Pre instruction for use. Indications for prestance, pharmacodynamics, pharmacokinetics, instructions for use. Instructions for medical use

Prestans is a drug containing a combination of two active substances (perindopril + amlodipine), which are used to treat essential hypertension and other cardiovascular disorders. In the official pharmacological classification of ATX, prestance is designated by the code C09BB04.

The drug "Prestans"

Description of the mechanism of action of the drug

Perindopril is not actually an effective substance, but only a so-called prodrug from which the active substance, perindoprilat, arises in the body. This product is an enzyme inhibitor (ACE) that produces the hypertensive hormone angiotensin II in the body from its precursor angiotensin I. In addition, the enzyme converts bradykinin, which dilates blood vessels, into an ineffective metabolite. On the one hand, ACE inhibition leads to a decrease in the concentration of angiotensin II in the blood, on the other hand, it contributes to the activity of bradykinin.

Attention! The second effect may also contribute to the development of dry cough.

Pharmacodynamics of the drug

Amlodipine inhibits the influx of calcium ions into the muscle cells of the heart and blood vessels. This influx, however, is necessary for muscle contraction. The hypotensive effect of amlodipine is based on a direct relaxing effect on the vascular muscles.

The exact mode of action by which amlodipine relieves spasms in the coronary arteries is not yet fully known. In any case, the two effects complement each other: amlodipine dilates all the small arteries and reduces the resistance against which the heart must pump blood. Since the heartbeat stays the same, it makes the work of the heart easier and reduces energy consumption and oxygen demand.

In addition, amlodipine probably causes dilation of the arteries in the heart, both in normal and affected areas. This improves the supply of oxygen to the organs in patients with coronary artery spasm (vasospastic angina). Prestans is excreted from the body for a long time, which must be taken into account when prescribing new drugs.

Attention! For more information on the pharmacology of Prestanza, see the RLS Handbook.

Indications for use Prestanza

Prestance is used in adults to lower high blood pressure that has no apparent physical cause. Sometimes Prestance is used to treat myocardial insufficiency.

Prestans: instructions for use

Prestans is indicated for the first line treatment of patients with hypertension. As a rule, the doctor prescribes one tablet per day, and then gradually increases the dosage to the therapeutic one - 2 tablets in the morning and evening.

With myocardial insufficiency, the tablet is divided in half. The drug is taken with food and washed down with a sufficient amount of liquid. It is worth noting that it is possible to increase the dose of Prestanza only under the guidance of the attending cardiologist.

Prestanz has been shown to be effective in elderly patients. Depending on the function of the kidneys, the doctor will exercise caution at the beginning of medical intervention. After the start of therapy, it is necessary to constantly check the function of nephrons in elderly patients.

Important! Prestanz is dispensed by prescription in pharmacies. Only a cardiologist can correctly draw up a treatment regimen for hypertension and prescribe drugs.

Analogues of the drug "Prestans"

The main trade names for Prestanza substitutes are:

• Dalneva (manufacturing country - Slovenia);
• Perindopril plus amlodipine (Russian production);
• Amlopress.

The drug "Amlesa"

Contraindications to the use of Prestanza

Absolute contraindications to the use of Prestanza:

• Hypersensitivity to ACE inhibitors in general and to calcium channel blockers of the dihydropyridine type;
• Hereditary predisposition to the formation of edema in various parts of the body;
• severe hypotension;
• Apoplexy or cardiogenic shock;
• aortic occlusion;
• Severe myocardial insufficiency;
• Irreversible dysfunction of nephrons.

Only after careful consideration of the benefits / risks and under the supervision of a physician, Prestanz can be used in the following cases:

• Congenital anomalies of the connective tissue in the blood vessels;
• General weakness of the heart muscle;
• Treatment of black patients because they are more likely to respond with angioedema;
• Primary hyperaldosteronism (hyperfunction of the adrenal glands);
• Moderate nephropathy (creatinine clearance 30 to 60 milliliters/min), however, the combination of drugs should be used with extreme caution.

Pregnancy and lactation

Prestance should not be used during the first three months of pregnancy unless deemed necessary by a doctor. In late pregnancy, use is completely prohibited.

Pregnancy

It is not known whether the individual components of Prestanza pass into breast milk. Therefore, the doctor will decide whether to stop breastfeeding or treatment with Prestanz. In doing so, he will assess the risks of the harmful effects of breastfeeding on the child and the benefits of therapy for the woman. Your doctor will likely prefer another high blood pressure therapy that is safer when used during breastfeeding, especially when feeding newborns or premature babies.

The safety and efficacy of Prestanza in children under 18 years of age have not been established. Therefore, the use of the drug in this age group is possible only at the discretion of the doctor.

Side effects of Prestanza

Frequent side effects of the drug:

• Dizziness;
• Cough;
• Water retention in tissues.

Common adverse reactions of Prestanza:

• Excess potassium in the blood;
• Increasing the concentration of monosaccharides in the blood;
• erythema multiforme;
• Chronic Fatigue Syndrome.

Unusual side effects of Prestanza:

• Runny nose;
• Excess immature blood cells;
• Hypersensitivity;
• Hyponatremia;
• affective disorders (including anxiety);
• Insomnia;
• Depression;
• Drowsiness;
• Taste disorders;
• Loss of consciousness;
• hearing loss;
• Tremor;
• Cardiopalmus;
• Inflammation of blood vessels;
• bronchoconstriction;
• dry mouth;
• Hyperhidrosis;
• Hair loss;
• subcutaneous bleeding;
• swelling of the face;
• Photosensitivity of the skin;
• Pain in the spinal column;
• Hyperkinesis;
• Pain in the joints;
• Myalgia;
• urinary disorders
• renal dysfunction;
• Erectile disfunction;
• Gynecomastia
• Pain in the chest;
• Malaise;
• Fibromyalgia;
• Changes in body weight.

Rare side effects of Prestanza:

• Syndrome of twilight consciousness;
• Elevated bilirubin in the blood.

Very rare side effects of the drug:

• A sharp decrease in the number of leukocytes in the blood;
• Decrease in the number of neutrophils;
• Agranulocytosis;
• pancytopenia;
• Coagulation disorders;
• Hemolytic anemia;
• Arterial hypertension;
• Acute nephropathy;
• Panic attack;
• Mental lability;
• Neurasthenia.

Side effects of the drug of unknown frequency:

• Unintentional movements of the face or tongue.

The above side effects have occurred in clinical trials with Prestans therapy. Pancytopenia manifests as sore throat or high fever. With such symptoms caused by the drug, it is recommended to immediately consult a doctor.

Prestans: interaction and compatibility of drugs

Prestance should not be used with other antihypertensive agents such as AT1 receptor antagonists or aliskiren. Otherwise, it may lead to a higher strength of unwanted side effects such as hypotension, hyperkalemia and decreased nephron function. Increased side effects are most often observed in diabetics.

Preparations containing angiotensin receptor antagonists

Prestanz should not be combined with potassium salts, potassium-sparing diuretics, other ACE inhibitors, non-steroidal anti-inflammatory drugs, heparin and substances to suppress the body's defenses. It is necessary to constantly monitor the content of potassium in the bloodstream to avoid the occurrence of life-threatening hyperkalemia.

It is strictly forbidden to drink this drug together with alcoholic beverages (alcohol). There are cases when such a combination led to cardiovascular collapse and long-term negative consequences.

With the introduction of an antidepressant containing lithium and Prestanza, the toxic first may increase. Therefore, co-administration is not recommended, and if medically necessary, it is important to carefully monitor the concentration of lithium in the blood.

The muscle relaxant Dantrolene should not be used with Prestance if the patient has a tendency to overheat the body. In animal studies, when amlodipine was combined with Dantrolene and Verapamil, fatal cardiac arrhythmias and peripheral and central circulatory disorders were observed.

The drug "Dantrolene"

If the following active ingredients are used together with Prestans, the physician should take special care:

• Anti-diabetic drugs (insulin, for example) can cause high blood sugar levels or hypoglycemia;
• Baclofen, beta-blockers (Concor), and vasodilators (containing nitrates) may increase the hypotensive effect;
• Non-potassium diuretics lead to a sharp decrease in blood pressure, especially in the case of salt deficiency after the start of therapy with an ACE inhibitor;
• Rifampicin and St. John's wort may weaken the effect of the drug;
• HIV-1 protease inhibitor, ketoconazole and itraconazole, macrolide antibiotics such as erythromycin can increase the concentration of the active substance so that a dose reduction is required;
• Antidiabetic agents from the group of gliptins (Saxagliptin, Sitagliptin, Vildagliptin) increase the risk of developing edema of smooth muscle cells;
• Tricyclic antidepressants, psychotropic drugs and anesthetics additionally lower blood pressure;
• Alpha-sympathomimetics, glucocorticoids and the antiepileptic drug tetracosactide weaken the main hypotonic effect of Prestans.

