Amaryl M tablets 2+500 mg 30 pcs. in St. Petersburg

Pharmacological properties of the drug Amaryl

Pharmacodynamics . Glimepiride is an oral hypoglycemic drug, a sulfonylurea derivative. The effect of glimepiride is realized by stimulating the release of insulin from pancreatic β-cells. Like other sulfonylureas, it increases the responsiveness of pancreatic β-cells to physiological stimulation by glucose. In addition, glimepiride, like other sulfonylurea derivatives, apparently has a pronounced extrapancreatic effect. Release of insulin. Sulfonylurea regulates insulin secretion by closing ATP-dependent potassium channels on the β-cell membrane. This closure leads to depolarization of the cell membrane, as a result of which calcium channels open slightly and a large amount of calcium enters the cell. This stimulates the release of insulin by exocytosis. Glimepiride binds with high tropism to a protein on the β-cell membrane associated with the ATP-dependent potassium channel, but not at the site to which sulfonylureas typically bind. Extrapancreatic activity. The extrapancreatic effect consists, in particular, of increasing the sensitivity of peripheral tissues to insulin and reducing the uptake of insulin by the liver. Transport of glucose from the blood to peripheral muscle and fat tissues occurs through special transport proteins localized on the cell membrane. It is the transport of glucose to these tissues that is the stage that limits the rate of glucose uptake. Glimepiride very quickly increases the number of active glucose transporters on the plasmalemma of muscle and fat cells, thereby stimulating glucose uptake. Glimepiride increases the activity of phospholipase C, specific for glycosyl-phosphatidylinositol. This may be due to the increased lipogenesis and glycogenesis that is observed in isolated fat and muscle cells under its influence. Gimepiride prevents the formation of glucose in the liver, increasing the intracellular concentration of fructose-2, 6-diphosphate, which, in turn, inhibits gluconeogenesis. General information. For healthy individuals, the minimum effective oral dose is 0.6 mg. The effect of glimepiride is dose-dependent and reproducible. The physiological response to intense physical activity, manifested by a decrease in insulin secretion, persists after taking glimepiride. There was no significant difference in the effect of the drug taken 30 minutes before or immediately before a meal. In patients with diabetes mellitus, a single daily dose can provide optimal metabolic control for 24 hours. Although the hydroxy derivative (a metabolite of glimepiride) causes a slight but statistically significant decrease in plasma glucose levels in healthy people, its effect on the overall effect of the drug is insignificant. Combination therapy with metformin. One study showed that for patients whose maximum daily dose of metformin did not provide sufficient metabolic control, concomitant therapy with glimepiride improved this control. Combination therapy with insulin. Data regarding the use of combination therapy with insulin are limited. For patients in whom the maximum daily dose of glimepiride did not provide sufficient glycemic control, concomitant insulin therapy can be started. Two studies found that combination treatment improved metabolic control as well as insulin monotherapy, but lower doses of insulin could be used during combination therapy. Pharmacokinetics. Absorption. The bioavailability of glimepiride after oral administration is complete. Eating does not have a significant effect on absorption, only its rate is slightly reduced. The maximum concentration (Cmax) in blood plasma is reached approximately 2.5 hours after oral administration (average 0.3 mcg/ml over several daily doses of 4 mg). There is a linear relationship between dose and Cmax and AUC. Distribution. Glimepiride has a very low volume of distribution (approximately 8.8 L), which is approximately equal to the volume of distribution of albumin, has a high degree of protein binding (99%) and low clearance (approximately 48 ml/min). In animals, glimepiride is excreted in milk. Glimepiride can cross the placenta, but does not penetrate the blood-brain barrier well. Biotransformation and elimination. The average half-life, which depends on the concentration in the blood plasma, when using multiple doses, is 5-8 hours. After taking high doses, a slight prolongation of the half-life was observed. After administration of a single dose of radiolabeled glimepiride, 58% of the label was found in the urine and 35% in the feces. The substance is not detected in unchanged form in the urine. Two metabolites are excreted in urine and feces, most likely products of metabolism in the liver (the main enzyme is cytochrome P2C9): a hydroxy derivative and a carboxy derivative. After oral administration of glimepiride, the terminal half-lives of these metabolites were 3–6 hours and 5–6 hours, respectively. A comparative analysis showed no significant differences in pharmacokinetics after single and repeated use of the drug, and the variability of results for one individual was very low. No significant accumulation was observed. Pharmacokinetics were similar in men and women, as well as in young and elderly (over 65 years of age) patients. For patients with low creatinine clearance, there was a trend toward increased clearance and decreased mean serum concentrations of glimepiride, most likely due to its more rapid elimination due to poorer protein binding. The excretion of 2 metabolites by the kidneys decreased. There was no additional risk of drug accumulation in these patients. In five patients without diabetes mellitus after bile duct surgery, pharmacokinetics were similar to those in healthy subjects.

