Amaryl M - Instructions For Use, Price, 2 Mg + 500 Mg, Reviews, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Amaryl M

Latin name: Amaryl M

ATX code: A10BD02

Active ingredient: metformin (Metformin) + glimepiride (Glimepiride)

Manufacturer: Handok Pharmaceuticals, Co. Ltd. (The Republic of Korea)

Description and photo update: 2019-10-07

Prices in pharmacies: from 698 rubles.

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Amaryl M is a hypoglycemic combined oral agent.

Release form and composition

The drug is produced in the form of film-coated tablets: biconvex, oval, white; tablets with a dosage of 1 mg + 250 mg - with HD125 engraving on one side; tablets with a dosage of 2 mg + 500 mg - with HD25 engraving on one side and a line on the other side (10 pcs. in PVC / aluminum blister, 3 blisters in a cardboard box and instructions for use of Amaril M).

1 tablet contains:

• active ingredients: micronized glimepiride - 1 or 2 mg and metformin hydrochloride - 250 or 500 mg, respectively;
• additional components: sodium carboxymethyl starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate, crospovidone, povidone K30;
• film casing: macrogol 6000, carnauba wax, hypromellose, titanium dioxide (E171).

Pharmacological properties

Pharmacodynamics

Amaryl M is a hypoglycemic agent, which contains two active ingredients - glimepiride and metformin.

Glimepiride

Glimepiride is an oral hypoglycemic drug that is a third generation sulfonylurea derivative. The active substance has a pancreatic effect by stimulating the production and release of insulin from β-cells of the pancreas, as well as an extrapancreatic effect, improving the sensitivity of muscle and adipose (peripheral) tissues to the influence of endogenous insulin.

Representatives of sulfonylurea derivatives increase insulin production by closing adenosine triphosphate (ATP) -dependent potassium channels localized in the cytoplasmic membrane of pancreatic β-cells. This blockage of potassium channels leads to depolarization of β-cells, which promotes the opening of calcium channels and an increase in the supply of calcium to cells.

The active substance binds / detaches at a high replacement rate from the protein β-cells of the pancreas (molecular weight 65 kD / SURX), which is associated with ATP-dependent potassium channels, but unlike other sulfonylurea derivatives, the connection is carried out at a different site (protein with mol.weight 140 kD / SUR1). This activates the release of insulin by exocytosis, but the amount of insulin produced during this process is significantly lower than with the action exerted by the usual, traditionally used derivatives of sulfonylureas (glibenclamide and others). The minimal stimulating effect of glimepiride on insulin production also reduces the risk of hypoglycemia.

Glimepiride demonstrates in a more pronounced degree, when compared with traditional sulfonylurea derivatives, extrapancreatic effects, in particular, a decrease in insulin resistance, antiatherogenic, antioxidant and antiplatelet properties.

Excretion of glucose from the blood is carried out by muscle and adipose tissues with the participation of special transport proteins localized in cell membranes (GLUT1 and GLUT4). In the presence of type 2 diabetes mellitus, the transport of glucose to these tissues refers to the stage of its utilization at a limited rate. Glimepiride provides a very rapid increase in the number and activity of glucose transporter molecules (GLUT1 and GLUT4), which in turn increases glucose uptake by peripheral tissues. The active substance has a weaker inhibitory effect on the ATP-dependent potassium channels of the heart muscle cells. Against the background of treatment with glimepiride, the ability of ischemic preconditioning of the myocardium remains.

The active substance leads to an increase in the activity of phospholipase C, thus increasing the drug-induced lipo- and glycogenesis, and also suppresses the release of glucose from the liver by increasing the intracellular level of fructose-2,6-bisphosphate, which in turn inhibits gluconeogenesis.

Glimepiride selectively inhibits cyclooxygenase activity and reduces the conversion of arachidonic acid to thromboxane A ₂, which plays an important role in platelet aggregation. The agent helps to reduce the level of lipids and significantly reduces their peroxidation, which is associated with its antiatherogenic effect. As a result of the effect of the drug, the concentration of endogenous alpha-tocopherol increases, as well as the activity of glutathione peroxidase, catalase and superoxide dismutase, which reduces the severity of oxidative stress in the body, which is constantly present in type 2 diabetes.