Amifostine may increase the antihypertensive effect of amlodipine. In rare cases, injected drugs can cause facial flushing, nausea and vomiting, and low blood pressure.

Grapefruit juice leads to a strong decrease in blood pressure in some patients and should therefore be avoided. This is due to the fact that grapefruit components are cytochrome P450 inhibitors.

A strong decrease in blood glucose concentration with simultaneous treatment with ACE antagonists and antidiabetic drugs seems more likely during the first weeks in patients with complicated nephropathy.

Instructions for use

Co-Prenessa comes with an instruction leaflet that you should read. Ignoring the recommendations can lead to unpleasant consequences.

Indications

Your doctor may prescribe this drug for essential hypertension.

1 tablet should be taken orally 1 time / day. It is best to take the tablets in the morning before meals.

Treatment with Co-Prenessa in the elderly begins with an initial dosage of 2 mg (1 tablet) 1 time / day. The content of creatinine in the blood plasma should be adjusted according to the sex, age, and weight of the patient.

Therapy can be started only if the condition of the kidneys is normal.

If the patient has been diagnosed with mild renal insufficiency, then dosage adjustment is not required. However, in the future, it is necessary to monitor the content of creatinine and potassium 1 week after the start of therapy, and then after 2-4 months.

If the patient has been diagnosed with liver failure, then adjustment of treatment is not required.

Release form and composition

The drug Co-Prenessa is available in the form of:

1. Tablets with a dose of 2 mg;
2. with a dosage of 4 mg;
3. with a dose of 8 mg.

The composition of one tablet includes perindopril, indapamide, as well as calcium chloride hexahydrate, crospovidone, lactose, magnesium stearate, microcrystalline cellulose, monohydrate, sodium bicarbonate.

The drug is available in 30, 60 and 90 tablets.

Interaction with other drugs

Joint reception of Co-Preness With:

Side effects

Co-Prenessa may cause a number of side effects. These include:

1. Decreased blood pressure, angina pectoris, leukopenia, agranulocytosis, anemia, thrombocytopenia, myocardial infarction, hypotension, neutropenia.
2. Headache, sleep disturbance, convulsions, dizziness, tinnitus, emotional agitation, depression (may be severe), and visual impairment.
3. Cough (dry), rhinitis, shortness of breath, pneumonia.
4. Constipation, nausea, dysgevesia, cholestasis, diarrhea, hepatitis, digestive disorders, pancreatitis, encephalopathy.
5. Lupus erythematosus, photosensitivity, necrolysis, skin rash, anaphylactic shock, Stevens-Johnson syndrome.
6. General weakness, erectile dysfunction.

People who are professionally involved in sports should take into account that the drug can give a positive reaction to doping control.

Contraindications

The drug has a number of contraindications, which include:

1. Anuria.
2. Azotemia.
3. Allergy to the components that make up the drug.
4. Hyperkalemia.
5. Stenosis of the arteries of one or two kidneys.

If the patient has been diagnosed with acute liver failure, then the medication is contraindicated.

Pregnancy and lactation

During pregnancy, this medication should be discontinued. This is due to the fact that the drug can have a negative effect on the fetus.

If it is not possible to refuse taking the medicine, then the doctor should choose a safe analogue.

During breastfeeding, the baby should also refuse to take Co-Prenessa.

If it is not possible to refuse the reception, then the baby must be transferred to artificial nutrition.

Storage

Under all conditions, the shelf life of Co-Prenessa is no more than 2 years. After the expiration date has passed, the medicine must be disposed of.

Price

The exact price of Co-Preness medicine must be specified in the pharmacies of the city. The instructions give an approximate cost.

The price is based on the dosage and number of tablets.

1. In Moscow, for 30 tablets at a dosage of 2 mg, you will have to pay 300 rubles.
2. For the drug Co-Prenessa (30 tablets) at a dosage of 4 mg, on average, you will have to pay 400 rubles.
3. The medicine (30 tablets) at a dosage of 8 mg costs an average of 490 rubles.

Ukraine:

1. In Kyiv pharmacies, for 30 tablets of Co-Prenessa at a dosage of 2 mg, you will have to pay 106.04 UAH.
2. For 30 tablets of the drug at a dosage of 4 mg, you will have to pay 144.25 UAH.
3. The drug (30 tablets) 8 mg costs 160.89 UAH on average.

The drug Prestarium A instructions for use refers to angiotensin converting enzyme (ACE) inhibitors. Tablets 2.5 mg, 5 mg, 10 mg A with arginine are used to reduce blood pressure when it rises. At what pressure to take, will be shown in the article. Patient reviews and doctors' recommendations indicate that this drug helps in the treatment of arterial hypertension and heart failure.

Release form and composition

The medicine is available in tablet form.

• Dosages: 2 mg, 4 mg and 8 mg.
• Dosages Prestarium A: 2.5 mg, 5 mg and 10 mg.
• Bi-Prestarium is available in doses of 5+5, 10+5 and 10+10 mg.

Each tablet contains perindopril tert-butylamine salt and additional components: magnesium stearate, hydrophobic silicon dioxide, lactose monohydrate.

Perindopril arginine + excipients (Prestarium A).

The composition of the drug Bi-Prestarium additionally includes amlodipine.

Prestarium Combi contains indapamide.

pharmachologic effect

The drug has a hypotensive effect, that is, it lowers blood pressure. With prolonged use of Prestarium, favorable conditions are created for restoring the elasticity of arterial vessels, and left ventricular hypertrophy also decreases.

The drug normalizes the work of the heart, reducing pre- and afterload, reduces myocardial hypertrophy and the frequency of arrhythmias. The drug reduces the total peripheral vascular resistance, reduces the filling pressure of the left and right ventricles and moderately reduces the heart rate.

What helps Prestarium?

Indications for the use of the drug include pathological conditions of the body, accompanied by an increase in the level of systemic arterial pressure, these include:

• Stable coronary artery disease: to reduce the risk of cardiovascular complications.
• Isolated arterial hypertension.
• Prevention of cardiovascular complications associated with intravascular thrombus formation.
• Prevention of the development of a repeated stroke of the brain against the background of high blood pressure.

Also, the drug is used in chronic heart failure to reduce the functional load on the heart by lowering blood pressure.

Instructions for use

Prestarium is prescribed orally 1 time per day in the morning, before meals. Arterial hypertension The recommended initial dose is 5 mg 1 time per day, in the morning. With the ineffectiveness of therapy within a month, the dose may be increased to 10 mg 1 time per day.

When prescribing ACE inhibitors to patients with severe activated RAAS (with renovascular arterial hypertension, impaired water-salt balance, diuretic therapy, severe arterial hypertension, cardiac decompensation), an unpredictable sharp decrease in blood pressure may occur, for the prevention of which it is recommended to stop taking diuretics 2-3 days before before the expected start of therapy with Prestarium.

The instruction informs that if it is impossible to cancel diuretics, the initial dose of the drug is 2.5 mg. In this case, it is necessary to monitor kidney function and the content of potassium in the blood serum. Subsequently, if necessary, the dose may be increased.

In elderly patients, treatment should begin with a dose of 2.5 mg per day, and then, if necessary, gradually increase it up to a maximum dose of 10 mg per day.

Reducing the risk of cardiovascular complications

With stable coronary artery disease, therapy with Prestarium should be started with a dose of 5 mg 1 time per day for 2 weeks. Then the daily dose should be increased to 10 mg 1 time per day (depending on kidney function).

Prevention of recurrent stroke

In patients with a history of cerebrovascular disease, Prestarium therapy should be initiated at a dose of 2.5 mg for the first 2 weeks prior to indapamide administration. Therapy should begin at any time (from 2 weeks to several years) after a stroke.

Heart failure

Treatment with Prestarium in combination with non-potassium-sparing diuretics and / or digoxin and / or beta-blockers is recommended to be started under close medical supervision, prescribing the drug at an initial dose of 2.5 mg 1 time per day, in the morning.

Subsequently, depending on tolerance and response to therapy, after 2 weeks of treatment, the dose of the drug can be increased to 5 mg 1 time per day.

In patients at high risk of developing symptomatic arterial hypotension, for example, with a reduced salt content with or without hyponatremia, hypovolemia, or taking diuretics, before starting the drug Prestarium, if possible, the listed conditions should be corrected.

Indicators such as blood pressure, kidney function and plasma potassium should be monitored both before and during therapy.