Amaryl tablets 4 mg No. 30

Compound

Active substance: glimepiride 4 mg.
Excipients: lactose monohydrate, sodium carboxymethyl starch (type A), povidone 25,000, microcrystalline cellulose, magnesium stearate, indigo carmine (E132).

Pharmacokinetics

When comparing data obtained with single and multiple (1 time/day) administration of glimepiride, no significant differences in pharmacokinetic parameters were revealed, and their variability between different patients was very low. There is no significant accumulation of the drug.

Suction

With repeated oral administration of the drug at a daily dose of 4 mg, Cmax in the blood serum is achieved in approximately 2.5 hours and is 309 ng/ml. There is a linear relationship between dose and Cmax of glimepiride in plasma, as well as between dose and AUC. When taken orally, the bioavailability of glimepiride is 100%. Food intake does not have a significant effect on absorption, except for a slight slowdown in its rate.

Distribution

Glimepiride is characterized by a very low Vd (about 8.8 l), approximately equal to the Vd of albumin, a high degree of binding to plasma proteins (more than 99%) and low clearance (about 48 ml/min).

Glimepiride is excreted in breast milk and penetrates the placental barrier.

Metabolism

Glimepiride is metabolized in the liver (mainly with the participation of the CYP2C9 isoenzyme) with the formation of 2 metabolites - hydroxylated and carboxylated derivatives, which are found in urine and feces.

Removal

T1/2 at plasma concentrations of the drug in serum corresponding to multiple dosing regimens is approximately 5-8 hours. After taking glimepiride in high doses, T1/2 increases slightly.

After a single oral dose, 58% of glimepiride is excreted by the kidneys and 35% through the intestines. Unchanged active substance is not detected in urine.

T1/2 of the hydroxylated and carboxylated metabolites of glimepiride were about 3-5 hours and 5-6 hours, respectively.

Pharmacokinetics in special clinical situations

Pharmacokinetic parameters are similar in patients of different sexes and different age groups.

In patients with impaired renal function (with low creatinine clearance), there is a tendency for the clearance of glimepiride to increase and for its mean serum concentrations to decrease, which is likely due to more rapid elimination of the drug due to its lower protein binding. Thus, in this category of patients there is no additional risk of accumulation of glimepiride.

Indications for use

Type 2 diabetes mellitus (as monotherapy or as part of combination therapy with metformin or insulin).

Contraindications

• Diabetes mellitus type 1,
• diabetic ketoacidosis, diabetic precoma and coma,
• severe liver dysfunction (lack of clinical experience with use),
• severe renal dysfunction, incl. patients on hemodialysis (lack of clinical experience with use),
• pregnancy,
• lactation (breastfeeding),
• children's age (lack of clinical experience of use),
• rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption,
• hypersensitivity to the components of the drug,
• hypersensitivity to other sulfonylurea derivatives and sulfonamide drugs (risk of developing hypersensitivity reactions).

With caution: the drug should be used in the first weeks of treatment (increased risk of hypoglycemia), in the presence of risk factors for the development of hypoglycemia (adjustment of the dose of glimepiride or the entire therapy may be required), in case of intercurrent diseases during treatment or when changing the patient’s lifestyle (change in diet and time of meals, increase or decrease in physical activity), with deficiency of glucose-6-phosphate dehydrogenase, with impaired absorption of food and drugs from the gastrointestinal tract (intestinal obstruction, intestinal paresis).

Directions for use and doses

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

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

Violations in taking the drug, for example, missing a dose, should not be compensated for by subsequent administration of the drug at a higher dose.

The doctor should instruct the patient in advance about the actions that should be taken in case of errors in taking the drug Amaryl® (in particular, when missing a dose or skipping a meal), or in situations where it is not possible to take the drug.

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

The initial dose of Amaryl® is 1 mg 1 time / 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 in only a small number of patients.

The doctor determines the time of taking Amaryl® and the distribution of doses during the day, taking into account the patient’s lifestyle (time of meals, amount of physical activity). The daily dose is prescribed in 1 dose, usually immediately 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 Amaryl® tablets.

Because Improved metabolic control is associated with increased insulin sensitivity, and the need for glimepiride may decrease during treatment. In order to avoid the development of hypoglycemia, it is necessary to promptly reduce the dose or stop taking the drug Amaryl®.

Conditions that may also require dose adjustment of glimepiride:

• weight loss;
• lifestyle changes (changes in diet, meal times, amount of physical activity);
• the occurrence of other factors that lead to a predisposition to the development of hypoglycemia or hyperglycemia.