Metformin

Metformin is a hypoglycemic drug belonging to the biguanide group, the hypoglycemic effect of which is observed only against the background of the preservation of insulin production (although reduced). The active substance does not affect the β-cells of the pancreas and does not stimulate the production of insulin, therefore, in therapeutic doses, it does not lead to the development of hypoglycemia in humans.

The mechanism of action of the drug has not yet been fully established, however, it is believed that metformin is able to enhance the effects of insulin, or potentiate the latter in the zones of peripheral receptors. The tool helps to increase the sensitivity of tissues to insulin due to an increase in the number of insulin receptors located on the surface of cell membranes. In addition, metformin slows down the process of gluconeogenesis in the liver, reduces the oxidation of fats and the formation of free fatty acids, reduces the level of triglycerides (TG), low density lipoproteins (LDL), and very low density lipoproteins (VLDL) in the blood. Metformin slightly reduces appetite and weakens the absorption of carbohydrates in the intestine. The drug helps to improve the fibrinolytic properties of blood as a result of inhibition of the tissue plasminogen activator inhibitor.

Pharmacokinetics

Glimepiride

With a course intake of the active substance in a daily dose of 4 mg, the maximum concentration (C _max) in the blood plasma is observed approximately 2.5 hours after administration and is 309 ng / ml. The relationship between the dose and C _{max of the} agent, as well as the dose and area under the concentration-time curve (AUC), are characterized by a linear relationship. When used orally, the absolute bioavailability of glimepiride is complete. The time of food intake does not have a pronounced effect on the absorption of the active substance from the gastrointestinal tract (GIT), with the exception of a slight decrease in its rate.

Glimepiride is characterized by a very low volume of distribution (V _d), approximately equal to V _{d of} albumin, as well as a high degree of binding to blood plasma proteins (more than 99%) and low clearance (about 48 ml / min).

After a single oral dose of glimepiride, 58% of the dose is excreted by the kidneys (in the form of metabolites), and 35% through the intestines. The half-life (T _½) at serum concentrations corresponding to repeated use of the drug varies from 5 to 8 hours. After taking the drug in high doses, a slight increase in T _½ was recorded. As a result of the metabolism of the drug in the liver, two inactive metabolites are formed, which are found in urine and feces. One of the metabolites is a carboxy derivative, and the other is a hydroxy derivative; after taking the active substance, the terminal T _{½ of} these biotransformation products was 5–6 and 3-5 hours, respectively.

Glimepiride is excreted in breast milk and crosses the placenta, but poorly crosses the blood-brain barrier (BBB). When comparing the pharmacokinetic parameters of the drug after its single and repeated use (2 times a day), no significant differences were found, their variability was different in different patients. No significant cumulation of the active ingredient was observed.

The pharmacokinetics of glimepiride in individuals of different sexes and different ages was similar. In the presence of functional disorders of the kidneys, with low creatinine clearance (CC), a tendency to an increase in the clearance of glimepiride and a decrease in its average serum level was recorded. These effects, presumably, are due to the faster elimination of the agent as a result of its weaker binding to plasma proteins. In patients from this group, therefore, there is no additional risk of glimepiride cumulation.

Metformin

After oral administration, metformin is completely absorbed from the gastrointestinal tract, the absolute bioavailability is approximately 50-60%. Plasma C _max (on average 2 μg / ml or 15 μmol) is observed after 2.5 hours. When taken simultaneously with food, the absorption of the active substance decreases and slows down.

Metformin practically does not form a bond with blood plasma proteins and is intensively distributed in tissues. It undergoes metabolic transformation to a very weak extent and is eliminated in the urine. In healthy volunteers, the clearance of the agent is 440 ml / min (4 times higher than CC), which indicates the presence of active tubular secretion. T _{½ of} metformin is approximately 6.5 hours, in patients with renal failure there is a possibility of its cumulation.