Contraindications

The drug Prestarium A is not prescribed for:

• angioedema;
• breastfeeding;
• galactosemia;
• intolerance to ACE inhibitors;
• carrying a pregnancy.

The use of the drug is limited to:

• treatment with immunosuppressants;
• after kidney transplant;
• with renovascular hypertension;
• with stenosis of the aortic valve;
• hyponatremia;
• with hyperkalemia;
• with systemic pathology of connective tissue;
• decrease in BCC (hemodialysis, salt-free diet, diarrheal syndrome, profuse vomiting, the use of diuretic drugs).

Side effects

The use of Prestarium can cause deterioration of kidney function, the development of acute renal failure, the appearance of cough, bronchospasm, rhinitis, eosinophilic pneumonia, breathing problems, dry mouth, pancreatitis, cholestatic jaundice, nausea, diarrhea, abdominal pain, constipation, rash and itching on the skin, erythema multiforme, taste disturbance, loss of appetite.

There are reviews of Prestarium, confirming that the medicine can cause:

• asthenia;
• impaired vision, sleep, sexual function;
• arrhythmia;
• increased sweating;
• dizziness;
• deterioration in mood;
• tinnitus;
• confusion;
• convulsions;
• angina;
• severe pressure drop
• heart attack or stroke.

In addition, against the background of treatment with Prestarium and analogues of the drug, neutropenia, thrombocytopenia, pancytopenia, agranulocytosis, hyperkalemia, increased activity of liver enzymes, leukopenia, decreased hemoglobin, hematocrit can be observed.

Children, during pregnancy and lactation

It is not recommended to use the drug Prestarium in the 1st trimester of pregnancy. When planning or confirming pregnancy, it is necessary to switch to alternative therapy. Adequate, well-controlled clinical studies on the effect of ACE inhibitors in the 1st trimester of pregnancy have not been conducted.

In a limited number of cases of the use of ACE inhibitors in the 1st trimester of pregnancy, no malformations associated with fetotoxicity were observed.

Perindopril is contraindicated in the 2nd and 3rd trimesters of pregnancy, because. there are data on the manifestation of fetotoxicity (decreased renal function, oligohydramnios (pronounced decrease in the volume of amniotic fluid), delayed formation of the skull bones) and neonatal toxicity (impaired renal function, hypotension, hyperkalemia).

If therapy with perindopril was carried out in the 2nd and / or 3rd trimesters of pregnancy, it is necessary to conduct an ultrasound examination of the function of the kidneys and the fetal skull. It is not known whether perindopril is excreted in human breast milk, therefore, the use of the drug during lactation (breastfeeding) is not recommended.

special instructions

Patients with chronic heart failure taking digoxin or diuretics are prescribed a minimal dose of the drug, while the treatment is carried out under close medical supervision. For elderly patients and patients with renal insufficiency, the dosage is selected strictly individually.

Before starting therapy, a kidney examination is mandatory. As a rule, treatment begins with a minimum dose of Prestarium, which, with an adequate patient response to treatment, is gradually increased. Patients with fluid and sodium deficiency are corrected for fluid and electrolyte disturbances before starting therapy.

During the period of treatment, it is forbidden to carry out hemodialysis using polyacrylonitrile membranes. This may increase the risk of an anaphylactic reaction.

drug interaction

The simultaneous use of Prestarium with diuretics, potassium and lithium preparations, muscle relaxants, anesthetics, neuroleptics, sympathomimetics, NSAIDs, tricyclic antidepressants, and also with some other antihypertensive drugs is not recommended.

When taken with tricyclic antidepressants or antipsychotics, the risk of postural hypotension increases. Indomycin reduces the antihypertensive effect of the drug. In combination with insulin, it can cause the development of hypoglycemia due to increased glucose tolerance.

Taking the drug with potassium-sparing diuretics, salt substitutes and potassium preparations reduces the content of aldosterone, which causes potassium retention in the body due to a violation of its excretion.

Analogues of the drug Prestarium

According to the structure, analogues are determined:

1. Arentopres.
2. Stoppress.
3. Hypernic.
4. Perindopril erbumine.
5. Parnavel.
6. Perindopril arginine.
7. Perindopril tert-butylamine.
8. Perinpress.
9. Coverex.

Holiday conditions and price

The average price of Prestarium A (tablets 5 mg No. 30) in Moscow is 480 rubles. In Kyiv, you can buy medicine for 126 hryvnia, in Kazakhstan - for 3540 tenge. Pharmacies in Minsk offer the drug for 18.2 Belarusian rubles. ruble. Released without a prescription.

The shelf life of the tablets is 3 years from the date of their manufacture. There are no special conditions for storing the drug. It should be stored in its original packaging and out of the reach of children.

The official medical instruction for the use of the manufacturer Prestarium is shown in the photo (click to enlarge):

Prestarium photo 1

Nutrition "Humana" for children: a brief description

The above baby food is made in Germany. This manufacturer is a powerful dairy complex, which includes more than 8,000 farm dairy enterprises.

"Humana" today is one of the main leaders in Europe among milk processing plants. In addition to baby food, this manufacturer also produces high-quality milk products.

Benefits of Humana baby food:

1. Products do not contain genetically modified components. These milk processing enterprises are in close connection with farms. The milk of a sick cow is not used at all for the production of baby food. Animals are fed only natural feed. Also, the company uses a closed production cycle (when there is no contact between milk and air).
2. Baby food is enriched with vitamins and other useful substances.
3. High
4. The baby food of this manufacturer is contained in special packaging, which is air- and light-tight.
5. All products are produced according to a single identical unique recipe for any country in the world. It meets all established quality standards.
6. The manufacturer is constantly working to improve existing and develop new products.

Types of products brand "Humana"

The Humana company offers its small consumers a wide range of milk mixtures developed according to a special recipe. The above products meet all the requirements of the WHO and the Society of European Pediatricians.

The composition of baby food includes skimmed milk, demineralized milk whey, vegetable fats, maltodextrin, calcium orthophosphate, fish oil, potassium chloride, vitamins (ascorbic acid, tocopherol acetate, niacin, pantothenic acid, retinol, riboflavin, pyridoxine, thiamine, folic acid, biotin , D3, K, cyanocoballamine), sodium citrate, iron, sodium chloride, and other auxiliary and special substances for a specific age category.

Baby food "Humana" includes such types as:

• liquid form (O-HA, Pre);
• basic infant formulas;
• milk porridge;
• medical nutrition;
• dairy-free cereals;
• hypoallergenic mixtures (HA-1-2, SL).

"Humana" - baby food for newborns

If the child was born prematurely, this manufacturer has developed a special mixture of Humana 0 for him.

"Humana PRE" - baby food, which is a ready-made mixture, which is contained in a special jar. It is made exclusively from fresh milk, so it has a slightly high cost.

One of the advantages of this food is that it is convenient to take it with you to the hospital or, for example, for a regular walk. "Humana PRE" is available only in liquid form, and experts advise you to start feeding a newborn with it.

The main products of the above manufacturer

The basic products of this manufacturer include the following products:

• "Humana 1" - is intended for infants under the age of six months.
• "Humana 2" - designed for a six-month-old baby.
• "Humana 3" - designed for a child aged 10 months.
• "Humana 4" - designed for a baby after a year.

The above designation by numbers greatly facilitates the binding to age and means a more satisfying product. But experts warn that it is necessary to switch to a new mixture only taking into account the weight and appetite of the child.

If, for example, a child at 5 months does not eat up and is naughty, it is already advisable for him to try the next product.

Special blends

Baby food "Humana Hypoallergenic" is intended for babies who have symptoms of an allergy to cow's milk protein. The main principle of the action of such a mixture is that it contains already split proteins. It is easily absorbed by the baby's body and does not cause allergies. This is what distinguishes Humana baby food from other mixtures, in which manufacturers often add drugs.

A special pride of this manufacturer is therapeutic nutrition, which is used in case of observation of gastrointestinal problems in a child. Experts recommend using the following mixtures, depending on disorders in the digestive system:

• with colic - "Anticolic";
• with diarrhea - LP + MCT;
• with constipation - "Bifidus".

It is worth noting that the above nutrition is not a fast-acting medicine. The mechanism of action of the mixture is aimed at stabilizing the work of the entire digestive system. Its main goal is to teach the body to cope with the disease.

Porridge from the manufacturer "Humana"

Dairy-free cereals are produced without added sugar and gluten. This food is the best option for a first meal for a baby who is showing symptoms of an allergy to cow's milk protein. Very often, experts recommend mixing these porridges with the manufacturer "Humana" offers its small consumers buckwheat, oatmeal, rice, corn-rice, corn-rice with apple and rice with pumpkin porridge without milk. Quite a wide range!

