Latin name: Amaryl M
ATX code: A10B D02
Active substance: Glimepiride,
metformin
Manufacturer: Handok Pharmaceuticals
(Republic of Korea)
Release from the pharmacy: On prescription
Storage conditions: t° up to 30 °C
Best before date: 3 years

Amaryl M oral tablets are intended for:

• For glycemic control in type II diabetes (as a complement to diet, exercise, weight loss)
• To reduce glycemia, if each of the active substances used separately does not give the desired result
• If a diabetic is prescribed a combination of metformin and glimepiride.

Composition, dosage, dosage form

The medicine is available with different concentrations of glimepiride and metformin. In one type of tablet their concentration is 1 mg and 250 mg, respectively, in the other - double the amount: 2 and 500 mg.

• The composition of additional ingredients is identical: lactose (in the form of monohydrate), sodium CMC, povidone-K30, CMC, crospovidone, E572.
• Film coating components: hypromellose, macrogol-6000, E171, E903.

Tablets of the same oval shape, convex on both sides, enclosed in a white coating of cling film. They differ in markings: on one of the surfaces of the 1mg/250mg pills the HD125 imprint is applied, and the more concentrated Amaryl-M (2/500) is marked with the HD25 icon.

Both types of Amaryl M are packaged in blisters of 10 pills. In a thick cardboard package - 3 plates with tablets, annotation.

Medicinal properties

A drug of combined action, its effect is due to the properties of the active components (glimepiride and metformin).

Glimepiride

The first substance belongs to the group of 3rd generation sulfonylurea derivatives. It has the ability to stimulate the production and release of insulin from pancreatic cells, increases the susceptibility of fat and muscle tissue to the effects of the endogenous substance. The hypoglycemic effect is achieved due to the higher, in contrast to 2nd generation sulfonamides, ability of the substance to regulate the amount of insulin produced by the body. This same property also ensures that the drug effectively reduces the threat of hypoglycemia.

Like other sulfonylurea derivatives, the Amaryl M component reduces insulin resistance, has an antioxidant effect, prevents the formation of blood clots, and minimizes damage to the cardiovascular system. Accelerates the transport of glucose into tissues and its utilization, stimulates glucose metabolism.

After systematic oral administration of 4 mg (daily dose), the highest concentration of the substance in the blood is formed after 2.5 hours. Eating food has virtually no effect on absorption, only slightly slowing down its rate.

Has the ability to penetrate into breast milk and pass through the placenta. It is transformed in the liver, forming two types of metabolites, which are then found in urine and feces.

A significant part of the substance is excreted from the body by the kidneys and a certain amount through the intestines.

Metformin

A substance with a hypoglycemic effect belongs to the group of biguanides. Its sugar-lowering ability can only manifest itself if the production of endogenous insulin is maintained. The substance does not affect the β-cells of the pancreas and does not in any way contribute to the production of insulin. When taken in recommended doses, it does not provoke a hypoglycemic effect.

The mechanism of its action has not yet been fully elucidated. It is believed to be able to enhance the effects of insulin. It is known that the substance increases tissue sensitivity to insulin by increasing the number of insulin receptors on cell membranes. In addition, metformin slows down the production of glucose in the liver, reduces the formation of free fatty acids, interferes with fat metabolism, and lowers the HT content in the blood. The substance reduces appetite, which helps diabetics maintain weight or lose weight.

After oral administration, it is completely absorbed from the gastrointestinal tract. Taking with food may reduce and inhibit absorption. Instantly distributed throughout tissues, almost does not bind to plasma proteins. Practically not metabilized.

Excretion from the body occurs through the kidneys. If the organ does not function effectively enough, there is a risk of accumulation of the substance.

Mode of application

The amount of the drug is calculated individually for each patient in accordance with glycemic indications. Treatment with Amaryl M, according to the instructions for use, is recommended to begin with the lowest dose at which adequate hypoglycemic control is possible. After this, the dosage can be changed depending on blood glucose levels.

If you miss a pill, you should not refill the missed medicine under any circumstances, otherwise this may cause a sharp decrease in glycemic levels. Patients should be advised in advance on what to do in such cases.

With improved glycemic control, when sensitivity to the effects of insulin increases, the need for medication may decrease during therapy with Amaryl M. To prevent hypoglycemia, you need to reduce the dosage in time or stop taking the pills.

The treatment regimen is determined by the treating doctor, but manufacturers recommend drinking it once or twice a day with meals. The highest permissible amount of metformin allowed for a single dose is 1 g, daily - 2 g.

To prevent hypoglycemia, at the beginning of therapy, the dosage of tablets should not be higher than the daily amount of metformin and glimepiride that the patient took in the previous course. If a diabetic is transferred to Amaryl-M from other drugs, then the dosage is calculated in accordance with the previously taken amount. If it is necessary to increase the dose of the medicine, it is best to increase it by half a tablet of Amaryl M 2 mg/500 mg.

The duration of the course is determined by a specialist; the drug is approved for long-term use.

During pregnancy and breastfeeding

The drug Amaryl M should not be used by pregnant women and women preparing for motherhood. The expectant mother should immediately inform her doctor about her intentions or the occurrence of pregnancy during therapy with a hypoglycemic agent, so that he can promptly prescribe another antihyperglycemic agent or transfer her to insulin therapy.

Studies conducted on laboratory animals have revealed that metformin contained in the drug can pose a threat to the development of the embryo/fetus and affect the child in the postpartum period.

It is known that metformin can easily pass into breast milk. Therefore, in order to prevent the substance from adversely affecting the baby’s body, a woman is recommended to give up lactation or switch to other drugs with a hypoglycemic effect, approved for nursing.

Contraindications and precautions

Average price: (1 mg/250 mg) – 735 rubles, (2 mg/500 mg) – 736 rubles.

Amaryl M tablets should not be taken if you have:

• Type I diabetes
• Complications of diabetes: ketoacidosis (including history), antecoma and coma
• Any form of metabolic acidosis (acute or chronic)
• Severe liver pathologies (due to lack of adequate experience with use)
• Hemodialysis
• Insufficient renal function and severe pathologies (there is a high probability of lactic acidosis)
• Any acute conditions that may adversely affect kidney function (dehydration, complex infections, use of drugs with iodine)
• Diseases that adversely affect the supply of oxygen to tissues (cardiac insufficiency, MI, shock)
• Predisposition of the body to lactic acidosis (including a history of lactic acidemia)
• Stressful conditions (complex injuries, thermal or chemical burns, surgical interventions, severe forms of infections with accompanying fever, blood poisoning)
• Unbalanced diet due to fasting, low-carbohydrate diets, exhaustion
• Absorption disorders of substances in the gastrointestinal tract (paresis and intestinal obstruction)
• Chronic alcohol addiction, acute alcohol overdose
• Lack of lactase in the body, galactose intolerance, GG malabsorption syndrome
• Preparation for conception, pregnancy, lactation
• Under 18 years of age (due to lack of guaranteed safety for a young body)
• High level of individual sensitivity or complete intolerance to the substances contained in the drug, as well as to any drugs with sulfonylurea derivatives, biguanides.

What you need to know when prescribing Amaryl M

At the beginning of therapy it is possible increased risk hypoglycemia, so over several weeks you need to more carefully check and, if necessary, adjust glycemia. Risk factors are:

• Patient's inability or unwillingness to comply with medical orders
• Poor nutrition (poor diet, irregular meals, non-renewable energy resources)
• Taking alcoholic drinks
• Metabolic disorder due to endocrine diseases (thyroid pathology, disruption of the functioning of areas of the brain responsible for metabolic processes)
• Addition of diseases that worsen the course of diabetes
• Taking other drugs without taking into account their compatibility with Amaryl M
• In the elderly: hidden deterioration in kidney function without symptoms
• Taking medications that affect the condition of the kidneys (taking diuretics that lower blood pressure, NSAIDs, etc.)
• Reduction or distortion of symptoms that are precursors of hypoglycemia.

Cross-drug interactions

When treating with Amaryl M, it must be taken into account that the two active components contained in its composition can separately or together enter into unwanted reactions with substances of other drugs. Ultimately, this may negatively affect the therapeutic effect or glycemic control and lead to unpredictable events.

Features of glimepiride

Metabolic transformation occurs with the direct participation of the CYP2C9 isoenzyme. Therefore, its properties change when combined with inhibitors or inducers of endogenous substances. If such combinations are necessary, it is necessary to check the correctness of the dosage and, if necessary, adjust it:

• The sugar-lowering effect of glimepiride is enhanced by the influence of ACE inhibitors, anabolic steroids, male hormones, drugs with coumarin derivatives, MAOIs, Cyclophosphamide, Fenfluramine, Pheniramidol, Fibratom, Fluconazole, salicylates, sulfonamides, tetracycline antibiotics, etc.
• The hypoglycemic effect is reduced when Amaryl M is combined with Acetazolamide, barbiturates, diuretics, sympathomimetics, GCS, large doses of nicotinic acid, glucagon, hormones (thyroid hormones, estrogens, progestogens), phenothiazine, Rifampicin, long-term use of laxatives.