When using Amaryl M with fixed doses of glimepiride and metformin (2 mg + 500 mg), the C _max and AUC values meet the bioequivalence criteria when compared with the same indicators when used as separate preparations of glimepiride at a dose of 2 mg and metformin at a dose of 500 mg. There were also no significant differences in safety, including the profile of side effects, between patients receiving Amaryl M 1 mg + 500 mg and patients receiving Amaryl M 2 mg + 500 mg.

Indications for use

Amaryl M is recommended for the treatment of type 2 diabetes mellitus, as an addition to physical activity and diet in order to reduce body weight in the following cases:

• lack of an adequate level of glycemic control when using metformin or glimepiride in monotherapy;
• replacing the combined treatment with metformin and glimepiride with one combination drug.

Contraindications

Absolute:

• diabetic ketoacidosis (including history data), diabetic coma and precoma, acute / chronic metabolic acidosis;
• type 1 diabetes mellitus;
• severe functional disorders of the liver;
• impaired renal function and renal failure [plasma creatinine level ≥ 1.2 mg / dL (110 μmol / L) in women and ≥ 1.5 mg / dL (135 μmol / L) in men, or a decrease in CC] - due to the risk of developing lactic acidosis and other undesirable effects of metformin;
• being on hemodialysis (due to lack of experience in use);
• acute conditions that can lead to impaired renal function (intravascular administration of iodine-containing contrast agents, severe infections, dehydration, shock);
• a history of lactic acidosis, a tendency to develop lactic acidosis;
• acute and chronic lesions that can cause tissue hypoxia (shock, heart / respiratory failure, acute and subacute myocardial infarction);
• stressful situations (burns, severe forms of febrile infections, severe trauma, surgery, septicemia);
• violation of absorption of food and drugs in the digestive tract (against the background of diarrhea, vomiting, intestinal obstruction, intestinal paresis);
• fasting, exhaustion, adherence to a hypocaloric diet (less than 1000 calories / day);
• chronic alcoholism, acute alcohol intoxication;
• lactase deficiency, galactose intolerance, glucose-galactose malabsorption;
• age up to 18 years;
• pregnancy and the period of planning pregnancy, breastfeeding;
• hypersensitivity to any of the constituents of Amaryl M, other sulfonamides or biguanides, as well as sulfonylurea derivatives.

Relative (use Amaryl M, mainly in the first weeks of therapy, should be done with extreme caution and with constant monitoring due to the increased risk of hypoglycemia):

• poor nutrition, skipping meals, irregular meals; inability or unwillingness to cooperate with a doctor (in most cases in elderly patients); diet change; mismatch between exercise intensity and carbohydrate intake; drinking ethanol-containing drinks, especially in combination with skipping meals; violations of the liver and / or kidneys; deficiency of hormones of the adrenal cortex or the anterior pituitary gland, thyroid dysfunction and some other uncompensated endocrine disorders that affect the metabolism of carbohydrates or the activation of mechanisms oriented towards an increase in blood glucose levels during hypoglycemia;lifestyle changes or the development of intercurrent diseases during therapy (for all of the above conditions, more careful monitoring of signs of hypoglycemia and blood glucose levels, as well as dose adjustment of Amaril M may be required);
• combined use (at the beginning of the course) of antihypertensive drugs or diuretics, as well as non-steroidal anti-inflammatory drugs (NSAIDs), or other situations that cause deterioration of renal function (increased threat of lactic acidosis and other undesirable effects of metformin);
• elderly age;
• performing hard physical work (due to the risk of lactic acidosis while taking metformin);
• insufficiency of glucose-6-phosphate dehydrogenase (due to the possible development of hemolytic anemia when using sulfonylurea derivatives);
• fading or absence of symptoms of adrenergic antiglycemic regulation in response to developing hypoglycemia (in elderly patients, with autonomic neuropathy or with the combined use of beta-blockers, clonidine, guanethidine and other sympatholytics; more careful control of blood glucose concentration is required).

Amaryl M, instructions for use: method and dosage

Amaryl M is taken orally, with meals, 1 or 2 times a day.

The dose of Amaryl M is determined individually depending on the target blood glucose concentration. It is recommended to use an antidiabetic agent in the lowest dose that allows achieving the necessary metabolic control.