Milk porridge "Humana" - baby food, the composition of which is distinguished by the presence of 13 vitamins, iodine, calcium and the absence of crystalline sugar. This is an exceptionally environmentally friendly product made from natural raw materials. The manufacturer offers a fairly large assortment of this food: multi-cereal porridge "Sweet Dreams", buckwheat, buckwheat with pear, buckwheat with apple, oatmeal, oatmeal with peach, corn-rice with vanilla, as well as milk porridge with cookies.

How to prepare the above food for children?

"Humana" - baby food, the instruction for which recommends preparing it as follows:

1. The required amount of water must be boiled and cooled to approximately 50 degrees Celsius. You can also heat baby water "Humana".

2. Pour the liquid into a bottle.

3. Add the desired number of measuring spoons of the mixture.

4. Close the bottle and shake it thoroughly until the mixture is completely dissolved.

Before you start feeding the baby, you need to check the temperature of the baby food in the bottle. Shake a few drops on the inside of your wrist.

One measuring spoon contains approximately 4.3 g of the mixture.

For a newborn baby, the amount of baby food is determined by the doctor. For babies aged 2 to 8 weeks, it is recommended to give 3 measured spoons per 90 ml of water. It is advisable to feed such a crumb 7-8 times a day.

For babies under the age of 4 months, food should be prepared from 5 measuring spoons and 150 ml of water. Food intake for such a child is carried out 5-6 times a day.

For crumbs after 4 months, the mixture is prepared from 6 measuring spoons and 180 ml of water. Feed such a baby should be 4-5 times a day.

After six months, the child eats 2-3 times. Use 5, 6 or 7 tablespoons of measured mixture for 150, 180 or 210 ml of water, respectively, depending on the baby's appetite.

"Humana" (baby food): reviews

Today you can meet quite a lot of responses from satisfied mothers who gave their aforementioned manufacturer. Women note that they are quite tasty (they tried it themselves). If the baby showed allergy symptoms, then pediatricians quickly prescribed the hypoallergenic product "Humana" (baby food).

Combined antihypertensive drug (ACE inhibitor + slow calcium channel blocker)

Active ingredients

Release form, composition and packaging

Pills white, oblong, biconvex, engraved "5/5" on one side and company logo - another.

Excipients: microcrystalline cellulose - 26 mg, lactose monohydrate - 65.233 mg, magnesium stearate - 0.52 mg, anhydrous colloidal silicon dioxide - 0.312 mg.

Packaging for hospitals:

Pills white, square, biconvex, engraved "5/10" on one side and company logo - another.

Excipients: microcrystalline cellulose - 52 mg, lactose monohydrate - 135.466 mg, magnesium stearate - 1.04 mg, anhydrous colloidal silicon dioxide - 0.624 mg.

29 pcs. - polypropylene bottles with a dispenser and a stopper containing a moisture-absorbing gel (1) - cardboard packs with first opening control.
30 pcs. - polypropylene bottles with a dispenser and a stopper containing a moisture-absorbing gel (1) - cardboard packs with first opening control.

Packaging for hospitals:
30 pcs. - polypropylene bottles with a dispenser and a stopper containing a moisture-absorbing gel (3) - cardboard packs with first opening control.

Pills white, triangular, biconvex, engraved "10/5" on one side and company logo - another.

Excipients: microcrystalline cellulose - 52 mg, lactose monohydrate - 137.401 mg, magnesium stearate - 1.04 mg, anhydrous colloidal silicon dioxide - 0.624 mg.

29 pcs. - polypropylene bottles with a dispenser and a stopper containing a moisture-absorbing gel (1) - cardboard packs with first opening control.
30 pcs. - polypropylene bottles with a dispenser and a stopper containing a moisture-absorbing gel (1) - cardboard packs with first opening control.

Packaging for hospitals:
30 pcs. - polypropylene bottles with a dispenser and a stopper containing a moisture-absorbing gel (3) - cardboard packs with first opening control.

Pills white, round, biconvex, engraved "10/10" on one side and company logo - another.

Excipients: microcrystalline cellulose - 52 mg, lactose monohydrate - 130.466 mg, magnesium stearate - 1.04 mg, anhydrous colloidal silicon dioxide - 0.624 mg.

29 pcs. - polypropylene bottles with a dispenser and a stopper containing a moisture-absorbing gel (1) - cardboard packs with first opening control.
30 pcs. - polypropylene bottles with a dispenser and a stopper containing a moisture-absorbing gel (1) - cardboard packs with first opening control.

Packaging for hospitals:
30 pcs. - polypropylene bottles with a dispenser and a stopper containing a moisture-absorbing gel (3) - cardboard packs with first opening control.

pharmachologic effect

Pharmacodynamics

Perindopril

Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (ACE inhibitor). ACE, or kininase II, is an exopeptidase that both converts angiotensin I to the vasoconstrictor angiotensin II and degrades the vasodilating bradykinin to an inactive heptapeptide.

Since ACE inactivates bradykinin, ACE suppression is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin systems, while the prostaglandin system is also activated.

Perindopril has a therapeutic effect due to the active metabolite, perindoprilat. Other metabolites do not have an inhibitory effect on ACE in vitro.

Arterial hypertension

Perindopril is a drug for the treatment of arterial hypertension of any severity. Against the background of its use, there is a decrease in both systolic and diastolic blood pressure in the supine and standing positions. Perindopril reduces OPSS, which leads to a decrease in blood pressure and an improvement in peripheral blood flow without changing heart rate.

As a rule, taking perindopril increases renal blood flow, while the glomerular filtration rate does not change.

The antihypertensive effect of the drug reaches a maximum after 4-6 hours after a single oral administration and lasts for 24 hours.

The antihypertensive effect 24 hours after a single oral dose is about 87-100% of the maximum antihypertensive effect. The reduction in blood pressure is achieved fairly quickly.

The therapeutic effect occurs less than 1 month after the start of therapy and is not accompanied by tachyphylaxis. Termination of treatment does not cause a rebound effect. Perindopril has a vasodilating effect, helps to restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy.

Stable coronary artery disease

The efficacy of perindopril in patients (12,218 patients over 18 years of age) with stable coronary artery disease without clinical symptoms of chronic heart failure was studied during a 4-year study. 90% of study participants had previously had an acute myocardial infarction and/or a revascularization procedure.

Most patients received standard therapy in addition to the study drug, including antiplatelet agents, lipid-lowering agents, and. The composite endpoint of cardiovascular death, non-fatal myocardial infarction, and/or cardiac arrest with successful resuscitation was selected as the primary outcome measure.

Therapy with perindopril tert-butylamine 8 mg once daily (equivalent to 10 mg perindopril arginine) resulted in a significant absolute risk reduction of 1.9% for the combined endpoint; in patients with prior myocardial infarction and/or a revascularization procedure, the absolute risk reduction was 2.2% compared to the placebo group.

Double blockade of the RAAS

There are data from clinical studies of combination therapy with an ACE inhibitor and an angiotensin II receptor antagonist (ARA II).

A clinical study was conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus, accompanied by confirmed target organ damage, as well as studies in patients with type 2 diabetes mellitus and diabetic nephropathy.

These studies did not reveal a significant positive effect of combination therapy on the occurrence of renal and / or cardiovascular events and on mortality rates, while the risk of developing hyperkalemia, acute renal failure and / or arterial hypotension increased compared with monotherapy.

Taking into account the similar intragroup pharmacodynamic properties of ACE inhibitors and ARA II, these results can be expected for the interaction of any other drugs, representatives of the classes of ACE inhibitors and ARA II.

Therefore, the use of ACE inhibitors in combination with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy.

There is evidence from a clinical study investigating the beneficial effects of adding aliskiren to standard therapy with an ACE inhibitor or ARA II in patients with type 2 diabetes and chronic kidney disease or cardiovascular disease, or a combination of these diseases. The study was terminated early due to an increased risk of adverse outcomes. Cardiovascular death and stroke were more common in the aliskiren group than in the placebo group; also adverse events and serious adverse events of special interest (hyperkalemia, arterial hypotension and impaired renal function) were recorded more often in the aliskiren group than in the placebo group.

Amlodipine

Amlodipine is a slow calcium channel blocker, a derivative of dihydropyridine. Amlodipine inhibits the transmembrane transition of calcium ions into cardiomyocytes and smooth muscle cells of the vascular wall.