Other possible reactions:

• When combined with H2-histamine receptor antagonists, beta blockers, Clonidine, Reserpine, the effect of Amaryl M may fluctuate, increasing or decreasing. To prevent negative conditions, it is imperative to carefully monitor glycemia and, in accordance with its indicators, change daily norm drug. In addition, drugs have a specific effect on NS receptors, as a result of which the response to treatment is disrupted. In turn, this can lead to a decrease in the severity of symptoms of hypoglycemia, which will increase the threat of its intensification.
• When combining glimepiride with ethanol against the background of excessive consumption or chronic form alcoholism, its hypoglycemic effect may be enhanced or weakened.
• When combined with coumarin derivatives and indirect anticoagulants, their effect changes in one direction or another.
• Absorption of glimepiride from the gastrointestinal tract is reduced under the influence of Colesevelam if it was taken before Amaryl M. But if you take the medicine in reverse order with an interval of at least 4 hours, then no negative consequences will not appear.

Features of the reaction of metformin with other drugs

Undesirable combinations include:

• Combination with ethanol. At acute poisoning Alcohol increases the risk of lactic acidosis, especially against the background of skipping meals or insufficient food consumption, or the presence of insufficient liver function. During therapy with Amaryl M, you should refrain from alcohol-containing drinks and medications.
• With iodine-containing contrast agents. When combining therapy with Amaryl M with procedures involving intravascular administration of contrast media, the risk of kidney damage increases. As a result of insufficient functioning of the organ, metformin accumulates with the subsequent development of lactic acidosis. To prevent an unfavorable scenario, Amaryl M should stop drinking 2 days before procedures with iodine-containing substances, and not take the same period after the end medical research. It is allowed to resume the course only after receiving data that there are no abnormalities in the condition of the kidneys.
• Combination with antibiotics that negatively affect the kidneys leads to the formation of lactic acidosis.

Possible combinations with metformin in which caution must be exercised:

• When combined with local or systemic corticosteroids, diuretics and 2-agonists, morning glycemia should be checked more often than usual (especially at the beginning of a complex cycle) so that it is possible to timely adjust the dosage during therapy or after discontinuation of certain drugs.
• When combined with ACE inhibitors and metformin, the first drugs can reduce glycemia, so dosage changes will be required during treatment or after discontinuation of the ACE inhibitor.
• When combined with drugs that can enhance the effect of metformin (insulin, anabolic steroids, sulfonylureas and derivatives, aspirin and salicylates), systematic monitoring of glucose levels is necessary for accurate and timely changes in the dosage of metformin after discontinuation of these drugs during ongoing treatment with Amaryl M.
• Similarly, glycemic control is necessary when Amaryl M is combined with medications that weaken its effect (corticosteroids, thyroid hormones, thiazide drugs, oral contraceptives, sympathomimetics, calcium antagonists, etc.) to adjust the dosage if necessary.

Side effects

The adverse effects of taking Amaryl M are due to both the individual properties of metformin and glimepiride, and their combined effect on processes in the body.

Glimepiride

The possible side effects listed below are based on clinical experience use of glimepiride and other sulfonylurea derivatives. Hypoglycemia may be prolonged. Appears as:

• Headache
• Constant hunger
• Nausea, vomiting
• General weakness
• Sleep disturbances (insomnia or drowsiness)
• Increased nervousness, anxiety
• Unreasonable aggressiveness
• Inability to concentrate, decreased attention
• Inhibition of psychomotor reactions
• Blackout
• Depressive state
• Sensitivity disorders in certain areas
• Decreased vision
• Speech disorders
• Seizures
• Fainting (possible coma)
• Difficulty breathing, bradycardia
• Cold, sticky sweat
• Tachycardia
• High blood pressure
• Rapid heartbeat
• Arrhythmias.

In some cases, when hypoglycemia is particularly severe, it may be confused with acute disorder blood circulation in the GM. The condition improves after eliminating hypoglycemia.

Other side effects

• Visual impairment: transient decrease in visual acuity (occurs especially often at the beginning of therapy). Caused by fluctuations in glycemia, resulting in swelling optic nerve, which is reflected in the angle of refraction.
• Gastrointestinal organs: nausea, vomiting, pain, diarrhea, bloating, feeling of fullness.
• Liver: hepatitis, activation of organ enzymes, jaundice, cholestasis. As pathologies progress, conditions that pose a threat to the patient’s life may develop. The condition may improve after stopping the medication.
• Hematopoietic organs: thrombocytopenia, sometimes leukopenia and other conditions due to changes in blood composition.
• Immunity: allergic and pseudoallergic symptoms (rash, itching, urticaria). Usually they manifest themselves in a mild degree, but sometimes they can progress, manifested by dyspnea, a drop in blood pressure, anaphylactic shock. Violations may also occur due to joint exposure to sulfonylurea or similar substances. It is necessary to contact a specialist.
• Other reactions: increased sensitivity of the dermis to sunlight and UV radiation.

Metformin

The most common adverse effect after taking medications with metformin is lactic acidosis. In addition, the substance can cause dysfunction internal systems and organs.

• Digestive organs: most often - nausea, vomiting, pain, flatulence, increased gas formation, lack of appetite. Symptoms are usually transient, characteristic of the initial stage of therapy. As you continue to take Amaryl, M disappear on their own. To alleviate the condition after taking the pills and prevent it, it is recommended to increase the dosage gradually and combine the medication with meals. If severe diarrhea and/or vomiting develops, dehydration and prerenal azotemia may result. In this case, therapy with Amaryl M should be interrupted until the state of health stabilizes.
• Senses: unpleasant “metallic” aftertaste
• Liver: disruption of the normal functioning of the organ, hepatitis (possible recovery after drug withdrawal). In case of liver problems, the patient should contact a healthcare professional as soon as possible.
• Skin: itching, rash, erythema.
• Hematopoietic organs: anemia, leuko- and thrombocytopenia. With a long course, there is a decrease in the content of vit. B12 in the blood, the occurrence of megaloblastic anemia.

Overdose

Conditions that may develop after taking large amounts of Amaryl M are due to the properties of its active components.

Glimepiride

The use of high doses of the substance is dangerous due to the development of hypoglycemia. A particularly strong threat arises with prolonged use. In this case, the unfavorable condition may pose a threat to the patient's life. Therefore, at the first suspicion of an overdose, you should immediately contact a doctor. If the patient is conscious, then before the ambulance arrives, you can help him by giving him carbohydrate foods, sugar or other sweets.

In case of threatening symptoms, the stomach is cleansed of the remnants of the tablets (vomiting is induced, the stomach is washed), after which the patient should be given activated charcoal to drink. In very difficult cases, the victim may need hospitalization.

Mild hypoglycemia, in which there is no loss of consciousness or neurological disorders, is eliminated by oral administration of dextrose/glucose and subsequent adjustment of the daily dosage of Amaryl M and the daily diet. The patient should be under close medical attention until the condition ceases to be dangerous.

In moderate and severe forms of hypoglycemia, accompanied by fainting and neurological disorders, the condition is considered critical. For this reason, immediate hospitalization is usually required. If the patient is in unconscious, he is injected with a saturated glucose solution intravenously. Administration of glucagon is also permitted. It is injected intravenously, intramuscularly or subcutaneously. After this, the patient is under round-the-clock observation for at least 1-2 days, since there is a possibility of a repeated attack of hypoglycemia. The risk of the condition returning may persist longer if the previous attack was protracted and extremely complex.

If an overdose occurs in a child, then the administration of dextrose should be accompanied by careful monitoring of glucose levels so that it is possible to react instantly if hyperglycemia occurs, an equally dangerous condition.

Metformin

As clinical data have shown, administration of the substance in a 10-fold higher amount did not lead to cases of a drop in glucose levels. But some diabetics developed lactic acidosis.

A severe overdose of the substance, as well as associated risk factors, can provoke lactic acid coma. In this case, only qualified medical care in a hospital can help the patient. The most effective method today is hemodialysis.

It is also possible that a consequence of taking overdoses may be the occurrence of acute form pancreatitis.

Analogs

To replace Amaryl M with another hypoglycemic medication, the patient should contact his treating endocrinologist. Exist different means, which have a similar effect: Galvus Met, Glibomet, Glimecomb, Glucovance, Gluconorm, Metglib.

Quimica Montpellier (Argentina)

average price packs (30 tablets): (2.5 mg/500 mg) – 219 rubles, (5 mg/500 mg) – 242 rubles.

A drug for lowering sugar in type 2 diabetics, if diet, physical activity and previous drug use do not produce results. It is also prescribed if the patient is prescribed tablets of two drugs with metformin and glibenclamide.

Produced in tablets for oral administration. Contains 2.5 or 5 mg metformin. Second active ingredient Glibenclamide is present in two forms in equal quantities.

The dosage regimen is determined individually for each patient. Maximum HF – 4 tablets.