Treatment with glimepiride is usually long-term.

Transferring a patient from taking another oral hypoglycemic drug to taking Amaryl®

There is no exact relationship between the doses of Amaryl® 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 Amaryl® from the maximum dose of another oral hypoglycemic drug). Any dose increase should be done in stages based on response to glimepiride, as recommended above. It is necessary to take into account the intensity and duration of the effect of the previous hypoglycemic agent. Interruption of treatment may be necessary to avoid additive effects that increase the risk of hypoglycemia.

Use in combination with metformin

In patients with inadequately controlled diabetes mellitus who are taking glimepiride or metformin at maximum daily doses, treatment with a combination of these two drugs may be initiated. In this case, previous treatment with either glimepiride or metformin is continued at the same doses, and additional administration of metformin or glimepiride is started at 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 initiated under strict medical supervision.

Use in combination with insulin

In patients with poorly controlled diabetes mellitus, insulin may be prescribed concomitantly when taking glimepiride at the maximum daily dose. In this case, the last dose of glimepiride prescribed to the patient remains unchanged. In this case, insulin treatment begins with low doses, which are gradually increased under the control of blood glucose concentrations. Combined treatment is carried out under close medical supervision.

Patients with impaired renal function may be more sensitive to the hypoglycemic effect of glimepiride. Data on the use of Amaryl® in patients with renal failure are limited.

Data on the use of Amaryl® in patients with liver failure are limited.

Storage conditions

Store at a temperature not exceeding 25 °C. Keep out of the reach of children.

Best before date

3 years.

special instructions

In specific clinical stress conditions, such as trauma, surgery, infections, and febrile fever, metabolic control may deteriorate in patients with diabetes, so temporary switching to insulin therapy may be necessary to maintain adequate metabolic control.

In the first weeks of treatment, the risk of developing hypoglycemia may increase, which requires particularly careful monitoring of blood glucose concentrations.

Factors that contribute to the risk of developing hypoglycemia include:

• the patient's reluctance or inability (more often observed in elderly patients) to cooperate with the doctor,
• malnutrition, irregular eating or skipping meals,
• imbalance between physical activity and carbohydrate intake,
• diet change,
• drinking alcohol, especially in combination with skipping meals,
• severe renal dysfunction,
• severe liver dysfunction (in patients with severe liver dysfunction, transfer to insulin therapy is indicated, at least until metabolic control is achieved),
• overdose of glimepiride,
• some decompensated endocrine disorders that impair carbohydrate metabolism or adrenergic counterregulation in response to hypoglycemia (for example, some disorders of the thyroid gland and anterior pituitary gland, adrenal insufficiency),
• simultaneous use of certain medications,
• taking glimepiride in the absence of indications for its use.

Treatment with sulfonylurea derivatives, which include glimepiride, can lead to the development of hemolytic anemia, therefore, in patients with glucose-6-phosphate dehydrogenase deficiency, special care should be taken when prescribing glimepiride; it is preferable to use hypoglycemic agents that are not sulfonylurea derivatives.

If the above risk factors for hypoglycemia are present, as well as if intercurrent diseases occur during treatment or changes in the patient's lifestyle, adjustment of the dose of glimepiride or the entire therapy may be necessary.

Symptoms of hypoglycemia, resulting from adrenergic counterregulation of the body in response to hypoglycemia, may be mild or absent when hypoglycemia develops gradually, in elderly patients, in patients with disorders of the autonomic nervous system, or in patients receiving beta-blockers, clonidine, reserpine , guanethidine and other sympatholytic agents.

Hypoglycemia can be quickly corrected by immediate administration of rapidly digestible carbohydrates (glucose or sucrose). As with other sulfonylureas, despite initial successful relief of hypoglycemia, hypoglycemia may recur. Therefore, patients should remain under constant monitoring. Severe hypoglycemia additionally requires immediate treatment and medical supervision, and in some cases, hospitalization of the patient.

During treatment with glimepiride, regular monitoring of liver function and peripheral blood patterns (especially the number of leukocytes and platelets) is required.

Side effects such as severe hypoglycemia, serious changes in blood count, severe allergic reactions, liver failure can be life-threatening, therefore, in the event of such reactions, the patient should immediately inform the attending physician about them, stop taking the drug and not resume taking it without a doctor’s recommendation .

Use in pediatrics

There are no data on the long-term effectiveness and safety of the drug in children.

Use in children

Contraindicated in children.

Pharmacodynamics

An oral hypoglycemic drug is a third generation sulfonylurea derivative.