The antihypertensive effect of amlodipine is due to a direct relaxing effect on the smooth muscle cells of the vascular wall. The detailed mechanism by which amlodipine exerts its antianginal action is not well established, but amlodipine is known to reduce total ischemic burden through two actions:

Causes expansion of peripheral arterioles, reducing OPSS (afterload). Since the heart rate does not change, the myocardial oxygen demand decreases;

Causes expansion of the coronary arteries and arterioles in both ischemic and intact areas. Their dilatation increases the supply of oxygen to the myocardium in patients with vasospastic angina (Prinzmetal's angina, or variant angina pectoris).

In patients with arterial hypertension, taking amlodipine 1 time / day provides a clinically significant decrease in blood pressure in the standing and lying position for 24 hours. The antihypertensive effect develops slowly, and therefore the development of acute arterial hypotension is uncharacteristic.

In patients with angina pectoris, taking amlodipine 1 time / day increases the total time of physical activity, increases the time to the development of an angina attack and to the onset of ST segment depression by 1 mm, and also reduces the frequency of angina attacks and consumption under the tongue.

Amlodipine does not have adverse metabolic effects and does not affect the concentration of plasma lipids. The drug can be used in patients with concomitant bronchial asthma, diabetes mellitus and gout.

Efficacy results suggest that amlodipine is associated with fewer hospitalizations for angina and fewer revascularization procedures in patients with coronary artery disease.

Heart failure

The results of hemodynamic studies, as well as the results of clinical studies in patients with chronic heart failure II-IV FC according to the NYHA classification, demonstrated that amlodipine does not lead to clinical deterioration, based on data on exercise tolerance, left ventricular ejection fraction and clinical symptoms.

In patients with chronic heart failure III-IV FC according to the NYHA classification, while taking digoxin, diuretics and ACE inhibitors, it was shown that taking amlodipine does not lead to an increased risk of mortality or mortality and morbidity associated with heart failure.

The results of long-term studies in patients with chronic heart failure III and IV according to the NYHA classification without clinical symptoms of coronary artery disease or objective data indicating the presence of coronary heart disease while taking stable doses of ACE inhibitors, cardiac glycosides and diuretics showed that taking amlodipine does not affect mortality rate from cardiovascular disease. In this population of patients, the use of amlodipine was accompanied by an increase in the number of reports of the development of pulmonary edema.

Prevention of myocardial infarction

The efficacy and safety of amlodipine at a dose of 2.5-10 mg/day, the ACE inhibitor lisinopril at a dose of 10-40 mg/day, and the thiazide diuretic chlorthalidone at a dose of 12.5-25 mg/day as a first-line drug was studied in patients with mild or moderate Hypertension and at least one of the additional risk factors for coronary complications, such as myocardial infarction or stroke, suffered more than 6 months before inclusion in the study, or other confirmed cardiovascular disease of atherosclerotic origin; diabetes; HDL cholesterol concentration less than 35 mg/dl; left ventricular hypertrophy according to ECG or echocardiography; smoking.

The main criterion for evaluating the effectiveness is the combined indicator of the frequency of deaths from coronary artery disease and the frequency of non-fatal myocardial infarction. There were no significant differences between the amlodipine and chlorthalidone groups in terms of the main evaluation criterion. The incidence of heart failure in the amlodipine group was significantly higher than in the chlorthalidone group - 10.2% and 7.7%, respectively, the overall incidence of deaths in the amlodipine and chlorthalidone groups did not differ significantly.

perindopril and amlodipine

Efficacy with long-term use of amlodipine in combination with perindopril and atenolol in combination with bendroflumethiazide in patients aged 40 to 79 years with hypertension and at least 3 of the additional risk factors, such as left ventricular hypertrophy according to ECG or echocardiography; type 2 diabetes; atherosclerosis of peripheral arteries; previous stroke or transient ischemic attack; male gender; age 55 and older; microalbuminuria or proteinuria; smoking; total cholesterol/HDL cholesterol ≥ 6; early development of coronary heart disease in the next of kin was studied in the ASCOT-BPLA study.

The main criterion for evaluating effectiveness is the combined rate of non-fatal myocardial infarction (including painless) and lethal outcomes of coronary artery disease.

The incidence of complications, provided for by the main evaluation criterion, in the amlodipine / perindopril group was 10% lower than in the atenolol / bendroflumethiazide group, however, this difference was not statistically significant. In the amlodipine/perindopril group, there was a significant reduction in the incidence of complications provided by additional efficacy criteria (except for fatal and non-fatal heart failure).

Pharmacokinetics

The amount of absorption of perindopril and amlodipine when using the drug Prestans does not differ significantly from that when using monodrugs.

Perindopril

Suction

When taken orally, perindopril is rapidly absorbed, Cmax in plasma is achieved within 1 hour. T 1/2 of perindopril from blood plasma is 1 hour.

Perindopril has no pharmacological activity. Approximately 27% of the total amount of perindopril taken orally enters the bloodstream as the active metabolite of perindoprilat. In addition to perindoprilat, 5 more metabolites are formed that do not have pharmacological activity. C max perindoprilat in plasma is achieved 3-4 hours after ingestion. Food intake slows down the conversion of perindopril to perindoprilat, thus affecting bioavailability. Therefore, the drug should be taken 1 time / day, in the morning, before meals.

Distribution

There is a linear relationship between the concentration of perindopril in plasma and its dose. V d free perindoprilat is approximately 0.2 l / kg. The relationship of perindoprilat with plasma proteins, mainly with ACE, is about 20% and is dose-dependent.

breeding

Perindoprilat is excreted from the body by the kidneys. The final T 1/2 of the free fraction is about 17 hours, so the equilibrium state is reached within 4 days.

Removal of perindoprilat is slowed down in the elderly, as well as in patients with heart and kidney failure (see section "Dosage regimen"). Therefore, in these groups of patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.

The dialysis clearance of perindoprilat is 70 ml/min.

The pharmacokinetics of perindopril is impaired in patients with liver cirrhosis: its hepatic clearance is reduced by 2 times. However, the amount of perindoprilat formed does not decrease, which does not require dose adjustment (see section "Dosage regimen" and "Special instructions").

Amlodipine

Suction

After oral administration, amlodipine is slowly absorbed from the gastrointestinal tract. Eating does not affect the bioavailability of amlodipine. C max amlodipine in plasma is achieved 6-12 hours after taking the drug inside. Absolute bioavailability is about 64-80%.

Distribution

V d - about 21 l / kg. In vitro studies have shown that about 97.5% of circulating amlodipine is bound to plasma proteins.

Metabolism and excretion

The final T 1/2 of amlodipine from blood plasma is 35-50 hours, which allows you to take the drug 1 time / day. Amlodipine is metabolized in the liver to inactive metabolites, with 10% of the dose taken unchanged and 60% excreted by the kidneys as metabolites. Amlodipine is not excreted from the body by dialysis.

The time from taking the drug to reaching Cmax of amlodipine does not differ in elderly and younger patients. In elderly patients, there is a slowdown in the clearance of amlodipine, which leads to an increase in AUC.

The increase in AUC and T 1/2 in patients with CHF corresponds to the expected value for this age group.

In patients with impaired renal function, changes in the concentration of amlodipine in the blood plasma do not correlate with the degree of renal failure. A slight increase in T 1/2 is possible.

There are limited data on the use of amlodipine in patients with hepatic impairment. In patients with hepatic insufficiency, a decrease in the clearance of amlodipine is observed, which leads to an increase in T 1/2 and AUC by approximately 40-60%.

Indications

- arterial hypertension and / or ischemic heart disease: stable angina pectoris in patients who require therapy with perindopril and amlodipine.

Contraindications

Perindopril

- hypersensitivity to perindopril or other ACE inhibitors;

- angioedema (Quincke's edema) in history (including against the background of taking other ACE inhibitors);

- hereditary / idiopathic angioedema;

- simultaneous use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and / or moderate and severe renal impairment (GFR<60 мл/мин/1.73 м 2 площади поверхности тела) (см. разделы "Лекарственное взаимодействие" и "Фармакологическое действие", подраздел "Фармакодинамика");

- simultaneous use with angiotensin II receptor antagonists (APA II) in patients with diabetic nephropathy (see section "Special Instructions");

- pregnancy (see section "Pregnancy and lactation");

Amlodipine

- hypersensitivity to amlodipine and other dihydropyridine derivatives;

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

- shock (including cardiogenic);

- obstruction of the outflow tract of the left ventricle (for example, clinically significant aortic stenosis);

- hemodynamically unstable heart failure after acute myocardial infarction;

- age up to 18 years (efficacy and safety have not been established).

prestance

- hypersensitivity to the excipients that make up the drug;

- renal failure (CC less than 60 ml / min);

- age up to 18 years (efficacy and safety have not been established);

- hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption.

