Enap 2.5 instructions for use. Indications for use. Why is high blood pressure dangerous?

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In this article, you can read the instructions for using the drug Enap. Reviews of site visitors - consumers of this medicine, as well as opinions of doctors of specialists on the use of Enap in their practice are presented. We kindly ask you to actively add your reviews about the drug: the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not declared by the manufacturer in the annotation. Enap analogues in the presence of existing structural analogues. Use for the treatment of arterial hypertension and pressure reduction in adults, children, as well as during pregnancy and lactation. Joint reception with alcohol and consequences.

Enap- antihypertensive drug, ACE inhibitor. Enalapril (the active substance of the drug Enap) is a "prodrug": as a result of its hydrolysis, enalaprilat is formed. The mechanism of action is associated with inhibition of ACE activity under the influence of enalaprilat. This leads to a decrease in the formation of angiotensin 2, which causes a direct decrease in aldosterone secretion. As a result, there is a decrease in peripheral vascular resistance, a decrease in systolic and diastolic blood pressure, post- and preload on the myocardium.

It dilates the arteries to a greater extent than the veins, while there is no reflex increase in heart rate.

The hypotensive effect is more pronounced with a high level of plasma renin than with normal or reduced levels. A decrease in blood pressure within therapeutic limits does not affect cerebral circulation, blood flow in the vessels of the brain is maintained at a sufficient level even against the background of reduced blood pressure. Enhances coronary and renal blood flow.

With prolonged use, the hypertrophy of the left ventricle of the myocardium and myocytes of the walls of the arteries of the resistive type decreases, prevents the progression of heart failure and slows down the development of left ventricular dilatation. Improves blood supply to ischemic myocardium.

Inhibits platelet aggregation.

Has some diuretic effect.

When taking the drug orally, the hypotensive effect develops after 1 hour, reaches a maximum after 4-6 hours and lasts up to 24 hours. In some patients, therapy for several weeks is necessary to achieve the optimal level of blood pressure. In heart failure, a noticeable clinical effect is observed with prolonged use - 6 months or more.

Pharmacokinetics

After taking the drug, about 60% of enalapril is absorbed orally. Eating does not affect absorption. Enalapril is metabolized in the liver to form the active metabolite enalaprilat, which is a more potent ACE inhibitor than enalapril. Enalaprilat readily crosses blood-tissue barriers, with the exception of the blood-brain barrier. A small amount crosses the placental barrier and is excreted in breast milk. It is excreted mainly by the kidneys - 60% (20% - in the form of enalapril and 40% - in the form of enalaprilat), through the intestines - 33% (6% - in the form of enalapril and 27% - in the form of enalaprilat).

Indications

• arterial hypertension;
• chronic heart failure (as part of combination therapy);
• asymptomatic dysfunction of the left ventricle (as part of combination therapy);
• hypertensive crisis (R form of Enap);
• hypertensive encephalopathy (R form).

Release form

Tablets 2.5 mg, 5 mg, 10 mg and 20 mg.

Enap NL tablets (HL), in combination with diuretic hydrochlorothiazide.

Enap N (H) tablets, in combination with diuretic hydrochlorothiazide.

Solution for intravenous administration of Enap R (R).

Instructions for use and dosage

The drug is taken orally, regardless of food intake, at the same time of day. If a drug is missed, it should be taken as soon as possible. If there are only a few hours left before the next dose, then you need to take only the next dose according to the scheme and do not take the missed dose. The dose should never be doubled. The dose of the drug should be adjusted depending on the patient's condition.

Dose adjustment is carried out depending on the achievement of a therapeutic effect (lowering blood pressure). In the absence of a clinical effect, the dose is increased after 1-2 weeks by 5 mg. Usually the maintenance dose is from 10 mg to 20 mg, if necessary and if well tolerated, the dose can be increased to 40 mg per day. The maximum daily dose is 40 mg. It is advisable to divide the high dose into 2 doses.

For patients who continue to take diuretics, the initial dose of the drug is 2.5 mg 1 time per day.

In elderly patients, a more pronounced hypotensive effect and a longer duration of action of the drug are more often observed, which is associated with a decrease in the rate of excretion of enalapril, so the recommended initial dose is 1.25 mg.

In the treatment of chronic heart failure, the recommended initial dose is 2.5 mg 1 time per day. The dose of Enap should be increased gradually until the maximum clinical effect is achieved, usually after 2-4 weeks. The usual maintenance dose is 2.5 mg to 10 mg once daily; the maximum maintenance dose is 20 mg 2 times a day.

In the treatment of asymptomatic left ventricular dysfunction, the recommended initial dose is 2.5 mg 2 times a day. Dose adjustment depends on the tolerability of the drug. The usual maintenance dose is 10 mg twice daily.

Treatment with Enap is long-term, usually throughout life, unless circumstances arise that require its cancellation.

Tablets should be swallowed whole with a small amount of liquid.

Side effect

• excessive decrease in blood pressure;
• orthostatic collapse;
• chest pain;
• angina;
• myocardial infarction (usually associated with a marked decrease in blood pressure);
• arrhythmias (bradycardia or tachycardia, atrial fibrillation);
• heartbeat;
• thromboembolism of the branches of the pulmonary artery;
• pain in the region of the heart;
• fainting;
• Raynaud's syndrome;
• dizziness;
• headache;
• insomnia;
• weakness;
• increased fatigue;
• drowsiness (2-3%);
• confusion;
• increased fatigue;
• increased excitability;
• depression;
• paresthesia;
• violation of the vestibular apparatus;
• hearing and vision impairment;
• noise in ears;
• bronchospasm/asthma;
• dyspnea;
• a sore throat;
• hoarseness of voice;
• dry mouth;
• anorexia;
• dyspeptic disorders (nausea, diarrhea or constipation, vomiting, pain in the abdomen);
• intestinal obstruction;
• impaired renal function;
• thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia;
• photosensitivity;
• alopecia;
• skin rash;
• angioedema of the face, limbs, lips, tongue, glottis and/or larynx;
• dysphonia;
• erythema multiforme;
• exfoliative dermatitis;
• toxic epidermal necrolysis;
• hives;
• vasculitis;
• stomatitis;
• glossitis;
• increased sweating;
• decreased libido;
• hot flashes;
• decrease in potency;
• increase in ESR.

Contraindications

• angioedema in history (including associated with the use of ACE inhibitors);
• porphyria;
• pregnancy;
• lactation (breastfeeding);
• children and adolescents under the age of 18 years (efficacy and safety have not been established);
• hypersensitivity to enalapril and other components of the drug;
• hypersensitivity to other ACE inhibitors.

Use during pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation (breastfeeding). If pregnancy occurs during treatment with Enap, the drug should be discontinued immediately.

special instructions

In the course of treatment with Enap, regular medical examinations are required, especially at the beginning of treatment and / or when selecting the optimal dose of the drug. The frequency of medical examinations is determined by the attending physician.

It should be borne in mind the possibility of developing arterial hypotension (even a few hours after taking the first dose) in patients with severe heart failure, severe renal dysfunction, as well as in patients with impaired water and electrolyte balance due to treatment with diuretics, salt-free diet, diarrhea, vomiting, as well as in patients on hemodialysis.

A pronounced decrease in blood pressure is usually manifested by nausea, an increase in heart rate, and fainting. In the event of arterial hypotension, the patient should be transferred to a horizontal position with a low headboard, and medical supervision is necessary.

Arterial hypotension and its severe consequences are rare and transient. Transient arterial hypotension is not a contraindication to further treatment with the drug. As soon as blood pressure stabilizes, you can continue therapy with the drug at the average recommended doses. Arterial hypotension can be avoided by interrupting treatment with diuretics and giving up a salt-free diet before starting treatment with Enap, if possible. The patient should be warned that if there are relapses of arterial hypotension, accompanied by nausea, increased heart rate and fainting, then a doctor's consultation is necessary.

Before starting treatment and during therapy, renal function should be monitored.

During the period of treatment with Enap, an increase in the content of potassium in the blood serum is possible, especially in patients with chronic renal failure, diabetes mellitus, while prescribing potassium-sparing diuretics (such as spironolactone, amiloride and triamterene) or potassium preparations. Such patients should be informed about the need to consult a doctor if muscle weakness and arrhythmias appear.

Patients receiving Enap should not drink alcohol because of the risk of arterial hypotension.

In the event of the development of side effects or angioedema (sharp swelling of the lips, face, neck, arms and legs, accompanied by suffocation and hoarseness), Enap should be canceled and appropriate treatment prescribed.

The drug should be discontinued before the study of the function of the parathyroid glands.

Before carrying out the planned surgical intervention, the anesthesiologist should be informed that the patient is receiving Enap, since there is a risk of arterial hypotension during general anesthesia.

It should be borne in mind that during treatment with Enap, allergic reactions may develop due to the use of certain types of filter membranes used in hemodialysis or other types of blood filtration.

During the period of allergy treatment (desensitization) to wasp or bee venom in patients receiving Enap, hypersensitivity reactions may develop.

Influence on the ability to drive vehicles and control mechanisms

In some cases, the drug can cause severe arterial hypotension and dizziness, especially at the beginning of treatment, thus providing an indirect and transient effect on the ability to drive vehicles and work with mechanisms.

drug interaction

The simultaneous use of Enap and diuretics or other antihypertensive drugs increases the effectiveness of these drugs.

Interaction with drugs used to treat heart failure (cardiac glycosides) has no clinical significance.

With the simultaneous use of Enap and non-steroidal anti-inflammatory drugs, incl. acetylsalicylic acid, it is possible to reduce the effectiveness of enalapril and increase the risk of impaired renal function.

With the simultaneous use of certain diuretics (spironolactone, amiloride or triamterene) and / or additional administration of potassium preparations, an increase in the level of potassium in the blood serum (hyperkalemia) is possible.

Enap weakens the effect of drugs containing theophylline. The simultaneous use of lithium preparations may increase the side effects of lithium.

Preparations containing cimetidine increase the duration of action of enalapril.

In patients receiving enalapril, there is a risk of arterial hypotension during general anesthesia.

Ethanol (alcohol) enhances the hypotensive effect of Enap.

Analogues of the drug Enap

Structural analogues for the active substance:

• Bagopril;
• Berlipril;
• Vasolapril;
• Vero-enalapril;
• Invoril;
• Korandil;
• Miopril;
• Renipril;
• Renitek;
• Ednit;
• Enazil 10;
• Enalacore;
• Enalapril;
• enalapril maleate;
• Enam;
• Enarenal;
• Enafarm;
• Envas;
• Envipril.

In the absence of analogues of the drug for the active substance, you can follow the links below to the diseases that the corresponding drug helps with and see the available analogues for the therapeutic effect.

Enap n is a drug belonging to the antihypertensive clinical and pharmacological group. The use of this remedy according to the recommendations of the attending physician allows you to reduce the risks of developing cardiovascular diseases and prevent existing diseases and pathologies.

The drug belongs to the category of well-tolerated drugs and rarely provokes the development of any complications and side effects. However, self-administration of the drug is categorically not recommended, as there is a risk of erroneous diagnosis and incorrect dosage distribution.

Properties and pharmacological action

Enap N is a combined drug, the action of which is due to the properties of its specific components. The main effect of the drug is antihypertensive.

The main components of Enap N are Enalapril and Hydrochlorothiazide. The use of a combination of these components allows you to intensively reduce blood pressure. Taking the components separately from each other does not give a similar effect. Thanks to the combination of Enalapril and Hydrochlorothiazide, the effect of Enap N lasts up to 24 hours.

The composition of the drug and the form of release

Release form Enap N is a tablet. Each tablet is yellow in color, round in shape with a beveled edge. On the one hand, there is risk.

The main components that make up the following:

• Enalapril maleate (10 mg per tablet);
• Hydrochlorothiazide (25 mg per tablet.

Auxiliary substances in the composition of the drug are as follows:

• sodium bicarbonate;
• lactose monohydrate;
• Anhydrous calcium hydrogen phosphate;
• Corn starch;
• magnesium stearate;
• Heolin yellow dye (E104).

One carton contains 2 blisters of 10 tablets.

Indications

Enap N is indicated for patients suffering from arterial hypertension. It can be used only if the patient is indicated for combined therapy.

Contraindications

Among the contraindications to the use of the drug are noted:

• Stenosis of the renal artery;
• Idiopathic angioedema type of edema;
• Angioedema of hereditary etiology or that occurred during previous treatment with ACE inhibitors;
• Severe impairment of renal function;
• Carrying out the procedure of hemodialysis;
• recent kidney transplantation;
• Gout;
• Anuria;
• Hyponatremia;
• Hypersensitivity to enalapril or other sulfonamide derivatives;
• Pregnancy or preparation for pregnancy;
• Simultaneous use with medicines containing aliskiren, if the patient has diabetes mellitus or has functional impairment of the kidneys.

Instructions for use

The appointment of this type of drugs to control blood pressure is indicated for patients who cannot control blood pressure with enalapril alone. Enap N is not prescribed to patients as initial therapy. At the first stage of therapy, it is recommended that the doctor prescribe the dosage of hydrochlorothiaz and enalapril separately. But often, if necessary, patients are not prescribed monotherapy and are recommended to immediately switch to taking a certain dosage of Enap N.

The dosage is prescribed by the doctor based on the diagnostic results, the patient's condition and the severity of the underlying disease.

Treatment begins with a small dose, which is gradually increased. The drug is taken with or without food. Usually the daily allowance is taken in the morning along with plenty of water.

The usual dose prescribed by doctors is 1 tablet 1 time per day.

If it is necessary to increase the dosage, the doctor may add another tablet. Reception remains the same - 1 time per day.

Enap N at a dosage of 10 mg and 25 mg, as well as 10 mg and 12.5 mg is intended to replace treatment that requires the use of enalapril and hydrochlorothiazide separately.

A special dosage may be prescribed in the following cases:

1. Impaired kidney function. In this case, the dosage of hydrochlorothiazide and enalapril should be as low as possible. At the same time, the doctor monitors the level of creatine and potassium every 1-2 months.
2. Elderly age. In old age, the use of the drug is carried out in the same dosages as at a younger age. If the patient has physiological renal failure, then in this case, the amount of enalapril is corrected.
3. special populations. If the patient has a reduced volume of salt or liquid, the initial dose of enalapril is not more than 5 mg.

Individual instructions

With special care, Enap N should be used in the following cases:

• Atherosclerosis;
• Chronic heart failure;
• Hyperkalemia;
• Elderly age;
• cardiac ischemia;
• Disturbances in the work of the kidneys and liver;
• Diabetes;
• Stenosis of the mouth of the aorta of a pronounced nature;
• Lack of brain bleeding;
• Connective tissue diseases of a systemic nature, including scleroderma, systemic lupus erythematosus and others;
• Diarrhea and vomiting.