Glimepiride reduces blood glucose concentrations, mainly by stimulating the release of insulin from pancreatic β-cells. Its effect is primarily associated with improving the ability of pancreatic β-cells to respond to physiological stimulation with glucose. Compared with glibenclamide, low doses of glimepiride cause the release of less insulin while achieving approximately the same reduction in blood glucose concentrations. This fact indicates that glimepiride has extrapancreatic hypoglycemic effects (increased tissue sensitivity to insulin and insulinomimetic effect).

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

Glimepiride closes potassium channels. This causes depolarization of β-cells and leads to the opening of voltage-sensitive calcium channels and the entry of calcium into the cell. As a result, an increase in intracellular calcium concentration activates insulin secretion through exocytosis.

Glimepiride binds and is released from the binding protein much faster and, accordingly, more often than glibenclamide. It is assumed that this property of the high rate of exchange of glimepiride with the protein that binds to it determines its pronounced effect of sensitization of β-cells to glucose and their protection from desensitization and premature exhaustion.

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

Insulinomimetic effect. Glimepiride has effects similar to those of insulin on glucose uptake into peripheral tissues and glucose output from the liver.

Glucose is absorbed by peripheral tissues by transporting it into muscle cells and adipocytes. Glimepiride directly increases the number of glucose transport molecules in the plasma membranes of muscle cells and adipocytes. An increase in the entry of glucose into 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 the release of glucose from the liver by increasing the concentration of fructose-2,6-bisphosphate, which inhibits gluconeogenesis.

Effect on platelet aggregation. Glimepiride reduces platelet aggregation in vitro and in vivo. This effect appears to be due to selective inhibition of COX, which is responsible for the formation of thromboxane A, an important endogenous platelet aggregation factor.

Antiatherogenic effect. Glimepiride helps normalize lipid levels, reduces the level of malonaldehyde in the blood, which leads to a significant reduction in lipid peroxidation. In animals, glimepiride leads to a significant reduction in the formation of atherosclerotic plaques.

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

Cardiovascular effects. Sulfonylureas also have effects on the cardiovascular system through ATP-sensitive potassium channels. Compared with traditional sulfonylurea derivatives, glimepiride has a significantly lesser effect on the cardiovascular system, which may be explained by the specific nature of its interaction with the ATP-sensitive potassium channel protein that binds to it.

In healthy volunteers, the minimum effective dose of glimepiride is 0.6 mg. The effect of glimepiride is dose-dependent and reproducible. The physiological response to physical activity (decreased insulin secretion) is preserved when taking glimepiride.

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

Combination therapy with metformin. In patients with insufficient metabolic control when using the maximum dose of glimepiride, combination therapy with glimepiride and metformin may be initiated. Two studies demonstrated improved metabolic control with combination therapy compared with either drug alone.

Combination therapy with insulin. In patients with insufficient metabolic control while taking maximum doses of glimepiride, concomitant insulin therapy may be initiated. Two studies found that this combination achieved the same improvement in metabolic control as insulin alone. However, combination therapy requires a lower dose of insulin.

Side effects

Metabolic: hypoglycemia is possible, which, as with the use of other sulfonylurea derivatives, can be prolonged. Symptoms of hypoglycemia - headache, hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, anxiety, aggressiveness, impaired concentration, vigilance and reaction speed, depression, confusion, speech disorders, aphasia, visual disturbances, tremors, paresis , sensory disturbances, dizziness, loss of self-control, delirium, cerebral spasms, drowsiness or loss of consciousness up to coma, shallow breathing, bradycardia. In addition, manifestations of adrenergic counterregulation in response to hypoglycemia may occur, such as the appearance of cold clammy sweat, anxiety, tachycardia, hypertension, angina, palpitations and cardiac arrhythmias. The clinical picture of severe hypoglycemia may resemble a stroke. Symptoms of hypoglycemia almost always disappear once it is corrected.

On the part of the organ of vision: transient visual impairment is possible (especially at the beginning of treatment), caused by changes in the concentration of glucose in the blood. Their cause is a temporary change in the swelling of the lenses, depending on the concentration of glucose in the blood, and due to this change in the refractive index of the lenses.

From the digestive system: rarely - nausea, vomiting, feeling of heaviness or fullness in the epigastrium, abdominal pain, diarrhea; in some cases - hepatitis, increased activity of liver enzymes and/or cholestasis and jaundice, which can progress to life-threatening liver failure, but may reverse when the drug is discontinued.

From the hematopoietic system: rarely - thrombocytopenia; in some cases - leukopenia, hemolytic anemia, erythrocytopenia, granulocytopenia, agranulocytosis and pancytopenia. During post-marketing use of the drug, cases of severe thrombocytopenia with platelet counts <10,000/μl and thrombocytopenic purpura have been reported (frequency unknown).