All contraindications related to perindopril and amlodipine above apply also to the combination drug Prestans.

Carefully

Renal artery stenosis (including bilateral), single functioning kidney, liver failure, renal failure, systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), immunosuppressant therapy, allopurinol, procainamide (risk of developing neutropenia, agranulocytosis), reduced BCC (diuretic intake, salt-free diet, vomiting, diarrhea), atherosclerosis, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure, simultaneous use of dantrolene, estramustine, potassium-sparing diuretics, potassium preparations, potassium-containing food salt substitutes and drugs lithium, hyperkalemia, surgery/general anesthesia, older age, hemodialysis with high-flow membranes (eg, AN69), desensitization therapy, LDL apheresis, aortic stenosis/mitral stenosis/hypertrophic obstructive cardiomyopathy, use in black patients, chronic heart failure non-ischemic etiology III-IV FC according to the NYHA classification.

Dosage

The drug is prescribed orally, 1 tab. 1 time / day, preferably in the morning before meals. The dose of the drug Prestanz is selected after previously performed dose titration of the individual components of the drug: perindopril and amlodipine in patients with arterial hypertension and / or coronary artery disease.

If therapeutically necessary, the dose of the drug Prestanz can be changed or an individual selection of doses of individual components can be carried out beforehand:

5 mg perindopril + 5 mg amlodipine or
5 mg perindopril + 10 mg amlodipine or
10 mg perindopril + 5 mg amlodipine or
10 mg perindopril + 10 mg amlodipine.

Special patient groups

Elderly patients and patients with renal insufficiency(see sections "Pharmacokinetics" and "Special Instructions")

Removal of perindoprilat from elderly patients and patients with renal insufficiency slowed down. Therefore, in such patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma. The drug Prestanz can be prescribed patients with CC ≥ 60 ml / min. Prestans is contraindicated patients with CC< 60 мл/мин (see section "Contraindications"). Such patients are recommended individual selection of doses of perindopril and amlodipine. Amlodipine, used in equivalent doses, is equally well tolerated by both elderly and younger patients. No change in dosing regimen is required in elderly patients, however, increasing the dose should be carried out with caution, which is associated with age-related changes and an increase in T 1/2. The change in the concentration of amlodipine in the blood plasma does not correlate with the severity of renal failure. Amlodipine is not excreted from the body by dialysis.

Patients with liver failure(see sections "Dosing regimen" and "Special instructions").

For patients with mild or moderate hepatic impairment dose selection should be done with caution. It is recommended to start taking the drug with low doses (see sections "Dosage regimen" and "Special instructions"). Search for the optimal initial and maintenance dose for patients with liver failure should be carried out individually, using drugs amlodipine and perindopril in monotherapy. The pharmacokinetics of amlodipine in patients with severe hepatic impairment not studied. For such patients, amlodipine should be started at the lowest dose and increased gradually.

The drug Prestanz should not be prescribed children and adolescents under 18 years of age

Side effects

The frequency of adverse reactions that were noted during monotherapy with perindopril and amlodipine is given as the following gradation: very often (≥1 / 10); often (≥1/100,<1/10); нечасто (≥1/1000, <1/100); редко (≥1/10 000, <1/1000); очень редко (<1/10 000), включая отдельные сообщения; неуточненной частоты (частота не может быть подсчитана по доступным данным).

From the hematopoietic and lymphatic systems: very rarely - leukopenia, neutropenia, agranulocytosis, pancytopenia, thrombocytopenia, hemolytic anemia in patients with congenital deficiency of glucose-6-phosphate dehydrogenase, decreased hemoglobin and hematocrit.

From the immune system: infrequently - allergic reactions.

From the side of metabolism: very rarely - hyperglycemia; unspecified frequency - hypoglycemia.

From the side of the central nervous system: often - drowsiness (especially at the beginning of treatment), dizziness (especially at the beginning of treatment), headache, paresthesia, vertigo; infrequently - insomnia, mood lability (including anxiety), sleep disturbance, tremor, hypesthesia, depression, fainting; rarely - confusion; very rarely - peripheral neuropathy, hypertonicity.

From the side of the organ of vision: often - visual impairment (including diplopia).

From the organ of hearing: often - tinnitus.

From the side of the cardiovascular system: often - a feeling of palpitations, flushes of blood to the skin of the face, a pronounced decrease in blood pressure; very rarely - angina pectoris, myocardial infarction, possibly due to an excessive decrease in blood pressure in patients at high risk (see section "Special instructions"), arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), stroke, possibly due to an excessive decrease in blood pressure in patients at high risk (see section "Special Instructions"), vasculitis.

From the respiratory system: often - shortness of breath, cough; infrequently - rhinitis, bronchospasm; very rarely - eosinophilic pneumonia.

From the digestive system: often - abdominal pain, nausea, vomiting, dyspepsia, diarrhea, constipation; infrequently - a change in the rhythm of defecation, dryness of the oral mucosa; very rarely - pancreatitis, gingival hyperplasia, gastritis.

From the side of the liver and biliary tract: very rarely - hepatitis, jaundice, increased activity of liver enzymes (most often in combination with cholestasis), cytolytic or cholestatic hepatitis (see section "Special Instructions").

From the skin and subcutaneous fat: often - skin itching, rash, exanthema; infrequently - angioedema of the face, extremities, lips, mucous membranes, tongue, vocal folds and / or larynx (see section "Special Instructions"), alopecia, hemorrhagic rash, discoloration of the skin, increased sweating, urticaria; very rarely - angioedema, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, photosensitivity.

From the musculoskeletal system and connective tissue: often - muscle spasms, swelling of the legs; infrequently - arthralgia, myalgia, back pain.

From the side of the kidneys and urinary tract: infrequently - impaired urination, nocturia, frequent urination, impaired renal function; very rarely - acute renal failure.

From the reproductive system and mammary glands: infrequently - impotence, gynecomastia.

General disorders and symptoms: often - edema, asthenia, increased fatigue; infrequently - chest pain, malaise, pain.

Laboratory indicators: infrequently - weight gain, weight loss; rarely - an increase in the concentration of bilirubin; unspecified frequency - an increase in the concentration of urea and creatinine in the blood serum, hyperkalemia (see section "Special Instructions").

Additional information on amlodipine: isolated cases of extrapyramidal syndrome have been reported.

Overdose

There is no information on drug overdose in humans.

Amlodipine

Information on amlodipine overdose is limited.

Symptoms: excessive peripheral vasodilation, leading to reflex tachycardia, a pronounced and persistent decrease in blood pressure, incl. with shock and death.

Treatment: a pronounced decrease in blood pressure caused by an overdose of amlodipine requires active measures aimed at maintaining the function of the cardiovascular system, including monitoring the performance of the heart and lungs, elevated position of the limbs, control of BCC and diuresis. To restore vascular tone and blood pressure, it may be useful to use a vasoconstrictor drug, if there are no contraindications to its use, to eliminate the effects of calcium channel blockade - in / in the introduction. In some cases, gastric lavage may be effective. Taking activated charcoal during the first 2 hours after taking amlodipine at a dose of 10 mg leads to a delay in the absorption of the drug. Because amlodipine actively binds to plasma proteins, hemodialysis is ineffective.

Perindopril

Data on perindopril overdose in humans are limited.

Symptoms: with an overdose of ACE inhibitors, there may be a pronounced decrease in blood pressure, shock, water and electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough.

Treatment: IV infusion of 0.9% solution. With a significant decrease in blood pressure, the patient should be transferred to the supine position with raised legs. If necessary, you can in / in enter a solution of catecholamines. With the help of dialysis, perindopril can be removed from the systemic circulation (see section "Special Instructions"). With the development of therapy-resistant bradycardia, it may be necessary to install an artificial pacemaker. It is necessary to constantly monitor the indicators of the main vital functions of the body, the concentration of creatinine and electrolytes in the blood serum.

drug interaction

Perindopril

Data from clinical studies show that dual blockade of the RAAS as a result of the simultaneous administration of ACE inhibitors, ARA II or aliskiren leads to an increase in the incidence of adverse events such as arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure), compared with situations when only one drug is used that affects the RAAS (see sections "Contraindications", "Special instructions" and "Pharmacological action").

Drugs that cause hyperkalemia

The combination of ACE inhibitors with drugs containing trimethoprim, incl. a fixed combination of trimethoprim and sulfamethoxazole increases the risk of hyperkalemia.

Simultaneous use is contraindicated

Aliskiren and medicines containing aliskiren. The simultaneous use of ACE inhibitors with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and / or moderate or severe renal impairment (GFR less than 60 ml / min / 1.73 m 2 body surface area) and is not recommended in other patients. (see section "Contraindications").