In childhood, the drug is not taken, since in medicine there are no facts about the benefits and harms of Enap N for an immature organism.

After taking Enap N, arterial hypotension may be observed for the first time. This is typical for patients with severe renal failure, hyponatremia, left ventricular dysfunction. If hypotension occurs with all its clinical manifestations, the patient needs medical attention, the volume of circulating blood is corrected by infusion of a 0.9% sodium chloride solution. In case of high blood pressure after the first intake of Enap N, it is not necessary to stop therapy, since such a reaction of the body is quite natural.

When taking the drug, it is necessary to constantly monitor the water and electrolyte balance. Abnormalities can be identified by dry mouth, drowsiness, general weakness, thirst, irritability, cramps in the calf muscles, tachycardia, nausea and vomiting.

The use of the drug in patients with liver failure and other liver diseases is complicated. Enap N should be used with caution, since hydrochlorothiazide can lead to hepatic coma. If jaundice occurs, the patient must urgently stop taking the drug and start symptomatic treatment.

Allergic reactions may occur. To save the patient from the resulting angioedema of the face, most often it is enough to stop taking Enap N and prescribe antihistamines.

Swelling of the tongue, pharynx, or larynx may be lethal.

To prevent incipient angioedema, the patient must urgently receive epinephrine and maintain a patent airway by intubation.

According to statistics, angioedema from taking ACE appears more often in representatives of the Negroid race. The development of adverse reactions to the drug is possible both in the case of the presence of individual intolerance to the drug, and in the absence of allergic reactions in the patient's history.

In the case of the planned surgical intervention, including dental operations, the patient must notify the doctor about taking Enap N. Also, when taking inhibitors, a cough often occurs. Usually it is dry, long, stops after the abolition of this group of drugs.

During pregnancy and lactation

During pregnancy, the drug Enap N is not used and the bearing of a child is a direct contraindication to the use of the medication.

• I trimester - the effect of an ACE inhibitor has not been established.
• II-III trimester - the impact is proven and is a negative factor affecting the condition of the newborn.

When using Enap N during pregnancy, the following conditions develop in newborns:

• kidney failure;
• Hypoplasia of the skull bones;
• arterial hypotension;
• Hyperkalemia.

An expectant mother may develop oligohydramnios - insufficiency of amniotic fluid. This condition can lead to deformation of the bones of the skull and face, as well as lung hypoplasia.

Taking Enap N and diuretics can lead to fetal jaundice, thrombocytopenia and other complex reactions that can also occur in adults.

Reception of Enap N during breastfeeding is contraindicated. A woman can take it only if she refuses to breastfeed her baby.

When driving and operating machinery

At the beginning of the use of the drug Enap N, some patients experience a pronounced decrease in blood pressure, drowsiness and slight dizziness. This may affect the patient's ability to drive a vehicle. It is also not recommended to engage in other potentially dangerous activities that require concentration. The speed of psychomotor reactions can also be reduced.

That is why, at the very beginning of using the drug to normalize blood pressure, it is worth refusing to work in hazardous industries, as well as driving a car or operating complex mechanisms.

Side effects

The correct intake of Enap n rarely leads to the development of side symptoms leading to a deterioration in the general condition of the patient and to his further hospitalization. The agent is well tolerated by the body and is excreted without problems through the intestines and through the kidneys during the day.

However, in medical practice, there are still cases when, for some reason, the drug has a negative effect on certain systems of the human body. Most often, the side effect of the drug is manifested when a large dosage is taken incorrectly, as well as when it is incorrectly distributed.

Metabolism	gout
central nervous system	headache, malaise, weakness, insomnia, asthenia, irritability, tinnitus, depression, tearfulness, tinnitus
Hematopoietic system	leukopenia, hemoglobin decline, bone marrow depression, decreased hematocrit, thrombocytopenia, neutropenia
The cardiovascular system	syncope, low blood pressure, tachycardia, chest pain, palpitations, hypotension
Digestive system	nausea, vomiting, indigestion, heartburn, feeling of heaviness in the stomach, abdominal pain, gas formation, dry mouth, stomatitis, obstruction, dyspepsia, pancreatitis, inflammation of the salivary glands
Respiratory system	cough, dyspnea, rhinitis, sinusitis, bronchospasm, hoarseness
reproductive system	decreased libido, impotence
Laboratory indicators	hyperglycemia, hyperuricemia, hypokalemia, hyperkalemia, hyponatremia, excessive concentration of urea in creatinine, increased liver activity
genitourinary system	kidney failure, kidney dysfunction
Dermatological abnormalities	rash, itching, skin redness, necrosis, alopecia
Allergic deviations	angioedema, intestinal edema, Steven-Johnson disease
Musculoskeletal system	arthralgia, muscle spasm

In more rare cases, the following symptoms may occur:

• Anemia;
• Fever;
• myocardial infarction;
• Stroke;
• angina;
• Heart failure;
• Anorexia;
• cold symptoms;
• Hepatitis;
• Jaundice;
• Asthma;
• Pneumonia;
• Pulmonary edema;
• Herpes zoster type.

To avoid possible side effects, the doctor is obliged to conduct a preliminary complete diagnostic examination of the patient.

Testing will help to identify an individual predisposition to intolerance to the drug.

If serious side effects occur, the drug should be discontinued without fail.

Overdose symptoms

An overdose of Enap n can occur if the drug is taken incorrectly. Sometimes the dose of the drug may be incorrectly calculated by the attending physicians. Further treatment is carried out, and then the drug is resumed.

In case of an overdose, the patient is concerned about the following symptoms:

• Heart rhythm disturbances;
• Weakness;
• Malaise;
• Diuresis;
• Pressure drop;
• Loss of consciousness (in difficult cases, coma);
• kidney failure;
• Disruptions in blood balance.

An overdose of the drug involves mandatory treatment.

In mild cases, the patient is shown gastric lavage, intake of absorbent substances and bed rest for several days. In more complex variants of oversaturation with the drug, the patient is supposed to be hospitalized. The hospital is taking a number of measures aimed at stabilizing the general condition, namely, increasing blood pressure, normalizing breathing and heart rate.

Analogues

In some cases, replacing Enap with an analogue is essential. This is done in case of intolerance by the patient to any component of the original drug, or if it is required to purchase a cheaper medication, but with identical properties.

Preliminary replacement of the medicine must be discussed with the doctor without fail. Enap n has the following names of analogues:

• Iruzid - 1 tablet contains 20 mg of lisinopril dihydrate and 25 mg of hydrochlorothiazide;
• Akkuzid - 1 dose of the drug contains 10 mg of quinapril, as well as hydrochloride, which corresponds to 10 mg of quinapril and 12.5 mg of hydrochlorothiazide;
• Lisothiazide - 1 dose of the drug contains 10.8 mg of lisinopril dihydrate, hydrochlorothiazide 12.5 mg;
• Lopril - 1 dose of the drug contains 10 mg of lisinopril, as well as 12.5 mg of hydrozlorthiazide;
• Enziks - 1 tablet of the drug consists of 10 mg of enalapril maleate.

Enap n has a sufficient number of analogues, which allows you to choose the optimally suitable drug for the patient, which will meet all the requirements and individual characteristics of the body.

Storage conditions

The drug Enap n is stored for 5 years, if the intended storage conditions are correctly observed and the product is not kept in excessively humid places. The drug is recommended to be stored in its original packaging.

Special temperature conditions are not required to preserve the medicinal properties of the drug. Therefore, it is not enough to store Enap in an ordinary first-aid kit. Should be carefully kept away from children and animals.

Taking such a medicine will not only not bring the expected benefits, but will also harm health.

Differences Enap, Enap N and Enap NL

Enap, Enap H and Enap Hl are inhibitors that reduce not only blood pressure, but also pressure in the pulmonary circulation. Despite similar names, these medicines do not have exactly the same properties. Using one drug in the absence of access to the one prescribed by your doctor is completely unacceptable.

Enap - the composition of the drug includes the active ingredient enalapril.

Enap N is a drug containing in its composition, in addition to the main active substance, also hydrochlorothiazide, which is a diuretic component. 1 tablet contains 25 mg. The appointment of this type of medication is relevant when the patient needs diuretics.

Enap NL contains enalapril maleate and a reduced dose of hydrochlorothiazide. In 1 tablet only 12.5 mg.

Only the attending physician can judge the advisability of taking this or that drug.

Patients need to remember that drugs for hypertension are prescribed for life.

Their cancellation or replacement is possible only in case of inefficiency or if side effects occur.

Price

Enap n belongs to the category of inexpensive drugs that are quite affordable for the average person. The cost of the drug Enap n depends on several factors, namely:

• Type of pharmacy (state, online pharmacy);
• Country and region where the drug is sold;
• Dosage.

So, the average price of 10 mg Enap n tablets is 197 rubles. As for the cost of 25 mg tablets, it is about 495 rubles.

Reviews

Like any drug, Enap n has its own advantages and disadvantages. Many users note the real effectiveness of the drug and use it as a "quick aid", which will quickly and effectively suppress high blood pressure. However, another part of the users is not completely satisfied with the result and notes an extremely fast addiction to the drug.

Experts also warn that the drug has the maximum effect only if it is used correctly and if the patient has not violated the recommendations prescribed to him. Also, in some cases, patients acquire a fake, which also, accordingly, does not give any healing effect.

Ekaterina, 52 years old, Yekaterinburg“It so happened that for several years I have been suffering from high blood pressure. The doctor prescribed Enap n for me, and now I don’t even leave the house without these pills. The drug copes well with the prevention of angina pectoris, allowing you to prevent possible heart attacks and strokes. Unfortunately, there are many contraindications that you should definitely consult with your doctor about.”

Olga, 46 years old, Ufa“Enap has been in our first aid kit for 2 years now. My husband drinks them for high blood pressure. He always carries at least a couple of pieces with him, if suddenly it is urgently necessary to reduce the pressure. Upset only one thing, that the remedy in our case caused a real addiction. If earlier one tablet was enough for my husband, then quite recently he had to take a whole course to stabilize his pressure.

Of the pluses, one can also highlight the availability of Enap. In our pharmacies, its cost does not exceed 90 rubles. The tablets begin to act quickly. After 15 minutes, you feel better and you can continue to do your usual activities.

Nikolai, 35 years old, Moscow I am quite young, I am only 35 years old, but the nature of my work has led me to suffer from occasional high blood pressure. I had to come to terms with the fact that I am hypertensive. My sister recommended me to try Enap. Surprised by the relatively low cost of the drug, I decided to try it. What did I have to lose?

I can say the following about the result. Enap does not help me, but relief comes in 30-40 minutes. Maybe I'm doing something wrong, but I seem to be following the instructions. Of course, I did not first go to the doctor with my problem, but I did not have time for this for many reasons. I take it periodically for about six months. Didn't notice any side effects."

Sergey, 38 years old, Voronezh“My father was seriously fond of Enap tablets. He has been taking them for a very long time. As he says, they relieve headaches and improve mood, and are generally indispensable for hypertension. If earlier one pill was enough for the father every few days, then in the last year the situation has become quite acute. Now dad drinks them every day and several pieces, otherwise the feeling of complete weakness. There was also a strong cough. After a doctor's appointment, it turned out that the abuse led to an overdose. Now we will treat hypertension itself, and we had to forget about the pills. ”

Clinical and pharmacological group

ACE inhibitor

Release form, composition and packaging

Pills white or almost white, round, biconvex, chamfered.

Excipients: sodium bicarbonate - 1.3 mg, lactose monohydrate - 64.9 mg, corn starch - 11.2 mg, hyprolose - 1.25 mg, talc - 3 mg, magnesium stearate - 0.85 mg.

Pills white or almost white, flat-cylindrical, with a risk and a chamfer.

Excipients: sodium bicarbonate - 2.6 mg, lactose monohydrate - 129.8 mg, corn starch - 22.4 mg, hyprolose - 2.5 mg, talc - 6 mg, magnesium stearate - 1.7 mg.

10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (6) - packs of cardboard.

Pills red-brown, flat-cylindrical, with a risk and a chamfer; white and burgundy inclusions are allowed on the surface and in the mass of the tablet.

Excipients: sodium bicarbonate - 5.1 mg, lactose monohydrate - 124.6 mg, corn starch - 21.4 mg, talc - 6 mg, magnesium stearate - 1.7 mg, iron dye red oxide (E172) - 1.2 mg.

10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (6) - packs of cardboard.

Pills light orange, flat-cylindrical, with a risk and a chamfer; white and brown-burgundy inclusions are allowed on the surface and in the mass of the tablet.

Excipients: sodium bicarbonate - 10.2 mg, lactose monohydrate - 117.8 mg, corn starch - 13.9 mg, talc - 6 mg, magnesium stearate - 1.7 mg, iron dye red oxide (E172) - 0.1 mg, iron dye yellow oxide (E172) - 0.3 mg.

10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (6) - packs of cardboard.
10 pieces. - blisters (50) - packs of cardboard.
10 pieces. - blisters (100) - packs of cardboard.

pharmachologic effect

Antihypertensive drug, ACE inhibitor. The mechanism of action is associated with inhibition of ACE activity, which leads to a decrease in the formation of angiotensin II.

Enalapril is a derivative of two amino acids: L-alanine and L-proline. After absorption, enalapril taken orally is hydrolyzed to enalaprilat, which inhibits ACE. The mechanism of its action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in the plasma content of which leads to an increase in plasma renin activity (by eliminating the negative feedback on changes in renin production) and a decrease in aldosterone secretion. Because ACE is identical to the enzyme kininase II, enalapril can also block the breakdown of bradykinin, a potent vasopressor peptide. The significance of this effect in the mechanism of action of enalapril has not been definitively established.

The antihypertensive effect of enalapril is associated primarily with the suppression of RAAS activity, which plays an important role in the regulation of blood pressure. Despite this, enalapril has an antihypertensive effect even in patients with arterial hypertension and low renin concentration.

Against the background of the use of enalapril, the level of blood pressure decreases regardless of the position of the body (both in the supine position and in the standing position) without a significant increase in heart rate. Symptomatic orthostatic hypotension rarely develops. In some patients, achieving optimal blood pressure reduction may require several weeks of therapy. Abrupt withdrawal of enalapril was not accompanied by a rise in blood pressure.

