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 use of the drug Enap. Reviews of site visitors - consumers of this medicine, as well as the opinions of specialist doctors on the use of Enap in their practice are presented. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Analogues of Enap in the presence of existing structural analogues. Use for the treatment of arterial hypertension and blood pressure reduction in adults, children, as well as during pregnancy and lactation. Concomitant use 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, and post- and preload on the myocardium.

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

The hypotensive effect is more pronounced with high plasma renin levels 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. Strengthens coronary and renal blood flow.

With long-term use, hypertrophy of the left ventricle of the myocardium and myocytes of the walls of resistive arteries 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 is necessary for several weeks to achieve optimal blood pressure levels. In heart failure, a noticeable clinical effect is observed with long-term use - 6 months or more.

Pharmacokinetics

After taking the drug orally, about 60% of enalapril is absorbed. Eating does not affect absorption. In the liver, enalapril is metabolized to form the active metabolite enalaprilat, which is a more active ACE inhibitor than enalapril. Enalaprilat easily penetrates histohematic barriers, with the exception of the blood-brain barrier. A small amount penetrates the placental barrier and is excreted in breast milk. Excreted primarily 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 left ventricular dysfunction (as part of combination therapy);
• hypertensive crisis (R form of Enap);
• hypertensive encephalopathy (R form).

Release forms

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

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

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

Solution for intravenous administration Enap R (R).

Instructions for use and dosage

The drug is taken orally, regardless of food intake, at the same time of day. If you miss a dose of the drug, 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 schedule and 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). If there is no 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.

Elderly patients are more likely to experience a more pronounced hypotensive effect and a longer duration of action of the drug, which is associated with a decrease in the rate of elimination 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 once a 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 from 2.5 mg to 10 mg once a day; the maximum maintenance dose is 20 mg 2 times a day.

When treating asymptomatic left ventricular dysfunction, the recommended initial dose is 2.5 mg 2 times a day. Dose adjustment depends on tolerability of the drug. Usually the maintenance dose is 10 mg 2 times a day.

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

The tablets should be swallowed whole with a small amount of liquid.

Side effect

• excessive decrease in blood pressure;
• orthostatic collapse;
• chest pain;
• angina pectoris;
• myocardial infarction (usually associated with a pronounced decrease in blood pressure);
• arrhythmias (bradycardia or tachycardia, atrial fibrillation);
• heartbeat;
• thromboembolism of the branches of the pulmonary artery;
• pain in the heart area;
• fainting;
• Raynaud's syndrome;
• dizziness;
• headache;
• insomnia;
• weakness;
• increased fatigue;
• drowsiness (2-3%);
• confusion;
• increased fatigue;
• increased excitability;
• depression;
• paresthesia;
• vestibular apparatus disorder;
• 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, abdominal pain);
• intestinal obstruction;
• renal dysfunction;
• 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;
• tides;
• decreased potency;
• increase in ESR.

Contraindications

• history of angioedema (including those associated with the use of ACE inhibitors);
• porphyria;
• pregnancy;
• lactation (breastfeeding);
• children and adolescents under 18 years of age (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 breastfeeding

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

During 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 several hours after taking the first dose) in patients with severe heart failure, severe renal impairment, as well as in patients with water and electrolyte imbalance caused by treatment with diuretics, a salt-free diet, diarrhea, vomiting, as well as in patients on hemodialysis.

A pronounced decrease in blood pressure is usually manifested by nausea, increased heart rate, and fainting. If arterial hypotension develops, the patient should be transferred to a horizontal position with a low headboard, and medical supervision is required.

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 has stabilized, drug therapy can be continued at the average recommended doses. Hypotension can be avoided by interrupting diuretic treatment and avoiding a salt-free diet before starting treatment with Enap, if possible. The patient should be warned that if relapses of arterial hypotension occur, accompanied by nausea, increased heart rate and fainting, then consultation with a doctor is necessary.

Renal function should be monitored before starting treatment and during therapy.

During treatment with Enap, an increase in potassium levels 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 supplements. Such patients should be informed of the need to consult a doctor if muscle weakness and arrhythmia occur.

Patients receiving Enap should not drink alcohol due to the risk of developing arterial hypotension.

In case of side effects or Quincke's edema (severe swelling of the lips, face, neck, arms and legs, accompanied by suffocation and hoarseness), Enap should be discontinued and appropriate treatment prescribed.

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

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

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

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

Impact on the ability to drive vehicles and operate machinery

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

Drug interactions

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

Interactions with drugs used to treat heart failure (cardiac glycosides) are not clinically significant.

With the simultaneous use of Enap and non-steroidal anti-inflammatory drugs, incl. acetylsalicylic acid may reduce the effectiveness of enalapril and increase the risk of renal dysfunction.

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

Enap weakens the effect of products containing theophylline. Concomitant use of lithium preparations may increase the side effects of lithium.

Drugs containing cimetidine increase the duration of action of enalapril.

Patients receiving enalapril are at risk of developing arterial hypotension during general anesthesia.

Ethanol (alcohol) enhances the hypotensive effect of Enap.

Analogues of the drug Enap

Structural analogues of the active substance:

• Bagopril;
• Berlipril;
• Vazolapril;
• Vero-Enalapril;
• Invoril;
• Corandil;
• Miopril;
• Renipril;
• Renitek;
• Ednit;
• Enazil 10;
• Enalacor;
• Enalapril;
• Enalapril maleate;
• Enam;
• Enarenal;
• Enafarm;
• Envas;
• Envipril.

If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.

Enap n is a drug belonging to the antihypertensive clinical and pharmacological group. The use of this product 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 is a well-tolerated drug and rarely provokes the development of any complications or side effects. However, self-administration of the drug is strictly not recommended, as there is a risk of erroneous diagnosis and incorrect dosage distribution.

Properties and pharmacological action

Enap N is a combination drug, the effect of which is determined by 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.

Composition of the drug and release form

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

The main components included are the following:

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

The excipients in the drug are as follows:

• Sodium bicarbonate;
• Lactose monohydrate;
• Anhydrous calcium hydrogen phosphate;
• Corn starch;
• Magnesium stearate;
• Cheolin yellow dye (E104).

One cardboard package 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 combination therapy.

Contraindications

Among the contraindications to the use of the drug are:

• Renal artery stenosis;
• Idiopathic angioedema type;
• Angioedema of hereditary etiology or that occurred during previous treatment with ACE inhibitors;
• Severe renal dysfunction;
• Carrying out hemodialysis procedures;
• Recent kidney transplant surgery;
• Gout;
• Anuria;
• Hyponatremia;
• Hypersensitivity to enalapril or other sulfonamide derivatives;
• Pregnancy or preparation for pregnancy;
• Simultaneous use with medications that contain aliskiren, if the patient has diabetes mellitus or has functional impairment of the kidneys.

Instructions for use

The prescription of this type of drug 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 dosages 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 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 regardless of food intake. Usually the daily dose is taken in the morning along with plenty of water.

Typically, the dose prescribed by doctors is 1 tablet once a day.

If it is necessary to increase the dosage, the doctor may add another tablet. The dose remains the same - once a day.