Potassium-sparing diuretics, potassium preparations and potassium-containing table salt substitutes: despite the fact that the content of potassium in the blood serum remains within the normal range, hyperkalemia may occur in some patients with the use of perindopril. Potassium-sparing diuretics (eg, spironolactone, eplerenone (a derivative of spironolactone), triamterene, amiloride), potassium preparations, and potassium-containing salt substitutes can lead to a significant increase in serum potassium. In this connection, the simultaneous use of an ACE inhibitor and the above funds is not recommended (see section "Special Instructions"). If simultaneous use is necessary (in the case of confirmed hypokalemia), care should be taken and regular monitoring of the content of potassium in the blood plasma and ECG parameters should be carried out.

Lithium preparations: with the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the content of lithium in the blood plasma and associated toxic effects may occur. The simultaneous use of perindopril and lithium preparations is not recommended. If necessary, such therapy requires regular monitoring of the content of lithium in the blood plasma (see section "Special Instructions").

Estramustine: the simultaneous use of estramustine with ACE inhibitors is accompanied by an increased risk of developing angioedema.

Racecadotril. It is known that ACE inhibitors (for example, perindopril) can cause the development of angioedema. The risk of its development may be increased when used together with racecadotril (an enkephalinase inhibitor used to treat acute diarrhea).

Mammalian Target of Rapamycin (mTOR) inhibitors (eg, sirolimus, everolimus, temsirolimus). In patients receiving concomitant therapy with mTOR inhibitors, the risk of developing angioedema may increase (see section "Special Instructions").

NSAIDs, including high doses (≥ 3 g/day): the simultaneous use of ACE inhibitors with NSAIDs (acetylsalicylic acid at a dose that has an anti-inflammatory effect, COX-2 inhibitors and non-selective NSAIDs) can lead to a decrease in the antihypertensive effect of ACE inhibitors. The simultaneous use of ACE inhibitors and NSAIDs can lead to deterioration of renal function, including the development of acute renal failure, and an increase in serum potassium, especially in patients with reduced renal function. Caution should be exercised when prescribing this combination, especially in elderly patients. Patients need to compensate for fluid loss and carefully monitor renal function both at the beginning of treatment and during treatment.

Hypoglycemic agents (insulin, sulfonylurea derivatives): ACE inhibitors may enhance the hypoglycemic effect of insulin and sulfonylurea derivatives in patients with diabetes mellitus. The development of hypoglycemia is observed very rarely (probably due to an increase in glucose tolerance and a decrease in the need for insulin).

Diuretics (thiazide and "loop"): in patients receiving diuretics, especially with excessive excretion of fluid and / or electrolytes, a significant decrease in blood pressure may be observed at the beginning of therapy with an ACE inhibitor, the risk of which can be reduced by discontinuing the diuretic, introducing an increased amount of fluid and / or salt, and also prescribing perindopril at a low dose with a further gradual increase.

Sympathomimetics may weaken the antihypertensive effect of ACE inhibitors.

Preparations of gold: when using ACE inhibitors, incl. perindopril, in patients receiving intravenous gold preparations (sodium aurothiomalate), a symptom complex was described, including flushing of the skin of the face, nausea, vomiting, arterial hypotension.

Simultaneous use with ACE inhibitors allopurinol, immunosuppressive agents, corticosteroids (if used systemically), and procainamide may be accompanied by an increased risk of leukopenia, especially in patients with existing renal impairment.

Means for general anesthesia: the simultaneous use of ACE inhibitors and agents for general anesthesia can lead to a hypotensive effect.

Dantrolene (in / in the introduction): in laboratory animals, cases of ventricular fibrillation with a lethal outcome and collapse were noted against the background of the use of verapamil and intravenous administration of dantrolene, accompanied by hyperkalemia. Due to the risk of developing hyperkalemia, simultaneous administration of slow calcium channel blockers, incl. amlodipine, in patients susceptible to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.

Drug combinations requiring special attention

CYP3A4 isoenzyme inducers: there are no data on the effect of inducers of the CYP3A4 isoenzyme on amlodipine. Simultaneous administration of inducers of the CYP3A4 isoenzyme (for example, rifampicin, St. John's wort preparations) can lead to a decrease in the plasma concentration of amlodipine. Caution should be exercised with the simultaneous use of amlodipine and inducers of microsomal oxidation.

CYP3A4 isoenzyme inhibitors: concomitant use of amlodipine and potent or moderate inhibitors of the CYP3A4 isoenzyme (protease inhibitors, azole antifungals, macrolides, such as erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. The clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients, and therefore monitoring of the clinical condition and dose adjustment may be required.

Combinations of drugs requiring attention

Amlodipine enhances the hypotensive effect of drugs with antihypertensive effects.

Other drug combinations

In clinical drug interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, warfarin, or cyclosporine.

Simultaneous administration of amlodipine and the use of grapefruit or grapefruit juice is not recommended, due to a possible increase in the bioavailability of amlodipine in some patients, which, in turn, may lead to an increase in the effects of lowering blood pressure.

prestance

Drug combinations requiring special attention

Baclofen: may increase the antihypertensive effect. Blood pressure and renal function should be monitored, if necessary, dose adjustment of amlodipine is required.

Combination of drugs requiring attention

Antihypertensives (eg, beta-blockers) and vasodilators may enhance the antihypertensive effect of perindopril and amlodipine. Caution should be exercised when co-administered with nitroglycerin, other nitrates or other vasodilators, as this may further reduce blood pressure.

Corticosteroids (mineral and glucocorticosteroids), tetracosactide reduce the antihypertensive effect (fluid retention and sodium ions as a result of the action of corticosteroids).

Alpha-blockers (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin)

Amifostine may enhance the antihypertensive effect of amlodipine.

Tricyclic antidepressants, antipsychotics, general anesthetics enhance the antihypertensive effect and increase the risk of orthostatic hypotension.

special instructions

The specific instructions for perindopril and amlodipine apply to Prestance.

Perindopril

Hypersensitivity/angioneurotic edema

When taking ACE inhibitors, incl. and perindopril, in rare cases, angioedema of the face, extremities, lips, mucous membranes, tongue, vocal folds and / or larynx may develop (see section "Side Effects"). This can happen at any time during therapy. If symptoms appear, the drug should be stopped immediately, and the patient should be observed until the signs of edema disappear completely. If the swelling only affects the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. If such symptoms appear, immediately inject epinephrine (adrenaline) subcutaneously and / or ensure airway patency. The patient should be under medical supervision until the symptoms disappear completely and permanently.

In patients with a history of Quincke's edema, not associated with the use of ACE inhibitors, there may be an increased risk of its development when taking this group of drugs (see section "Contraindications").

In rare cases, during therapy with ACE inhibitors, angioedema of the intestine develops. In this case, patients have abdominal pain as an isolated symptom or in combination with nausea or vomiting, in some cases, without previous angioedema of the face and with a normal level of C1-esterase. The diagnosis is established by computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after discontinuation of ACE inhibitors. Therefore, in patients with pain in the abdomen receiving ACE inhibitors, when conducting differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine (see section "Side effect").

Co-administration with mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus)

Patients receiving therapy with mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) may be at increased risk of developing angioedema (eg, swelling of the airways or tongue with or without impaired respiratory function) (see section "Drug Interactions").

Anaphylactoid reactions during LDL apheresis

In rare cases, patients receiving ACE inhibitors during LDL apheresis using dextran sulfate may develop life-threatening anaphylactoid reactions. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.

Anaphylactoid reactions during desensitization

There are separate reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy (for example, hymenoptera venom). In these same patients, an anaphylactoid reaction was avoided by temporarily discontinuing ACE inhibitors, and an anaphylactoid reaction occurred again if the drug was accidentally taken.

Neutropenia, agranulocytosis, thrombocytopenia, anemia

While taking ACE inhibitors, neutropenia/agranulocytosis, thrombocytopenia and anemia may occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. With extreme caution, perindopril should be used in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function.

Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should report any signs of an infectious disease (eg, sore throat, fever) to their doctor.

Double blockade of the RAAS

There is evidence that the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure). Thus, dual blockade of the RAAS by the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended (see sections "Drug Interactions" and "Pharmacological Effects"). If double blockade therapy is considered absolutely necessary, it should only be carried out under strict medical supervision and with regular monitoring of renal function, blood electrolytes and blood pressure.

The use of ACE inhibitors in combination with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see section "Contraindications").