During the period of drug therapy, it is required to regularly set the level of glucose in the blood and urine, as well as the percentage of glycosylated hemoglobin in the blood.

If you accidentally missed the next dose, in no case should you compensate for the missed dose by using a higher dose later.

In the event of a missed meal or dose, or in the event of situations where it is not possible to take Amaryl M, the patient should establish a plan of action with the doctor in advance.

Since improved metabolic control is associated with increased tissue sensitivity to insulin, a decrease in the need for glimepiride may be observed during therapy. To prevent the occurrence of hypoglycemia, it is necessary to promptly reduce the dose of Amaril M or stop taking it.

The maximum single dose of metformin is 1000 mg, the maximum daily dose is 2000 mg. The maximum daily dose of glimepiride is 8 mg. Glimepiride doses exceeding 6 mg per day are more effective in only a small number of patients.

In the case of a transfer of a patient from the use of a combination of individual drugs of glimepiride and metformin to Amaryl M, the dose of the latter is set based on the doses of active substances that the patient is already taking. If it is necessary to increase the dose, it is recommended to titrate the daily dose of the drug in increments of only 1 tablet at a dosage of 1 mg + 250 mg or ½ tablet Amaryl M 2 mg + 500 mg.

The course of treatment is usually long.

Side effects

Glimepiride

• metabolism and nutrition: the development of hypoglycemia, including a protracted one, with symptoms such as acute hunger, vomiting, nausea, lethargy, drowsiness, lethargy, anxiety, decreased alertness and concentration, sleep disturbance, aggressiveness, headache pain, helplessness, dizziness, loss of self-control, impaired vision / speech, slowing down of psychomotor reactions, aphasia, paresis, depression, tremor, impaired sensitivity, delirium, confusion, convulsions, bradycardia, shallow breathing, loss of consciousness up to coma; in addition, it is possible to develop an adrenergic reaction to hypoglycemia, its signs - skin stickiness, increased sweating, increased blood pressure (BP), increased anxiety, a feeling of increased heart rate, tachycardia, angina pectoris, arrhythmia;an attack of severe hypoglycemia has a similar clinical picture with acute cerebrovascular accident. All of the above symptoms are almost always resolved after the elimination of hypoglycemia;
• immune system: allergic / pseudo-allergic reactions - itching, rashes, urticaria, proceeding mainly in a mild form (however, cases of transition to a severe form, accompanied by shortness of breath or a decrease in blood pressure, up to the onset of anaphylactic shock, were recorded, in connection with which it is necessary to immediately consult a doctor when urticaria), cross-allergy with other sulfonylurea derivatives, sulfonamides or similar agents, allergic vasculitis;
• lymphatic system and blood system: thrombocytopenia; isolated cases - hemolytic anemia, leukopenia, erythrocytopenia, agranulocytosis, granulocytopenia, pancytopenia (careful monitoring of the condition is necessary due to the possible threat of pancytopenia or aplastic anemia; if such phenomena appear, drug treatment must be discontinued and appropriate therapy carried out);
• liver and biliary tract: increased activity of liver enzymes; cholestasis, jaundice and other liver dysfunctions; hepatitis with a risk of progression to life-threatening liver failure, but also with possible regression after drug withdrawal;
• organs of the digestive tract: a feeling of fullness in the stomach, nausea, abdominal pain, vomiting, diarrhea;
• organ of vision: visual impairment, mainly at the beginning of the course due to fluctuations in the level of glucose in the blood, causing a temporary change in the swelling of the lens and, as a result, a change in its refractive index;
• others: hyponatremia, photosensitization.