Enap N in dosages 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. Renal dysfunction. In this case, the dosage of hydrochlorothiazide and enalapril should be as low as possible. In this case, the doctor monitors the level of creatine and potassium every 1-2 months.
2. Elderly age. In old age, the drug is used 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 adjusted.
3. Special populations. If the patient has a reduced amount of salt or fluid, the initial dose of enalapril is no more than 5 mg.

Individual instructions

Enap N should be used with special caution in the following cases:

• Atherosclerosis;
• Chronic heart failure;
• Hyperkalemia;
• Elderly age;
• Cardiac ischemia;
• Disturbances in the functioning of the kidneys and liver;
• Diabetes;
• Stenosis of the aortic mouth of a pronounced nature;
• Lack of cerebral 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 there is no evidence in medicine 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, and left ventricular dysfunction. If hypotension occurs with all its clinical manifestations, the patient requires medical assistance, the volume of circulating blood is corrected by infusion of a 0.9% sodium chloride solution. If high blood pressure occurs after the first dose of Enap N, there is no need to stop therapy, since such a reaction of the body is completely natural.

When taking the drug, constant monitoring of water and electrolyte balance is necessary. Deviations can be identified by dry mouth, drowsiness, general weakness, thirst, increased excitability, 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, as hydrochlorothiazide can lead to hepatic coma. If jaundice occurs, the patient must immediately stop taking the drug and begin symptomatic treatment.

Allergic reactions may occur. To relieve the patient of 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 can be fatal.

To prevent incipient angioedema, the patient must be promptly administered epinephrine and maintain a patent airway by intubation.

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

In case of 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-lasting, and stops after stopping the use of drugs from this group.

During pregnancy and lactation

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

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

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

• Kidney failure;
• Hypoplasia of the skull bones;
• Arterial hypotension;
• Hyperkalemia.

The 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 hypoplasia of the lungs.

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

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

That is why, at the very beginning of using the drug to normalize blood pressure, you should refuse to work in hazardous industries, as well as from driving a car or operating complex machinery.

Side effects

Correct use of Enap n rarely leads to the development of side symptoms, leading to a deterioration in the patient’s general condition and further hospitalization. The drug is well tolerated by the body and is excreted without problems through the intestines and kidneys within 24 hours.

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

Metabolism	gout
central nervous system	headache, malaise, weakness, insomnia, asthenia, excessive excitability, tinnitus, depression, tearfulness, ringing in the ears
Hematopoietic system	leukopenia, decrease in hemoglobin, bone marrow suppression, decreased hematocrit, thrombocytopenia, neutropenia
The cardiovascular system	fainting, decreased blood pressure, tachycardia, chest pain, rapid heartbeat, hypotension
Digestive system	nausea, vomiting, intestinal upset, 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, shortness of breath, 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	renal failure, renal 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 identify an individual’s predisposition to intolerance to the drug.

If serious side effects occur, the drug must be discontinued.

Overdose symptoms

An overdose of Enap can occur when the drug is taken incorrectly. Sometimes the dose of the drug may be incorrectly calculated by the attending physician. Subsequently, 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;
• Decreased pressure;
• Loss of consciousness (in difficult cases, coma);
• Kidney failure;
• Disturbances in blood balance.

An overdose of the drug requires mandatory treatment.

In mild cases, the patient is prescribed gastric lavage, taking absorbent substances and bed rest for several days. In more complex cases of drug oversaturation, hospitalization of the patient is assumed. The hospital carries out a number of measures aimed at stabilizing the general condition, namely increasing blood pressure, normalizing breathing and heart rate.

Analogs

In some cases, replacing Enap with an analogue is extremely necessary. This is done if the patient is intolerant to any component of the original drug or if it is necessary to purchase a cheaper medication, but with identical properties.

Preliminary replacement of the medicine must be discussed with the doctor. Enap n has the following names of analogues:

• Iruzide - 1 tablet contains 20 mg of lisinopril dihydrate and 25 mg of hydrochlorothiazide;
• Accusid - 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;
• Lysothiazide - 1 dose of the drug contains 10.8 mg of lisinopril dihydrate, hydrochlorothiazide 12.5 mg;
• Lopril - 1 dose of the medicine contains 10 mg of lisinopril, as well as 12.5 mg of hydrosolorthiazide;
• Enzix - 1 tablet of the drug consists of 10 mg of enalapril maleate.

Enap n has a sufficient number of analogues, which allows you to select 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 can be stored for 5 years if the intended storage conditions are followed correctly and the product is not kept in excessively humid places. It is recommended to store the medicine in its original packaging.

Special temperature conditions are not required to preserve the medicinal properties of the medicine. Therefore, it is 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 your health.

Differences between 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 their similar names, these medications do not have exactly the same properties. Using one drug without access to the one prescribed by your doctor is completely unacceptable.

Enap - the drug contains the active ingredient enalapril.

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

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

Only the attending physician can judge the advisability of taking a particular drug.

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

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

Price

Enap n belongs to the category of inexpensive drugs that are quite accessible to 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 medicine is sold;
• Dosage.

Thus, the average price for 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 help” that will quickly and effectively suppress high blood pressure. However, another part of users are not completely satisfied with the results obtained and note extremely rapid addiction to the drug.

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

Ekaterina, 52 years old, Ekaterinburg“It so happened that I have been suffering from high blood pressure for several years now. The doctor prescribed Enapn for me, and now I don’t even leave the house without these pills. The drug copes well with the prevention of angina pectoris, preventing 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 medicine cabinet for 2 years now. My husband takes them for high blood pressure. He always carries at least a couple of them with him in case he suddenly needs to lower his blood pressure urgently. The only thing that upset me was that the product in our case was really addictive. If earlier one tablet was enough for my husband, then just recently he had to take a whole course to stabilize his blood pressure.

One of the advantages is the accessibility of Enap. In our pharmacies its cost does not exceed 90 rubles. The tablets begin to act quickly. After just 15 minutes, you feel better and can continue to do your usual activities.

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

I can say the following about the result. Enap helps me, but relief comes after 30-40 minutes. Maybe I'm doing something wrong, but I seem to be following the instructions. Of course, I didn’t go to the doctor first with my problem, but I didn’t have time for that for many reasons. I take it periodically for about six months. I didn’t notice any side effects.”

Sergey, 38 years old, Voronezh“My father was seriously interested in Enap tablets. He had been taking them for a very long time. As he says, they relieve headaches and improve mood, and are generally irreplaceable for hypertension. If previously one tablet every few days was enough for my father, in the last year the situation has become quite acute. Now dad drinks several of them every day, otherwise he feels completely overwhelmed. I also developed a severe cough. After visiting a doctor, it turned out that the abuse led to an overdose. Now we will treat hypertension itself, and we had to forget about 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 score 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) - cardboard packs.
10 pieces. - blisters (6) - cardboard packs.

Pills red-brown, flat-cylindrical, with a notch and a chamfer; White and burgundy inclusions are allowed on the surface and in the bulk 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, red iron oxide dye (E172) - 1.2 mg.

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

Pills light orange in color, flat-cylindrical, with a score 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, red iron oxide dye (E172) - 0.1 mg, yellow iron oxide dye (E172) - 0.3 mg.

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

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 content of which in the blood plasma leads to an increase in the activity of plasma renin (by eliminating the negative feedback to 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 the activity of the RAAS, 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 concentrations.

