Enalapril - instructions for use. Enalapril: instructions for use, analogues and reviews, prices in Russian pharmacies Enalapril international name

Enalapril is considered one of the most effective medicines of its group. With it, you can lower blood pressure and control it throughout the entire period of treatment. Enalapril is classified as an ACE inhibitor.

In addition to a pronounced hypotensive effect, it has the ability to improve blood flow and prevent certain diseases. Today we will learn about the features of this medicine, indications, instructions for using Enalapril, its price, analogues and reviews of doctors and patients about it.

Features of the drug

The drug is not recommended to be combined with alcoholic beverages, so as not to increase the hypotensive effect.
Enalapril affects the ability to concentrate, so it is recommended to refrain from working with complex mechanisms.
On the initial stage treatment, it is also necessary to abandon complex work, including those associated with danger or requiring attention, since dizziness is possible.
During treatment, you need to be more careful in hot weather, as well as during classes. physical activity, since there is a risk of a more severe decrease in blood pressure due to low circulating blood volume.

It is always necessary to warn doctors about the treatment with Enalapril before surgery, including dental surgery.

The following video will tell in more detail about the features of the drug Enalapril:

Compound

The tablet contains the active substance enalapril maleate at a dosage of 5, 10, 20 mg. Components that are auxiliary:

sugar,
magnesium stearate or calcium stearate,
lactose,
medical gelatin,
potato starch.

Dosage forms

Enalapril is available in tablet form. The price range is very affordable. So, in the smallest dosage (5 mg), 2 blisters of 10 tablets each will cost 10-20 rubles. The cost of the drug usually does not exceed 100 rubles.

Pharmacological action and pharmacodynamics

The drug belongs to the group of antihypertensive drugs. Its action is aimed at inhibiting the activity of angiotensin enzymes, which directly leads to a decrease in the production of aldosterone. The consequence of this is a decrease in diastolic and systolic blood pressure.
Enalapril also helps to dilate blood vessels, improves blood flow in the kidneys and brain.
After prolonged use, a decrease in left ventricular hypertrophy is noted, which makes it possible to slow down or even prevent development.
The blood supply to the myocardium also improves.
Enalapril has some diuretic effect and lowers platelet aggregation.

An hour later, a hypotensive effect is noticeable, it will be maximum after 6 hours. The full effect persists throughout the day. In some groups of patients, longer therapy (usually several weeks) is required to show a stable result.

If there is heart failure, then the treatment should last about 6 months in order to show a noticeable clinical effect.

Pharmacokinetics

Absorption of the drug after use is 60%. About half of the agent binds to proteins. In the process of metabolism, a metabolite is formed, which is absorbed in the body. Enalapril is modified into enalaprilat, a more bioavailable (40%) and active ACE inhibitor.

The drug is able to penetrate into breast milk and the placenta. The half-life is about 11 hours. Up to 60% is excreted by the kidneys, and another 33% through the intestines. With peritoneal dialysis and hemodialysis, it is completely removed.

Indications

Enalapril is necessary for different types. Often it replaces ineffective antihypertensive drugs. For use, it is also prescribed in the presence of:

bronchospastic conditions,
heart failure
diabetic nephropathy,
chronic renal failure,
Raynaud's disease, as well as as a complex therapy for other diseases.

It is not recommended for use during pregnancy, as it is capable of exerting some negative consequences on the fetus. However, it can be used if the comparative benefits of it are much higher than the possible risks.

Enalapril is not prescribed to children because there is no data on the efficacy and safety of such treatment.

Instructions for use

inside. Application is not associated with the time of eating. The initial dosage should be 5 mg, in the future, after getting used to it, it is adjusted.

Usually for treatment it is enough to take 10 mg of Enalapril once. The maximum dosage of the drug is 40 mg. After taking the drug and until the stabilization of blood pressure (usually 2-3 hours), the patient is under observation. After therapy with Enalapril at the maximum dosage, you should switch to maintenance treatment using 10-20 mg per day.

Before starting therapy, stop taking diuretics 2-3 days before the first use of the tablets. If it is impossible to cancel them, the initial dosage should be significantly reduced (up to 2.5 mg).

In the presence of renovascular hypertension, the maximum dosage is 20 mg. Treatment begins with a small dose.
With an initial dosage of 2.5 mg, increasing it every few days.
Patients with low systolic blood pressure should start therapy with 1.25 mg tablets. Within 4 weeks, the dose is adjusted.

The duration of treatment determines the effectiveness of therapy. In the presence of a pronounced effect of lowering blood pressure, lower the dose of Enalapril. The drug is suitable for the complex use of antihypertensive drugs, as well as for monotherapy.