Allergic reactions: rarely - allergic and pseudo-allergic reactions, such as itching, urticaria, skin rash. Such reactions are almost always mild, but can develop into severe reactions with shortness of breath, a sharp decrease in blood pressure, which sometimes progress to anaphylactic shock; in some cases - allergic vasculitis.

Other: in some cases - hyponatremia, photosensitivity.

If symptoms of hives appear, you should consult a doctor immediately.

Use during pregnancy and breastfeeding

Amaryl® is contraindicated for use during pregnancy. In case of planned pregnancy or if pregnancy occurs, the woman should be transferred to insulin therapy.

It has been established that glimepiride is excreted in breast milk. During lactation, the woman should be switched to insulin or breastfeeding should be stopped.

Interaction

Glimepiride is metabolized with the participation of the CYP2C9 isoenzyme, which should be taken into account when using the drug simultaneously with inducers (for example, rifampicin) or inhibitors (for example, fluconazole) of CYP2C9.

Potentiation of the hypoglycemic effect and, in some cases, the associated possible development of hypoglycemia can be observed when Amaryl® is combined with one of the following drugs: insulin, other hypoglycemic agents for oral administration, ACE inhibitors, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine, pheniramidol, fibrates, fluoxetine, guanethidine, ifosfamide, MAO inhibitors, fluconazole, PAS, pentoxifylline (high parenteral doses), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpyrazone, cla rithromycin, sulfonamides, tetracyclines, tritoqualine, trophosfamide.

A decrease in the hypoglycemic effect and an associated increase in blood glucose concentration is possible when combined with one of the following drugs: acetazolamide, barbiturates, corticosteroids, diazoxide, diuretics, sympathomimetic agents (including epinephrine), glucagon, laxatives (with long-term use ), nicotinic acid (in high doses), estrogens and progestogens, phenothiazines, phenytoin, rifampicin, iodine-containing thyroid hormones.

Histamine H2 receptor blockers, beta-blockers, clonidine and reserpine can both enhance and reduce the hypoglycemic effect of glimepiride.

Under the influence of sympatholytic agents such as beta-blockers, clonidine, guanethidine and reserpine, signs of adrenergic counterregulation in response to hypoglycemia may be reduced or absent.

While taking glimepiride, the effect of coumarin derivatives may be enhanced or weakened.

Single or chronic consumption of alcohol can either enhance or weaken the hypoglycemic effect of glimepiride.

Bile acid sequestrants: Colesevelam binds to glimepiride and reduces the absorption of glimepiride from the gastrointestinal tract. When glimepiride is administered at least 4 hours before colesevelam is administered orally, no interaction is observed. Therefore, glimepiride should be taken at least 4 hours before taking colesevelam.

Overdose

Symptoms: in case of acute overdose, as well as long-term treatment with glimepiride in excessively high doses, severe life-threatening hypoglycemia may develop.

Treatment: Hypoglycemia can almost always be quickly reversed by immediate intake of carbohydrates (glucose or a lump of sugar, sweet fruit juice or tea). In this regard, the patient should always have at least 20 g of glucose (4 lumps of sugar) with him. Sweeteners are ineffective in treating hypoglycemia.

Until the doctor decides that the patient is out of danger, the patient requires careful medical observation. It should be borne in mind that hypoglycemia may recur after the initial restoration of blood glucose concentrations.

If a patient suffering from diabetes is treated by different doctors (for example, while staying in the hospital after an accident, when sick on the weekend), he must inform them about his illness and previous treatment.

Sometimes it may be necessary to hospitalize the patient, even if only as a precaution. Significant overdose and severe reactions with manifestations such as loss of consciousness or other serious neurological damage are medical emergencies and require immediate treatment and hospitalization.

In case of loss of consciousness, it is necessary to administer a concentrated solution of dextrose (glucose) intravenously (for adults, starting with 40 ml of a 20% solution). As an alternative, adults can administer glucagon intravenously, subcutaneously or intramuscularly, for example, at a dose of 0.5-1 mg.

When treating hypoglycemia due to accidental ingestion of Amaryl® in infants or young children, the dextrose dose should be carefully adjusted to avoid the possibility of dangerous hyperglycemia; administration of dextrose should be carried out under constant monitoring of blood glucose concentrations.

In case of an overdose of Amaryl®, gastric lavage and activated charcoal may be required.

After rapid restoration of blood glucose concentrations, it is imperative to carry out an intravenous infusion of a dextrose solution at a lower concentration to prevent the resumption of hypoglycemia. Blood glucose concentrations in such patients should be continuously monitored over a 24-hour period. In severe cases with prolonged hypoglycemia, the risk of low blood glucose levels may persist for several days

As soon as an overdose is detected, you must immediately inform your doctor.