With the use of enalapril, blood pressure levels decrease regardless of body position (both in a supine and standing position) without a significant increase in heart rate. Symptomatic orthostatic hypotension is rare. In some patients, achieving optimal blood pressure reduction may require several weeks of therapy. Abrupt withdrawal of enalapril was not accompanied by an increase in blood pressure.

Effective inhibition of ACE activity usually occurs 2-4 hours after a single oral dose of enalapril. The onset of antihypertensive action when taken orally is usually 1 hour, reaching a maximum after 4-6 hours. The duration of action depends on the dose. When used in 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. Renal blood flow increases, but the speed
glomerular filtration rate does not change. However, in patients with an initially low glomerular filtration rate, its level usually increased.

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

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 the heart rate decreases (usually in patients with chronic heart failure, the heart rate is increased). The pulmonary capillary wedge pressure is also reduced. With long-term use, enalapril increases exercise tolerance and reduces the severity of heart failure (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. In case of left ventricular dysfunction, enalapril reduces the risk of major ischemic outcomes (including the incidence of myocardial infarction and the number of hospitalizations for unstable angina).

Pharmacokinetics

Suction

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

Distribution and metabolism

Enalapril is rapidly and actively hydrolyzed to form enalalrylate, a powerful ACE inhibitor. Cmax of enalaprilat in the blood serum is observed 3-4 hours after oral administration. In patients with normal renal function, Css of enalalrylate in blood plasma was achieved on the 4th day of therapy.

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

Apart from conversion to enalaprilat, enalapril does not undergo significant biotransformation.

Removal

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 detected in urine.

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

Pharmacokinetics in special groups of patients

In patients with mild to moderate renal failure (creatinine clearance 30-60 ml/min (0.6-1 ml/sec)) after taking enalapril at a dose of 5 mg 1 time/day, the AUC of enalalrylate is approximately 2 times greater than in patients with normal kidney function. In severe renal failure (creatinine clearance ≤30 ml/min), the AUC increased approximately 8-fold. 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

History of angioedema associated with the use of ACE inhibitors;

Hereditary angioedema or idiopathic angioedema;

Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (KR

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

The drug 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 bevel. Packed in blisters of 10 pcs.
• The drug Enap 5 mg is white or almost white tablets, flat-cylindrical, with a chamfer and a score. Packed in blisters of 10 pcs.
• Enap 10 mg is a red-brown tablet, flat-cylindrical, with a chamfer and a notch. There may be white and burgundy inclusions inside and on the surface of the tablet. Packed in blisters of 10 pcs.
• Enap 20 mg is a light orange tablet, flat-cylindrical, with a chamfer and a notch. There may be inclusions of white and brown-burgundy color inside and on the surface of the tablet. Packed in blisters of 10 pcs.

Cardboard packs contain 2, 3, 6 blisters.

pharmachologic effect

The drug Enap is an antihypertensive drug. The mechanism of action of enalapril is based on inhibition of ACE activity, which results 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 observed. Since ACE is identical to kininase II, enalapril has the ability to block the destruction of bradykinin (this is a peptide that produces a vasopressor effect). At the moment, it is not completely known what the significance of this effect is in the mechanism of action of the substance enalapril.

The antihypertensive effect of the active substance is primarily associated with inhibition of the activity of the RAAS, 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 using this drug, blood pressure decreases regardless of the position of the human body, while heart rate does not increase significantly.

Development symptomatic orthostatic hypotension occurs only in rare cases. Sometimes it takes several weeks of taking the medicine to achieve a significant reduction in blood pressure. When the drug was abruptly discontinued, there was no increase in blood pressure.

Pronounced inhibition of ACE activity is usually observed 2-4 hours after ingestion of the tablet. The antihypertensive effect is usually felt 1 hour after taking the drug orally, the maximum effect occurs after 4-6 hours. The duration of action depends on the dose of the medicine. If the patient takes the doses of Enap that the doctor recommended, then the hemodynamic and antihypertensive effects are 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, no significant change in heart rate is observed. Renal blood flow increases, but no change in glomerular filtration rate is observed. But there is an increase in this indicator in people with low glomerular filtration rate.

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

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

There is a decrease in pulmonary capillary wedging. With prolonged use of tablets, enalapril increases tolerance to physical stress and reduces the severity of symptoms. heart failure. In people with mild to moderate CHF, the drug slows 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, the number of hospitalizations decreases due to angina pectoris).

Pharmacokinetics and pharmacodynamics

After reception 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 use, while food intake does not affect absorption. The substance is actively hydrolyzed, during which enalaprilat, an ACE inhibitor, is formed. The highest concentration of enalaprilat is recorded 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 conversion of the substance to 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 detected in the urine.

Indications for use of 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 asymptomatic left ventricular dysfunction(in combination treatment);
• to reduce the frequency of manifestations myocardial infarction;
• in order to reduce the frequency of hospitalizations of people with unstable angina.

What Enap tablets are for, and whether they should be used in each specific case, the patient should consult a doctor.

Contraindications

The following contraindications to the use of Enap are noted:

• increased sensitivity to the substance enalapril, as well as to other components of the drug;
• angioedema a history that developed during treatment with ACE inhibitors;
• idiopathic angioedema, and Quincke's edema hereditary type;
• porphyria;
• use simultaneously with aliskiren in patients with kidney disease or diabetes mellitus;
• glucose-galactose malabsorption syndrome, lactose intolerance, lactase deficiency (Enap contains lactose);
• pregnancy and period of natural feeding;
• The patient's age is under 18 years.

Enap blood pressure tablets are carefully prescribed:

• people with renal artery stenosis;
• patients with hyperkalemia;
• people after transplantation kidneys;
• with primary hyperaldosteronism;
• with reduced blood volume;
• hypertrophic obstructive cardiomyopathy;
• mitral stenosis, aortic;
• systemic connective tissue diseases;
• diabetes mellitus;
• inhibition of hematopoiesis;
• cerebrovascular diseases;
• renal failure.

Blood pressure medication should be taken with caution by people who follow diet with a reduced content of table salt, for those who are on hemodialysis and those taking diuretics and immunosuppressants.

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

Side effects

During treatment, the following side effects may occur (negative effects in each group are presented in order from more frequent to less common):

• hematopoiesis: anemia, neutropenia, decrease in hematocrit concentration and hemoglobin, agranulocytosis, thrombocytopenia, inhibition of hematopoiesis, pancytopenia, autoimmune diseases, lymphadenopathy;
• metabolism: hypoglycemia;
• nervous system: depression, headache, disturbances of consciousness, drowsiness, insomnia, paresthesia, high excitability, vertigo, sleep disturbances;
• heart and blood vessels: dizziness, noticeable decrease in blood pressure, chest pain, angina pectoris, heart rhythm disturbances, palpitations, stroke or myocardial infarction, Raynaud's syndrome;
• sense organs: changes in taste, 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: renal dysfunction, proteinuria, renal failure, impotence, gynecomastia, oliguria;
• musculoskeletal system: muscle cramps;
• laboratory test indicators: hyperkalemia, increased serum creatinine levels; 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 stipulate that patients take the drug orally, regardless of food intake. It is recommended to take the medicine at the same time of day with a small amount of liquid.