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic arterial hypotension rarely develops in patients without concomitant diseases. The risk of excessive reduction in blood pressure is increased in patients with reduced BCC, which may occur during diuretic therapy, with a strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe arterial hypertension with high renin activity (see sections "Drug interaction" and "side effect"). In patients with an increased risk of developing symptomatic arterial hypotension, blood pressure, renal function and serum potassium should be carefully monitored during treatment with Prestans.

A similar approach is also used in patients with angina pectoris and cerebrovascular diseases, in whom severe arterial hypotension can lead to myocardial infarction or cerebrovascular accident.

In the event of arterial hypotension, the patient should be transferred to the supine position with raised legs. If necessary, the BCC should be replenished with the help of an intravenous injection of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further administration of the drug. After the restoration of BCC and blood pressure, treatment can be continued.

Mitral stenosis, aortic stenosis, hypertrophic obstructive cardiomyopathy

Perindopril, like other ACE inhibitors, should be used with caution in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as in patients with mitral stenosis. Amlodipine is contraindicated in patients with left ventricular outflow tract obstruction.

Impaired kidney function

Patients with renal insufficiency (CC less than 60 ml / min) are recommended to individually select doses of perindopril and amlodipine (see section "Dosage regimen"). Such patients need regular monitoring of the content of potassium and creatinine in the blood serum (see section "Side Effects").

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney during therapy with ACE inhibitors, an increase in the content of urea and creatinine in the blood serum is possible, which usually disappears when therapy is discontinued. More often this effect is observed in patients with renal insufficiency. The additional presence of renovascular hypertension causes an increased risk of developing severe arterial hypotension and renal failure in such patients.

In some patients with arterial hypertension without signs of damage to the kidney vessels, an increase in the concentration of urea and creatinine in the blood serum is possible, especially with the simultaneous administration of perindopril with a diuretic, usually insignificant and transient. More often this effect is observed in patients with a previous impaired renal function.

Liver failure

In rare cases, against the background of taking ACE inhibitors, cholestatic jaundice occurs. With the progression of this syndrome, fulminant necrosis of the liver develops, sometimes with a fatal outcome. The mechanism by which this syndrome develops is unclear. If jaundice or a significant increase in the activity of liver enzymes occurs while taking ACE inhibitors, you should stop taking the drug (see the "Side Effects" section) and consult a doctor.

ethnic differences

In patients of the Negroid race, more often than in representatives of other races, angioedema develops while taking ACE inhibitors.

Perindopril, like other ACE inhibitors, may have a less pronounced antihypertensive effect in patients of the black race compared to representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race often have low renin activity.

Cough

During therapy with an ACE inhibitor, a dry cough may occur. Cough persists for a long time while taking drugs of this group and disappears after their cancellation. This should be considered in the differential diagnosis of cough.

Surgery/general anesthesia

In patients who are planned to undergo major surgery or the use of anesthesia agents that cause arterial hypotension, the use of perindopril may block the formation of angiotensin II against the background of compensatory renin release. Treatment should be stopped the day before surgery. With the development of arterial hypotension according to the indicated mechanism, blood pressure should be maintained by replenishing the BCC.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, incl. and perindopril. Risk factors for hyperkalemia are renal failure, impaired renal function, age over 70 years, diabetes mellitus, certain concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing table salt substitutes, as well as the use of other drugs that increase the content of potassium in the blood plasma (for example, heparin). The use of potassium preparations, potassium-sparing diuretics, potassium-containing table salt substitutes can lead to a significant increase in the content of potassium in the blood, especially in patients with reduced kidney function.

Hyperkalemia can lead to serious, sometimes fatal heart rhythm disturbances. If simultaneous administration of perindopril and the above drugs is necessary, treatment should be carried out with caution against the background of regular monitoring of the content of potassium in the blood serum (see section "Drug Interactions").

Patients with diabetes

When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic agents for oral administration or insulin, during the first month of therapy, it is necessary to carefully monitor the concentration of glucose in the blood (see section "Drug Interactions").

Amlodipine

The efficacy and safety of amlodipine in hypertensive crisis has not been established.

Heart failure

Treatment of patients with heart failure should be carried out with caution. When using amlodipine in patients with chronic heart failure III and IV FC according to the NYHA classification, pulmonary edema may develop. Blockers of slow calcium channels, including amlodipine, should be used with caution in patients with chronic heart failure, due to a possible increase in the risk of adverse events from the cardiovascular system and mortality.

Liver failure

In patients with impaired liver function T 1/2 and AUC of amlodipine increases. Dosing recommendations have not been established. Amlodipine should be started at the lowest possible dose and precautions should be taken both at the beginning of treatment and when increasing the dose. In patients with severe hepatic insufficiency, the dose should be increased gradually, ensuring careful monitoring of the clinical condition.

Elderly patients

In elderly patients, increasing the dose should be carried out with caution (see sections "Dosage regimen" and "Pharmacokinetics").

kidney failure

Patients with renal insufficiency can take amlodipine in standard doses. Changes in plasma concentrations of amlodipine do not correlate with the degree of renal failure. Amlodipine is not excreted from the body by dialysis.

prestance

Special instructions regarding amlodipine and perindopril apply to the drug Prestans.

Excipients

Due to the presence of lactose in the composition of the drug, Prestanz should not be prescribed to patients with hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Influence on the ability to drive vehicles and mechanisms

Although there was no negative effect on the ability to drive vehicles or other complex mechanisms while taking the drug Prestanz, however, due to the possible excessive decrease in blood pressure, the development of dizziness, drowsiness and other adverse reactions, caution should be exercised in these situations, especially at the beginning of treatment. and with increasing doses.

Pregnancy and lactation

The drug is contraindicated in pregnancy.

Pregnancy

Perindopril

The use of ACE inhibitors is not recommended for use in the first trimester of pregnancy (see section "Special Instructions"). The use of ACE inhibitors is contraindicated in the II and III trimesters of pregnancy (see sections "Contraindications" and "Special Instructions").

At the moment, there are no conclusive epidemiological data on the teratogenic risk when taking ACE inhibitors in the first trimester of pregnancy. However, a slight increase in the risk of fetal developmental disorders cannot be ruled out. When planning pregnancy, the drug should be discontinued and other antihypertensive drugs approved for use during pregnancy should be prescribed. If pregnancy occurs, ACE inhibitor therapy should be stopped immediately and, if necessary, another therapy should be prescribed.

It is known that the effect of ACE inhibitors on the fetus in the II and III trimesters of pregnancy can lead to a violation of its development (decrease in kidney function, oligohydramnios, slowing of the ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

If the patient received ACE inhibitors in the II and III trimesters of pregnancy, an ultrasound is recommended to assess the condition of the skull and kidney function of the fetus / child.

Newborns whose mothers received ACE inhibitors during pregnancy should be under close medical supervision due to the risk of arterial hypotension (see sections "Contraindications" and "Special Instructions").

Amlodipine

The safety of amlodipine during pregnancy has not been established.

In experimental studies on animals, the fetotoxic and embryotoxic effects of the drug were established when it was used in high doses. Use during pregnancy is possible only in the absence of a safer alternative and when the disease carries a greater risk to the mother and fetus.

breastfeeding period

Perindopril

Due to the lack of information regarding the use of perindopril during lactation, the use of perindopril is not recommended, it is preferable to adhere to alternative treatment during breastfeeding with a more studied safety profile, especially when feeding newborns or premature babies. There are no data on the excretion of perindopril in breast milk.

Amlodipine

There are no data on the excretion of amlodipine in breast milk. The decision to continue/stop therapy or breastfeeding should be made taking into account the benefits of breastfeeding for the baby and the benefits of taking amlodipine for the mother.

Impact on fertility

Perindopril

There was no effect of perindopril on reproductive function or fertility.

Amlodipine

In some patients treated with slow calcium channel blockers, biochemical changes were found in the head of spermatozoa. However, there are currently insufficient clinical data regarding the potential effect of amlodipine on fertility. In a rat study, undesirable effects on male fertility were identified.

Application in childhood

Prestans should not be prescribed children and adolescents under 18 years of age due to the lack of data on the efficacy and safety of the use of perindopril and amlodipine in these groups of patients, both in the form of monotherapy and in combination therapy.

For impaired renal function

Removal of perindoprilat from patients with renal insufficiency slowed down. Therefore, in such patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma. Prestans may be appointed patients with QC ≥ 60 ml / min. Prestans is contraindicated patients with QC< 60 мл/мин . Such patients are recommended individual selection of doses of perindopril and amlodipine. The change in the concentration of amlodipine in the blood plasma does not correlate with the severity of renal failure.

For impaired liver function

Caution should be exercised when prescribing Prestans patients with liver failure due to the lack of recommendations on the dosage of the drug in such patients.