Metformin

• lymphatic system and blood system: anemia, thrombocytopenia, leukocytopenia; with long-term use - as a rule, an asymptomatic decrease in the content of vitamin B ₁₂ in the serum as a result of a decrease in its intestinal absorption (the plasma level of folic acid in the blood does not significantly decrease); in the presence of megaloblastic anemia, it is necessary to take into account the likelihood of a decrease in the absorption of vitamin B ₁₂ caused by taking metformin;
• liver and biliary tract: abnormal liver function tests or hepatitis, which, if metformin is not treated, may reverse;
• organs of the gastrointestinal tract: nausea, abdominal pain, vomiting, increased gas production, flatulence, diarrhea, anorexia (observed mainly at the beginning of the course and are transient, with continued therapy spontaneously resolve; in some cases, a temporary dose reduction may be required, since development these symptoms at the beginning of treatment are dose-dependent, their severity can be reduced by gradually increasing the dose and taking the drug with meals), an unpleasant / metallic taste in the mouth (observed at the beginning of the course and disappears on its own), severe diarrhea and / or vomiting, which can cause dehydration and prerenal renal failure (if they occur, you should temporarily stop taking the drug),nonspecific gastrointestinal symptoms in patients with type 2 diabetes mellitus with a stabilized state (can be caused not only by drug treatment, but also by the development of lactic acidosis or intercurrent diseases);
• skin and subcutaneous tissue: itching, rash, erythema;
• metabolism and nutrition: lactic acidosis, hypoglycemia.

The use of a free combination of drugs metformin and glimepiride, as well as a combined drug Amaryl M with fixed doses of the latter, is associated with the same safety characteristics as when using metformin and glimepiride separately.

Overdose

Glimepiride

Due to the fact that one of the active ingredients of Amaril M is glimepiride, an overdose in acute form or caused by prolonged use of the drug in high doses can lead to severe, life-threatening hypoglycemia. After establishing the fact of an overdose of glimepiride, it is necessary to urgently consult a doctor, and before his appointment, immediately take sugar, preferably in the form of dextrose (glucose). In case of taking a life-threatening dose of the drug, it is required to rinse the stomach and take activated charcoal. If necessary, hospitalization is possible as a preventive measure.

Mild hypoglycemia, without neurological manifestations and loss of consciousness, needs to be treated with oral dextrose (glucose) and changes in the dose of the drug and / or diet. The patient needs intensive monitoring until the doctor is sure that the patient is out of danger. It should be borne in mind that after the initial achievement of normalization of blood glucose levels, hypoglycemia may develop again.

In the event of a severe overdose and the appearance of serious neurological disorders, including loss of consciousness, an urgent hospitalization of the patient is required. Against the background of unconsciousness, an intravenous (iv) jet infusion of a concentrated glucose (dextrose) solution is shown, for example, the introduction of a 20% glucose (dextrose) solution to adults at an initial dose of 40 ml. An alternative therapy in adults is the use of glucagon, for example, in doses of 0.5-1 mg IV, intramuscularly (IM) or subcutaneously (SC). The threat of a recurrence of hypoglycemia in severe cases can persist for several days, as a result of which the patient's condition should be monitored for at least 24–48 hours.

If children accidentally take glimepiride, it is necessary to carefully select the dose of injected dextrose and to carry out concomitant constant monitoring of blood glucose levels due to the risk of dangerous hyperglycemia.

Metformin

On the background of oral administration of metformin in an amount of up to 85 g, hypoglycemia was not recorded, but sometimes lactic acidosis occurred. With a pronounced overdose of metformin or the presence of concomitant risk factors in the patient, lactic acidosis may develop, which requires emergency medical care in a hospital. The most effective way to eliminate metformin and lactate from the body is hemodialysis. Under conditions of good hemodynamics, metformin can be excreted by hemodialysis with a clearance of up to 170 ml / min. In case of an overdose of metformin, there is a threat of acute pancreatitis.

special instructions

Lactic acidosis is a very rare, but quite severe metabolic complication (with high mortality in the absence of appropriate treatment) resulting from the accumulation of metformin during the treatment period. Against the background of taking metformin, lactic acidosis is observed mainly in the presence of diabetes mellitus with severe renal failure, including with congenital renal lesions and renal hypoperfusion, often with numerous concomitant pathologies that require medical / surgical treatment. Risk factors associated with the development of lactic acidosis include: prolonged fasting, intense consumption of ethanol-containing drinks, ketoacidosis, poorly controlled diabetes mellitus, conditions that cause tissue hypoxia, liver failure. Lactic acidosis can present with hypothermia, abdominal pain,acidotic dyspnea followed by coma. This complication is characterized by a decrease in blood pH, an increase in the level of lactate in the blood (more than 5 mmol / l), an electrolyte imbalance with an increase in anion deficiency and a lactate / pyruvate ratio. If metformin is the cause of lactic acidosis, its plasma level usually exceeds 5 mcg / ml.