Pros:

• Efficiency
• Available remedy
• Good quality.

Minuses:

• There are many contraindications.

A drug Amaryl has primarily prolonged, pancreatic, extrapancreatic effects. The mechanism of action is to stimulate the secretion and release of insulin from the beta cells of the pancreas. It also increases the sensitivity of fat and muscle tissue to the action of insulin. It acts by blocking the cytoplasmic ATP-dependent potassium channels of pancreatic beta cells. This is accompanied by the opening of calcium channels in the beta cell membranes and increased penetration of calcium into them (depolarization).
Amaryl's active ingredient, glimepiride, quickly detaches and binds to beta-cell protein, which has a molecular weight of 65 kDa/SURX and is associated with adenosine triphosphate-dependent potassium channels. It differs from other sulfonylurea derivatives in that it does not interact with the beta cell protein with a molecular weight of 140 kDa/SUR1. This leads to exocytosis of insulin, and the content of released insulin is much less than with the influence of other traditional drugs. The slight stimulating effect of amaryl on insulin secretion by beta cells leads to a lower risk of hypoglycemia.
The extrapancreatic effect of amaryl leads to a decrease in insulin resistance and a slight effect on the cardiovascular system. It has antiplatelet, antiatherogenic and antioxidant effects.
Increased utilization of glucose from fat and muscle tissue is carried out thanks to the presence in cell membranes specific transport proteins. In non-insulin-dependent diabetes, the penetration of glucose into these tissues is limited at the disposal stage. Amaryl quickly increases the activity of transport proteins, due to which glucose is absorbed better. There is also an increase in the number of transport proteins with the use of amaryl. There is virtually no blocking effect on ATP-dependent potassium channels of cardiac myocytes. The possibility of metabolic adaptation of cardiomyocytes to ischemic conditions remains. The activity of specific glycosyl-phosphatidylinositol phospholipase C increases, due to which glycogenesis and lipogenesis, correlated with amaryl intake, are observed.
Amaryl blocks hepatic glucose production by increasing the content of fructose-2,6-bisphosphate in hepatocytes (the latter also blocks gluconeogenesis).
While taking the drug, there is a blocking of COX secretion and a decrease in the transformation of arachidonic acid into thromboxane A2, due to which platelet aggregation (antithrombotic effect) decreases. Under the influence of amaryl, an increase in the concentration of alpha-tocopherol, which is formed endogenously, is observed. There is also an increase in the activity of superoxide dismutase, catalase and glutathione peroxidase, which is manifested by a decrease in the severity of oxidative reactions in diabetes mellitus.

Indications for use

Non-insulin-dependent diabetes mellitus (type 2) - as monotherapy or in combination with insulin (or metformin).

Mode of application

Amaryl taken orally. The tablets are not chewed, washed down with about 150 ml of water. It is important not to forget to eat after taking the drug.
The starting and maintenance dosage is set by the doctor individually depending on the level of glucose in the blood serum and its excretion in the urine.
First, the drug is used at a dose of 1 mg/day; if necessary, the daily dose can be gradually increased to 6 mg. The dose is increased at intervals of 1-2 weeks according to the following scheme: 1 mg/day-2 mg/day-3 mg/day-4 mg/day-6 mg/day of amaryl. It is recommended not to exceed amaryl doses of more than 6 mg/day. The frequency and time of use of the drug is determined individually by the doctor, which depends on the patient’s lifestyle. As a rule, the daily dose of Amaryl is prescribed 1 time per day during or before the first large meal (breakfast). If the morning dose was not taken, then during or before the second meal. The therapy is long-term.
Using a combination of amaryl-metformin. For patients taking metformin who experience insufficient reductions in serum glucose levels, supplemental amaryl can be started. If the daily dosage of metformin does not change, then Amaryl therapy is started with a dose of 1 mg/day. Subsequently, the dose of Amaryl can be increased to achieve the desired reduction in serum glucose levels to a maximum of 6 mg/day.
Using a combination of amaryl-insulin. To stabilize blood serum glucose levels in cases where monotherapy or the use of the amaryl-metformin combination is ineffective, a combination of insulin and amaryl is used. In this case, the dose of Amaryl is left the same, and insulin therapy is started with small doses. In the future, it is possible to increase the administered insulin. Therapy should be accompanied by monitoring of serum glucose concentrations. Treatment is carried out under the supervision of the attending physician. An insulin-amaryl regimen can reduce insulin requirements by approximately 40%.
Replacing another antidiabetic drug with amaryl. Initial treatment begins with 1 mg/day of amaryl, regardless of the dose of the previous drug (even if it was the maximum). Depending on the therapeutic effect amaryl, you can increase the dose according to the above rules. In some cases, it is necessary to discontinue Amaryl due to possible hypoglycemia (especially if a drug with a high half-life - chlorpropramide) was used before Amaryl. Therapy is stopped for several days (due to the likely additive effect).
Replacing insulin with amaryl. In cases where patients with diabetes mellitus Type 2 patients are prescribed insulin, but the insulin-secreting function of the beta cells of the pancreas remains intact; the patient can be switched to taking Amaryl with the exception of insulin. In this case, Amaryl therapy begins with a dose of 1 mg/day.

Side effects

Metabolism: the occurrence of hypoglycemic reactions soon after taking amaryl (such reactions are very difficult to correct).
Nervous system: headache, sleep disturbances, drowsiness, feeling tired, aggressiveness, anxiety, changes in concentration and speed of psycho-motor reactions, visual and speech disorders, dizziness, confusion, depression, sensory disturbances, aphasia, incoordination, paresis, helplessness, cerebral spasms, loss of self-control, tremor, loss or confusion, delirium, coma, anxiety, cold, sticky sweat.
Gastrointestinal tract: vomiting, epigastric discomfort, hunger, abdominal pain, diarrhea, jaundice, cholestasis, increased liver transaminases, hepatitis, liver failure, nausea.
Cardiovascular system: tachycardia, heart rhythm disturbances, arterial hypertension, bradycardia, angina pectoris.
Organ of vision: transient visual impairment as a result of changes in blood glucose levels (especially at the beginning of therapy).
Respiratory system: shallow breathing.
Hematopoietic system: leukopenia, thrombocytopenia (moderate or severe), erythrocytopenia, aplastic or hemolytic anemia, granulocytopenia, pancytopenia, agranulocytosis.
Hypersensitivity reactions: urticaria, itching, skin rash, allergic vasculitis. Allergic reactions are usually mild, but sometimes progression to anaphylactic shock is possible. A cross-reaction is possible with sulfonylureas and sulfonamides.
Others: hyponatremia, photosensitivity.

Contraindications

A drug Amaryl contraindicated for:
. Ketoacidosis of diabetic origin, diabetic coma and precoma,
. insulin-dependent diabetes mellitus (type 1),
. severe renal dysfunction (including patients on hemodialysis),
. severe violations liver functions,
. individual hypersensitivity to amaryl (glimepiride) or other components of the drug, other sulfonylureas, sulfonamides.

Pregnancy

Amaryl should not be prescribed to pregnant women or breastfeeding women. If the patient is planning a pregnancy, then she must be switched to insulin administration with the exception of Amaryl. If the patient is breastfeeding, then insulin administration is continued or breastfeeding is stopped (since amaryl passes into breast milk).

Interaction with other drugs

In combination with insulin, other drugs for the treatment of hypoglycemia, allopurinol, angiotensin-converting factor inhibitors, male sex hormones, anabolic steroids, coumarin derivatives, chloramphenicol, fenfluramine, fluoxetine, fibrates, pheniramidol, MAO inhibitors, guanethidine, pentoxifylline (when administered parenterally in large doses ), miconazole, azapropazone, phenylbutazone, quinolones, probenecid, oxyphenbutazone, salicylates, sulfinpyrazone, tetracyclines, long-acting sulfonamides, tritoqualine, tro-, cyclo-, and isophosphamide may increase the hypoglycemic effect of amaryl.
In combination with adrenaline (epinephrine) and sympathomimetics, acetazolamide, glucocorticosteroids, glucagon, diazoxide, barbiturates, saluretics, laxatives (with prolonged use), thiazide diuretics, nicotinic acid in large doses, phenytoin, phenothiazine, rifampicin, progestogens and estrogens, otherwise , hormones thyroid gland, lithium salts may reduce the hypoglycemic effect of amaryl.
When amaryl is combined with reserpine, clonidine and histamine H2 receptor blockers, both a decrease and an increase in the hypoglycemic effect are possible.
It is possible to reduce or weaken the effects of coumarin and its derivatives in combination with amaryl. Long-term or single use of enthanol-containing drugs and drinks can either weaken or enhance the hypoglycemic effect of Amaryl.

Overdose

In case of an overdose of Amaryl, hypoglycemia is possible for 12-72 hours when taking Amaryl in a high dose. Hypoglycemia may re-develop after blood glucose levels are restored.