Effective inhibition of ACE activity usually occurs 2-4 hours after a single oral dose of enalapril. The time of onset of the antihypertensive effect when taken orally is usually 1 hour, reaching a maximum after 4-6 hours. The duration of action depends on the dose. When used at recommended doses, the antihypertensive effect and hemodynamic effects are maintained for at least 24 hours.

In patients with essential hypertension, a decrease in blood pressure is accompanied by a decrease in peripheral vascular resistance and an increase in cardiac output.
ejection, while the heart rate does not change or changes slightly. The renal blood flow increases, but the rate
glomerular filtration is unchanged. However, in patients with initially low glomerular filtration rate, its level usually increased.

In patients with diabetic / non-diabetic nephropathy, while taking enalapril, albuminuria / proteinuria and renal excretion of IgG decreased.

In patients with chronic heart failure (CHF) during therapy with cardiac glycosides and diuretics
the use of enalapril is accompanied by a decrease in peripheral vascular resistance and blood pressure, an increase in cardiac output, while heart rate decreases (usually in patients with chronic heart failure, heart rate is increased). It also reduces the wedge pressure of the pulmonary capillaries. With long-term use, enalapril increases exercise tolerance and reduces the severity of heart failure (assessed according to NYHA criteria). Enalapril in patients with mild to moderate heart failure slows down its progression, and also slows down the development of left ventricular dilatation. With left ventricular dysfunction, enalapril reduces the risk of developing major ischemic outcomes (including the incidence of myocardial infarction and the number of hospitalizations for unstable angina).

Pharmacokinetics

Suction

After taking the drug, about 60% of enalapril is absorbed orally. Cmax of enalapril in serum is achieved 1 hour after ingestion. Eating does not affect absorption.

Distribution and metabolism

Enalapril is rapidly and actively hydrolyzed to form enalarylate, a potent ACE inhibitor. Cmax of enalaprilat in serum are observed 3-4 hours after ingestion. In patients with normal renal function, Css of enalarylat in plasma was achieved on the 4th day of therapy.

The binding of enalaprilat to plasma proteins in the range of therapeutic doses is 60%.

In addition to being converted to enalaprilat, enalapril does not undergo significant biotransformation.

breeding

T1 / 2 of enalapril with repeated use is 11 hours. Enalaprilat is excreted mainly by the kidneys. Enalaprilat (about 40% of the dose) and unchanged enalapril (about 20%) are predominantly determined in the urine.

Enalaprilat is removed by hemodialysis, the excretion rate is 1.03 ml/s (62 ml/min).

Pharmacokinetics in special groups of patients

In patients with mild to moderate renal insufficiency (CC 30-60 ml / min (0.6-1 ml / sec)) after taking enalapril at a dose of 5 mg 1 time / day, the AUC of enalarylat is approximately 2 times greater than in patients with normal kidney function. In severe renal failure (CC ≤30 ml / min), the AUC increased by about 8 times. T1 / 2 of enalaprilat after repeated use in severe renal failure is prolonged, and the time to reach Css is delayed.

Indications

Essential hypertension;

Chronic heart failure (as part of combination therapy);

Prevention of the development of clinically significant heart failure in patients with asymptomatic left ventricular dysfunction (as part of combination therapy);

Prevention of coronary ischemia in patients with left ventricular dysfunction in order to reduce the incidence of myocardial infarction and reduce the frequency of hospitalizations for unstable angina.

Contraindications

Angioedema in history associated with the use of ACE inhibitors;

Hereditary angioedema or idiopathic angioedema;

Simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (CC

The composition of the drug Enap includes an active component enalapril maleate(may contain 2.5 mg / 5 mg / 10 mg / 20 mg).

The preparation also contains additional components: sodium bicarbonate, corn starch, magnesium stearate, lactose monohydrate, hyprolose, dye, talc.

Release form

Enap tablets are produced containing different amounts of the active ingredient.

• Enap 2.5 mg is white or almost white tablets, biconvex, round, with a chamfer. Packed in blisters of 10 pcs.
• Enap 5 mg is white or almost white tablets, flat-cylindrical, with a chamfer and a risk. Packed in blisters of 10 pcs.
• Enap 10 mg is a red-brown tablet, flat-cylindrical, with a chamfer and a risk. There may be white and burgundy blotches inside and on the surface of the tablet. Packed in blisters of 10 pcs.
• Enap 20 mg is light orange tablets, flat-cylindrical, with a chamfer and a risk. There may be blotches of white and brown-burgundy color inside and on the surface of the tablet. Packed in blisters of 10 pcs.

In cardboard packs - 2, 3, 6 blisters.

pharmachologic effect

Enap is an antihypertensive drug. The mechanism of action of enalapril is based on the inhibition of ACE activity, resulting in a decrease in the production of angiotensin II.

The substance Enalapril is a derivative of amino acids: L-alanine And L-proline. After the substance has been taken orally, it is hydrolyzed to enalaprilat, which inhibits ACE. Under its influence, the production of angiotensin II from angiotensin I decreases, due to a decrease in its level in plasma, an increase in plasma renin activity and a decrease in aldosterone secretion are noted. Since ACE is identical to kininase II, there is the ability of enalapril to block the destruction of bradykinin (this is a peptide that produces a vasopressor effect). At the moment, it is not completely known what is the significance of this effect in the mechanism of action of the substance enalapril.

The antihypertensive effect of the active substance is primarily associated with the inhibition of RAAS activity, which plays an important role in the regulation process. blood pressure. But even in people with high blood pressure and low renin concentrations, the antihypertensive effect of enalapril is noted.

After the use of this drug, blood pressure decreases, regardless of the position in which the human body is, while the heart rate does not increase significantly.

Development symptomatic orthostatic hypotension occurs only in rare cases. Sometimes it takes several weeks of medication to achieve a pronounced decrease in blood pressure. With a sharp withdrawal of the drug, there was no rise in blood pressure.

Pronounced inhibition of ACE activity, as a rule, is observed 2-4 hours after ingestion of the tablet. The antihypertensive effect is usually felt 1 hour after ingestion of drugs inside, the maximum effect occurs after 4-6 hours. The duration of action depends on the dose of the drug. If the patient takes those doses of Enap that the doctor recommended to him, then the hemodynamic and antihypertensive effect is maintained for at least 24 hours.

In people who are sick essential hypertension, with a decrease in blood pressure, there is a decrease in peripheral vascular resistance and an increase in cardiac output. However, there was no significant change in heart rate. Renal blood flow increases, no change in glomerular filtration rate is observed. But there is an increase in this indicator in people with a low glomerular filtration rate.

In people suffering diabetic nephropathy And non-diabetic, when taking enalapril, albuminuria / proteinuria and excretion of IgG by the kidneys decreased.

In patients suffering from CHF in the treatment of diuretics and cardiac glycosides and the use of enalapril, there is a decrease in blood pressure, OPSS, an increase in cardiac output, a decrease in heart rate (as a rule, this figure is increased in people with chronic heart failure).

There is a decrease in the jamming of the pulmonary capillaries. With prolonged use of tablets, enalapril increases tolerance to physical loads, reduces the severity of manifestations heart failure. In people with mild to moderate CHF, the drug slows down the progression of the disease, and also reduces the rate of development of left ventricular dilatation.

In people suffering from left ventricular dysfunction, Enap reduces the likelihood of major ischemic outcomes (the frequency of manifestations decreases myocardial infarction reduced the number of hospitalizations due to angina pectoris).

Pharmacokinetics and pharmacodynamics

After taking enalapril rapid absorption is noted - the degree of absorption is about 60%. The highest concentration of enalapril in the blood is observed 1 hour after application, while eating does not affect absorption. The substance is actively hydrolyzed, during which enalaprilat, an ACE inhibitor, is formed. The highest concentration of enalaprilat is fixed 3-4 hours after oral administration. With repeated use of enalapril, the half-life is 11 hours.

Enalapril does not undergo significant biotransformation in the body, with the exception of the transformation of the substance into enalaprilat.

It is mainly excreted from the body by the kidneys. Enalaprilat at a dose of 40% and unchanged enalapril at a dose of 20% are determined in the urine.

Indications for use Enap

The following indications for the use of Enap are determined:

• essential hypertension;
• CHF(in combination treatment);
• in order to prevent the manifestation of severe heart failure in those patients who are diagnosed with asymptomatic left ventricular dysfunction(in combination treatment);
• to reduce the frequency of manifestation myocardial infarction;
• to reduce the rate of hospital admissions for people with unstable angina.

From what tablets Enap, and whether they should be used in each case, the patient should consult a doctor.

Contraindications

There are such contraindications to the use of Enap:

• increased sensitivity to a substance enalapril, as well as to other components of the drug;
• angioedema in history, which developed during the period of treatment with ACE inhibitors;
• idiopathic angioedema, and angioedema hereditary type;
• porphyria;
• application at the same time aliskiren in patients with kidney disease or diabetes;
• syndrome of glucose-galactose malabsorption, lactose intolerance, lack of lactase (the composition of Enap drugs contains lactose);
• pregnancy and the period of natural feeding;
• the patient's age is under 18 years.

Enap pressure tablets are carefully prescribed:

• people from stenosis of the renal arteries;
• patients with hyperkalemia;
• people after transplants kidneys;
• with primary hyperaldosteronism;
• with reduced BCC;
• hypertrophic obstructive cardiomyopathy;
• mitral stenosis, aortic;
• systemic ailments of the connective tissue;
• diabetes;
• oppression of hematopoiesis;
• cerebrovascular diseases;
• kidney failure.

Caution, pressure medicine should be taken by people who comply diet with a reduced salt content, those who stay on hemodialysis and those taking diuretics and immunosuppressants.

Before taking Enap, people who are over 65 years old should consult a doctor.

Side effects

The following side effects may occur during treatment (negative effects in each group are given in order from more frequent to rarer):

• hematopoiesis: anemia, neutropenia, decrease in hematocrit concentration and hemoglobin, agranulocytosis, thrombocytopenia, oppression of hematopoiesis, pancytopenia, autoimmune diseases, lymphadenopathy;
• metabolism: hypoglycemia;
• nervous system: depression, headache, impaired consciousness, drowsiness, insomnia, paresthesia, high excitability, vertigo, sleep disturbances;
• heart and blood vessels: dizziness, a marked decrease in blood pressure, chest pain, angina pectoris, heart rhythm disturbance, palpitations, stroke or myocardial infarction, Raynaud's syndrome;
• sensory organs: taste changes, tinnitus, blurred vision;
• digestion: diarrhea, nausea, flatulence, abdominal pain, intestinal obstruction, constipation, vomit, pancreatitis, dyspepsia, anorexia, dryness of the oral mucosa, peptic ulcer, impaired bile secretion and liver function, hepatitis, hepatic necrosis, glossitis, cholestasis, stomatitis, aphthous ulcers;
• respiratory system: cough, sore throat, rhinorrhea, hoarseness, bronchospasm, dyspnea, allergic alveolitis, eosinophilic pneumonia, rhinitis;
• skin: rash, manifestations of hypersensitivity, angioedema, severe sweating, itching, alopecia, hives, erythema multiforme, erythroderma, exfoliative dermatitis, epidermal toxic necrolysis, pemphigus;
• genitourinary system: impaired renal function, proteinuria, renal failure, impotence, gynecomastia, oliguria;
• musculoskeletal system: muscle cramps;
• indicators of laboratory tests: hyperkalemia, an increase in the level of creatinine in the blood serum; hyponatremia; an increase in the concentration of urea in the blood, the activity of liver enzymes, the level of bilirubin in the blood;
• other manifestations: syndrome of inappropriate ADH secretion, fever, myalgia, myositis, arthritis, vasculitis, serositis, leukocytosis, increase in ESR, photosensitivity reactions.

Enap tablets, instructions for use (Method and dosage)

The official instructions for the use of Enap provide that patients take the drug orally, regardless of food intake. It is recommended to drink the medicine at the same time of day with a small amount of liquid.

At arterial hypertension initially, the drug is prescribed at a dose of 5 to 20 mg once a day, the dosage depends on the severity of hypertension. In the case of mild hypertension, a daily intake of 5 mg or 10 mg of the drug is recommended.

In people with severe RAAS activation, BP may drop too much. In this case, it is recommended to use low doses of the drug - 5 mg per day, under the supervision of a specialist.

Before taking the medicine, it must be taken into account that previous treatment with large doses of diuretic drugs can lead to dehydration and an increased risk of arterial hypotension at the very beginning of treatment. In this case, it is recommended to use a dose of not more than 5 mg per day. It is necessary to stop taking diuretics 2-34 days before starting Enap. During treatment, it is important to monitor the condition of the kidneys, to determine the content of potassium in the blood.

Maintenance dose - 20 mg once a day. If there is such a need, then the daily dose is increased to 40 mg, the dosage is determined individually.

With CHF, as well as with left ventricular dysfunction, the initial dose is 2.5 mg of the drug per day. Sometimes, for the treatment of heart failure, diuretics, beta-blockers, and cardiac glycosides are simultaneously prescribed.

After correction arterial hypertension the dose can be gradually increased - by 2.5-5 mg every 3-4 days, bringing it up to a maintenance dose of 20 mg per day. The highest allowable dose is 40 mg per day.

Since in the course of treatment there is a possibility of developing renal failure and arterial hypotension, it is necessary to carefully monitor blood pressure and kidney function during treatment. There is no need to discontinue the drug if hypotension develops after the first dose.

People with kidney disease need to increase the intervals between the use of tablets or reduce the dose of the drug.

Overdose

If an overdose occurs, then after about 6 hours there is a pronounced decrease in blood pressure. Collapse may develop, the water and electrolyte balance may be disturbed, hyperventilation, renal failure, bradycardia are also manifested due to an overdose, dizziness, tachycardia, convulsions, strong heartbeat.

In case of an overdose, you need to transfer the person to a horizontal position, while the head should be at the level of the body. If the overdose is mild, you need to wash the stomach, give Activated carbon. It is practiced in severe cases of an overdose of Enap in / in the introduction of a 0.9% solution sodium chloride, intravenous plasma substitutes, catecholamines can also be practiced.

Enalaprilat can be removed from the body using hemodialysis, the excretion rate is 62 ml per minute.

People with bradycardia are given a pacemaker. In case of overdose, careful monitoring of serum electrolytes and concentrations should be carried out. creatinine.

Interaction

With a double blockade of the RAAS, that is, in the case of simultaneous administration of ACE inhibitors, angiotensin II receptor antagonists or aliskiren, the risk of arterial hypotension. If such a combination is necessary, it is necessary to carefully monitor the functioning of the kidneys, water and electrolyte balance, and blood pressure.

It is contraindicated to combine enalapril and aliskiren people with diabetes and kidney disease.