If there is a suspicion of the development of lactic acidosis, it is necessary to urgently stop taking metformin and place the patient in a hospital.

The threat of lactic acidosis is aggravated with increasing severity of renal impairment and with age. The risk of this complication can be reduced with regular monitoring of renal function and the use of the lowest effective dose of metformin. It is also necessary to beware of taking the drug for conditions associated with dehydration or hypoxemia.

If there are clinical / laboratory signs of liver disease, Amaryl M should not be taken, since the ability to eliminate lactate can be significantly reduced against the background of liver dysfunction. It is required to temporarily stop using the drug before carrying out studies with intravascular administration of radio-opaque substances containing iodine, and before any surgical interventions. Do not take metformin for 48 hours before and 48 hours after surgery with general anesthesia.

It should be borne in mind that lactic acidosis often develops rather slowly and manifests itself only with such nonspecific symptoms as feeling unwell, increasing drowsiness, myalgia, nonspecific gastrointestinal disorders, and respiratory disorders. Against the background of severe acidosis, a decrease in blood pressure, hypothermia, and resistant bradyarrhythmia can be observed. If these symptoms appear, you should immediately consult a doctor.

Lactic acidosis can be detected in patients with diabetes mellitus with metabolic acidosis and in the absence of ketonemia and ketonuria (signs of ketoacidosis).

During the first week of the course of drug therapy, careful monitoring of blood glucose levels is required due to the threat of hypoglycemia, especially if there is an increased risk of its development. In some cases, a dose adjustment of Amaril M or the entire therapy may be necessary.

Symptoms of hypoglycemia, reflecting adrenergic antihypoglycemic regulation, which is a response to hypoglycemia that has arisen, may be very mild or completely absent in the case of gradual development of the latter, as well as in the elderly, against the background of autonomic neuropathy or in combination therapy with beta-blockers, guanethidine clonidine and other sympatholytics.

In order to maintain the target glycemia, it is necessary to follow a diet, exercise, reduce body weight, and, if necessary, take antidiabetic drugs regularly. Symptoms of improperly regulated blood glucose may include: dry skin, oliguria, thirst, including pathologically severe, and others.

It is almost always possible to quickly stop hypoglycemia with the help of immediate intake of carbohydrates - sugar or glucose, for example, a sugar cube, tea with sugar, fruit juice containing sugar, etc. For these purposes, the patient should always have at least 20 g of sugar with him, substitutes for the latter are ineffective.

During treatment, it is recommended to periodically monitor the level of hemoglobin / hematocrit, the number of erythrocytes, as well as indicators of renal function (serum creatinine in the blood): at least 1 time per year - with normal kidney function, at least 2-4 times a year - in in the case of blood serum CC at the upper limit of normal and in elderly patients.

Influence on the ability to drive vehicles and complex mechanisms

During treatment, mainly at the beginning of the course, when switching from one drug to another or with irregular use of Amaril M, there may be a deterioration in the rate of reactions. When driving a car or other moving complex mechanisms during therapy, care must be taken, especially if there is a tendency to hypoglycemia and / or a decrease in the severity of its precursors.

Application during pregnancy and lactation

Amaryl M is contraindicated to take during pregnancy due to the possible adverse effect on the development of the fetus. When a pregnancy occurs or is planning, patients need to notify the attending physician.

Insulin therapy should be prescribed for women with carbohydrate metabolism disorders that cannot be corrected only with diet and exercise.

In order to avoid the ingestion of an antidiabetic agent with breast milk into the child's body, the use of Amaril M during lactation is contraindicated. If it is necessary to treat hypoglycemia, the patient should switch to insulin therapy or stop breastfeeding.

Pediatric use

Amaril M is contraindicated in patients under the age of 18, since the safety and effectiveness of its use in children and adolescents with type 2 diabetes mellitus have not been studied.