At arterial hypertension Initially, the medicine is prescribed in a dose of 5 to 20 mg once a day, the dosage depends on the severity of hypertension. In case of mild hypertension, it is recommended to take 5 mg or 10 mg of the drug per day.

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

Before taking the medicine, you need to consider that previous treatment with large doses of diuretics may 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 no 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 and determine the potassium content 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.

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

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

Since during treatment there is a possibility of developing renal failure and arterial hypotension, it is necessary to carefully monitor blood pressure and renal 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 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, water-electrolyte balance may be disrupted, and hyperventilation, renal failure, bradycardia may also occur due to overdose. dizziness, tachycardia, convulsions, palpitations.

In case of an overdose, the person must be placed in a horizontal position, with the head at body level. If the overdose is mild, you need to rinse the stomach, give Activated carbon. Practiced in severe cases of overdose of Enap, intravenous administration of a 0.9% solution sodium chloride, intravenous use of plasma substitutes and catecholamines can also be practiced.

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

For people with bradycardia, a pacemaker is placed. In case of overdose, careful monitoring of serum electrolyte levels and concentrations is necessary. creatinine.

Interaction

With double blockade of the RAAS, that is, in the case of simultaneous use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren, the risk increases arterial hypotension. If such a combination is necessary, renal function, water and electrolyte balance, and blood pressure must be carefully monitored.

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

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

With previous therapy with diuretics, blood volume may decrease and the likelihood of arterial hypotension may increase while taking enalapril. This effect can be reduced by stopping diuretics, increasing daily intake of water and salt, and reducing the dosage of enalapril.

When used simultaneously with enalapril, alpha-blockers, beta-blockers, methyldopa, CCBs, ganglion-blocking agents, nitroglycerin or other nitrates, an additional decrease in blood pressure is likely.

When taken in parallel with lithium preparations, there is a transient increase in lithium concentration, as well as lithium intoxication. When taking thiazide diuretics, it is possible to increase the serum concentration of lithium. Such combinations are not recommended; if their use is necessary, careful monitoring of serum lithium concentrations is important.

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

When taken simultaneously with Enap, NSAIDs may reduce the antihypertensive effect. 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 is enhanced by ethanol.

Sympathomimetics reduce the antihypertensive effect of ACE inhibitors.

Enalapril reduces the effect of drugs that contain theophylline.

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

Taking enalapril and cyclosporine simultaneously leads to an increased likelihood of hyperkalemia.

When taking antacids, the bioavailability of ACE inhibitors decreases.

Terms of sale

Enap is sold by prescription.

Storage conditions

Enap should be kept away from children and stored at temperatures up to 25 °C.

Best before date

Enap can be stored for 3 years.

special instructions

After the first dose of Enap, arterial hypotension may develop. In case of severe hypotension, the patient should be placed horizontally; if necessary, a 0.9% solution should be administered. Sodium chloride.

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

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

There are descriptions of cases 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, taking procainamide, allopurinol. In this case, severe infections that cannot be treated may develop. antibiotics. When taking Enap, such patients require periodic monitoring of the level of leukocytes in the blood.

There is a possibility of angioedema in people receiving Enap. At the first signs of this condition, immediate discontinuation of the drug and consultation with a doctor is necessary. An increased risk of developing this condition has been noted in patients with a history of angioedema.

While taking the drug, in rare cases, the development of anaphylactoid reactions has been observed in people who have been desensitized by Hymenoptera venom.

While taking the medication, patients may develop counterproductive dry cough, disappearing after discontinuation of enalapril.

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

It is important to drive carefully and practice other activities that require concentration while being treated with Enap.

Enap's analogs Level 4 ATX code matches:

Analogues of Enap are sold - drugs Enap R, Berlipril, Bagopril, Vazolapril, 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 drug Enam and Enap contains enalapril maleate as an active component. Only the drug manufacturing countries differ. But they act similarly.

Enap and Enap N - differences

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

The drug is not prescribed to 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 subsequent months of pregnancy. Today, the risk of developing teratogenic effects cannot be excluded. If pregnancy has been confirmed, then the drug should be discontinued immediately.

If a woman took ACE inhibitors during pregnancy, ultrasound should be performed periodically to assess the level of amniotic fluid, and ultrasound of the fetal skull and kidneys should be performed. The active substance is detected in breast milk, therefore, lactation must be stopped during treatment.

Enalapril maleate (enalapril)

Composition and release form of the drug

Pills light orange in color, flat-cylindrical, with a score 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, red iron oxide dye (E172) - 0.1 mg, yellow iron oxide dye (E172) - 0.3 mg.

10 pieces. - blisters (2) - cardboard packs.
10 pieces. - blisters (3) - cardboard packs.
10 pieces. - blisters (6) - cardboard packs.
10 pieces. - blisters (10) - cardboard packs (for hospitals).
10 pieces. - blisters (20) - cardboard packs (for hospitals).
10 pieces. - blisters (50) - cardboard packs (for hospitals).
10 pieces. - blisters (100) - cardboard packs (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, there is a secondary increase in renin activity due to the elimination of negative feedback on the release of renin 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.

Thanks to its vasodilating effect, it reduces roundabout percentage (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, with long-term use, enalapril increases exercise tolerance and reduces the severity of heart failure (assessed by NYHA criteria). Enalapril in patients with mild to moderate heart failure slows its progression and also slows down the development of left ventricular dilatation. In case of left ventricular dysfunction, enalapril reduces the risk of 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. Concomitant food intake does not affect absorption. Metabolized in the liver by hydrolysis with the formation of enalaprilat, due to the pharmacological activity of which a hypotensive effect is realized. The binding of enalaprilat to plasma proteins is 50-60%.

T1/2 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 unchanged by the kidneys.

Indications

Arterial hypertension (including renovascular), chronic failure (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 renal artery stenosis of a solitary kidney, hyperkalemia, porphyria, concomitant use with aliskiren in patients with diabetes mellitus or impaired renal function (CK<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 it is 80 mg.

Side effects

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

From the cardiovascular system: orthostatic hypotension, fainting, 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, impaired liver function, increased activity of liver 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 - renal dysfunction, 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.

Other: rarely - hyperkalemia, muscle cramps.

Drug interactions

When used simultaneously with cytostatics, the risk of developing leukopenia increases.

With the simultaneous use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium supplements, 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 potassium retention in the body while 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 and thiazide diuretics, the antihypertensive effect is enhanced. There is a risk of developing hypokalemia. Increased risk of renal dysfunction.

When used simultaneously with azathioprine, anemia may develop, which is due to 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 may reduce the antihypertensive effect of enalapril.

It has not been conclusively established whether acetylsalicylic acid reduces the therapeutic effectiveness 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, the antihypertensive effect may be enhanced.

When used simultaneously with NSAIDs (including indomethacin), the antihypertensive effect of enalapril is reduced, apparently due to inhibition of the synthesis of prostaglandins under the influence of NSAIDs (which are believed to play a role in the development of the hypotensive effect of ACE inhibitors). The risk of developing renal dysfunction increases; hyperkalemia is rarely observed.

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

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

Syncope has been reported when used concomitantly with clozapine.