Impact on the ability to drive vehicles and operate machinery

At the beginning of treatment, after changing treatment, or when taking glimepiride irregularly, a decrease in concentration and speed of psychomotor reactions due to hypo- or hyperglycemia may be observed. This may adversely affect the ability to drive vehicles or operate various machines and mechanisms.

Use of the drug Amaryl

Successful treatment of diabetes depends on the patient's adherence to an appropriate diet, regular physical activity, and constant monitoring of blood and urine glucose levels. The patient's failure to comply with the diet cannot be compensated for by taking pills or insulin. The drug is used by adults. Dosing depends on the results of blood and urine glucose tests. The initial dose is 1 mg (1/2 tablet of 2 mg) of glimepiride per day. If such a dose achieves disease control, it should be used for maintenance therapy. If glycemic control is not optimal, the dose should be increased to 2, 3 or 4 mg glimepiride per day in stages (at intervals of 1-2 weeks). Doses greater than 4 mg per day provide better results only in selected cases. The maximum recommended dose is 6 mg of Amaryl per day. If the maximum daily dose of metformin does not provide sufficient glycemic control, the patient may be started on concomitant therapy with glimepiride. While maintaining the previous dosage of metformin, the drug should be started with a low dose, which can then be gradually increased to the maximum daily dose, focusing on the desired level of metabolic control. Combination therapy should be carried out under the supervision of a physician. If the maximum daily dose of Amaryl does not provide sufficient glycemic control, concomitant insulin therapy may be initiated if necessary. While maintaining previous glimepiride dosing, insulin treatment should begin at a low dose, which can then be increased based on the desired level of metabolic control. Combination therapy should be carried out under close medical supervision. Usually one dose of Amaryl per day is enough. It is recommended to take it shortly before or during a substantial breakfast or (if there is no breakfast) shortly before or during the first main meal. Errors in the use of the drug, such as missing a dose, should never be corrected by taking a subsequent higher dose. The tablet should be swallowed without chewing, washed down with liquid. If a patient develops a hypoglycemic reaction to a dose of 1 mg per day, this means that the disease can only be controlled by diet. Improved control of diabetes mellitus is accompanied by an increase in insulin sensitivity, so the need for glimepiride may decrease during the course of treatment. To avoid hypoglycemia, the dose should be gradually reduced or therapy should be interrupted altogether. The need to review dosage may also arise if the patient's body weight or lifestyle changes or other factors increase the risk of hypo- or hyperglycemia. Switching from oral hypoglycemic agents to Amaryl . You can usually switch from other oral hypoglycemic drugs to taking Amaryl. During such a transition, the potency and half-life of the previous agent should be taken into account. In some cases, especially if the antidiabetic drug has a long half-life (for example, chlorpropamide), it is recommended to wait several days before taking Amaryl. This will reduce the risk of hypoglycemic reactions due to the additive effect of the two drugs. The recommended starting dose is 1 mg glimepiride per day. As noted above, the dose can be increased in stages based on response to the drug. Switching from insulin to Amaryl . In exceptional cases, patients with type II diabetes mellitus receiving insulin may be advised to replace it with Amaryl. This transition should be carried out under close medical supervision.

Amaryl's analogs

A foreign analogue of Amaryl is the drug Glimepiride-Teva. It is produced by the Croatian company Pliva Hrvatska.

Russian analogues of the drug Amaryl are:

• Glemaz, from the Valiant company.
• Glimepiride from the companies Atoll, Pharmproject, Pharmstandard and Vertex.
• Diamerid from the Akrikhin company.
• Glimepiride Canon from the company Kanonpharma.

All manufacturers produce their drugs in dosages of 1, 2, 3, 4 mg. The cost of a specific drug must be clarified at pharmacies.

Side effects of the drug Amaryl

Based on the experience with the use of Amaryl and other sulfonylurea derivatives, it is necessary to take into account the possibility of developing the following side effects of the drug: From the blood and lymphatic system Sometimes: moderate to severe thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, erythrocytopenia, hemolytic anemia and pancytopenia, which are usually disappear after stopping treatment. Immune disorders Very rare: allergic vasculitis, mild hypersensitivity reactions, which can progress to severe forms with the development of dyspnea, decreased blood pressure, and sometimes shock. Possible cross-allergy with sulfonylureas, sulfonamides or related compounds. Metabolism: Sometimes: hypoglycemic reactions, which mostly occur immediately, can become severe and are not always easy to correct. The occurrence of these reactions depends, as with other types of hypoglycemic therapy, on subjective factors such as dietary habits and dosage. Organ of vision During treatment (especially at the beginning), transient visual impairment may be observed due to changes in blood glucose levels. From the gastrointestinal tract Very rarely: nausea, vomiting, diarrhea, pressure or sensations of fullness in the stomach, abdominal pain, which rarely may require discontinuation of therapy. From the hepatobiliary system Increased levels of liver enzymes may be observed. Very rare: liver dysfunction (eg bile stagnation and jaundice), hepatitis, which may progress to liver failure. Skin and subcutaneous tissue disorders Hypersensitivity reactions - itching, rash and urticaria. Very rare: photosensitivity. Laboratory values ​​Very rare: hyponatremia.