Hypoglycemia manifests itself the following symptoms: increase blood pressure, increased sweating, nausea, vomiting, arrhythmia, pain in the heart, anxiety, sharp increase appetite, apathy, dizziness, drowsiness, headache, anxiety, palpitations, aggressiveness, impaired concentration, tremor, confusion, paresis, depression, sensory disturbances, tachycardia, convulsions of central origin. In some cases, hypoglycemia manifests itself as symptoms of a stroke. There is a risk of developing a coma. Therapy for hypoglycemia should begin with taking a piece of sugar, sweet tea or juice. The patient is warned to keep approximately 20 g of glucose with him at all times (in the form of 4 lumps of sugar, for example). Various sweeteners are ineffective in treatment. In severe cases, hospitalization is necessary. Vomiting is induced, and the patient is dehydrated (water with activated charcoal orally, laxative). Dextrose is administered parenterally (40% solution 50 ml intravenously). Subsequently, diluted dextrose (10% solution) is used. Treatment is accompanied by constant monitoring of serum glucose levels. Other symptoms are relieved by symptomatic treatment.
If amaryl is accidentally taken by people without diabetes (children), the development of hyperglycemia must be avoided. The dose of dextrose is carefully selected against the background of monitoring serum glucose levels.

Release form

Amaryl- tablets have a dividing strip, elongated in shape. Glimepiride tablets of 1 ml are pink in color. Amaryl 2 ml - green tablets. Amaryl 3 mg - light yellow tablets. Amaryl 4 mg - green. The package contains 2 blisters, each containing 15 tablets.

Storage conditions

Amaryl stored at a temperature not exceeding 25°C. Shelf life - 3 years.

Compound

Active ingredient: glimepiride.
Inactive components: lactose monohydrate, polyvidone 25,000, sodium starch glycolate, microcrystalline cellulose, magnesium stearate, dye (for amaryl 1 mg - iron oxide red (E172), for amaryl 2 mg - iron oxide yellow (E172) and indigo carmine (E132) , for amaryl 3 mg - yellow iron oxide (E172), for amaryl 4 mg - indigo carmine (E132).

Additionally

When treating with Amaryl, it is necessary to remember about conditions that require transferring the patient to parenteral insulin administration (polytraumas, surgical treatment, diseases with increased body temperature, extensive burns, changes in food absorption from gastrointestinal tract in diseases - intestinal obstruction, intestinal paresis and others).
When combining amaryl-metformin, it is necessary to take into account that taking high doses of metformin and glimepiride is accompanied by a pronounced improvement in metabolism in patients with uncontrolled diabetes mellitus. In the case of high doses of metformin and amaryl, if control is still insufficient, the patient can be switched to a combination of amaryl-insulin.
Factors that provoke the development of hypoglycemia: low patient compliance, inadequate, irregular nutrition, changes in the usual diet, skipping meals, alcohol consumption, fasting, changes in the balance between carbohydrate intake and physical activity, severe dysfunction of the liver and kidneys; concomitant uncompensated diseases of the endocrine system, amaryl overdose, thyroid dysfunction, adrenal insufficiency, pituitary insufficiency, combination with other drugs.
Signs of hypoglycemia are leveled out in the elderly, patients with neurocirculatory dystonia, patients taking beta-blockers, reserpine, clonidine, guanethidine, and sympatholytics.
The dose of the drug is selected individually depending on the glucose level in the blood. If the next dose is missed, it is strictly forbidden to take a higher next dose. The patient should tell the doctor if they are taking too high a dose of Amaryl. In case of diabetes compensation, an improvement in insulin sensitivity may be observed, so it is possible to reduce the dose of Amaryl (or even discontinue the drug). It is necessary to adjust the dose of Amaryl when various factors, which can provoke hypoglycemia or hyperglycemia, as well as in case of lifestyle changes. It must be remembered that proper diet, correction of physical activity, weight loss are of great importance for the treatment of diabetes mellitus while taking Amaryl.
It is necessary to inform the patient that he should immediately inform the attending physician of all side effects, which develop during therapy with amaryl. It is also necessary to inform him about the factors that cause both hyper- and hypoglycemia and the symptoms of these conditions.
Amaryl therapy should be accompanied by regular monitoring of glucose levels in the blood serum and urine, and determination of the concentration of glycosylated hemoglobin. Regular monitoring of these laboratory parameters helps to identify possible primary or secondary drug resistance in a timely manner.
Laboratory monitoring also includes determination of liver function, clinical analysis blood. During drug therapy, the speed of psycho-motor reactions may decrease, so working with precision machinery and driving a car is contraindicated. This is especially true for the initial stages of treatment with amaryl.

Main settings

Name:	AMARIL
ATX code:	A10BB12 -

Catad_pgroup Oral hypoglycemic agents

Amaryl - instructions for use

INSTRUCTIONS
By medical use drug (Amaryl®)

Registration number: P No. 015530/01 dated 04/12/2004

Tradename: Amaryl

International generic name(INN): glimepiride / glimepiride.

Dosage form: pills .

Compound

One tablet of Amaryl 1.0 mg contains:
Active substance- 1 mg glimepiride.
Excipients: lactose monohydrate, sodium starch glycollate, polyvidone 25000, microcrystalline cellulose, magnesium stearate, red iron oxide (E172).

One tablet of Amaryl 2.0 mg contains:
Active substance- 2 mg glimepiride.
Excipients: lactose monohydrate, sodium starch glycollate, polyvidone 25000, microcrystalline cellulose, magnesium stearate, iron oxide yellow (E172), indigo carmine.

One tablet of Amaryl 3.0 mg contains:
Active substance- 3 mg glimepiride.
Excipients: lactose monohydrate, sodium starch glycollate, polyvidone 25000, microcrystalline cellulose, magnesium stearate, iron oxide yellow (E172).

One tablet of Amaryl 4.0 mg contains:
Active substance- 4 mg glimepiride.
Excipients: lactose monohydrate, sodium starch glycollate, polyvidone 25000, microcrystalline cellulose, magnesium stearate, indigo carmine.

Description: oblong flat tablets with a score line on both sides, Pink colour with "NMK/Company Logo" engraved on both sides (1 mg), green with "NMM/Company Logo" engraved on both sides (2 mg), pale yellow with "NMN/Company Logo" engraved on both sides ( 3 mg) and blue color with "NMO/company logo" engraved on both sides (4 mg).

Pharmacotherapeutic group

Hypoglycemic agent for oral use of the third generation sulfonylurea group. ATX code: A10BB12.

Pharmacological properties

Pharmacodynamics
Glimepiride, active substance Amaryla is a hypoglycemic (diabetic-lowering) drug for oral use - a new (III) generation sulfonylurea derivative.
Glimepiride stimulates the secretion and release of insulin from the beta cells of the pancreas (pancreatic effect), improves the sensitivity of peripheral tissues (muscle and fat) to the action of its own insulin (extrapancreatic effect).
Insulin release
Sulfonylureas regulate insulin secretion by closing ATP-dependent potassium channels located in the cytoplasmic membrane of pancreatic beta cells. By closing potassium channels, they cause depolarization of beta cells, which promotes the opening of calcium channels and increased calcium entry into the cells. Glimepiride binds and dissociates at a high displacement rate to pancreatic beta cell protein (65 kDa/SURX), which associates with ATP-dependent potassium channels but differs from the usual binding site of traditional sulfonylureas (140 kDa protein /SUR1). This process leads to the release of insulin by exocytosis, while the quality of the secreted insulin is significantly lower than with traditional sulfonylureas. The least stimulating effect of glimepiride on insulin secretion also provides a lower risk of developing hypoglycemia.
Extrapancreatic activity
In addition, pronounced extrapancreatic effects of glimepiride were shown (reduced insulin resistance, less impact on the cardiovascular system, antiatherogenic, antiaggregation and antioxidant effects), which traditional sulfonylurea derivatives also have, but to a much lesser extent. Increased utilization of glucose from the blood by peripheral tissues (muscle and fat) occurs with the help of special transport proteins (GLUT1 and GLUT4) located in cell membranes. Glucose transport to these tissues in type 2 diabetes is a rate-limiting step in glucose utilization. Glimepiride very quickly increases the number and activity of glucose transport molecules (GLUT1 and GLUT4), which leads to increased glucose uptake by peripheral tissues.
Glimepiride has a weaker inhibitory effect on the K.atp channels of cardiomyocytes. When taking glimepiride, the ability of myocardial metabolic adaptation to ischemia is preserved.
Glimepiride increases the activity of glycosyl-phosphatidylinositol-specific phospholipase C, with which drug-induced lipogenesis and glycogenesis can correlate in isolated muscle and fat cells. Glimepiride inhibits hepatic glucose production by increasing intracellular concentrations of fructose-2,6-bisphosphate, which in turn inhibits gluconeogenesis.
Glimepiride selectively inhibits cyclooxygenase and reduces the conversion of arachidonic acid to thromboxane A2, which promotes platelet aggregation, thus exerting an antithrombotic effect. Glimepiride helps normalize lipid levels, reduces the level of minor aldehyde in the blood, which leads to a significant reduction in lipid peroxidation, which contributes to the antiatherogenic effect of the drug. Glimepiride increases the level of endogenous α-tocopherol, the activity of catalase, glutathione peroxidase and superoxide dismutase, which helps reduce the severity of oxidative stress in the patient’s body, which is constantly present in type 2 diabetes mellitus.