ACE inhibitors reduce the loss of potassium under the influence of diuretics. When using enalapril and potassium-sparing diuretics, potassium-containing products, as well as potassium-containing substitutes, hyperkalemia may develop. With this combination, it is important to ensure the control of serum potassium levels.

With previous diuretic therapy, BCC may decrease and the likelihood of arterial hypotension may increase while taking enalapril. Such exposure can be reduced by canceling diuretics, increasing the daily intake of water and salt, and reducing the dosage of enalapril.

With simultaneous use with enalapril of alpha-blockers, beta-blockers, methyldopa, CCB, ganglionic blocking agents, nitroglycerin or other nitrates, an additional decrease in blood pressure is likely.

When taken in parallel with lithium preparations, a transient increase in the concentration of lithium is noted, as well as lithium intoxication. When taking thiazide diuretics, an increase in the serum concentration of lithium is possible. Such combinations are not recommended, and if necessary, careful monitoring of serum lithium concentrations is important.

When taken simultaneously with enalapril, a number of anesthetic drugs, antipsychotics, tricyclic antidepressants, blood pressure may further decrease.

When taken simultaneously with Enap NSAIDs, the antihypertensive effect may decrease. There may also be a deterioration in kidney function, especially in those patients who suffer from kidney disease. The effect is reversible.

When taken simultaneously with Enap hypoglycemic agents And insulin the hypoglycemic effect may be activated and the risk of hypoglycemia increases.

The antihypertensive effect of the drug enhances ethanol.

Sympathomimetics reduce the antihypertensive effect of ACE inhibitors.

Enalapril reduces the effect of drugs that contain theophylline.

When taken simultaneously with Enap immunosuppressants, cytostatics, allopurinol increases the likelihood of leukopenia. In people with impaired renal function when taking allopurinol and ACE inhibitors increases the risk allergies.

Taking enalapril and cyclosporine at the same time leads to an increase in the likelihood of hyperkalemia.

When taking antacids, the bioavailability of ACE inhibitors is reduced.

Terms of sale

Enap (Enap) is sold by prescription.

Storage conditions

Enap should be protected from children, stored at temperatures up to 25 ° C.

Best before date

Enap can be stored for 3 years.

special instructions

After the first intake of drugs Enap, arterial hypotension may develop. With severe hypotension, the patient should be placed horizontally, if necessary, inject him with a 0.9% solution sodium chloride.

After the patient's condition stabilizes, treatment can be continued.

Very rarely, during treatment, a syndrome may develop, starting with cholestatic jaundice And hepatitis A, later it develops into liver necrosis. If the patient develops jaundice, stop treatment immediately and consult a specialist.

There is a case report of neutropenia or agranulocytosis in people using ACE inhibitors.

This medicine should be used very carefully in people with connective tissue diseases, provided that they are undergoing immunosuppressive treatment, take procainamide, allopurinol. In this case, the development of severe infections that are not treatable is possible. antibiotics. When Enap is taken by such patients, periodic monitoring of the level of leukocytes in the blood is necessary.

There is a possibility of angioedema in people receiving Enap. At the first signs of such a condition, you need to immediately stop the drug and consult a doctor. An increased risk of developing this condition was noted in patients with a history of angioedema.

In the process of taking the drug, in rare cases, the development of anaphylactoid reactions in people who have undergone desensitization with Hymenoptera venom has been noted.

In the process of taking the drug, patients may develop an unproductive dry cough, disappearing after the abolition of enalapril.

Specialists should be warned that the patient is taking Enap before performing surgery with a general anesthesia.

It is important to carefully drive vehicles and practice other activities that require concentration of attention during treatment with Enap.

Enap's analogs Coincidence in the ATX code of the 4th level:

Analogues of Enap are being implemented - drugs Enap R, Berlipril, Bagopril, Vasolapril, Renipril, Invoril, Ednit, Enalapril and etc.

Enalapril or Enap - which is better?

Users who are prescribed drugs with the active ingredient enalapril are often interested in whether Enalapril and Enap tablets are the same thing, and what is the difference between them? In fact, the active ingredient in both drugs is similar. Accordingly, they produce the same effect on the body. The only difference is the country of origin.

Enam and Enap - differences

As part of the LS Enam and Enap contains enalapril maleate as an active ingredient. Only the country-manufacturers of medicines differ. But they act in the same way.

Enap and Enap N - differences

Part Enap N includes hydrochlorothiazide and enalapril, that is, in addition to hypotensive, this agent also produces a diuretic effect.

The drug is not prescribed for children under 18 years of age.

With alcohol

During pregnancy and lactation

Pregnant women should not drink Enap both in the first trimester and in the subsequent months of pregnancy. To date, the risk of developing teratogenic effects has not been excluded. If pregnancy has been confirmed, in this case, the remedy should be canceled immediately.

If a woman took ACE inhibitors during pregnancy, it is necessary to periodically conduct an ultrasound to assess the level of amniotic fluid, to conduct an ultrasound of the bones of the skull and kidneys of the fetus. The active substance is determined in breast milk, therefore, lactation should be stopped for the duration of treatment.

Enalapril maleate (enalapril)

Composition and form of release of the drug

Pills light orange, flat-cylindrical, with a risk and a chamfer; white and brown-burgundy inclusions are allowed on the surface and in the mass of the tablet.

Excipients: - 10.2 mg, lactose monohydrate - 117.8 mg, corn starch - 13.9 mg, talc - 6 mg, magnesium stearate - 1.7 mg, iron dye red oxide (E172) - 0.1 mg, iron dye yellow oxide (E172) - 0.3 mg.

10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (6) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard (for hospitals).
10 pieces. - blisters (20) - packs of cardboard (for hospitals).
10 pieces. - blisters (50) - packs of cardboard (for hospitals).
10 pieces. - blisters (100) - packs of cardboard (for hospitals).

pharmachologic effect

ACE inhibitor. It is a prodrug from which the active metabolite enalaprilat is formed in the body. It is believed that the mechanism of antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II (which has a pronounced vasoconstrictor effect and stimulates the secretion of aldosterone in the adrenal cortex).

As a result of a decrease in the concentration of angiotensin II, a secondary increase in renin activity occurs due to the elimination of negative feedback on renin release and a direct decrease in aldosterone secretion. In addition, enalaprilat appears to have an effect on the kinin-kallikrein system, preventing the breakdown of bradykinin.

Due to the vasodilating effect, it reduces OPSS (afterload), wedge pressure in the pulmonary capillaries (preload) and resistance in the pulmonary vessels; increases cardiac output and exercise tolerance.

In patients with chronic heart failure, long-term use of enalapril increases exercise tolerance and reduces the severity of heart failure (as assessed by NYHA criteria). Enalapril in patients with mild to moderate heart failure slows down its progression, and also slows down the development of left ventricular dilatation. With left ventricular dysfunction, enalapril reduces the risk of developing major ischemic outcomes (including the incidence of myocardial infarction and the number of hospitalizations for unstable angina).

Pharmacokinetics

When taken orally, about 60% is absorbed from the gastrointestinal tract. Simultaneous ingestion of food does not affect absorption. It is metabolized in the liver by hydrolysis with the formation of enalaprilat, due to the pharmacological activity of which the hypotensive effect is realized. The binding of enalaprilat to plasma proteins is 50-60%.

T 1/2 of enalaprilat is 11 hours and increases with renal failure. After oral administration, 60% of the dose is excreted by the kidneys (20% as enalapril, 40% as enalaprilat), 33% is excreted through the intestines (6% as enalapril, 27% as enalaprilat). After intravenous administration of enalaprilat, 100% is excreted by the kidneys unchanged.

Indications

Arterial hypertension (including renovascular), chronic insufficiency (as part of combination therapy).

Essential hypertension.

Chronic heart failure (as part of combination therapy).

Prevention of the development of clinically significant heart failure in patients with asymptomatic left ventricular dysfunction (as part of combination therapy).

Prevention of coronary ischemia in patients with left ventricular dysfunction in order to reduce the incidence of myocardial infarction and reduce the frequency of hospitalizations for unstable angina.

Contraindications

History of angioedema, bilateral renal artery stenosis or stenosis of the renal artery to a solitary kidney, hyperkalemia, porphyria, concomitant use with aliskiren in patients with diabetes mellitus or impaired renal function (CC<60 мл/мин), беременность, период лактации (грудного вскармливания), детский и подростковый возраст до 18 лет, повышенная чувствительность к эналаприлу и другим ингибиторам АПФ.

Dosage

When taken orally, the initial dose is 2.5-5 mg 1 time / day. The average dose is 10-20 mg / day in 2 divided doses.

Maximum daily dose when taken orally is 80 mg.

Side effects

From the nervous system: dizziness, headache, tiredness, fatigue; very rarely when used in high doses - sleep disorders, nervousness, depression, imbalance, paresthesia, tinnitus.

From the side of the cardiovascular system: orthostatic hypotension, syncope, palpitations, pain in the heart area; very rarely when used in high doses - hot flashes.

From the digestive system: nausea; rarely - dry mouth, abdominal pain, vomiting, diarrhea, constipation, abnormal liver function, increased activity of hepatic transaminases, increased concentration of bilirubin in the blood, hepatitis, pancreatitis; very rarely when used in high doses - glossitis.

From the hematopoietic system: rarely - neutropenia; in patients with autoimmune diseases - agranulocytosis.

From the urinary system: rarely - impaired renal function, proteinuria.

From the respiratory system: dry cough.

From the reproductive system: very rarely when used in high doses - impotence.

Dermatological reactions: very rarely when used in high doses - hair loss.

Allergic reactions: rarely - skin rash, Quincke's edema.

Others: rarely - hyperkalemia, muscle cramps.

drug interaction

With simultaneous use with cytostatics, the risk of developing leukopenia increases.

With the simultaneous use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and dietary supplements containing potassium, hyperkalemia may develop (especially in patients with impaired renal function), because. ACE inhibitors reduce the content of aldosterone, which leads to a retention of potassium in the body against the background of limiting the excretion of potassium or its additional intake into the body.

With the simultaneous use of opioids and anesthetics, the antihypertensive effect of enalapril is enhanced.

With the simultaneous use of "loop" diuretics, thiazide diuretics, the antihypertensive effect is enhanced. There is a risk of developing hypokalemia. Increased risk of impaired renal function.

With simultaneous use with azathioprine, anemia may develop, which is due to the inhibition of erythropoietin activity under the influence of ACE inhibitors and azathioprine.

A case of the development of an anaphylactic reaction and myocardial infarction with the use of allopurinol in a patient receiving enalapril is described.

In high doses, it can reduce the antihypertensive effect of enalapril.

It has not been conclusively established whether acetylsalicylic acid reduces the therapeutic efficacy of ACE inhibitors in patients with coronary artery disease and heart failure. The nature of this interaction depends on the course of the disease.

Acetylsalicylic acid, by inhibiting COX and prostaglandin synthesis, can cause vasoconstriction, which leads to a decrease in cardiac output and worsening of the condition of patients with heart failure receiving ACE inhibitors.

With the simultaneous use of beta-blockers, methyldopa, nitrates, hydralazine, prazosin, an increase in the antihypertensive effect is possible.

With simultaneous use with NSAIDs (including indomethacin), the antihypertensive effect of enalapril decreases, apparently due to inhibition of prostaglandin synthesis under the influence of NSAIDs (which are believed to play a role in the development of the hypotensive effect of ACE inhibitors). Increased risk of developing renal dysfunction; rarely observed hyperkalemia.

With the simultaneous use of insulin, hypoglycemic agents of sulfonylurea derivatives, hypoglycemia may develop.

With the simultaneous use of ACE inhibitors and interleukin-3, there is a risk of arterial hypotension.

With simultaneous use with clozapine, there are reports of the development of syncope.

With simultaneous use with clomipramine, an increase in the action of clomipramine and the development of toxic effects are reported.

With simultaneous use with co-trimoxazole, cases of hyperkalemia have been described.

With simultaneous use with lithium carbonate, the concentration of lithium in the blood serum increases, which is accompanied by symptoms of lithium intoxication.

With simultaneous use with orlistat, the antihypertensive effect of enalapril decreases, which can lead to a significant increase in blood pressure, the development of a hypertensive crisis.

It is believed that with simultaneous use with procainamide, an increased risk of developing leukopenia is possible.

With simultaneous use with enalapril, the effect of drugs containing theophylline decreases.

There are reports of the development of acute renal failure in patients after kidney transplantation, while the use of cyclosporine.

With simultaneous use with cimetidine, T 1/2 of enalapril increases and its concentration in blood plasma increases.

It is believed that it is possible to reduce the effectiveness of antihypertensive agents when used simultaneously with erythropoietins.

With simultaneous use with ethanol, the risk of arterial hypotension increases.

special instructions

It is used with extreme caution in patients with autoimmune diseases, diabetes mellitus, impaired liver function, severe aortic stenosis, subaortic muscular stenosis of unknown origin, hypertrophic cardiomyopathy, and loss of fluid and salts. In the case of previous treatment with saluretics, in particular in patients with chronic heart failure, the risk of developing orthostatic hypotension increases, therefore, before starting treatment with enalapril, it is necessary to compensate for the loss of fluid and salts.

With long-term treatment with enalapril, it is necessary to periodically monitor the picture of peripheral blood. Sudden discontinuation of enalapril does not cause a sharp increase in blood pressure.

During surgical interventions during the period of treatment with enalapril, arterial hypotension may develop, which should be corrected by the introduction of a sufficient amount of fluid.

Before examining the function of the parathyroid glands, enalapril should be discontinued.

Influence on the ability to drive vehicles and mechanisms

Care must be taken when driving vehicles or performing other work that requires increased attention, because. dizziness is possible, especially after taking the initial dose of enalapril.

Pregnancy and lactation

Contraindicated for use during pregnancy. In the event of pregnancy, enalapril should be discontinued immediately.

Enalapril is excreted in breast milk. If necessary, its use during lactation should decide on the termination of breastfeeding.

Application in childhood

The safety and efficacy of enalapril in children have not been established.

For impaired liver function

Use with extreme caution in patients with impaired liver function.

Compound

Each tablet contains 10 mg or 20 mg of enalapril maleate.

Tablets 10 mg

Excipients: sodium bicarbonate, lactose monohydrate, maize starch, iron oxide red E 172, talc, magnesium stearate.

Tablets 20 mg

Excipients: sodium bicarbonate, lactose monohydrate, maize starch, iron oxide red E172, iron oxide yellow E172, talc, magnesium stearate.