When used simultaneously with clomipramine, increased effects of clomipramine and the development of toxic effects are reported.

When used simultaneously with co-trimoxazole, cases of hyperkalemia have been described.

When used simultaneously with lithium carbonate, the concentration of lithium in the blood serum increases, which is accompanied by symptoms of lithium intoxication.

When used simultaneously with orlistat, the antihypertensive effect of enalapril is reduced, which can lead to a significant increase in blood pressure and the development of a hypertensive crisis.

It is believed that when used simultaneously with procainamide, there may be an increased risk of developing leukopenia.

When used simultaneously with enalapril, the effect of drugs containing theophylline is reduced.

There are reports of the development of acute renal failure in patients after kidney transplantation when used simultaneously with cyclosporine.

When used simultaneously with cimetidine, the half-life of enalapril increases and its concentration in the blood plasma increases.

It is believed that the effectiveness of antihypertensive drugs may be reduced when used simultaneously with erythropoietins.

When used simultaneously with ethanol, the risk of developing arterial hypotension increases.

special instructions

Use with extreme caution in patients with autoimmune diseases, diabetes mellitus, liver dysfunction, 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 peripheral blood picture. Sudden cessation of enalapril does not cause a sharp increase in blood pressure.

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

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

Impact on the ability to drive vehicles and machinery

Caution is required when driving vehicles or performing other work that requires increased attention, because Dizziness may occur, especially after taking the initial dose of enalapril.

Pregnancy and lactation

Contraindicated for use during pregnancy. If pregnancy occurs, enalapril should be stopped immediately.

Enalapril is excreted in breast milk. If it is necessary to use it during lactation, the issue of stopping breastfeeding should be decided.

Use in childhood

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

For liver dysfunction

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, red iron oxide E 172, talc, magnesium stearate.

Tablets 20 mg

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

Description

10 mg tablets: round, flat tablets of a reddish-brown color, with a beveled edge and a notch on one side, with individual inclusions of white on the surface and in the bulk of the tablet. The notch is not intended to break the tablet.

Tablets 20 mg: round, flat tablets of light orange color with a beveled edge and a notch on one side, with individual inclusions of white on the surface and in the bulk of the tablet. The notch is not intended 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 pressor compound angiotensin II and, as a consequence, 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 suppression of the renin-angiotensin-aldosterone system, which plays the most important role in the regulation of blood pressure, the drug also has a hypotensive effect in patients with low renin levels. Taking enalapril by 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, achieving a 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, with maximum reduction in blood pressure achieved within 4-6 hours after administration. The duration of action depends on the dose. However, at recommended doses, 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 arterial resistance with an increase in cardiac output and little or no change in heart rate. After administration of enalapril, there was an increase in renal blood flow; glomerular filtration rate did not change; There were no signs of sodium or water retention. However, in patients with reduced glomerular filtration, an increase in this indicator was observed.

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 used together with thiazide-type diuretics, the hypotensive effect is additive. In this case, 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; pulmonary capillary wedge pressure (PCP) decreases. Enalapril therapy normalizes the condition of heart failure and improves exercise tolerance. These effects persist throughout therapy. In patients with mild or moderate heart failure, the drug slows the progression of cardiac dilatation and heart failure (decreasing left ventricular end-diastolic and systolic volume and improving ejection fraction).

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 the blood serum is achieved within one hour. The degree of absorption is about 60%, while food intake does not affect absorption. After absorption, enalapril is quickly 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 orally. The effective half-life for enalaprilat accumulation after repeated oral administration of enalapril is 11 hours. In patients with normal renal function, stable serum concentrations of enalaprilat are 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 is no evidence of significant metabolism of enalapril.

Removal

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%).

Renal dysfunction

Exposure to enalapril and enalaprilat is increased in patients with renal impairment. In patients with mild or moderate renal impairment (creatinine clearance 0.6-1 ml/sec), after taking the drug 5 mg once daily, the AUC value of enalaprilat is approximately twice as high as in patients with normal renal function; whereas in severe renal failure (creatinine clearance 0.5 ml/sec), the AUC value increases approximately eightfold. At this level of renal impairment, the effective half-life of enalaprilat is prolonged and the time to reach steady state is prolonged.

Enalaprilat can be removed from the circulatory system using hemodialysis. The dialysis clearance of enalaprilat is 1.03 ml/sec.

Children and teenagers

Significant differences in pharmacokinetics in children compared to adults have not been established. Data show an increase in AUC (standardized to dose per body weight) with increasing age; however, no increase in AUC was observed when data were standardized to 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 failure (GFR< 60мл/мин/1,73 м2).

Directions for use and doses

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 initial dose is 5 mg - 10 mg per day. In patients with significant activity of the renin-angiotensin-aldosterone system (eg, renovascular hypertension, loss of water and/or salts, cardiac decompensation or severe hypertension), an excessive drop in blood pressure may be observed at the beginning of treatment. In such patients, it is recommended to begin treatment under medical supervision with a dose of 5 mg or less. Previous treatment with high doses of diuretics may lead to hypovolemia and the risk of hypotension at the beginning of treatment. In such patients, the recommended starting dose is 2.5 mg. If possible, diuretic therapy should be discontinued 2-3 days before starting treatment with enalapril. During treatment, it is necessary to monitor renal 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 starting 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, the dose should be gradually increased to the usual maintenance dose of 20 mg, taken as a single dose or divided into two doses (depending on patient tolerance).

* patients with impaired renal function or those on diuretic treatment should exercise special caution

Blood pressure and renal function should be monitored before and after initiating 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 occur during long-term therapy with enalapril, and does not exclude further use of the drug. During treatment, it is necessary to monitor renal function and serum potassium levels.

Dosage for renal failure

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

* On days free from dialysis, the dose should be adjusted according to blood pressure.

Use in elderly patients

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

Clinical experience with the use of enalapril maleate in children with hypertension is limited.

For patients who can swallow tablets, the dose should be individualized depending on the patient's condition and blood pressure response. 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 enalapril maleate once a day. The dosage should be adjusted according to the patient's needs. 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, drug side effects are presented in order of decreasing importance.

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

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

Research:

Frequent - hyperkalemia, hypercreatininemia;

Uncommon - increased serum urea, hyponatremia;

Rare - increased liver enzymes, increased serum bilirubin.

Disorders of the cardiovascular system:

Very common - dizziness;

Frequent - hypotension (including orthostatic hypotension);

Uncommon - orthostatic hypotension, palpitations;

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

Blood and lymphatic system disorders:

Uncommon - anemia (including aplastic and hemolytic);

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

Endocrine system disorders:

Frequency not known - syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Nervous system disorders:

Frequent - headache, drowsiness;

Uncommon: insomnia, dizziness;

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

Visual disorders:

Frequent - blurred vision.

Disorders of the respiratory system, chest and mediastinal organs:

Very common - non-productive dry cough;

Frequent - difficulty breathing;

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

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

Gastrointestinal disorders:

Very common - nausea;

Frequent - diarrhea, abdominal pain, change in taste;

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

Rare - stomatitis/aphthous ulceration, glossitis;

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

Uncommon - renal dysfunction, renal failure, proteinuria;

Rare - oliguria.