Pharmacokinetics
With repeated doses of glimepiride in a daily dose of 4 mg, the maximum concentration in the blood serum (Cmax) is reached after approximately 2.5 hours and is 309 ng/ml; There is a linear relationship between dose and Cmax, as well as between dose and AUC (area under the concentration-time curve). When glimepiride is taken orally, its bioavailability is complete. Food intake does not have a significant effect on absorption, with the exception of a slight slowdown in the rate of absorption. Glimepiride is characterized by a very low volume of distribution (about 8.8 L), approximately equal to the volume of distribution of albumin, a high degree of binding to plasma proteins (more than 99%) and low clearance (about 48 ml/min).
After a single oral dose of glimepiride, 58% is excreted in urine and 35% in feces. No unchanged substance was detected in the urine. The half-life at plasma serum concentrations of the drug corresponding to multiple dosing regimens is 5-8 hours. After taking high doses, the half-life increases slightly. Two inactive metabolites are detected in urine and feces, resulting from metabolism in the liver, one of them is a hydroxy derivative, and the other is a carboxy derivative. After oral administration of glimepiride, the terminal half-life of these metabolites is 3-5 hours and 5-6 hours, respectively.
Glimepiride is released from breast milk and penetrates the placental barrier. The drug penetrates the blood-brain barrier poorly. Comparison of single and repeated (2 times a day) administration of glimepiride did not reveal significant differences in pharmacokinetic parameters, and their variability was very low between different patients. There was no significant accumulation of the drug.
Pharmacokinetic parameters are similar in patients of different sexes and different age groups. In patients with impaired renal function (with low creatinine clearance), there was a trend towards increased clearance of glimepiride and a decrease in its mean serum concentrations, 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 drug accumulation.

Indications for use

Diabetes mellitus type 2 (in monotherapy or as part of combination therapy with metformin or insulin).

Contraindications

• diabetes mellitus type 1;
• diabetic ketoacidosis, diabetic precoma and coma;
• hypersensitivity to glimepiride or to any inactive component of the drug, to other sulfonylurea derivatives or to sulfonamide drugs (risk of developing hypersensitivity reactions);
• severe liver dysfunction;
• severe renal dysfunction (including patients on hemodialysis);
• pregnancy and lactation.

Carefully

Particular attention should be paid to conditions that require transferring the patient to insulin therapy: extensive burns, severe multiple trauma, major surgical interventions, as well as impaired absorption of food and drugs in the gastrointestinal tract (intestinal obstruction, intestinal paresis, etc.).

Use during pregnancy and lactation

Glimepiride is contraindicated for use in pregnant women. In case of planned pregnancy or if pregnancy occurs, the woman should be transferred to insulin therapy.
Since glimepiride appears to pass into breast milk, it should not be prescribed to women during lactation. In this case, it is necessary to switch to insulin therapy or stop breastfeeding.

Directions for use and doses

Initial dose and dose selection
At the beginning of treatment, 1 mg of Amaryl is prescribed 1 time per day. If necessary, the daily dose can be gradually increased under regular monitoring of blood glucose concentrations (at intervals of 1-2 weeks) and in the following order: 1 mg - 2 mg - 3 mg - 4 mg - 6 mg Amaryl per day. The maximum recommended daily dose is 6 mg.

Time and frequency of administration The daily dose is determined by the doctor taking into account the patient’s lifestyle. As a rule, it is sufficient to administer the daily dose in 1 dose immediately before or during a large breakfast or, if the daily dose has not been taken, immediately before or during the first large meal.
Amaryl tablets are taken whole, without chewing, with a sufficient amount of liquid (about 0.5 cups). It is very important not to skip meals after taking Amaryl.

Duration of treatment
As a rule, treatment with Amaryl is long-term.

Use in combination with metformin
In case of insufficient stabilization of blood glucose concentrations in patients taking metformin, concomitant therapy with Amaryl can be started.
While maintaining the dose of metformin at the same level, treatment with Amaryl begins with a minimum dose of 1 mg, and then its dose is gradually increased depending on the desired level of glycemic control, up to a maximum daily dose of 6 mg. Combination therapy should be carried out under close medical supervision.

Use in combination with insulin
In cases where it is not possible to achieve normalization of blood glucose concentrations by taking the maximum dose of Amaryl in monotherapy or in combination with the maximum dose of metformin, a combination of glimepiride with insulin is possible.
In this case, the last dose of Amaryl prescribed to the patient remains unchanged.
In this case, insulin treatment begins with a minimum dose, with a possible subsequent gradual increase in the dose of insulin under the control of blood glucose concentrations. Combined treatment requires mandatory medical supervision. While maintaining long-term glycemic control, this combination therapy can reduce insulin requirements by up to 40%.

Transferring a patient from another oral hypoglycemic drug to Amaryl
There is no exact relationship between the doses of Amaryl and other oral hypoglycemic drugs. When transferring from such drugs to Amaryl, the initial daily dose of the latter should be 1 mg (even if the patient is transferred to Amaryl from the maximum dose of another oral hypoglycemic drug). Any increase in the dose of Amaryl should be done in stages, taking into account the response to glimepiride in accordance with the recommendations above. The dose used and the duration of effect of the previous hypoglycemic agent must be taken into account. In some cases, especially when taking hypoglycemic drugs with a long half-life (for example, chlorpropamide), it may be necessary to temporarily discontinue treatment for several days to avoid additive effects that increase the risk of hypoglycemia.

Transferring a patient from insulin to Amaryl
In exceptional cases, if patients with type 2 diabetes mellitus receive insulin therapy, then when the disease is compensated and the secretory function of pancreatic β-cells is preserved, they may be advised to switch to Amaryl. The transfer must be carried out under the close supervision of a physician. In this case, transferring the patient to Amaryl begins with a minimum dose of glimepiride of 1 mg.

Use for renal and liver failure (See section "Contraindications").

Side effect

Metabolism In rare cases, hypoglycemic reactions may develop. These reactions mainly occur soon after taking the drug and are not always easily controlled. May occur: headache, hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, anxiety, aggressiveness, disturbances in concentration, attention and reaction, depression, confusion, speech and visual disturbances, aphasia, tremor, paresis, sensory disturbances , dizziness, visual disturbances, incoordination, helplessness, loss of self-control, delirium, cerebral spasms, confusion or loss of consciousness, including coma, shallow breathing, bradycardia. In addition, as a result of the adrenergic mechanism feedback Symptoms such as cold, clammy sweat, restlessness, tachycardia, hypertension, angina, and abnormal heart rhythms may occur. From the organs of vision During treatment (especially at the beginning), transient visual disturbances may be observed due to changes in the concentration of glucose in the blood. From the digestive system Sometimes nausea, vomiting, a feeling of heaviness or discomfort in the epigastrium, abdominal pain, diarrhea may occur; very rarely leading to cessation of treatment, in rare cases - increased activity of liver enzymes, cholestasis, jaundice, hepatitis (up to the development of liver failure). From the hematopoietic system Rarely, thrombocytopenia (moderate to severe), leukopenia, hemolytic or aplastic anemia, erythrocytopenia, granulocytopenia, agranulocytosis and pancytopenia are possible. Allergic reactions Sometimes itching, urticaria, and skin rash are possible. Such reactions are usually moderate, but can progress, accompanied by a drop in blood pressure, dyspnea, and even the development of anaphylactic shock. If symptoms of hives appear, you should consult a doctor immediately. Cross-allergy with other sulfonylurea derivatives, sulfonamides, or similar substances is possible, and the development of allergic vasculitis is also possible. Other side effects In exceptional cases, photosensitivity and hyponatremia may develop. If the patient detects any of the above side effects, other unwanted effects, he should consult his doctor.

Overdose

After ingestion large dose With glimepiride, hypoglycemia may develop, lasting from 12 to 72 hours, which may recur after the initial restoration of blood glucose concentrations. Hypoglycemia can almost always be quickly reversed by immediate intake of carbohydrates (glucose or sugar, for example in the form of a sugar cube, 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. In most cases, observation in a hospital setting is recommended. Treatment includes induction of vomiting, fluid intake (water or lemonade with activated carbon (adsorbent) and sodium sulfate (laxative). When taking a large amount of the drug, gastric lavage is indicated, followed by activated carbon and sodium sulfate. Clinical picture severe hypoglycemia may be similar to the clinical picture of stroke, so it requires immediate treatment under the supervision of a physician, and under certain circumstances, hospitalization of the patient. As soon as possible, dextrose is started, if necessary in the form of an intravenous bolus of 50 ml of a 40% solution, followed by an infusion of a 10% solution with careful monitoring of blood glucose concentrations. Further treatment should be symptomatic.
Symptoms of hypoglycemia may be smoothed out or completely absent in elderly patients, in patients suffering from autonomic neuropathy or receiving simultaneous treatmentβ-blockers, clonidine, reserpine, guanethidine or other sympatholytic agents.
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.
When treating hypoglycemia that has developed as a result of accidental administration of Amaryl to infants or small children, the indicated dose of dextrose (50 ml of a 40% solution) should be carefully monitored in order to avoid dangerous hyperglycemia. In this regard, continuous and careful monitoring of blood glucose concentrations is necessary.