Special instructions for the use of the drug Amaryl

Amaryl should be taken shortly before or during meals. If meals are taken at different times each time or are skipped altogether, taking the drug may cause hypoglycemia. Symptoms of hypoglycemia may include: headache, severe hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, anxiety, aggressiveness, impaired concentration and reaction time, depression, disorientation, speech and vision disorders, aphasia, tremor, paresis, impairment sensitivity, dizziness, helplessness, loss of self-control, delirium, convulsions, fainting, up to the development of coma, shallow breathing and bradycardia. In addition, signs of adrenergic counterregulation such as hyperhidrosis, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris, and cardiac arrhythmia may occur. The clinical picture of a severe hypoglycemic attack may resemble a stroke. Symptoms can almost always be quickly reduced by taking carbohydrates (sugar) immediately. Artificial sweeteners will not be effective. Based on experience with other sulfonylurea derivatives, it is known that treatment measures may initially be successful, but despite this, symptoms of hypoglycemia may reappear. Severe or prolonged hypoglycemia, which can only be temporarily relieved by eating regular amounts of sugar, requires immediate medical treatment and sometimes hospitalization. Factors contributing to hypoglycemia:

• reluctance or (more often in older patients) inability to maintain productive contact with a doctor;
• malnutrition, irregular or skipped meals, periods of fasting;
• change in diet;
• imbalance between physical activity and carbohydrate consumption;
• drinking alcohol, especially in combination with skipping meals;
• renal failure;
• severe liver dysfunction;
• Amaryl overdose;
• certain uncompensated disorders of the endocrine system affecting the metabolism of carbohydrates, or the inverse regulation of hypoglycemia (for example, certain dysfunctions of the thyroid gland, insufficiency of the anterior pituitary gland or adrenal cortex), simultaneous use of certain medications (see INTERACTIONS ).

Treatment with Amaryl requires constant monitoring of glucose levels in the blood and urine. In addition, it is recommended to control the amount of glycosylated hemoglobin. During use of the drug, regular monitoring of liver function and blood count (especially the number of leukocytes and platelets) is necessary. In stressful situations (for example, accidents, urgent operations, infections accompanied by fever), a temporary transfer of the patient to the use of insulin may be indicated. There are no data regarding the use of Amaryl for patients with severe liver dysfunction or those for whom dialysis is indicated. Patients with severe renal or hepatic impairment should be switched to insulin. The drug is contraindicated in patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption. Pregnancy period Risk associated with diabetes. Deviations from normal blood glucose levels during pregnancy may increase the likelihood of birth defects and perinatal mortality. Therefore, it is necessary to carefully monitor glycemia during pregnancy to avoid teratogenic risk. During pregnancy, insulin should be used. If you become pregnant, you should inform your doctor. Risk associated with glimepiride. There are no data regarding the use of glimepiride during pregnancy. According to the results of animal experiments, the drug has a toxic effect on reproductive function, probably associated with the pharmacological (hypoglycemic) effect of glimepiride. Therefore, glimepiride is contraindicated throughout pregnancy. When using glimepiride and planning or becoming pregnant, the woman should be switched to insulin therapy as soon as possible. Breastfeeding It is not known whether glimepiride is excreted in breast milk. Glimepiride is known to pass into the breast milk of rats. It is recommended to discontinue treatment with glimepiride during breastfeeding, since other sulfonylureas are detected in breast milk and there is a risk of hypoglycemia in the newborn. Impact on the ability to drive vehicles or operate machinery . The ability to concentrate and reaction time may be reduced due to hypoglycemia or hyperglycemia or, for example, due to deterioration of vision. This may create a risk in situations where such ability is particularly important (for example, driving a car or operating machinery). The patient should be warned not to develop hypoglycemia while driving. This is especially true for those individuals who have little or no ability to recognize the warning signs of hypoglycemia, and those who experience frequent episodes of hypoglycemia. The need to drive or operate machinery under these circumstances must be carefully considered.

Reviews

Amaryl is more expensive than Maninil or Diabeton MV. Therefore, not a very large number of people use it to treat diabetes. This explains the fact that there are not too many reviews about it.