Description

Tablets 10 mg: round, flat reddish-brown tablets, with a bevelled edge and a notch on one side, with separate white patches on the surface and in the mass of the tablet. The notch is not designed to break the tablet.

Tablets 20 mg: round, flat tablets of light orange color with a bevelled edge and a notch on one side, with separate white patches on the surface and in the mass of the tablet. The notch is not designed to break the tablet.

Pharmacotherapeutic group

Pharmacotherapeutic group: Angiotensin-converting enzyme (ACE) inhibitors. ATX code: C09AA02.

Pharmacological properties

Pharmacodynamics

Enalapril maleate is a salt of maleic acid and enalapril, a derivative of two amino acids (L-alanine and L-proline). After absorption, enalapril undergoes hydrolysis to enalaprilat, which inhibits ACE, which leads to a decrease in the plasma concentration of the angiotensin II pressor compound and, as a result, to an increase in plasma renin activity and a decrease in aldosterone secretion. The drug can also block the breakdown of bradykinin, a powerful vasodepressor (vasodilator) peptide.

Although the mechanism by which enalapril exerts its hypotensive effect is primarily through the suppression of the renin-angiotensin-aldosterone system, which plays the most important role in the regulation of blood pressure, the drug also exerts an antihypertensive effect in patients with low renin levels. The use of enalapril in patients with hypertension leads to a decrease in blood pressure in both the supine and standing positions without an increase in heart rate. Symptomatic postural hypotension is rare. In some patients, reaching the level of blood pressure reduction may require several weeks of therapy. Abrupt withdrawal of enalapril is not accompanied by a rapid increase in blood pressure.

Effective suppression of ACE activity usually develops within 2-4 hours after ingestion of an individual dose of enalapril. The onset of antihypertensive activity is usually observed within an hour, the maximum reduction in blood pressure is achieved within 4-6 hours after administration. The duration of action depends on the dose. However, in the recommended amounts, the antihypertensive and hemodynamic effects persist for at least 24 hours.

In hemodynamic studies in patients with essential hypertension, a decrease in blood pressure was accompanied by a decrease in peripheral resistance in the arteries with an increase in cardiac output and little or no change in heart rate. After the introduction of enalapril, there was an increase in renal blood flow; glomerular filtration rate did not change; no signs of sodium or water retention were observed. However, in patients with reduced glomerular filtration, an increase in this indicator was noted.

In short-term clinical studies of patients with kidney disease with or without diabetes mellitus, a decrease in albuminuria and a decrease in urinary excretion of IgG and total protein were observed after taking enalapril.

When combined with thiazide-type diuretics, the hypotensive effect is additive. At the same time, enalapril can reduce or prevent the development of hypokalemia caused by taking thiazides.

In patients with heart failure during therapy with digitalis and diuretics, enalapril reduces peripheral resistance and blood pressure. Cardiac output increases while heart rate (usually elevated in patients with heart failure) decreases; the wedge pressure in the pulmonary capillaries (DZLK) decreases. Therapy with enalapril normalizes the condition in heart failure and improves exercise tolerance. These effects persist throughout therapy. In patients with mild or moderate heart failure, the drug slows down the progression of heart dilatation and heart failure (decrease in the end diastolic and systolic volume of the left ventricle and improve the ejection fraction (ejection)).

In patients with left ventricular dysfunction, enalapril reduces the risk of major cardiovascular events, myocardial infarction and the number of hospitalizations for unstable angina.

Pharmacokinetics

Suction

Enalapril is rapidly absorbed from the gastrointestinal tract; the maximum concentration in blood serum is reached within one hour. The degree of absorption is about 60%, while eating does not affect absorption. After absorption, enalapril is rapidly and completely hydrolyzed to enalaprilat, an active ACE inhibitor. The peak concentration of enalaprilat in the blood serum is observed 4 hours after taking enalapril inside. The effective half-life for accumulation of enalaprilat after repeated oral administration of enalapril is 11 hours. In patients with normal renal function, a stable serum concentration of enalaprilat is achieved four days after the start of treatment.

Distribution

In the range of therapeutically significant concentrations, the binding of enalaprilat to serum proteins is 60%.

Metabolism

With the exception of conversion to enalaprilat, there are no signs of significant metabolism of enalapril.

breeding

Enalaprilat is excreted mainly by the kidneys. The main components in the urine are enalaprilat, which accounts for 40% of the dose, and unchanged enalapril (about 20%).

Impaired kidney function

Exposure to enalapril and enalaprilat is increased in patients with renal insufficiency. In patients with mild or moderate renal insufficiency (creatinine clearance 0.6-1 ml / s), after taking the drug 5 mg once a day, the AUC value of enalaprilat is approximately two times higher than in patients with normal renal function; whereas in severe renal insufficiency (creatinine clearance 0.5 ml / s), the AUC value increases by approximately eight times. At this level of renal failure, the effective half-life of enalaprilat is prolonged and the time to steady state is increased.

Enalaprilat can be removed from the circulatory system by hemodialysis. Enalaprilat dialysis clearance is 1.03 ml/sec.

Children and teenagers

Significant differences in pharmacokinetics in children compared with adults have not been established. The data show an increase in AUC (standardized for dose per body weight) with increasing age; however, no increase in AUC was observed when data were standardized for body surface area. At steady state, the mean effective half-life of accumulated enalaprilat was 14 hours.

Indications for use

Treatment of arterial hypertension.

Treatment of symptomatic heart failure.

Prevention of symptomatic heart failure in patients with asymptomatic left ventricular dysfunction (ejection fraction< 35 %).

Contraindications

Hypersensitivity to enalapril, other components of the drug or other ACE inhibitors.

A history of angioedema caused by the use of ACE inhibitors.

Hereditary or idiopathic angioedema.

Second and third trimester of pregnancy.

The simultaneous use of Enap and aliskiren-containing drugs is contraindicated in patients with diabetes mellitus or renal insufficiency (GFR< 60мл/мин/1,73 м2).

Dosage and administration

The dose is selected individually depending on the patient's condition. hypertension

The initial dose is 5 mg - 20 mg, depending on the degree of hypertension and the patient's condition. The drug is taken once a day. For moderate hypertension, the recommended starting dose is 5 mg to 10 mg per day. In patients with marked activity of the renin - angiotensin - aldosterone system (for example, renovascular hypertension, loss of water and / or salts, cardiac decompensation or severe hypertension), an excessive drop in blood pressure may occur at the beginning of treatment. In such patients, it is recommended to start treatment under medical supervision with a dose of 5 mg or less. Prior treatment with high doses of diuretics may lead to hypovolemia and the risk of hypotension at the start of treatment. In such patients, the recommended starting dose is 2.5 mg. If possible, 2-3 days before the start of treatment with enalapril, diuretic therapy should be canceled. During treatment, it is necessary to monitor kidney function and potassium levels.

The usual maintenance dose is 10-20 mg per day. The maximum maintenance dose is 40 mg per day.

Heart failure/ asymptomatic left ventricular dysfunction

The initial dose of enalapril maleate in patients with symptomatic heart failure or asymptomatic left ventricular dysfunction is 2.5 mg once daily. The initial effect on blood pressure should be carefully monitored.

For the treatment of symptomatic heart failure, enalapril maleate is usually used in combination with diuretics and beta-blockers and, if necessary, also with digitalis glycosides.

If, after initiation of treatment for heart failure, symptomatic hypotension is absent or effectively eliminated, then the dose should be gradually increased to the usual maintenance dose of 20 mg, taken once or divided into two doses (depending on patient tolerance).

* Patients with impaired renal function or who are treated with diuretics should be especially careful

Blood pressure and renal function should be monitored before and after initiation of treatment with enalapril maleate, as hypotension and (less commonly) subsequent renal failure have been reported. In patients taking diuretics, the dose should be reduced if possible before starting treatment with enalapril. The appearance of hypotension at the beginning of treatment does not mean that such a reaction will also occur during long-term therapy with enalapril, and does not preclude further use of the drug. During treatment, it is necessary to monitor kidney function and serum potassium levels.

Dosage in renal failure

In patients with renal insufficiency, the intervals between taking enalapril should be extended and / or the dosage reduced.

* On non-dialysis days, the dose should be adjusted according to blood pressure readings.

Use in elderly patients

The dose should be adjusted according to the patient's renal function. Use in children

Clinical experience with enalapril maleate in children with hypertension is limited.

For patients who can swallow tablets, the dose should be adjusted individually depending on the patient's condition and response from blood pressure. For patients weighing 20 to 50 kg, the recommended starting dose is 2.5 mg enalapril maleate per day; for patients weighing 50 kg or more - 5 mg of enalapril maleate once a day. The dosage should be selected depending on the needs of the patient. The maximum recommended dose of enalapril maleate for patients weighing 20-50 kg is 20 mg per day; for patients weighing 50 kg or more - 40 mg of enalapril maleate per day.

Treatment with Enap is long-term, usually throughout life, unless circumstances arise that require its cancellation.

Side effect

Side effects that may occur during treatment with Enap are classified into groups depending on the frequency of occurrence:

Very common (≥ 1/10), frequent (≥ 1/100 to< 1/10), нечастые (>1/1000 to< 1/100), редкие (≥ 1/10000 до < 1/1000) очень редкие (< 1/10000), частота неизвестна (не могут быть оценены по доступным данным).

Within each group, side effects of the drug are presented in order of decreasing significance.

Side effects observed during treatment with Enap are usually mild, transient in nature and do not require discontinuation of the drug.

The frequency of side effects is listed by individual organ systems.

Research:

Frequent - hyperkalemia, hypercreatininemia;

Infrequent - increase in serum urea, hyponatremia;

Rare - increased liver enzymes, increased serum bilirubin.

Cardiovascular disorders:

Very common - dizziness;

Frequent - hypotension (including orthostatic hypotension);

Infrequent - orthostatic hypotension, palpitations;

Rare - syncope, myocardial infarction or stroke, possibly due to excessive hypotension in high-risk patients, chest pain, arrhythmias, angina pectoris, bradycardia or tachycardia, atrial fibrillation, hemodynamic vertebrobasilar insufficiency, Raynaud's phenomenon.

Blood and lymphatic system disorders:

Infrequent - anemia (including aplastic and hemolytic);

Rare - neutropenia, decreased hemoglobin, decreased hematocrit, thrombocytopenia, agranulocytosis, bone marrow suppression, pancytopenia, lymphadenopathy, autoimmune diseases.

Endocrine system disorders:

The frequency is not known - syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

Nervous system disorders:

Frequent - headache, drowsiness;

Infrequent - insomnia, dizziness;

Rare - confusion, nervousness, depression, paresthesia, sleep anomaly, sleep disturbances.

Violations of the organ of vision:

Frequent - blurred vision.

Respiratory, thoracic and mediastinal disorders:

Very common - unproductive dry cough;

Frequent - shortness of breath;

Infrequent - rhinorrhea, pharyngitis, hoarseness, bronchospasm / asthma;

Rare - inflammation of the upper respiratory tract, lung infiltrates; rhinitis, allergic alveolitis/eosinophilic pneumonia.

Gastrointestinal disorders:

Very common - nausea;

Frequent - diarrhea, abdominal pain, change in taste;

Infrequent - intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, anorexia, gastric irritation, dry mouth, gastric and duodenal ulcers;

Rare - stomatitis / aphthous ulceration, glossitis;

Very rare, frequency unknown - intestinal angioedema. Renal and urinary tract disorders:

Infrequent - renal dysfunction, renal failure, proteinuria;

Rare - oliguria.

Skin and subcutaneous tissue disorders:

Frequent - rash, hypersensitivity / angioedema;

Infrequent - increased sweating, itching, urticaria, alopecia;

Rare - exudative erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrosis, pemphigus, erythroderma, photosensitivity.

Metabolic and nutritional disorders:

Infrequent - hypoglycemia.

Complications of a general nature and reactions at the injection site:

Frequent - asthenia, fatigue;

Infrequent - muscle cramps, hyperemia, tinnitus, malaise, fever.

Liver and biliary tract disorders:

Rare - liver failure, hepatocellular or cholestatic hepatitis, including hepatic necrosis, cholestasis, including jaundice.

Reproductive system and mammary gland disorders:

Infrequent - impotence;

Rare - gynecomastia.

Mental disorders:

Frequent - depression.

A complex of symptoms has been reported: fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, positive ANF, elevated ESR, eosinophilia, and leukocytosis.

In the event of severe side effects, treatment should be discontinued.

Overdose

Data regarding overdose in humans are limited.

Main symptom overdose is hypotension, starting six hours after taking the tablets and accompanied by blockade of the renin-angiotensin system and stupor.

Other symptoms: circulatory shock, electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.

Treatment: intravenous infusion of saline. If necessary, it is also possible to carry out treatment with infusion of angiotensin II and/or catecholamines intravenously. If the tablets have been taken recently, then measures should be taken to eliminate enalapril maleate (for example, vomiting, gastric lavage, administration of absorbents and sodium sulfate).

Enalaprilat can be removed from the general circulation by hemodialysis (62 ml/min). For bradycardia that does not respond to treatment, treatment with a pacemaker is indicated. Vital signs, electrolyte levels and serum creatinine concentration should be constantly (long-term) monitored.

Interaction with other drugs, as well as other types of interaction

Potassium-sparing diuretics, potassium supplements

ACE inhibitors reduce diuretic-induced potassium loss. Potassium-sparing diuretics (eg, spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes can lead to hyperkalemia. If combined use is indicated due to proven hypokalemia, then it should be used with caution and with regular monitoring of potassium in the blood serum.

Diuretics (thiazide or loop diuretics)

Prior treatment with high doses of diuretics may lead to hypovolemia and the risk of severe hypotension. The hypotensive effect can be reduced by discontinuing diuretics, compensating for the lack of salts and fluids in the body, or taking low doses of enalapril at the initial stage of treatment.

Other antihypertensive agents

The simultaneous use of enalapril and other antihypertensive drugs may increase the antihypertensive effect of enalapril. Simultaneous use with nitroglycerin, other nitrates or vasodilators may also lead to a decrease in blood pressure.

Double renin blockade- angiotensin -aldosterone system

Dual blockade of the renin-angiotensin-aldosterone system with combined use of angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with an increased risk of side effects such as hypotension, hyperkalemia, and decreased renal function (including acute renal failure) compared with the use of one of the agents that affect the renin-angiotensin-aldosterone system (see section "Precautions").

Lithium

A reversible increase in the concentration of lithium in the blood serum and its toxic effect have been reported with the combined use of lithium and ACE inhibitors. The simultaneous use of ACE inhibitors and thiazide diuretics can lead to an increase in lithium levels and increase the risk of lithium toxicity. Therefore, the co-administration of enalapril and lithium is not recommended. If this combination is still necessary, then careful monitoring of the level of lithium in the blood serum should be carried out.