Interaction with other drugs

Increased hypoglycemic effect and related possible development hypoglycemia may be observed with simultaneous use of glimepiride with insulin or other oral hypoglycemic drugs, metformin, angiotensin-converting enzyme inhibitors, allopurinol, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclo-, tro- and isophosphamides, fenfluramine, fibrates, fluoxetine, tics (guanethidine), monoamine oxidase inhibitors, miconazole, pentoxifylline (when administered parenterally in high doses), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolones, salicylates and aminosalicylic acid, sulfinpyrazone, some long-acting sulfonamides, tetracyclines, tritoqualine.
Weakening the hypoglycemic effect and an associated increase in blood glucose concentration can be observed with simultaneous use of glimepiride with acetazolamide, barbiturates, glucocorticosteroids, diazoxide, saluretics, thiazide diuretics, epinephrine and other sympathomimetic agents, glucagon, laxatives (with long-term use), nicotinic acid (in high doses) and nicotinic acid derivatives, estrogens and progestogens, phenothiazines, chlorpromazine, phenytoin, rifampicin, thyroid hormones, lithium salts.
H2 receptor blockers, clonidine and reserpine can both enhance and weaken the hypoglycemic effect of glimepiride.
While taking glimepiride, an increase or decrease in the effect of coumarin derivatives may be observed.
Single or chronic consumption of alcohol can either enhance or weaken the hypoglycemic effect of glimepiride.

special instructions

Combination therapy with metformin
In patients with poorly controlled type 2 diabetes mellitus, when maximum doses of metformin are used in monotherapy, a significant improvement in metabolic control is observed when glimepiride is added to treatment (combination therapy with metformin).

Combination therapy with insulin
In patients with poorly controlled type 2 diabetes while taking maximum doses of glimepiride and metformin, combination therapy: glimepiride + insulin can be started. When using this combination, improved metabolic control is achieved.
In the first weeks of treatment, irregular eating or skipping meals may increase the risk of hypoglycemia, which requires particularly careful monitoring of the patient. Factors contributing to the development of hypoglycemia include:

• reluctance or (especially in old age) insufficient ability of the patient to cooperate with the doctor;
• inadequate, irregular nutrition, skipping meals, fasting, changes in the usual diet;
• imbalance between physical activity and carbohydrate intake;
• drinking alcohol, especially in combination with skipping meals;
• renal dysfunction;
• severe liver dysfunction;
• Amaryl overdose;
• some uncompensated diseases of the endocrine system that affect carbohydrate metabolism (for example, thyroid dysfunction, pituitary insufficiency or adrenal insufficiency);
• simultaneous use of certain other drugs (see section “Interaction with other drugs”).

The doctor should be informed about the above factors and about episodes of hypoglycemia, since they require particularly strict monitoring of the patient. If such factors are present that increase the risk of hypoglycemia, the dose of glimepiride or the entire treatment regimen should be adjusted. This must also be done in the case of an intercurrent illness or a change in the patient’s lifestyle.
Glimepiride should be taken at the recommended doses and at the prescribed times.
Errors in the use of the drug, for example, missing a dose, should never be corrected by subsequent administration of a higher dose. The doctor and the patient should discuss in advance the measures that should be taken in case of such errors (for example, skipping a drug dose or meal) or in situations where it is impossible to take the next dose of the drug at the prescribed time. The patient should immediately inform the doctor if the dose of the drug is too high.
If a patient develops a hypoglycemic reaction while taking 1 mg of glimepiride per day, this indicates that this patient can normalize blood glucose levels with diet alone.

Dose adjustment
When compensation for type 2 diabetes mellitus is achieved, insulin sensitivity increases. In this regard, the need for glimepiride may decrease during treatment. To avoid the development of hypoglycemia, it is necessary to temporarily reduce the dose or discontinue glimepiride. Dose adjustment should also be carried out when the patient’s body weight changes, when his lifestyle changes, or when other factors appear that increase the risk of developing hypo- or hyperglycemia.
Adequate diet, regular and sufficient physical exercise and, if necessary, weight loss have the same important to achieve optimal blood glucose control, as does taking glimepiride regularly. Regular monitoring of blood glucose and glycosylated hemoglobin levels helps detect primary or secondary drug resistance.
Clinical symptoms of hyperglycemia (insufficient reduction of blood glucose levels) are: increased frequency of urination, extreme thirst, dry mouth and dry skin.
During treatment with glimepiride, regular monitoring of liver function and peripheral blood patterns (especially the number of leukocytes and platelets) is required.
There is no experience with the use of glimepiride in patients with severely impaired liver and kidney function or patients on hemodialysis. Patients with severely impaired renal and liver function are advised to switch to insulin therapy.
In stressful situations (for example, trauma, surgery, infectious diseases accompanied by fever), it may be necessary to temporarily transfer the patient to insulin therapy.
At the beginning of treatment, when switching from one drug to another, or when taking glimepiride irregularly, a decrease in the patient’s concentration and speed of psychomotor reactions due to hypo- or hyperglycemia may occur. This may adversely affect the ability to drive vehicles or operate various machines and mechanisms. Since certain side effects, such as: severe hypoglycemia, serious changes in the blood picture, severe allergic reactions, liver failure, can, under certain circumstances, pose a threat to life; in the event of undesirable or severe reactions, the patient must immediately inform the attending physician about them and in no case continue taking the drug without his recommendation.

Release form

Storage conditions

List B.
At a temperature no higher than +25°C, out of the reach of children!

Best before date

3 years. Do not use after the expiration date stated on the package.

Conditions for dispensing from pharmacies

On prescription.

Manufactured by Aventis Pharma Deutschland GmbH, Germany.
Brüningstrasse 50, D-65926, Frankfurt am Main, Germany.

Send consumer complaints to the address of the company’s representative office in Russia:
101000, Moscow, Ulansky lane, 5

Amaryl is considered popular among diabetics. Its use allows patients to control their condition and minimize the likelihood of developing hyperglycemia. This medication is prescribed only to people with type II diabetes.

Compound

The active ingredient in Amaryl is glimepiride. The tablets also contain auxiliary components. Their list will depend on the dosage of glimepiride. Different combinations of additional substances in tablets are due to different colors.

INN ( international name): glimepiride (Latin name Glimepiride).

Amaryl M1, M2 is also sold in pharmacies. In addition to glimepiride, the tablets contain metformin in an amount of 250 or 500 mg, respectively. Only an endocrinologist has the right to prescribe this combination drug.

Release form

Amaryl goes on sale in the form of tablets. The color depends on the dosage of the active substance:

• 1 mg glimepiride – pink;
• 2 – green;
• 3 – light yellow;
• 4 – blue.

They differ in the markings applied to the tablets.

pharmachologic effect

Glimepiride has a hypoglycemic effect on the body. It is a third generation sulfonylurea derivative.

Amaryl has a primarily prolonged effect. When taking the tablets, the pancreas is stimulated and the work of beta cells is activated. As a result, insulin begins to be released from them, the hormone enters the blood. This helps lower sugar levels after meals.

At the same time, glimepiride has an extrapancreatic effect. It increases the sensitivity of muscle and fat tissue to insulin. When using the drug, a general antioxidant, antiatherogenic, and antiplatelet effect is observed.

Amaryl differs from other sulfonylurea derivatives in that when it is used, the content of released insulin is less than when using other hypoglycemic drugs. Due to this, the risk of hypoglycemia is minimal.

Strengthening the process of glucose utilization in muscle and fat tissues becomes possible due to the presence of special transport proteins in cell membranes. Amaryl increases their activity.

The drug practically does not block ATP-sensitive potassium channels of cardiac myocytes. They retain the ability to adapt to ischemic conditions.

When treated with Amaryl, the production of glucose by liver cells is blocked. This effect is due to the increasing content of fructose-2,6-biophosphate in hepatocytes. This substance stops gluconeogenesis.

The drug helps block the secretion of cyclooxygenase and reduce the process of transformation of thromboxane A2 from arachidonic acid. Due to this, the intensity of platelet aggregation decreases. Under the influence of Amaryl, the severity of oxidative reactions that are observed in non-insulin-dependent diabetes decreases.

Indications

Glimepiride-based drugs are prescribed to patients with type II disease if physical activity and diet do not allow them to control sugar levels.

The instructions for use indicate that it is allowed to combine Amaryl with metformin and insulin injections.