Disorders of the skin and subcutaneous tissues:

Common - rash, hypersensitivity/angioedema;

Uncommon - increased sweating, itching, urticaria, alopecia;

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

Metabolic and nutritional disorders:

Uncommon: hypoglycemia.

General complications and reactions at the injection site:

Frequent - asthenia, fatigue;

Uncommon: muscle cramps, hyperemia, ringing in the ears, malaise, fever.

Disorders of the liver and biliary tract:

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

Disorders of the reproductive system and mammary glands:

Uncommon - impotence;

Rare - gynecomastia.

Mental disorders:

Frequent - depression.

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

If severe side effects occur, treatment should be discontinued.

Overdose

Data regarding overdose in humans are limited.

Main symptom overdose is hypotension, which begins six hours after taking the tablets and is 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 solution. If necessary, treatment with intravenous infusion of angiotensin II and/or catecholamines can also be performed. If the tablets have been taken recently, 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 cannot be treated, treatment with a pacemaker is indicated. Continuous monitoring of vital signs, electrolytes, and serum creatinine concentrations is essential.

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

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 may cause hyperkalemia. If combined use is indicated due to proven hypokalemia, use should be done with caution and with regular monitoring of serum potassium.

Diuretics (thiazide or loop diuretics)

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

Other antihypertensive drugs

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

Double renin blockade- angiotensin -aldosterone system

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

Lithium

A reversible increase in serum lithium concentrations and toxic effects have been reported when lithium is taken concomitantly with ACE inhibitors. Concomitant use of ACE inhibitors and thiazide diuretics may lead to increased lithium levels and increase the risk of lithium toxicity. Therefore, co-administration of enalapril and lithium is not recommended. If this combination is still necessary, then the level of lithium in the blood serum should be carefully monitored.

Tricyclicantidepressants / neuroleptics / anesthetics / narcotic drugs

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

Nonsteroidal 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 may lead to deterioration of renal function. This effect is usually reversible. In rare cases, acute renal failure may occur, especially in patients with impaired renal function (for example, elderly or dehydrated patients).

Antidiabetic drugs

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 combination 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 beta-blockers.

Cardiac glycosides

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

Cimetidine

When taking Enap and cimetidine together, the half-life of Enap may be prolonged. If the patient is already taking the above medications, he should inform the doctor that he is taking Enap.

Precautionary measures

Symptomatic hypotension

In uncomplicated arterial hypertension, symptomatic hypotension is rare. It is most likely to occur in hypertensive patients due to hypovolemia, for example, due to diuretic treatment, 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 caused by high-dose loop diuretics, hyponatremia, or kidney damage. In such patients, treatment should be started under medical supervision, with strict adherence to the selected doses of enalapril and/or diuretic. A similar principle may apply to patients with coronary artery disease or cerebrovascular disease, in whom a sudden decrease 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, an intravenous infusion of 0.9% sodium chloride solution should be prescribed to replenish plasma volume. Transient hypotension is not a contraindication for treatment with enalapril. After adjustment of blood pressure and plasma volume, patients generally tolerate subsequent treatment well.

In some heart failure patients 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 discontinue treatment. If hypotension becomes symptomatic, a dose reduction and/or discontinuation of the diuretic and/or enalapril is required.

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

Concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia, and renal dysfunction (including acute renal failure).

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

Due to its absolute necessity, dual RAAS blockade therapy should only be prescribed under specialist supervision 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 prescribed with extreme caution in patients with left ventricular outflow tract obstruction. In cases of cardiogenic shock and severe hemodynamic obstruction of the left ventricular outflow tract, the use of these drugs should be avoided.

Renal dysfunction

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.

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

Renovascular hypertension

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

Kidney transplant

Due to the lack of experience with its use, treatment with enalapril is not recommended for 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 liver necrosis and (sometimes) death. The mechanism of this syndrome is unknown. If jaundice or a clear increase in liver enzymes occurs during treatment with ACE inhibitors, treatment should be stopped immediately and the patient should be carefully 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 prescribed with extreme caution to patients with collagen vascular disease (for example, systemic lupus erythematosus, scleroderma), as well as those on immunosuppressive drugs, allopurinol or procainamide, or a combination of these factors, especially with pre-existing renal impairment. Some of these patients may develop serious infections, in some cases not responding to intensive antibiotic therapy. If enalapril is used in such patients, periodic monitoring of the white blood cell count 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 must 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 adrenaline (0.3-0.5 ml subcutaneous solution of adrenaline in a ratio of 1:1000) and ensure free patency of the airways.

Patients with a history of angioedema unrelated to treatment with ACE inhibitors are at increased risk of developing angioedema while taking ACE inhibitors.

Anaphylactoid reaction during desensitization

In patients taking ACE inhibitors, during desensitization against wasp or bee venom, 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 desensitization.

Anaphylactoid reactions during LDL apheresis

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

Patients undergoing hemodialysis treatment

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

Patients with diabetes mellitus

In patients with diabetes mellitus being treated with oral antidiabetic agents 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 treatment is discontinued. This should be included in the differential diagnosis.

Surgicalinterventions/ 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, blood potassium levels may increase in some patients. The risk of developing hyperkalemia is higher in patients with renal insufficiency, diabetes mellitus, and those concomitantly 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 drugs is considered appropriate, it is recommended to regularly monitor the level of potassium in the blood serum. Lithium

The 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 use for other indications. Limited information is available on pharmacokinetics for children older than 2 months. Enalapril is recommended for use in children only for the treatment of hypertension.

Ethnic characteristics

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

Special precautions regarding excipients

Enap contains lactose. Patients with the rare hereditary disorder galactose intolerance, lactose intolerance and glucose-galactose malabsorption 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, but a slight increase in risk cannot be excluded. Unless continued treatment with ACE inhibitors is considered necessary, patients planning pregnancy should switch to alternative antihypertensive treatment that has an established safety profile for use during pregnancy.

If pregnancy is established, then taking ACE inhibitors should be stopped immediately and, if necessary, treatment with alternative agents 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 (decreased renal function, oligohydramnios, delayed skull ossification) and a 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 renal and cranial function.

Neonates whose mothers took ACE inhibitors should be closely monitored for hypotension.

Lactation period

Pharmacokinetic data indicate very low concentrations in breast milk. Despite the fact that these concentrations are considered clinically insignificant, the use of Enap is not recommended when breastfeeding premature infants 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 use. At a later stage, taking Enap by nursing mothers may be considered in cases where treatment is necessary for the mother and the child is being monitored to identify any side effects.

Impact on ability to drivecar andwork with machinery

In some patients, the drug may cause severe hypotension and dizziness, especially at the initial stage of treatment, thus having an indirect and temporary effect on the ability to drive a car and operate machinery.

Release form and packaging

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

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

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

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

Storage conditions

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

Keep out of the reach of children.

Best before date

Conditions for 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 mark on one side and a chamfer.

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

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

pharmachologic effect

pharmachologic effect- hypotensive.

Pharmacodynamics

Enalapril is an antihypertensive drug whose mechanism of action 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 content of which in the blood plasma leads to an increase in the activity of plasma renin (by eliminating the negative feedback to 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 the activity of the RAAS, 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 concentrations.

