and terminal T1 / 2 decreased by 32% without any significant changes in furosemide renal clearance. Information on the interaction of metformin and furosemide with long-term use is absent.

 

Since nifedipine: a clinical study of interaction of metformin and Nifedipine in their single dose in healthy volunteers have shown that the simultaneous use of nifedipine increases Cmax and AUC of metformin in the plasma by 20% and 9%, respectively, and also increases the amount of metformin excreted by the kidneys. Metformin had a minimal effect on the pharmacokinetics of nifedipine.

 

With cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim and vancomycin) cationic drugs can be output via tubular secretion in the kidney, it is theoretically able to react with metformin as a result of competition for the common tubular transport system. This interaction between metformin and oral cimetidine was observed in healthy volunteers in clinical studies of the interaction of metformin and cimetidine in single and multiple applications,where there was a 60% increase in Cmax in plasma and the total concentration of metformin in the blood and a 40% increase in plasma and total AUC metformin. At once reception of changes T1 / 2 was not. Metformin did not affect the pharmacokinetics of cimetidine. Despite the fact that this interaction remains purely theoretical (with the exception of cimetidine), careful monitoring of patients and correction of the dose of metformin and / or the drug interacting with it should be carried out in the case of simultaneous administration of cationic drugs released from the body by the secretory system of the proximal tubules of the kidneys.

 

With propranolol, ibuprofen: no changes in their pharmacokinetic parameters were observed in healthy volunteers in studies on a single dose of metformin and propranolol, as well as metformin and ibuprofen.

 

Analogues of the drug Amaryl

 

Structural analogs for the active substance:

• Amaryl M;
• Glemaz;
• Glemauno;
• Glimepiride;
• Glumex;
• Meglimide.

 

Analogues on the pharmacological group (hypoglycemic agents):

• Avandamet;
• Antidiab;
• Arfazetine;
• Astroson;
• Bagomet;
• Bagomet Plus;
• Victoria;
• Galvus;
• Galvus Met;
• Hillemal;
• Glemaz;
• Glybenez;
• Glybenez retard;
• Glibenclamide;
• Glidiab;
• Gliclazide;
• Glicon;
• Glimepiride;
• Glitisol;
• Gliiformin;
• Glukobay;
• Gluconorm;
• Glucophage;
• Glucophage Long;
• Guarem;
• Diabetolong;
• Diabeton;
• Diabetes;
• Diaglitazone;
• Invokana;
• Maniglid;
• Maninil;
• Meglymide;
• Metglybe;
• Metogamma;
• Metformin;
• Metformin hydrochloride;
• Novonorm;
• Novoformin;
• Pioglit;
• Reclild;
• Silubin retard;
• Siofor;
• Starlix;
• Formethine;
• Formina Pliva;
• Forsiga;
• Chloropropamide;
• Euglucon;
• Januvia.

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