Tricyclicantidepressants / antipsychotics / anesthetics / drugs

The simultaneous use of certain anesthetics, tricyclic antidepressants and neuroleptics with ACE inhibitors can lead to an additional decrease in blood pressure.

Non-steroidal anti-inflammatory drugs (NSAIDs)

Chronic use of NSAIDs may reduce the antihypertensive effect of ACE inhibitors. NSAIDs and ACE inhibitors have an additive effect on increasing serum potassium, which can lead to deterioration of kidney function. This effect is usually reversible. In rare cases, acute renal failure may occur, especially in patients with impaired renal function (eg, elderly or dehydrated patients).

Antidiabetic agents

Epidemiological studies suggest that the concomitant use of ACE inhibitors and antidiabetic drugs (insulin or oral antidiabetic drugs) may lead to hypokalemia. This symptom is most likely to occur in patients with kidney damage during the first weeks of combined treatment.

Alcohol

Alcohol enhances the hypotensive effect of ACE inhibitors. Sympathomimetics

Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.

Acetylsalicylic acid, thrombolytics andβ- blockers

Enalapril can be safely administered concomitantly with acetylsalicylic acid (in cardiac dosage), thrombolytics and β-blockers.

cardiac glycosides

The simultaneous use of Enap and cardiac glycosides does not have a clinically significant adverse interaction.

Cimetidine

With the joint administration of Enap and cimetidine, the half-life of Enap may be lengthened. If the patient is already taking the above drugs, he should inform the doctor that he is taking Enap.

Precautionary measures

Symptomatic hypotension

Symptomatic hypotension is rare in uncomplicated hypertension. It is most likely to occur in hypertensive patients with hypovolemia, for example, due to diuretic treatment, a salt-depleted diet, dialysis, diarrhea, or vomiting. Symptomatic hypotension may also occur in patients with heart failure with or without concomitant renal failure. More likely to occur in patients with more severe heart failure due to high doses of loop diuretics, hyponatremia, or kidney damage. In such patients, treatment should be started under medical supervision, with strict adherence to selected doses of enalapril and / or diuretic. A similar principle can be applied to patients with ischemic heart disease or cerebrovascular disease, in whom a sudden drop in blood pressure can lead to myocardial infarction or stroke. If hypotension develops, the patient should be placed in the supine position and, if necessary, intravenous infusion of 0.9% sodium chloride solution should be given to replenish plasma volume. Transient hypotension is not a contraindication for enalapril treatment. After adjusting blood pressure and plasma volume, patients subsequently generally tolerate treatment well.

In some patients with heart failure with normal or low blood pressure, enalapril may cause an additional decrease in blood pressure. This effect is predictable and is usually not a reason to stop treatment. If hypotension becomes symptomatic, dose reduction and/or discontinuation of the diuretic and/or enalapril is required.

Double blockade of renin-angiotensin-aldosterone system (RAAS)

The simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia, impaired renal function (including acute renal failure).

Due to the dual blockade of the RAAS, the combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended.

The appointment of therapy for dual blockade of the RAAS, due to its absolute necessity, should occur only under the supervision of a specialist and subject to frequent close monitoring of renal function, electrolytes and blood pressure.

Stenosis of the aortic or mitral valve of the heart / hypertrophiccardiomyopathy

As with all vasodilators, ACE inhibitors should be used with extreme caution in patients with left ventricular outflow tract obstruction. In cases of cardiogenic shock and severe hemodynamic obstruction of the outflow tract of the left ventricle, the use of these drugs should be avoided.

Impaired kidney function

In patients with impaired renal function (creatinine clearance< 1,33 мл/сек) начальную дозу следует подбирать согласно клиренсу креатинина. Поддерживающие дозы назначают в соответствии с реакцией пациента на лечение. При этом регулярно следует контролировать уровни креатинина и калия в сыворотке крови.

In patients with severe heart failure or underlying kidney disease, including renal artery stenosis, renal failure may occur during treatment with enalapril. With timely diagnosis and appropriate treatment, this disease is usually reversible.

Some patients with overt pre-existing kidney disease have developed minimal and transient increases in serum urea and creatinine levels when enalapril was given concomitantly with a diuretic. In such cases, it may be necessary to reduce the dosage of ACE inhibitors and / or cancel diuretics. This situation should increase the likelihood of predisposing renal artery stenosis.

Renovascular hypertension

Patients with bilateral renal artery stenosis or stenosis of the artery of one functioning kidney, who are treated with ACE inhibitors, have an increased risk of developing hypotension and renal failure. In this case, a decrease in kidney function can be manifested only by minor changes in the level of creatinine in the blood serum. In such patients, treatment should begin at low doses and under medical supervision; during treatment, careful titration and monitoring of renal function is necessary.

kidney transplant

Due to lack of experience with enalapril, treatment with enalapril is not recommended in patients with a recent kidney transplant.

Liver failure

During treatment with ACE inhibitors, in rare cases, a syndrome may occur that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is unknown. If jaundice or a marked increase in liver enzymes develop during treatment with ACE inhibitors, treatment should be discontinued immediately and the patient should be closely monitored and treated if necessary.

Neutropenia/agranulocytosis

Neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. Neutropenia rarely occurs in patients with normal renal function and no other complications. Enalapril should be used with extreme caution in patients with vascular collagenosis (eg, systemic lupus erythematosus, scleroderma), as well as in patients treated with immunosuppressive drugs, allopurinol or procainamide, or in patients with a combination of these factors, especially with pre-existing impaired renal function. Some of these patients may develop serious infections, in some cases not responding to intensive antibiotic therapy. If enalapril is used in such patients, then periodic monitoring of the number of leukocytes is recommended. Patients should be instructed to report any signs of infection.

Hypersensitivity/ angioedema

During treatment with ACE inhibitors, including enalapril, in rare cases, angioedema of the face, extremities, lips, tongue, pharynx and / or larynx may develop at any stage of treatment. In such cases, enalapril should be discontinued immediately. Appropriate monitoring should be carried out to ensure that all symptoms have disappeared before the patient is discharged from the hospital.

Angioedema of the face and lips usually does not require treatment; antihistamines may be used to relieve symptoms. Angioedema of the larynx can be fatal. In case of angioedema of the tongue, pharynx or larynx, which can cause airway obstruction, it is necessary to immediately prescribe epinephrine (0.3-0.5 ml subcutaneous adrenaline solution in a ratio of 1:1000) and ensure free airway patency.

Patients with a history of angioedema unrelated to treatment with ACE inhibitors have an increased risk of developing angioedema while receiving ACE inhibitors.

Anaphylactoid reaction during desensitization

In patients taking ACE inhibitors, life-threatening anaphylactoid (allergic type) reactions may occur in rare cases during desensitization against wasp or bee venom. These reactions can be avoided by temporarily stopping treatment with ACE inhibitors before each desensitization.

Anaphylactoid reactions during LDL apheresis

In patients receiving ACE inhibitors, during low-density lipoprotein (LDL) apheresis with dextran sulfate, life-threatening anaphylactoid (allergic-type) reactions may occur in rare cases. These reactions can be avoided by temporarily stopping treatment with ACE inhibitors before each apheresis.

Patients on hemodialysis treatment

There have been reports of hypersensitivity reactions and allergic-type reactions (anaphylactoid reactions) in patients undergoing dialysis using high flux density membranes (eg AN 69) and concomitantly treated with ACE inhibitors. If hemodialysis is necessary, the patient should be transferred to another class of drugs, or another type of membrane should be used for dialysis.

Patients with diabetes

In diabetic patients treated with oral antidiabetic drugs or insulin, blood glucose levels should be carefully monitored during the first few months of concomitant treatment with ACE inhibitors. Cough

During treatment with ACE inhibitors, a persistent, dry, non-productive cough may occur, which stops after discontinuation of treatment. This should be included in the differential diagnosis.

Surgicalintervention/ anesthesia

In patients undergoing major surgery or during anesthesia with drugs that cause hypotension, enalapril may block the formation of angiotensin II secondary to compensatory renin release. Hypotension associated with this mechanism can be corrected by increasing blood volume.

Hyperkalemia

During treatment with ACE inhibitors, including enalapril, the level of potassium in the blood may increase in some patients. The risk of developing hyperkalemia is higher in patients with renal insufficiency, diabetes mellitus, who are simultaneously taking potassium-sparing diuretics, potassium supplements, or other drugs that can cause hyperkalemia (eg, heparin). In cases where the simultaneous use of the above-mentioned agents is considered appropriate, it is recommended to regularly monitor the level of potassium in the blood serum. Lithium

The appointment of a combination of lithium and enalapril is usually not recommended. Use in children

There is limited, effective and safe experience in children over 6 years of age with hypertension. There is no experience with other indications. Limited pharmacokinetic data are available for children over 2 months of age. Enalapril is recommended for use in children only for the treatment of hypertension.

Ethnic features

Like other ACE inhibitors, enalapril is less effective in lowering blood pressure in dark-skinned patients; a possible cause is the predominance of a state of reduced renin secretion in dark-skinned hypertensive patients.

Special precautions regarding excipients

Enap contains lactose. Patients with a rare hereditary disorder of galactose intolerance, lactose intolerance and malabsorption of glucose - galactose should not take this drug.

Pregnancy and lactation

Pregnancy

Epidemiological data regarding the risk of teratogenesis due to the use of ACE inhibitors during the first trimester of pregnancy are not conclusive, however, a slight increase in risk cannot be ruled out. Unless continued treatment with ACE inhibitors is deemed necessary, patients planning pregnancy should switch to an alternative antihypertensive treatment that has an established safety profile for use during pregnancy.

If pregnancy is established, then ACE inhibitors should be stopped immediately and, if necessary, treatment with alternative means should be started.

It is known that the use of ACE inhibitors in women during the second and third trimesters of pregnancy has a fetotoxic effect (decrease in renal function, oligohydramnios, delayed ossification of the skull) and neonatal toxic effect (renal failure, hypotension, hyperkalemia).

If the use of ACE inhibitors occurred in the second trimester of pregnancy, it is recommended to conduct ultrasound monitoring of the function of the kidneys and skull.

Newborns whose mothers have taken ACE inhibitors should be carefully monitored for hypotension.

lactation period

Pharmacokinetic data indicate a very low concentration in breast milk. Despite the fact that these concentrations are considered clinically insignificant, the use of Enap is not recommended for breastfeeding premature babies and in the first weeks after birth due to the hypothetical risk of effects on the cardiovascular system and kidneys due to the lack of sufficient clinical experience with the use. In a later period, the use of Enap by nursing mothers may be considered in cases where treatment is necessary for the mother, and the child is observed for any side effects.

Impact on ability to drivecar andwork with machinery

In some patients, the drug can cause severe hypotension and dizziness, especially at the initial stage of treatment, thus exerting an indirect and temporary effect on the ability to drive a car and work with mechanisms.

Release form and packaging

20 tablets of 10 mg (blister of 10 tablets, 2 blisters per pack).

20 tablets of 20 mg (blister of 10 tablets, 2 blisters per pack).

30 tablets of 10 mg (blister of 10 tablets, 3 blisters per pack).

30 tablets of 20 mg (blister of 10 tablets, 3 blisters per pack).

Storage conditions

Store at a temperature not exceeding 25 °C in the original packaging to protect against moisture.

Keep out of the reach of children.

Best before date

Terms of dispensing from pharmacies

On prescription.

Manufacturer

Krka, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia.

Compound

Description of the dosage form

Tablets, 2.5 mg: white or almost white, round, biconvex, chamfered.

Tablets, 5 mg: white or almost white, round, flat-cylindrical, with a risk on one side and a chamfer.

Tablets, 10 mg: red-brown, round, flat-cylindrical, with a risk on one side and a chamfer. White and burgundy inclusions are allowed on the surface and in the mass of the tablet.

Tablets, 20 mg: light orange, round, flat-cylindrical, with a risk on one side and a chamfer. On the surface and in the mass of the tablet, white and brown-burgundy inclusions are allowed.

pharmachologic effect

pharmachologic effect- hypotensive.

Pharmacodynamics

Enalapril is an antihypertensive drug, the mechanism of action of which is associated with inhibition of ACE activity, leading to a decrease in the formation of angiotensin II.

Enalapril is a derivative of two amino acids: L-alanine and L-proline. After absorption, enalapril taken orally is hydrolyzed to enalaprilat, which inhibits ACE. The mechanism of its action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in the plasma content of which leads to an increase in plasma renin activity (by eliminating the negative feedback on changes in renin production) and a decrease in aldosterone secretion. Since ACE is identical to the enzyme kininase II, enalapril can also block the destruction of bradykinin, a peptide that has a powerful vasopressor effect. The significance of this effect in the mechanism of action of enalapril has not been definitively established.

The antihypertensive effect of enalapril is associated primarily with the suppression of RAAS activity, which plays an important role in the regulation of blood pressure. Despite this, enalapril has an antihypertensive effect even in patients with arterial hypertension and low renin concentration.

Against the background of the use of enalapril, the level of blood pressure decreases regardless of the position of the body (both in the supine position and in the standing position) without a significant increase in heart rate. Symptomatic orthostatic hypotension rarely develops. In some patients, achieving optimal blood pressure reduction may require several weeks of therapy. Abrupt withdrawal of enalapril was not accompanied by a rise in blood pressure.

Effective inhibition of ACE activity usually occurs 2-4 hours after a single oral dose of enalapril. The time of onset of the antihypertensive effect is usually 1 hour when taken orally, reaching a maximum after 4-6 hours. The duration of action depends on the dose. At the recommended doses, the antihypertensive effect and hemodynamic effects are maintained for at least 24 hours.

In patients with essential hypertension, a decrease in blood pressure is accompanied by a decrease in peripheral vascular resistance and an increase in cardiac output, while the heart rate does not change or changes slightly. The renal blood flow increases, but the glomerular filtration rate does not change. However, in patients with initially low glomerular filtration rate, its level usually increased.

In patients with diabetic / non-diabetic nephropathy, while taking enalapril, albuminuria / proteinuria and renal excretion of IgG decreased.

In patients with CHF during therapy with cardiac glycosides and diuretics, the use of enalapril is accompanied by a decrease in peripheral vascular resistance and blood pressure, an increase in cardiac output, while heart rate decreases (usually in patients with CHF, heart rate is increased). The wedge pressure of the pulmonary capillaries also decreases. With long-term use, enalapril increases exercise tolerance and reduces the severity of heart failure, assessed by the criteria NYHA. Enalapril in patients with mild to moderate heart failure slows down its progression, and also slows down the development of left ventricular dilatation.