With the use of enalapril, blood pressure levels decrease regardless of body position (both in a supine and standing position) without a significant increase in heart rate. Symptomatic orthostatic hypotension is rare. In some patients, achieving optimal blood pressure reduction may require several weeks of therapy. Abrupt withdrawal of enalapril was not accompanied by an increase in blood pressure.

Effective inhibition of ACE activity usually occurs 2-4 hours after a single oral dose of enalapril. The onset of antihypertensive action usually takes 1 hour when taken orally, reaching a maximum after 4-6 hours. The duration of action depends on the dose. When using 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 heart rate does not change or changes slightly. Renal blood flow increases, but the glomerular filtration rate does not change. However, in patients with an initially low glomerular filtration rate, its level usually increased.

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

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

In case of left ventricular dysfunction, enalapril reduces the risk of 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 extent of absorption of enalapril is approximately 60%. Tmax of enalapril in blood serum is 1 hour after oral administration. Eating does not affect absorption. Enalapril is rapidly and actively hydrolyzed to form enalaprilat, a potent ACE inhibitor. Tmax of enalaprilat is 3-4 hours after oral administration. T1/2 of enalapril with repeated use is 11 hours. In patients with normal renal function, C ss of enalaprilat in blood plasma was achieved on the 4th day of therapy.

Distribution

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

Biotransformation (metabolism)

Apart from conversion to enalaprilat, enalapril does not undergo significant biotransformation.

Removal

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

Special patient groups

Renal dysfunction. In patients with mild to moderate renal impairment (creatinine clearance 36-60 ml/min (0.6-1 ml/s) after taking enalapril 5 mg once daily, 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 approximately 8 times. T1/2 of enalaprilat after repeated use in severe renal failure is prolonged, and the time to reach steady state is delayed. Enalaprilat is removed when hemodialysis, excretion rate - 1.03 ml/s (62 ml/min).

Indications of the drug Enap ®

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 with the aim of:

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 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 (since the drug Enap ® contains lactose);

pregnancy;

breastfeeding period;

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

Carefully: bilateral renal artery stenosis or stenosis of the artery of a single kidney; primary hyperaldosteronism; hyperkalemia; condition after kidney transplantation; aortic stenosis and/or mitral stenosis (with hemodynamic impairment); hypertrophic obstructive cardiomyopathy (HOCM); conditions with reduced blood volume (including diarrhea, vomiting); systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus); cardiac ischemia; inhibition 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 use with immunosuppressants and diuretics; patients over 65 years of age.

Use during pregnancy and breastfeeding

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

The use of ACE inhibitors, incl. the drug 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 us to draw definitive conclusions. However, the possibility of a risk of their development cannot be excluded. 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.

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

Taking ACE inhibitors in the second and third trimesters can cause fetotoxicity reactions (impaired renal function, oligohydramnios, delayed ossification of fetal skull bones) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia).

If an ACE inhibitor was taken in the second and third trimesters of pregnancy, it is recommended to perform an ultrasound of the fetal kidneys and skull bones.

In those rare cases where the use of an ACE inhibitor during pregnancy is considered necessary, periodic ultrasound 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 occurs when there is irreversible damage to the fetus.

If ACE inhibitors are used during pregnancy and the development of oligohydramnios is observed, 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 status 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 detected in breast milk in trace concentrations, therefore, if it is necessary to use the drug Enap ® , breastfeeding should be stopped.

Side effects

WHO classification of the incidence of side effects: 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 hematopoietic organs: uncommon - anemia (including aplastic and hemolytic); rarely - neutropenia, decreased 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; uncommon - confusion, insomnia, drowsiness, paresthesia, increased excitability, vertigo; rarely - changes in the nature of dreams, sleep disorders.

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

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

From the respiratory system: very often - cough; uncommon - 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; uncommon - ileitis, intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, anorexia, dry oral mucosa, peptic ulcer; rarely - impaired liver function and biliary excretion, hepatitis (hepatocellular or cholestatic), including hepatic necrosis, cholestasis (including jaundice), stomatitis/aphthous ulcers, glossitis; very rarely - angioedema of the intestine.

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

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

From the genitourinary system: uncommon - renal dysfunction, proteinuria, renal failure, impotence; rarely - oliguria, gynecomastia.

From the musculoskeletal system: infrequently - muscle cramps.

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

Other: frequency unknown - syndrome of inappropriate ADH secretion.

Adverse events identified during post-marketing use of the drug, but no causal relationship with the drug has 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 pulmonary 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 case of double blockade of the RAAS, i.e. with 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 simultaneous use of drugs is necessary, it is recommended to monitor blood pressure, renal function and water and electrolyte balance.

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

Potassium-sparing diuretics and potassium supplements

ACE inhibitors reduce potassium loss caused by diuretics.

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

If concomitant use is necessary, use caution and regularly monitor serum potassium levels.

Diuretics (thiazide or loop)

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

Other antihypertensive drugs

Concomitant use of beta-blockers, alpha-blockers, ganglion-blocking agents, methyldopa, CCBs, nitroglycerin or other nitrates with enalapril can further reduce blood pressure.

Lithium

With the simultaneous use of ACE inhibitors with lithium preparations, a transient increase in serum lithium concentration and the development of lithium intoxication were observed. The use of thiazide diuretics may lead to an additional increase in serum lithium concentrations and the risk of lithium toxicity during concomitant use of ACE inhibitors. Concomitant use of enalapril with lithium is not recommended. If this combination is necessary, serum lithium concentrations should be carefully monitored.

Tricyclic antidepressants/antipsychotics (neuroleptics)/anaesthetics/narcotics

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

NSAIDs

Concomitant 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 increasing serum potassium, which may lead to a 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 during the use of diuretics).

Before starting therapy, it is necessary to replenish the blood volume. During treatment, it is recommended to monitor renal 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 enhanced hypoglycemic effect with a risk of developing 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

It is safe to use enalapril simultaneously with acetylsalicylic acid (as an antiplatelet agent), thrombolytics and beta-blockers.

Weakens the effect of medications containing theophylline.

Allopurinol, cytostatics and immunosuppressants (including methotrexate, cyclophosphamide)

Concomitant use with ACE inhibitors may increase the risk of developing leukopenia. When used simultaneously with allopurinol, the risk of developing an allergic reaction increases, especially in patients with impaired renal function.

Cyclosporine

Concomitant use with ACE inhibitors may increase the risk of developing hyperkalemia.

Antacids

Antacids may reduce the bioavailability of ACE inhibitors.

Gold preparations

When using ACE inhibitors, incl. enalapril, patients receiving intravenous gold (sodium aurothiomalate) were described to have a symptom complex including facial skin flushing, nausea, vomiting, and arterial hypotension.

No clinically significant pharmacokinetic interactions of enalapril were observed with hydrochlorothiazide, furosemide, digoxin, timolol, methyldopa, warfarin, indomethacin, sulindac and cimetidine. When used simultaneously with propranolol, the concentration of enalaprilat in the blood serum decreases, but this effect is clinically insignificant.

Directions for use and doses

Inside, Regardless of the time of meal, preferably at the same time of day, with 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. For mild arterial 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 - 5 mg / day or less under the supervision of a physician.

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

The usual maintenance dose is 20 mg once daily.