With impaired renal function

Amaril M is contraindicated in cases of impaired renal function and renal failure [serum creatinine level ≥ 1.2 mg / dL (110 μmol / L) in women and ≥ 1.5 mg / dL (135 μmol / L) in men, or a decrease in CC] due to the increased threat of lactic acidosis and other adverse reactions to metformin. Treatment with the drug is also contraindicated in patients on hemodialysis and in the presence of acute conditions that can lead to impaired renal function, such as intravascular administration of iodine-containing contrast agents, severe infectious lesions, dehydration, shock.

For violations of liver function

In the presence of severe violations of the liver, taking Amaril M is contraindicated due to the lack of experience in its use. To achieve optimal glycemic control, insulin administration is necessary in this case.

Use in the elderly

Due to the increased risk of lactic acidosis and other adverse reactions of metformin in elderly patients, Amaryl M should be used with extreme caution (due to the possible frequent asymptomatic decrease in renal function), especially in conditions leading to deterioration of renal function, such as starting therapy with diuretics, antihypertensive drugs, as well as NSAIDs. The dose should be carefully titrated and renal function monitored regularly.

Drug interactions

Glimepiride

• inducers (rifampicin) and inhibitors (fluconazole) of the isoenzyme CYP2C9: glimepiride is metabolized with the participation of cytochrome P ₄₅₀ CYP2C9; the likelihood of weakening the hypoglycemic effect of glimepiride increases when combined with CYP2C9 inducers, and the risk of hypoglycemia increases when these drugs are canceled without adjusting the dose of glimepiride; the threat of hypoglycemia and side effects of glimepiride is aggravated when combined with inhibitors of the CYP2C9 isoenzyme, and the risk of weakening the hypoglycemic effect increases when CYP2C9 inhibitors are canceled without adjusting the dose of glimepiride;
• drugs that enhance the hypoglycemic effect - oral antidiabetic drugs, insulin, allopurinol, angiotensin-converting enzyme (ACE) inhibitors, male sex hormones, anabolic steroids, coumarin anticoagulants, chloramphenicol, disopyramidosulfuric acid, feniloxin, monoamine oxidase (MAO) inhibitors, fluconazole, aminosalicylic acid, miconazole, pentoxifylline (with parenteral administration of high doses), probenecid, phenylbutazone, salicylates, antimicrobial agents of the quinolone group, sulfonamide derivatives, sulfinpyrazone, tritropocvazone the threat of the development of hypoglycemia, as well as the deterioration of glycemic control against the background of the abolition of these drugs without adjusting the dose of glimepiride;
• drugs that weaken the hypoglycemic effect - glucocorticosteroids (GCS), barbiturates, acetazolamide, diuretics, diazoxide, epinephrine (adrenaline) or other sympathomimetics, laxatives (long course), glucagon, nicotinic acid (high doses), progestogens, estrogen, phenytogen phenothiazines, thyroid hormones, rifampicin: the likelihood of worsening glycemic control increases, and if these drugs are discontinued without changing the dose of glimepiride, the threat of hypoglycemia is aggravated;
• blockers of H ₂ -histamine receptors, reserpine, clonidine, guanethidine, beta-blockers: an increase / decrease in the hypoglycemic effect may be observed (careful monitoring of blood glucose levels is required);
• ethanol: it is possible to weaken / increase the hypoglycemic effect of glimepiride;
• colesevelam (bile acid sequestrants): absorption of glimepiride from the gastrointestinal tract decreases; it is recommended to take Amaryl M at least 4 hours before using the wheelset;
• beta-blockers, guanethidine, clonidine, reserpine: a weakening / blocking of adrenergic counterregulation reactions arising in response to the onset of hypoglycemia and aimed at increasing blood glucose levels may be recorded, which leads to a weakening of the manifestations of hypoglycemia, contributing to its more imperceptible development for the patient and the doctor, and as a result, it complicates the timely detection and treatment of this disease;
• indirect anticoagulants, coumarin derivatives: it is possible to increase or decrease their effects.