Dr. Bernstein insists that the prescription of hypoglycemic drugs is not justified, even if there are indications for use. He argues that the drugs cause harm by exacerbating existing metabolic disorders. To normalize the condition, you can use not sulfonylurea derivatives, but a diet in combination with a special treatment regimen.

Contraindications

Amaryl should not be prescribed to patients who:

• insulin dependence;
• ketoacidosis, diabetic coma;
• kidney function is impaired (including in cases where hemodialysis is necessary);
• disruptions in liver function;
• individual intolerance or hypersensitivity to glimepiride, excipients, and other sulfonylurea drugs;
• childhood.

Doctors should not prescribe the drug to patients who are malnourished, eat irregularly, or limit caloric intake, consuming less than 1000 kcal. A contraindication is a violation of the process of absorption of food from the gastrointestinal tract.

Side effects

Before you start taking Amaryl, you should read the instructions for the drug. Patients should be aware of the complications that may occur.

The most well-known side effect is metabolic disorders. The patient may begin to develop hypoglycemia soon after taking the pill. At home, this condition is difficult to normalize; the help of doctors will be required. But a sudden decrease in blood glucose occurs in rare cases, not more often than 1 patient out of 1000.

When taking Amaryl, the following complications also arise:

• Gastrointestinal tract: diarrhea, feeling of hunger, epigastric pain, jaundice, nausea, hepatitis, development of liver failure;
• hematopoietic organs: thrombocytopenia, agranulocytosis, erythrocytopenia, leukopenia;
• nervous system: increased drowsiness, fatigue, headaches, increased anxiety, aggressiveness, speech disorders, confusion, paresis, cerebral spasms, the appearance of sticky cold sweat;
• organs of vision: transient disturbances due to changes in blood sugar levels.

Some develop hypersensitivity reactions. Patients complain of itching, skin rashes, urticaria, and allergic vasculitis. Typically, such side effects are mild; in individual cases, the possibility of anaphylactic shock cannot be excluded.

Instructions for use

Amaryl is allowed to be taken as prescribed by your doctor. The specialist will select the initial dosage for each patient personally. It depends on the concentration of glucose in the blood and the intensity of sugar excretion in the urine.

At the beginning of therapy, it is recommended to take tablets containing 1 mg of glimepiride. It is necessary to increase the dose gradually. Switch to 2 mg tablets no earlier than 1-2 weeks after the start of therapy. At the initial stages, the doctor monitors the patient’s condition and adjusts the treatment depending on the reaction to the drug. The maximum permissible daily dose is 6-8 mg of glimepiride.

If the desired therapeutic effect cannot be achieved even when taking the maximum permissible quantity Amaryl, then insulin is additionally prescribed.

It is necessary to take the tablets before the main meal once a day. Doctors recommend drinking the drug before breakfast. If necessary, it is allowed to shift the appointment time to lunch.

Refusing to eat after drinking Amaryl is strictly prohibited. After all, this will provoke a sharp drop in glucose concentration. Hypoglycemia can lead to neurological disorders and cause diabetic coma, of death.

The tablets are swallowed whole without chewing.

Overdose

Amaryl must be taken in quantities prescribed by a doctor. An overdose causes the development of hypoglycemia. A sharp drop in sugar sometimes provokes a diabetic coma.

If the permissible consumption limit is exceeded, nausea, vomiting, and epigastric pain occur. Various side effects may occur:

• visual impairment;
• drowsiness;
• tremor;
• convulsions;
• coma;
• problems with coordination.

In case of overdose, it is necessary to rinse the stomach. After cleaning, enterosorbents are given. At the same time, a glucose solution is administered intravenously. Further tactics actions are developed depending on the patient's condition. In severe cases, the patient is hospitalized in the intensive care unit.

Interaction

Before prescribing Amaryl, the doctor must find out what medications the patient is taking. Some medications enhance, while others reduce, the hypoglycemic effect of glimepiride.

When conducting research, it was found that a sharp decrease in blood sugar is observed when consuming:

• oral antidiabetic agents;
• Phenylbutazone;
• Oxyphenbutazone;
• Azapropazone;
• Sulfinpyrazone;
• Metformin;
• Tetracycline;
• Miconazole;
• salicylates;
• MAO inhibitors;
• male sex hormones;
• anabolic steroids;
• quinol antibiotics;
• Clarithromycin;
• Fluconazole;
• sympatholytics;
• fibrates.

Therefore, it is not recommended to start drinking Amaryl on your own without obtaining an appropriate prescription from a doctor.

The following drugs reduce the effectiveness of glimepiride:

• progestogens;
• estrogens;
• thiazide diuretics;
• saluretics;
• glucocorticoids;
• nicotinic acid (when used in high doses);
• laxative medications (subject to long-term use);
• barbiturates;
• Rifampicin;
• Glucagon.

This effect must be taken into account when selecting the dosage.

Sympatholytics (beta blockers, Reserpine, Clonidine, Guanethidine) have an unpredictable effect on the hypoglycemic effect of Amaryl.

When consuming coumarin derivatives, please note: glimepiride enhances or weakens the effect of these drugs on the body.

The doctor selects drugs for hypertension, non-steroidal anti-inflammatory drugs, and other popular drugs for the patient.

Amaryl is combined with insulin and metformin. This combination is required when taking glimepiride fails to achieve the desired metabolic control. The dosage of each drug is determined by the doctor individually.

• metformin;
• sitagliptin;
• glimepiride.

This combination of active ingredients makes it possible to enhance the effectiveness of therapy and help better control the condition of diabetics.

Terms of sale

You can purchase Amaryl in pharmacies if you have a prescription from your doctor.

Storage Features

Glimepiride-based tablets should be kept in a dark place, protected from direct sunlight, out of the reach of children. Storage temperature – up to +30 o C.

Best before date

The drug can be used for 36 months from the date of release.

Analogs

The treating endocrinologist should select a suitable substitute for Amaryl. He may prescribe an analogue made from the same active substance, or select a medicine made from other components.

Patients may be prescribed Russian substitute Diameride, which is relatively cheap. For 30 tablets of a drug made on the basis of glimepiride, with a dosage of 1 mg, patients will pay 179 rubles in a pharmacy. As the concentration of the active substance increases, the cost increases. For Diamerid in a dosage of 4 mg you will have to pay 383 rubles.

If necessary, replace Amaryl with the drug Glimepiride, which is produced Russian company Vertex. These tablets are inexpensive. For a pack of 30 pcs. for 2 mg you will have to pay 191 rubles.

The cost of Glimepiride Canon, which is produced by Canonpharma, is even lower. The price of a package of 30 tablets of 2 mg is considered cheap, it is 154 rubles.

If patients are intolerant to glimepiride, they are prescribed other analogues based on metformin (Avandamet, Glimecomb, Metglib) or vildagliptin (Galvus). They are selected taking into account individual characteristics the patient's body.

Alcohol and Amaryl

It is impossible to predict in advance how alcohol-containing drinks will affect a person who is taking drugs based on glimepiride. Alcohol can weaken or enhance the hypoglycemic effect of Amaryl. Therefore, they cannot be used at the same time.

Hypoglycemic medication must be taken for long period. Because of this, a categorical ban on the consumption of alcoholic beverages becomes a problem for many.

Pregnancy, lactation

During the period of intrauterine gestation or breastfeeding of a newborn, sulfonylurea derivatives should not be used. In the blood of a pregnant woman, the glucose concentration should be within normal limits. After all, hyperglycemia leads to an increased risk of developing birth defects development, increases infant mortality rates.

Pregnant women are switched to insulin. You can eliminate the possibility of a toxic effect of the drug on the child in utero if you stop using sulfonylureas at the stage of planning conception.

During lactation, therapy with Amaryl is prohibited. The active substance passes into breast milk and the newborn's body. When breastfeeding, it is necessary for the woman to completely switch to insulin therapy.

One of the most common antidiabetic drugs from the sulfonylurea group is Amaryl.

Thanks to the active and additional components, the drug helps lower glucose concentrations and effectively reduces the severity of symptoms of diabetes.

The antidiabetic drug Amaryl is accepted for oral use. The generally accepted international name of the drug is Amaryl. The drug is produced in Germany, manufactured by Aventis Pharma Deutschland GmbH.

On this page you will find all the information about Amaryl: full instructions on application to this drug, average prices in pharmacies, complete and incomplete analogues of the drug, as well as reviews of people who have already used Amaryl. Would you like to leave your opinion? Please write in the comments.

Clinical and pharmacological group

Oral hypoglycemic drug.

Conditions for dispensing from pharmacies

Dispensed with a doctor's prescription.

Prices

How much does Amaryl cost? The average price in pharmacies depends on the form of release:

• Amaryl tablets 1 mg, 30 pcs. – from 262 rub.
• Amaryl tablets 2 mg, 30 pcs. – from 498 rub.
• Amaryl tablets 3 mg, 30 pcs. – from 770 rub.
• Amaryl tablets 4 mg, 30 pcs. – from 1026 rub.