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

CHF and left ventricular dysfunction

The initial dose of Enap ® is 2.5 mg/day once; Treatment 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, and, 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 drug tolerance. Dose selection is carried out over 2-4 weeks. The maximum daily dose is 40 mg in 2 divided doses.

1st week: 1-3 days - 2.5 mg/day in 1 dose; Days 4-7 - 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 taken in patients with impaired renal function and those taking diuretics.

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

Special patient groups

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

When creatinine Cl is 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 per day of hemodialysis (enalaprilat is eliminated during hemodialysis).

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

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

Overdose

Symptoms: approximately 6 hours after ingestion - a pronounced decrease in blood pressure, up to the development of collapse, water-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 blood 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 expanders, and, if necessary, intravenous administration of catecholamines. Enalaprilat can be eliminated by hemodialysis, the elimination rate is 62 ml/min. In patients with bradycardia that is resistant to therapy, pacemaker placement is indicated. Serum electrolytes and serum creatinine concentrations should be carefully monitored.

special instructions

Arterial hypotension

Symptomatic hypotension rarely occurs in patients with uncomplicated 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, a salt-free diet, diarrhea, vomiting or hemodialysis. The development of symptomatic 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 begin 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 diseases, in whom a sharp excessive decrease in blood pressure can lead to the development of myocardial infarction or cerebrovascular accident.

If severe arterial hypotension develops, the patient should be placed in a horizontal position, legs should be raised and, if necessary, a 0.9% sodium chloride solution should be administered intravenously.

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

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 discontinue 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

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

Renal dysfunction

In patients with renal failure (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 when treated with Enap ®. The changes were usually reversible after discontinuation of the drug Enap ® .

In some patients with arterial hypertension who did not have renal disease before treatment, there was a slight and transient increase in the concentration of urea and creatinine in the blood serum when using the drug Enap ® simultaneously with a diuretic. In such cases, it may be necessary to reduce the dose of Enap ® and/or discontinue the diuretic. This situation indicates the possibility of hidden renal artery stenosis.

Renovascular hypertension

In patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney, when treated with ACE inhibitors, the risk of developing arterial hypotension and renal failure is increased. Only minor changes in serum creatinine concentration may indicate a decrease in renal function. In such patients, treatment should be started with small doses under close medical supervision. The dose should be titrated carefully and renal function monitored.

Kidney transplant

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

Liver dysfunction

In rare cases, therapy with ACE inhibitors was accompanied by the development of a syndrome starting with cholestatic jaundice and hepatitis up to the development of fulminant liver necrosis. The mechanism of development of this syndrome is unknown. If jaundice appears or a significant increase in the activity of liver enzymes, it is necessary to immediately stop treatment with an ACE inhibitor, carefully monitor the patient and, if necessary, treat.

Neutropenia/agranulocytosis

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

Hypersensitivity/angioedema

In patients receiving ACE inhibitors, including enalapril, there have been reports of angioedema of the face, extremities, lips, vocal folds and/or larynx at any time after the start of treatment. You should immediately discontinue the drug Enap ® and monitor the patient until symptoms disappear completely. Even in cases where only the tongue is swollen and there is only difficulty swallowing without respiratory distress, patients may require long-term observation because the use of antihistamines and corticosteroids may be insufficient.

Angioedema of the larynx or tongue can be fatal in very rare cases. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction, especially after a history of airway surgery. If there is swelling of the tongue, vocal folds or larynx, appropriate therapy is indicated, which may include: subcutaneous administration 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 ACE inhibitor therapy, the incidence of angioedema is higher than among patients of other races.

Patients with a history of angioedema not associated with ACE inhibitors are at increased risk of developing angioedema when taking any ACE inhibitor.

Anaphylactoid reactions during desensitization with Hymenoptera (Hymenoptera) venom

Patients taking ACE inhibitors during hymenoptera venom desensitization 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

Life-threatening anaphylactoid reactions have occurred in rare cases in patients taking ACE inhibitors during LDL apheresis with dextran sulfate. It is necessary to temporarily replace drugs of another group.

Hemodialysis

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

Hypoglycemia

In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be carefully 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 stopping the use of ACE inhibitors, which must be taken into account in the differential diagnosis of cough during the use of an ACE inhibitor.

Surgery/general anesthesia

Before surgery (including dental procedures), you must warn the surgeon/anesthesiologist about the use of the drug Enap ® . During major surgery or general anesthesia with the use of drugs that cause arterial hypotension, ACE inhibitors may block the formation of angiotensin II in response to compensatory release of renin. If 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 the drug Enap ®. Risk factors for the development of hyperkalemia are renal failure, old age (over 70 years), diabetes mellitus, some concomitant conditions (decrease in blood volume, 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 table salt substitutes containing potassium can lead to a significant increase in serum potassium levels, especially in patients with impaired renal function. Hyperkalemia can cause serious heart rhythm problems, sometimes fatal. The simultaneous use of the above drugs should be carried out with caution under the control of potassium levels in the blood serum.

Lithium

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

Ethnic characteristics

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, therefore the drug is contraindicated in patients with lactase deficiency, lactose intolerance, and glucose-galactose malabsorption syndrome.

Impact on the ability to perform potentially hazardous activities that require special attention and speed of reactions (for example, driving vehicles, working with machinery). 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 the drug 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 made of combined material OPA/Al/PVC and aluminum foil, 10 pcs. 2, 3, 6 or 9 blisters in a cardboard pack.

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

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

tablets 5mg

Pharmacotherapeutic group

Antihypertensives - 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 penetrates the placenta. Excreted mainly by the kidneys. A decrease in blood pressure appears 1 hour after administration, reaches a maximum at 6 hours and continues for 1 day. In some patients, therapy for several weeks is necessary to achieve optimal blood pressure levels. In case of heart failure, long-term (for 6 months) treatment increases exercise tolerance, helps to reduce heart size, and reduces mortality. The hypotensive effect of enalapril is due to a decrease in the blood levels of angiotensin II and aldosterone, 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 changing the 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 a 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, angina pectoris, chronic renal failure.

Contraindications

Hypersensitivity, pregnancy, breastfeeding, childhood.

Cautions for use

Caution must be exercised when prescribing the drug to patients on a low-salt or salt-free diet. Before and during treatment, monitoring of blood pressure, renal function, the concentration of transaminases and alkaline phosphatase in the vascular bed is necessary (if their levels increase, 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).

Interactions with drugs

The simultaneous administration 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. When taking potassium-sparing diuretics and/or potassium supplements simultaneously, hyperkalemia is possible, and drugs containing theophylline may reduce their effect.

Side effects

Central nervous system depression, depression, ataxia, convulsions, drowsiness or insomnia, peripheral neuropathy, disturbances of vision, taste, smell, ringing in the ears, conjunctivitis, lacrimation, hypotension, myocardial infarction, acute cerebrovascular accident (as a result of hypotension), cardiac arrhythmia ( atrial tachy- or bradycardia, atrial fibrillation), orthostatic hypotension, angina attack, thromboembolism of the branches of the pulmonary artery, bronchospasm, dyspnea, nonproductive cough, interstitial pneumonitis, bronchitis and other upper respiratory tract infections, 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, Quincke's edema, 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.