With left ventricular dysfunction, enalapril reduces the risk of developing major ischemic outcomes (including the incidence of myocardial infarction and the number of hospitalizations for unstable angina).

Pharmacokinetics

Suction

After oral administration, enalapril is rapidly absorbed, the degree of absorption of enalapril is approximately 60%. T max enalapril in serum - 1 hour after ingestion. Eating does not affect absorption. Enalapril is rapidly and actively hydrolyzed to form enalaprilat, a potent ACE inhibitor. T max enalaprilat - 3-4 hours after ingestion. T 1/2 of enalapril with repeated use is 11 hours. In patients with normal renal function, C ss of enalaprilat in plasma was achieved on the 4th day of therapy.

Distribution

Communication with proteins of a blood plasma of an enalaprilat in the range of therapeutic doses makes 60%.

Biotransformation (metabolism)

In addition to being converted to enalaprilat, enalapril does not undergo significant biotransformation.

breeding

Enalaprilat is mainly excreted by the kidneys. Enalaprilat (about 40% of the dose) and unchanged enalapril (about 20%) are predominantly determined in the urine.

Special patient groups

Impaired kidney function. In patients with mild to moderate renal insufficiency (Cl creatinine 36-60 ml / min (0.6-1 ml / s) after taking enalapril at a dose of 5 mg 1 time per day, the AUC of enalaprilat is approximately 2 times greater than in patients with normal renal function.In severe renal failure (Cl creatinine ≤30 ml / min): AUC increased by about 8 times.T 1/2 of enalaprilat after repeated use in severe renal failure is extended, and the time to reach an equilibrium state is delayed.Enalaprilat is removed when hemodialysis, excretion rate - 1.03 ml / s (62 ml / min).

Enap ® indications

essential hypertension;

chronic heart failure (as part of combination therapy);

prevention of the development of clinically significant heart failure in patients with asymptomatic left ventricular dysfunction (as part of combination therapy);

prevention of coronary ischemia in patients with left ventricular dysfunction in order to:

Reducing the incidence of myocardial infarction;

Reducing the frequency of hospitalizations for unstable angina.

Contraindications

hypersensitivity to enalapril, other components of the drug or other ACE inhibitors;

history of angioedema associated with previous use of ACE inhibitors, hereditary angioedema angioedema or idiopathic angioedema;

simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (Cl creatinine less than 60 ml / min);

porphyria;

lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (because Enap ® contains lactose);

pregnancy;

breastfeeding period;

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

Carefully: bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; primary hyperaldosteronism; hyperkalemia; condition after kidney transplantation; aortic stenosis and / or mitral stenosis (with impaired hemodynamics); hypertrophic obstructive cardiomyopathy (GOKMP); conditions with reduced BCC (including diarrhea, vomiting); systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus); cardiac ischemia; oppression of bone marrow hematopoiesis; cerebrovascular diseases (including cerebrovascular insufficiency); diabetes; renal failure (proteinuria - more than 1 g / day); liver failure; patients on a salt-restricted diet or on hemodialysis; simultaneous reception with immunosuppressants and diuretics; patients over 65 years of age.

Use during pregnancy and lactation

The use of ACE inhibitors, incl. the drug Enap ® in the first trimester of pregnancy is not recommended.

The use of ACE inhibitors, incl. Enap ® is contraindicated in the second and third trimesters of pregnancy.

Epidemiological data on the risk of teratogenic effects of ACE inhibitors during pregnancy do not allow definitive conclusions to be drawn. However, the risk of their development cannot be ruled out. If it is necessary to use ACE inhibitors, the patient must be transferred to therapy with another approved antihypertensive drug with a proven safety profile for pregnant women.

When pregnancy is confirmed, Enap ® should be discontinued as soon as possible.

Taking ACE inhibitors in the II and III trimesters can cause fetotoxicity reactions (impaired kidney function, oligohydramnios, slowing down of ossification of the fetal skull bones) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia).

If an ACE inhibitor was taken in the II and III trimesters of pregnancy, it is recommended to conduct an ultrasound scan of the kidneys and bones of the fetal skull.

In those rare cases where the use of an ACE inhibitor during pregnancy is considered necessary, periodic ultrasonography should be performed to assess the amniotic fluid index. If oligohydramnios is detected during ultrasound, it is necessary to stop taking the drug. Patients and physicians should be aware that oligohydramnios develops when there is irreversible damage to the fetus.

If ACE inhibitors are used during pregnancy and oligohydramnios develops, then, depending on the week of pregnancy, a stress test, a non-stress test, or a fetal biophysical profile may be necessary to assess the functional state of the fetus.

Newborns whose mothers took ACE inhibitors during pregnancy should be monitored, given the risk of developing arterial hypotension. Enalapril, which crosses the placenta, can be partially removed from the neonatal circulation by peritoneal dialysis, and theoretically it can be removed by exchange transfusion.

Enalapril and enalaprilat are found in breast milk in trace concentrations, therefore, if it is necessary to use the drug Enap ®, breastfeeding should be stopped.

Side effects

Classification of the frequency of development of side effects WHO: very often - ≥1 / 10; often - from ≥1 / 100 to<1/10; нечасто — от ≥1/1000 до <1/100; редко — от ≥1/10000 до <1/1000; очень редко — <1/10000; частота неизвестна — не может быть оценена на основе имеющихся данных. В каждой группе нежелательные эффекты представлены в порядке уменьшения их серьезности.

From the side of the hematopoietic organs: infrequently - anemia (including aplastic and hemolytic); rarely - neutropenia, a decrease in the concentration of hemoglobin and hematocrit in the blood serum, thrombocytopenia, agranulocytosis, inhibition of bone marrow hematopoiesis, pancytopenia, lymphadenopathy, autoimmune diseases.

From the side of metabolism: infrequently - hypoglycemia.

From the nervous system: often - headache, depression; infrequently - confusion, insomnia, drowsiness, paresthesia, irritability, vertigo; rarely - a change in the nature of dreams, sleep disorders.

From the sense organs: often - changes in taste perception; infrequently - tinnitus; very rarely - blurred vision.

From the CCC: very often - dizziness; often - a pronounced decrease in blood pressure (including orthostatic hypotension), syncope, chest pain, heart rhythm disturbances, angina pectoris; infrequently - palpitations, myocardial infarction or stroke, possibly due to a sharp drop in blood pressure in patients at high risk; rarely - Raynaud's syndrome.

From the respiratory system: very often - cough; infrequently - rhinorrhea, sore throat and hoarseness, bronchospasm / bronchial asthma; rarely - shortness of breath, pulmonary infiltrates, rhinitis, allergic alveolitis / eosinophilic pneumonia.

From the digestive system: very often - nausea; often - diarrhea, abdominal pain, flatulence; infrequently - ileitis, intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, anorexia, dryness of the oral mucosa, peptic ulcer; rarely - impaired liver function and bile secretion, hepatitis (hepatocellular or cholestatic), including hepatic necrosis, cholestasis (including jaundice), stomatitis / aphthous ulcers, glossitis; very rarely - angioedema of the intestine.

From the side of the skin: often - skin rash, hypersensitivity reactions / angioedema (angioneurotic edema of the face, extremities, lips, tongue, pharynx and / or larynx is described); infrequently - increased sweating, pruritus, urticaria, alopecia; rarely - erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus (pemphigus), erythroderma.

A symptom complex is described, which may include fever, myalgia/myositis, arthralgia/arthritis, serositis, vasculitis, increased ESR, leukocytosis and eosinophilia, a positive test for antinuclear antibodies. Skin rash, photosensitivity reactions, or other skin manifestations may occur.

From the genitourinary system: infrequently - impaired renal function, proteinuria, renal failure, impotence; rarely - oliguria, gynecomastia.

From the musculoskeletal system: infrequently - muscle cramps.

Laboratory indicators: often - hyperkalemia, increased serum creatinine concentration; infrequently - an increase in the concentration of urea in the blood serum, hyponatremia; rarely - an increase in the activity of liver enzymes, an increase in the concentration of bilirubin in the blood serum.

Others: frequency unknown - syndrome of inappropriate ADH secretion.

Adverse events identified during the post-marketing use of the drug, but a causal relationship with the use of the drug has not been established: urinary tract infections, upper respiratory tract infections, bronchitis, cardiac arrest, atrial fibrillation, herpes zoster, melena, ataxia, thromboembolism of the branches of the pulmonary artery and lung infarction, hemolytic anemia, including cases of hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.

Interaction

Double blockade of the RAAS

The risk of developing arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) is higher in the case of a double blockade of the RAAS, i.e. with the simultaneous use of angiotensin II receptor antagonists, ACE inhibitors or aliskiren, in comparison with the use of a drug from one of the listed groups. If necessary, the simultaneous use of drugs is recommended to control blood pressure, kidney function and water and electrolyte balance.

The simultaneous use of enalapril with aliskiren in patients with diabetes mellitus or impaired renal function (Cl creatinine less than 60 ml / min) is contraindicated.

Potassium-sparing diuretics and potassium supplements

ACE inhibitors reduce potassium loss due to diuretics.

The simultaneous use of enalapril and potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing substitutes, as well as the use of other drugs that increase the content of potassium in the blood plasma (for example, heparin) can lead to hyperkalemia.

If necessary, simultaneous use should be careful and regularly monitor the serum potassium content.

Diuretics (thiazide or loop)

Prior therapy with high doses of diuretics may lead to a decrease in BCC and an increased risk of arterial hypotension during the initiation of enalapril therapy. Excessive antihypertensive effect can be reduced by discontinuing the diuretic, increasing water or salt intake, and also by starting treatment with enalapril at a low dose.

Other antihypertensive drugs

Simultaneous with enalapril, the use of beta-blockers, alpha-blockers, ganglion blockers, methyldopa, CCB, nitroglycerin or other nitrates can further reduce blood pressure.

Lithium

With the simultaneous use of ACE inhibitors with lithium preparations, a transient increase in the serum concentration of lithium and the development of lithium intoxication were observed. The use of thiazide diuretics may lead to an additional increase in serum lithium concentration and the risk of lithium intoxication with the simultaneous use of ACE inhibitors. Co-administration of enalapril with lithium is not recommended. Serum lithium concentrations should be carefully monitored if such a combination is required.

Tricyclic antidepressants/antipsychotics (neuroleptics)/anesthetics/narcotics

The simultaneous use of certain anesthetics, tricyclic antidepressants and antipsychotics (neuroleptics) with ACE inhibitors can lead to an additional decrease in blood pressure.

NSAIDs

The simultaneous use of NSAIDs (including selective COX-2 inhibitors) may weaken the antihypertensive effect of ACE inhibitors or angiotensin II receptor antagonists.

NSAIDs and ACE inhibitors have an additive effect on the increase in serum potassium, which can lead to deterioration of renal function, especially in patients with impaired renal function. This effect is reversible.

In rare cases, acute renal failure may develop, especially in patients with impaired renal function (for example, in elderly patients or with severe hypovolemia, including against the background of the use of diuretics).

Before starting therapy, it is necessary to replenish the BCC. During treatment, it is recommended to monitor kidney function.

Oral hypoglycemic agents and insulin

Epidemiological studies suggest that the simultaneous use of ACE inhibitors and hypoglycemic agents (insulin and oral hypoglycemic agents) may lead to an increase in the hypoglycemic effect with the risk of hypoglycemia. More often, hypoglycemia develops in the first weeks of therapy in patients with impaired renal function.

ethanol

Ethanol enhances the antihypertensive effect of ACE inhibitors.

Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.

Acetylsalicylic acid, thrombolytics and beta-blockers

The simultaneous use of enalapril with acetylsalicylic acid (as an antiplatelet agent), thrombolytics and beta-blockers is safe.

Weakens the effect of drugs containing theophylline.

Allopurinol, cytostatics and immunosuppressants (including methotrexate, cyclophosphamide)

Simultaneous use with ACE inhibitors may increase the risk of developing leukopenia. With simultaneous use with allopurinol, the risk of developing an allergic reaction increases, especially in patients with impaired renal function.

Cyclosporine

Simultaneous use with ACE inhibitors may increase the risk of hyperkalemia.

Antacids

Antacids may decrease the bioavailability of ACE inhibitors.

Preparations of gold

When using ACE inhibitors, incl. enalapril, patients receiving an intravenous gold preparation (sodium aurothiomalate), a symptom complex was described, including flushing of the skin of the face, nausea, vomiting, arterial hypotension.

There was no clinically significant pharmacokinetic interaction of enalapril with hydrochlorothiazide, furosemide, digoxin, timolol, methyldopa, warfarin, indomethacin, sulindac and cimetidine. With simultaneous use with propranolol, the concentration of enalaprilat in the blood serum decreases, but this effect is clinically insignificant.

Dosage and administration

inside, regardless of the time of eating, preferably at the same time of day, drinking a small amount of liquid.

Arterial hypertension

The initial dose is from 5 to 20 mg 1 time per day, depending on the severity of arterial hypertension and the patient's condition. With mild hypertension, the recommended initial dose is 5-10 mg / day.

In patients with severe activation of the RAAS (for example, with renovascular hypertension, salt loss and / or dehydration, decompensated heart failure or severe arterial hypertension), an excessive decrease in blood pressure at the beginning of treatment is possible. In such situations, it is recommended to start therapy with a low initial dose of 5 mg / day or less under the supervision of a physician.

Prior therapy with high doses of diuretics may lead to dehydration and an increased risk of arterial hypotension at the beginning of therapy with Enap ® ; the recommended starting dose is 5 mg/day. Treatment with diuretics should be discontinued 2-3 days before the start of the use of the drug Enap ® . Caution should be exercised when using the drug Enap ®, monitor kidney function and serum potassium levels.

The usual maintenance dose is 20 mg once daily.

The dosage is selected individually, if necessary, can be increased to a maximum daily dose of 40 mg.

CHF and left ventricular dysfunction

The initial dose of the drug Enap ® is 2.5 mg / day once; treatment in this case must be started under the close supervision of a physician.

The drug Enap ® for the treatment of heart failure can be used simultaneously with diuretics and / or beta-blockers, if necessary - with cardiac glycosides. In the absence of symptomatic arterial hypotension at the beginning of therapy or after its correction, the dose should be increased gradually (by 2.5-5 mg every 3-4 days) to the usual maintenance dose of 20 mg / day, which is prescribed either once or in 2 doses, depending on the tolerance of the drug. Dose selection is carried out within 2-4 weeks. The maximum daily dose is 40 mg in 2 divided doses.