Metformin

Combinations not recommended:

• gentamicin and other antibiotics with a significant nephrotoxic effect: the threat of lactic acidosis may increase;
• iodine-containing contrast agents for intravascular administration: the development of renal failure may be observed, and as a result, the accumulation of metformin and an increased risk of lactic acidosis; it is necessary to temporarily cancel metformin before or during the study and not resume taking it within 48 hours after the completion of the manipulation; therapy with metformin can only be started after tests have been performed and normal indicators of kidney function have been obtained;
• ethanol: the threat of lactic acidosis development increases against the background of acute alcohol intoxication, especially when you skip a meal or lack it, as well as with liver failure; this combination should be avoided.

Combinations requiring caution:

• ACE inhibitors: may lower blood glucose; during use and after the withdrawal of these drugs, it may be necessary to change the doses of the hypoglycemic agent;
• GCS (for systemic / local use), beta ₂ -adrenostimulants and diuretics with internal hyperglycemic activity: it is recommended to carry out, especially at the beginning of combination treatment, more frequent monitoring of morning blood glucose concentration; it may be necessary to change the dose of hypoglycemic therapy;
• drugs that reduce the hypoglycemic effect of metformin - thyroid hormones, pyrazinamide, epinephrine, estrogens, GCS, phenothiazines, isoniazid, diuretics (including thiazide ones), nicotinic acid, oral contraceptives, slow calcium channel blockers, sympathomimetics phenytoin: there may be a decrease in hypoglycemic action; monitoring of blood glucose is required;
• drugs that increase the hypoglycemic effect of metformin - insulin, salicylates (including acetylsalicylic acid), MAO inhibitors, beta-blockers (including propranolol), sulfonylureas, anabolic steroids: an increase in the hypoglycemic effect of metformin may be recorded; the patient's condition and blood glucose levels should be monitored.

Interactions requiring special attention:

• nifedipine: with a single use of nifedipine and metformin, an increase in the blood plasma AUC and C _{max of the} latter by 9 and 20%, respectively, was recorded, as well as an increase in the amount of metformin excreted by the kidneys; the pharmacokinetics of nifedipine had a minimal effect;
• furosemide: with a single dose, there was an increase in the plasma C _{max of} metformin in the blood by 22%, and AUC - by 15%, while no significant changes in renal clearance were recorded; when compared with the monotherapy regimen, C _max and AUC of furosemide with this combination decreased by 31 and 12%, respectively, terminal T _½ decreased by 32% without significant changes in the value of renal clearance;
• cationic drugs - digoxin, procainamide, amiloride, morphine, quinine, quinidine, triamterene, vancomycin, ranitidine, trimethoprim: it is necessary to carefully monitor the condition and adjust the dose of metformin and / or the drug interacting with it, against the background of concomitant simultaneous use of cationic drugs, since the latter are eliminated by tubular secretion in the kidneys and can theoretically interact with metformin, competing for the general transport system of the kidney tubules.

Analogs

Amaril M analogues are: Glidica M, Glibenclamide + Metformin, Glibenfazh, Bagomet Plus, Glibomet, Glimecomb, Glukovans, Gluconorm, Gluconorm Plus, Metglib, Metglib Force, etc.

Terms and conditions of storage

Store out of the reach of children at a temperature not exceeding 30 ° C.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Amaril M

According to reviews of Amaril M, the drug is an effective hypoglycemic agent that reduces the concentration of glucose in the blood and maintains it at a safe level. Patients note that in order to achieve a positive result of therapy, it is also necessary to follow an appropriate diet and receive feasible physical activity.

The disadvantage of the remedy, according to reviews, is a large number of contraindications, as well as undesirable phenomena that often occur during therapy. Many patients are unhappy with the high, in their opinion, the cost of Amaril M.

Price for Amaryl M in pharmacies

The price of Amaryl M 2 mg + 500 mg can be 778-1072 rubles. per package containing 30 film-coated tablets.

Amaryl M: prices in online pharmacies

Drug name Price Pharmacy

Amaryl M 2 mg + 500 mg film-coated tablets 30 pcs. 698 r Buy

Amaryl M tablets p.p. 2mg + 500mg 30 pcs. 746 RUB Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!