Release form and composition

Amaryl is available in tablet form in several dosages: 1, 2, 3 and 4 mg. Its properties are due to the active substance – glimepiride, a sulfonylurea derivative. Lactose monohydrate, povidone, magnesium stearate, microcrystalline cellulose and dyes E172 or E132 are used as excipients.

Regardless of the dosage, all tablets have a dividing line and engraving. As distinctive feature– the color of the tablet itself: 1 mg is pink, 2 mg is green, 3 mg is pale yellow and 4 mg is blue.

pharmachologic effect

Glimepiride, the active substance of the drug, has a positive effect on the pancreas, helps regulate insulin production and its entry into the blood. In turn, insulin lowers the amount of sugar in the blood.

Thanks to the effects of glimepiride, calcium from the blood enters tissue cells and helps prevent the formation of atherosclerotic plaques on the walls of blood vessels.

Metformin also helps reduce blood glucose, but in a different way: it improves hepatic circulation and converts blood sugar into glycogen, a substance safe for patients with diabetes. In addition, metmorphine promotes better absorption of glucose by muscle cells.

It has been established that glimepiride is more effective in combination with metformin. For this reason, Amaryl M was created - a drug convenient for both patients and doctors.

Indications for use

According to the instructions, Amaryl is prescribed for type 2 diabetes mellitus (non-insulin-dependent diabetes).

The active substance glimepiride stimulates the production of insulin by the pancreas and its release into the blood. Insulin, in turn, reduces the amount of sugar in the blood. Glimepiride improves potassium metabolism in cells and also helps prevent the formation of atherosclerotic plaques on the walls of blood vessels.

Contraindications

According to the instructions, Amaryl is contraindicated in the following cases:

• Rare hereditary diseases(lactase deficiency, galactose intolerance, glucose-galactose malabsorption);
• Hypersensitivity to the active or auxiliary components of the drug;
• Diabetes mellitus type 1;
• Severe liver dysfunction;
• Diabetic precoma and coma, diabetic ketoacidosis;
• Pregnancy and breastfeeding;
• Severe liver dysfunction (including patients on hemodialysis);
• Childhood.

When using Amaryl, caution should be exercised when:

• Impaired absorption of food and drugs from the gastrointestinal tract (intestinal paresis, intestinal obstruction);
• The presence of risk factors for the development of hypoglycemia;
• Intercurrent diseases during therapy or when the patient’s lifestyle changes (changes in diet or meal times, decrease or increase in physical activity);
• Glucose-6-phosphate dehydrogenase deficiency.

Use during pregnancy and lactation

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.

Instructions for use Amaryl

The instructions for use indicate that Amaryl tablets are taken orally, do not chew them, and are washed down with about 150 ml of water. It is important not to forget to eat after taking the drug. The starting and maintenance dosage is set by the doctor individually depending on the level of glucose in the blood serum and its excretion in the urine.

• First, the drug is used at a dose of 1 mg/day; if necessary, the daily dose can be gradually increased to 6 mg. The dose is increased at intervals of 1-2 weeks according to the following scheme: 1 mg/day-2 mg/day-3 mg/day-4 mg/day-6 mg/day of amaryl. It is recommended not to exceed amaryl doses of more than 6 mg/day. The frequency and time of use of the drug is determined individually by the doctor, which depends on the patient’s lifestyle. As a rule, the daily dose of Amaryl is prescribed 1 time per day during or before the first large meal (breakfast). If the morning dose was not taken, then during or before the second meal. The therapy is long-term.

Using a combination of amaryl-metformin. For patients taking metformin who experience insufficient reductions in serum glucose levels, supplemental amaryl can be started. If the daily dosage of metformin does not change, then Amaryl therapy is started with a dose of 1 mg/day. Subsequently, the dose of Amaryl can be increased to achieve the desired reduction in serum glucose levels to a maximum of 6 mg/day.

Using a combination of amaryl-insulin. To stabilize blood serum glucose levels in cases where monotherapy or the use of the amaryl-metformin combination is ineffective, a combination of insulin and amaryl is used. In this case, the dose of Amaryl is left the same, and insulin therapy is started with small doses. In the future, it is possible to increase the administered insulin. Therapy should be accompanied by monitoring of serum glucose concentrations. Treatment is carried out under the supervision of the attending physician. An insulin-amaryl regimen can reduce insulin requirements by approximately 40%.

Replacing another antidiabetic drug with amaryl. Initial treatment begins with 1 mg/day of amaryl, regardless of the dose of the previous drug (even if it was the maximum). Depending on the therapeutic effect of amaryl, you can increase the dose according to the above rules. In some cases, it is necessary to discontinue Amaryl due to possible hypoglycemia (especially if a drug with a high half-life, chlorpropramide, was used before Amaryl). Therapy is stopped for several days (due to the likely additive effect).

Replacing insulin with amaryl. In cases where patients with type 2 diabetes are prescribed insulin, but their insulin-secreting function of pancreatic beta cells remains intact, the patient can be switched to taking Amaryl with the exception of insulin. In this case, Amaryl therapy begins with a dose of 1 mg/day.

Side effects

The use of Amaryl may cause the following adverse reactions:

• Digestive system: rarely - abdominal pain, attacks of nausea, diarrhea, vomiting, feeling of fullness and heaviness in the epigastrium; in some cases - increased activity of cholestasis and/or liver enzymes, hepatitis, jaundice, life-threatening liver failure.
• Organ of vision: at the beginning of therapy, transient visual disturbances are possible, triggered by changes in blood glucose levels.
• Hematopoietic system: in some cases - granulocytopenia, leukopenia, pancytopenia, hemolytic anemia, agranulocytosis and erythrocytopenia; rarely - thrombocytopenia. Cases of severe thrombocytopenia and thrombocytopenic purpura have been reported during post-marketing use of Amaryl.
• Allergic manifestations: rarely - pseudo-allergic and allergic reactions (urticaria, skin rashes and itching). Such reactions are usually mild, but can become severe reactions with sharp decline Blood pressure, shortness of breath, anaphylactic shock, allergic vasculitis (in rare cases).
• Metabolism: as with other sulfonylurea derivatives, prolonged hypoglycemia is possible. Signs of this disorder are nausea, headache, vomiting, feelings of hunger and fatigue, impaired concentration, drowsiness, paresis, sleep disturbances, loss of self-control, anxiety, bradycardia, aggressiveness, sensory disturbances, loss of vigilance and reaction speed, visual disturbances, depression , delirium, confusion, speech disorders, aphasia, tremor, dizziness, cerebral spasms, shallow breathing, loss of consciousness up to coma. In addition, signs of adrenergic counterregulation in response to hypoglycemia may be observed (restlessness, the appearance of sticky cold sweats, angina pectoris, tachycardia, cardiac arrhythmias, palpitations and arterial hypertension). The clinical picture of severe hypoglycemia resembles a stroke.
• Other: in some cases - photosensitivity, hyponatremia.

Symptoms of overdose: severe, life-threatening hypoglycemia (with long-term treatment glimepiride in high doses and acute overdose of the drug).

Overdose

In case of an overdose of Amaryl, nausea, abdominal pain, and vomiting may occur. Hypoglycemia may occur, which may cause tremors, anxiety, visual disturbances, drowsiness, coordination problems, convulsions, and coma.

In case of overdose, gastric lavage is indicated, followed by the use of enterosorbents. Glucose administration should be started as soon as possible. Further therapy is symptomatic. In case of severe overdose, hospitalization in the intensive care unit is required.

special instructions

When prescribing Amaryl or Amaryl M to a patient, a doctor must warn about the possibility of side effects, and most importantly, about the occurrence of hypoglycemia if the patient takes the medicine but forgets to eat. In this case, the patient is recommended to always carry candy or sugar pieces with him in order to be able to quickly raise his blood sugar level.

In addition to systematically checking blood and urine glucose levels, during treatment with Amaryl and Amaryl M, blood composition and liver function are also regularly monitored.

In stressful circumstances, accompanied by the release of adrenaline into the blood, the effectiveness of Amaryl and Amaryl M is reduced. Such situations can be accidents, conflicts in the family or at work, illnesses with a high rise in temperature. In such cases, the practice is to temporarily transfer the patient to insulin.

Drug interactions

The hypoglycemic effect is enhanced by the simultaneous use of amaryl with insulin and other hypoglycemic drugs, some antibiotics (tetracyclines, sulfonamides, clarithromycin), high doses of pentoxifylline, fluoxetine, fluconazole, anabolic steroids, ACE inhibitors (captopril, enalapril, ramipril, perindopril, lisinopril, etc.). A combination of amaryl with barbiturates, laxatives, diuretics, high doses of nicotinic acid, and rifampicin will have the opposite effect.

Beta-blockers (carvedilol, atenolol, bisoprolol, metoprolol, etc.), reserpine, clonidine, coumarin derivatives and alcohol can increase or decrease the hypoglycemic effect of amaryl.