Patients consider the positive properties of the drug to be that it allows you to lower blood sugar levels, and you need to take it once a day.

Negative reviews concern that Amaryl can cause hypoglycemia, and over time it leads to problems with the pancreas.

Author of the article:

Alekseeva Maria Yurievna |
Therapist Education: From 2010 to 2021 practicing physician at the therapeutic hospital of the central medical unit No. 21, the city of Elektrostal. Since 2021 he has been working at diagnostic center No. 3. Our authors

Drug interactions Amaryl

Concomitant use of Amaryl with certain medications can cause both a decrease and an increase in the hypoglycemic effect of glimepiride. Therefore, other drugs should be taken only as directed or with the advice of a doctor. Glimepiride is metabolized by cytochrome P450 2C9 (CYP2C9). It is known that due to simultaneous administration of inducers (for example, rifampicin) or inhibitors of CYP2C9 (for example, fluconazole), this metabolism may be altered. Results from an in vivo showed that fluconazole, one of the most potent inhibitors of CYP2C9, approximately doubled the AUC of glimepiride. The existence of these types of interactions is evidenced by the experience of using Amaryl and other sulfonylurea derivatives. Potentiation of the hypoglycemic effect, and therefore, in some cases, hypoglycemia, may occur in case of simultaneous use of glimepiride with such drugs as phenylbutazone, azapropazone and oxyphenbutazone, sulfinpyrazone, insulin and oral antidiabetic drugs, some long-acting sulfonamides, metformin, tetracyclines, salicylates and PAS, MAO inhibitors, anabolic steroids and male sex hormones, quinolone antibiotics, chloramphenicol, probenecid, coumarin anticoagulants, miconazole, fenfluramine, pentoxifylline (when used parenterally in high doses), fibrates, tritoqualine, ACE inhibitors, fluconazole, fluoxetine, allopurinol, sympatholytics , cyclo-, tro- and ifosfamides. A decrease in the hypoglycemic effect and, accordingly, an increase in blood glucose levels can occur with the simultaneous use of the following drugs: estrogens and progestogens, saluretics, thiazide diuretics, drugs that stimulate thyroid function, glucocorticoids, phenothiazine derivatives, chlorpromazine, adrenaline and sympathomimetics, nicotinic acid (in high dose) and its derivatives, laxatives (long-term use), phenytoin, diazoxide, glucagon, barbiturates and rifampicin, acetozolamide. H2-receptor antagonists, β-adrenergic receptor blockers, clonidine and reserpine can lead to both potentiation and reduction of the hypoglycemic effect. Under the influence of sympatholytics, such as beta-adrenergic blockers, clonidine, guanethidine and reserpine, the manifestations of adrenergic counterregulation of hypoglycemia may be reduced or absent altogether. Alcohol consumption may increase or decrease the hypoglycemic effect of glimepiride in unexpected ways. Glimepiride can both increase and decrease the effect of coumarin derivatives.

Amaryl M

Amaryl M is a combination drug that contains metformin in addition to glimepiride. This allows you to more effectively lower blood sugar levels and protect a person from diabetes complications, which can be very severe.

However, it is best to start treatment with a drug based only on metformin. If the desired effect cannot be achieved, then you need to get medical advice.

Analogues of the drug Amaryl M

There are no analogues of the drug Amaryl M. Therefore, if a person decides to replace this drug with something else, then preference should be given to drugs based on metformin, without any additions, for example, the drug Glucophage.

Amaryl drug overdose, symptoms and treatment

May lead to hypoglycemia, which lasts from 12 to 72 hours, and after the first reduction in the severity of symptoms, it may reappear. Symptoms may appear 24 hours after absorption of the drug. In general, in-clinic observation is recommended for such patients. Nausea, vomiting and epigastric pain may occur. Hypoglycemia can often be accompanied by neurological symptoms such as restlessness, tremors, blurred vision, coordination, drowsiness, coma and seizures. Treatment consists primarily of preventing drug absorption. To do this, you need to induce vomiting, drink water or lemonade, take activated charcoal and sodium sulfate. If a large amount of glimepiride is taken, gastric lavage is indicated, followed by the use of activated carbon and sodium sulfate. In case of severe overdose, hospitalization in the intensive care unit is necessary. Glucose administration should be started as soon as possible: if necessary, first a one-time intravenous injection of 50 ml of 50% solution, and then an infusion of 10% solution, constantly monitoring glycemia. Further treatment is symptomatic. When treating hypoglycemia, especially in young children who have accidentally taken Amaryl, the dose of glucose administered should be carefully monitored to avoid the possible development of dangerous hyperglycemia. It is important to constantly monitor glycemia.