1st week: 1-3rd day - 2.5 mg / day in 1 dose; 4-7th day - 5 mg / day in 2 divided doses.

2nd week: 10 mg/day in 1 or 2 doses.

3rd and 4th weeks: 20 mg / day in 1 or 2 doses.

Special precautions should be observed in patients with impaired renal function and taking diuretics.

Given the risk of developing arterial hypotension and renal failure (observed much less frequently), blood pressure and kidney function should be carefully monitored before and after starting the use of the drug Enap ®. In patients taking diuretics, diuretic doses, if possible, should be reduced before taking the drug Enap ®. The development of arterial hypotension after taking the first dose does not mean that arterial hypotension will persist with prolonged use, and does not indicate the need to stop using the drug.

Special patient groups

Impaired kidney function. In patients with impaired renal function, the intervals between use should be increased and / or the dose of Enap ® should be reduced.

With Cl creatinine from 30 to 80 ml / min, the initial dose is 5-10 mg / day; from 10 to 30 ml / min - 2.5-5 mg / day; less than 10 ml / min - 2.5 mg on the day of hemodialysis (enalaprilat is excreted during hemodialysis).

In the interval between hemodialysis sessions, the dose of the drug should be selected under the control of blood pressure.

Elderly patients. In elderly patients, a more pronounced antihypertensive effect and a longer duration of action of the drug are more often observed, which is associated with a decrease in the rate of excretion of enalapril, so the recommended initial dose is 1.25 mg. The dose is selected depending on the function of the kidneys.

Overdose

Symptoms: about 6 hours after ingestion - a pronounced decrease in blood pressure, up to the development of collapse, water and electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough, convulsions, stupor. After oral administration of 300 and 440 mg of enalapril, serum concentrations of enalaprilat in plasma exceeded the usual therapeutic concentrations by 100 and 200 times, respectively.

Treatment: the patient should be placed in a horizontal position with a low headboard. In mild cases, gastric lavage and ingestion of activated charcoal are indicated, in more severe cases, intravenous infusion of 0.9% sodium chloride solution, plasma substitutes, and, if necessary, intravenous administration of catecholamines. It is possible to remove enalaprilat by hemodialysis, the excretion rate is 62 ml / min. Patients with bradycardia resistant to therapy are shown setting a pacemaker. Serum electrolytes and serum creatinine should be closely monitored.

special instructions

Arterial hypotension

Symptomatic arterial hypotension rarely develops in patients with uncomplicated arterial hypertension. Arterial hypotension with all clinical manifestations can be observed after the first dose of Enap ® in patients with hypovolemia, as a result of diuretic therapy, salt-free diet, diarrhea, vomiting or hemodialysis. The development of symptomatic arterial hypotension is more likely in patients with severe heart failure due to the use of high doses of diuretics, hyponatremia, or impaired renal function. In these patients, treatment should be started under the supervision of a physician until the optimal dose adjustment of Enap ® and / or diuretic. Similar tactics can be applied to patients with coronary artery disease or cerebrovascular disease, in whom a sharp excessive decrease in blood pressure can lead to the development of myocardial infarction or cerebrovascular accident.

In case of severe arterial hypotension, the patient should be given a horizontal position, legs should be raised and, if necessary, 0.9% sodium chloride solution should be injected intravenously.

Transient arterial hypotension is not a contraindication to further treatment with Enap ® after stabilization of blood pressure and BCC.

In some patients with heart failure and normal or low blood pressure, it may be further reduced when taking Enap ®. This effect is predictable and is not usually a reason to stop therapy. If arterial hypotension is accompanied by clinical symptoms, the dose should be reduced and / or the diuretic and / or Enap should be discontinued.

Aortic or mitral stenosis, HOCM

As with all vasodilators, ACE inhibitors should be used cautiously in patients with valvular obstruction and left ventricular outflow tract hypertrophy. It should not be given to patients with cardiogenic shock and hemodynamically significant left ventricular obstruction.

Impaired kidney function

In patients with renal insufficiency (Cl creatinine<80 мл/мин (1,33 мл/с) начальную дозу препарата Энап ® следует подбирать в первую очередь с учетом Cl креатинина и затем — клинического ответа на лечение. У таких пациентов следует регулярно контролировать содержание калия и концентрацию креатинина в сыворотке крови.

In patients with severe heart failure and kidney disease, including renal artery stenosis, renal failure may develop during treatment with Enap ®. Changes were usually reversible after discontinuation of the drug Enap ® .

In some patients with arterial hypertension, in whom no kidney disease was detected before the start of treatment, a slight and transient increase in the concentration of urea and creatinine in the blood serum was observed when using the drug Enap ® simultaneously with a diuretic. In such cases, it may be necessary to reduce the dose of the drug Enap ® and / or cancel the diuretic. This situation indicates the possibility of latent stenosis of the renal artery.

Renovascular hypertension

Patients with bilateral renal artery stenosis or stenosis of the artery of the only functioning kidney when treated with ACE inhibitors have an increased risk of arterial hypotension and renal failure. Only minor changes in serum creatinine concentration can indicate a decrease in kidney function. In such patients, treatment should be initiated at low doses under close medical supervision. It is necessary to carefully titrate the dose and monitor renal function.

kidney transplant

There is no experience with the use of Enap ® in patients who have recently undergone kidney transplantation. Therefore, the treatment of such patients with Enap ® is not recommended.

Impaired liver function

In rare cases, therapy with ACE inhibitors was accompanied by the development of a syndrome beginning with cholestatic jaundice and hepatitis up to the development of fulminant liver necrosis. The mechanism by which this syndrome develops is unknown. If jaundice occurs or a significant increase in the activity of liver enzymes, treatment with an ACE inhibitor should be stopped immediately, the patient should be carefully monitored and, if necessary, treated.

Neutropenia/agranulocytosis

In patients treated with ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia, and anemia have been described. Neutropenia rarely develops in patients with normal renal function in the absence of other complications. The drug Enap ® must be used with great caution in patients with connective tissue diseases (including systemic lupus erythematosus, scleroderma), while receiving immunosuppressive therapy, allopurinol or procainamide, as well as with a combination of these factors, especially with existing impaired renal function . These patients may develop severe infections that are not amenable to intensive antibiotic therapy. If patients still take the drug Enap ®, then it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that in case of any signs of infection, it is necessary to immediately consult a doctor.

Hypersensitivity/angioedema

In patients treated with ACE inhibitors, including enalapril, there have been reports of the development of angioedema of the face, extremities, lips, vocal cords and / or larynx at any time after the start of treatment. You should immediately stop the drug Enap ® and observe the patient until the symptoms disappear completely. Even in the case of swelling of the tongue only, when there is only difficulty in swallowing without respiratory distress syndrome, patients may require long-term observation, because. the use of antihistamines and corticosteroids may not be sufficient.

Angioedema of the larynx or tongue can be fatal in very rare cases. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction, especially after a history of airway surgery. In the presence of swelling of the tongue, vocal cords or larynx, appropriate therapy is indicated, which may include: s / c injection of a 0.1% solution of epinephrine (adrenaline) (0.3-0.5 ml) and / or measures aimed at recovery airway patency (intubation or tracheostomy).

Among black patients receiving therapy with an ACE inhibitor, the incidence of angioedema is higher than among patients of other races.

Patients with a history of angioedema unrelated to ACE inhibitors have an increased risk of developing angioedema when taking any ACE inhibitor.

Anaphylactoid reactions during desensitization with hymenoptera (hymenoptera) venom

Patients treated with ACE inhibitors during desensitization with hymenoptera venom have rarely developed life-threatening anaphylactoid reactions. To prevent such reactions, it is necessary to temporarily stop taking the ACE inhibitor during desensitization procedures.

Anaphylactoid reactions during LDL apheresis

Patients treated with ACE inhibitors during LDL apheresis with dextran sulfate have rarely developed life-threatening anaphylactoid reactions. It is necessary to temporarily replace the drugs of another group.

Hemodialysis

Due to the increased risk of anaphylactoid reactions, the drug should not be used in patients on hemodialysis using high-flow polyacrylonitrile membranes (AN69 ®) undergoing LDL apheresis with dextran sulfate. If it is necessary to carry out hemodialysis, it is advisable to use dialysis membranes of a different type or antihypertensive drugs of another group.

hypoglycemia

In diabetic patients receiving oral hypoglycemic agents or insulin, blood glucose levels should be closely monitored during the first month of treatment with an ACE inhibitor.

Cough

When using the drug Enap ®, a dry, unproductive, prolonged cough may occur, which disappears after discontinuation of the use of ACE inhibitors, which must be taken into account in the differential diagnosis of cough against the background of the use of an ACE inhibitor.

Surgery/general anesthesia

Before surgery (including dental procedures), it is necessary to warn the surgeon / anesthetist about the use of the drug Enap ®. During major surgery or general anesthesia with the use of drugs that cause arterial hypotension, ACE inhibitors can block the formation of angiotensin II in response to compensatory renin release. If at the same time a pronounced decrease in blood pressure develops, explained by a similar mechanism, it can be corrected by the introduction of plasma substitutes.

Hyperkalemia

May develop during treatment with ACE inhibitors, incl. and drug Enap ® . Risk factors for the development of hyperkalemia are renal failure, advanced age (over 70 years), diabetes mellitus, some concomitant conditions (decrease in BCC, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride) , as well as potassium preparations or potassium-containing substitutes and the use of other drugs that increase the content of potassium in the blood plasma (for example, heparin). The use of potassium supplements, potassium-sparing diuretics and salt substitutes containing potassium can lead to a significant increase in serum potassium, especially in patients with impaired renal function. Hyperkalemia can lead to serious heart rhythm disturbances, sometimes fatal. The simultaneous use of the above drugs should be carried out with caution under the control of the content of potassium in the blood serum.

Lithium

The simultaneous use of lithium salts and the drug Enap ® is not recommended.

Ethnic features

The drug Enap ® , like other ACE inhibitors, has a less pronounced antihypertensive effect in patients of the Negroid race compared to representatives of other races.

Special information on excipients

The drug Enap ® contains lactose, so the drug is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

Influence on the ability to perform potentially hazardous activities that require special attention and speed of reactions (for example, driving vehicles, working with mechanisms). When using the drug Enap ®, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (dizziness may develop due to a sharp decrease in blood pressure, especially after taking the initial dose of Enap ® in patients taking diuretics ).

Release form

1. Production at JSC "Krka, d.d., Novo Mesto". Slovenia.

Tablets, 2.5 mg, 5 mg, 10 mg and 20 mg. In a blister of combined material OPA/Al/PVC and aluminum foil, 10 pcs. 2, 3, 6 or 9 blisters in a carton pack.

Tablets, 10 mg and 20 mg. In a blister, 10 pcs. 10, 20, 50 or 100 blisters in a carton pack (for hospitals).

Packing and / or packaging at the Russian enterprise KRKA-RUS LLC.

tablets 5mg

Pharmacotherapeutic group

Antihypertensive - angiotensin-converting enzyme inhibitors

Pharmacological properties

Hypotensive, cardioprotective. It undergoes biotransformation in the liver with the formation of an active metabolite - enalaprilat. Enalaprilat easily passes through histohematic barriers, excluding the BBB, and crosses the placenta. Excreted mainly by the kidneys. The decrease in blood pressure manifests itself 1 hour after administration, reaches a maximum by 6 hours and lasts for 1 day. In some patients, therapy for several weeks is necessary to achieve an optimal level of blood pressure. In heart failure, long-term (within 6 months) treatment increases exercise tolerance, reduces heart size, and reduces mortality. The hypotensive effect of enalapril is due to a decrease in the content of angiotensin II and aldosterone in the blood, an increase in the concentration of bradykinin and PGE2. A decrease in total peripheral vascular resistance is accompanied by an increase in cardiac output without a change in heart rate, a decrease in pressure in the pulmonary capillaries and unloading of the pulmonary circulation, which results in an increase in exercise tolerance and a decrease in the size of the dilated heart.

Enap-5 - indications for use

Hypertension, symptomatic arterial hypertension, heart failure, diabetic nephropathy, secondary hyperaldosteronism, Raynaud's disease, scleroderma, complex therapy of myocardial infarction, exertional angina, chronic renal failure.

Contraindications

Hypersensitivity, pregnancy, breastfeeding, childhood.

Usage Precautions

Care must be taken when prescribing the drug to patients on a low-salt and salt-free diet. Before and during treatment, it is necessary to monitor blood pressure, kidney function, the concentration of transaminases and alkaline phosphatase in the vascular bed (with an increase in their content, treatment is canceled). The drug is prescribed with caution in case of impaired renal function (dose selection should be carried out under the control of enalapril in the blood).

Interaction with drugs

The simultaneous appointment of other antihypertensive drugs, barbiturates, lithium preparations, tricyclic antidepressants, thiazine derivatives or alcohol intake leads to a sharp decrease in blood pressure. Analgesics and non-steroidal anti-inflammatory drugs reduce the effect of the drug. Simultaneous treatment with cytostatics, immunosuppressants and corticosteroids leads to leukopenia. With the simultaneous use of potassium-sparing diuretics and / or potassium preparations, hyperkalemia is possible, and preparations containing theophylline reduce their effect.

Side effects

CNS depression, depression, ataxia, convulsions, drowsiness or insomnia, peripheral neuropathy, visual disturbances, taste, smell, tinnitus, conjunctivitis, lacrimation, hypotension, myocardial infarction, acute cerebrovascular accident (as a consequence of hypotension), heart rhythm disturbance ( atrial tachy- or bradycardia, atrial fibrillation), orthostatic hypotension, angina attack, thromboembolism of the pulmonary artery branches, bronchospasm, dyspnea, unproductive cough, interstitial pneumonitis, bronchitis and other infections of the upper respiratory tract, rhinorrhea, stomatitis, xerostomia, glossitis, anorexia, dyspepsia, melena, constipation, pancreatitis, liver dysfunction (cholestatic hepatitis, hepatocellular necrosis), kidney dysfunction, oliguria, urinary tract infections, gynecomastia, impotence, neutropenia, thrombocytopenia, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, herpes zoster, alopecia, photodermatitis, allergic reactions (Stevens-Johnson syndrome, urticaria, angioedema, anaphylactic shock, etc.).

Overdose

Symptoms: hypotension, development of myocardial infarction, acute cerebrovascular accident and thromboembolic complications against the background of a sharp decrease in blood pressure. Treatment: intravenous administration of isotonic sodium chloride solution and symptomatic therapy.