Contraindications

Age up to 18 years;
sensitivity to the components of the remedy;
the presence of angioedema in history, if the cause of its appearance was associated with therapy with ACE inhibitors;
pregnancy;
lactation;
porphyria.

Side effects

Digestive system: pancreatitis, hepatitis, jaundice, impaired liver function, dry mouth, abdominal pain, stool problems, nausea, increased activity of liver transaminases.
urinary system: protein in the urine, impaired kidney function.
Nervous system: fatigue and fatigue, dizziness, pain in the head. At high doses, paresthesia, nervousness, sleep problems, tinnitus, and depression are possible.
Heart and blood vessels: tides - in rare cases; orthostatic hypotension, pain in the heart and rapid pulse, fainting, hot flashes.
Respiratory system: cough, bronchospasm, pharyngitis, shortness of breath, interstitial pneumonitis, rhinorrhea.
hematopoiesis: in the presence of autoimmune diseases, agranulocytosis is noted; Neutropenia is rare but possible.
Impact on reproductive opportunities: sometimes impotence appears when using high doses.
allergic reactions: angioedema, itching, skin rash, polymorphic erythema, serositis, myositis, vasculitis, Steven-Johnson syndrome, stomatitis, angioedema of the extremities and face.
Impact on laboratory parameters: increase in ESR, decrease in hemoglobin and hematocrit; neutropenia, hyperbilirubinemia, increased urea content, eosinophilia.
Muscle cramps and hyperkalemia develop relatively rarely. Possible problems with vestibular apparatus, the appearance of alopecia.

special instructions

Cautions

Enalapril is always used with extreme caution when:

liver failure,
stenosis of the renal arteries,
salt-free diet
complex therapy with immunosuppressants,
weakened state after surgery,
hyperkalemia,
diabetes.

It's also important to know:

Surveillance is also important for patients over 65 years of age. Particular attention is paid to people with cardiovascular diseases, in whom a sharp decrease in blood pressure can provoke, or other serious consequences.
If enalapril was previously treated with saluretics, there is a risk of orthostatic hypotension. To eliminate the likelihood of its development, it will be necessary to restore the level of salts and fluids before using the tablets.
Long-term therapy requires regular monitoring of the composition of peripheral blood. If a surgical intervention is performed during the treatment period, then a sufficient amount of fluid is administered to prevent arterial hypotension.
When forced to take Enalapril during pregnancy, it is necessary to establish control over the condition of the newborn. This will help to timely determine the deterioration of cerebral and renal blood flow, which occurs under the influence of ACE inhibitors, oliguria, neurological disorders and hyperkalemia.
The single dose should be adjusted and reduced if the patient suffers from reduced renal function. Cancel Enalapril before examining the function of the parathyroid glands.

Overdose

Overdose treatment is associated with symptomatic therapy, as well as the introduction of sodium chloride (isotonic solution) intravenously. Before this, the patient is transferred to a horizontal position, and the head should be located lower. For mild cases, gastric lavage is sufficient. An overdose is accompanied by the following symptoms:

violation cerebral circulation in acute form
myocardial infarction,
collapse,
state of mental retardation,
convulsions.

Interaction with other tools

The risk of leukopenia increases with simultaneous therapy with cytostatics and immunosuppressants.
Hyperkalemia is most likely to develop when used together with enalapril potassium preparations and dietary supplements. ACE inhibitors lead to retention of potassium in the body, which can aggravate the condition.
The antihypertensive effect is increased if the patient is taking opioid analgesics. The same effect is possible when taking "loop" diuretics.
There is a risk of impaired renal function and hyperkalemia.
The development of anemia occurs with the use of azathioprine, since it, together with Enalapril, has a depressing effect on the activity of erythropoietin.

Enalapril, the instructions for use of which contain complete data on the drug, is an effective and safe remedy.

The drug is dispensed by prescription.

According to the instructions for use, Enalapril is a tablet that is white in color and has a convex configuration. On one side of the tablet there is a risk. It allows you to easily and accurately split the disc in half.

Depending on the amount of active substance Enalapril, the dosage of which is determined by a specialist, is divided into:

Enalapril tablets 5 mg;
Enalapril 10 mg (instruction for use contains a complete list of components);
20 mg.

Instruction Enalapril distinguishes two types of components:

active substance;
auxiliary components.

Table 1. Enalapril (the composition of the drug is given according to the instructions for use)

Active ingredient: Enalapril
Enalapril maleate	It has a vasodilating effect, leads to a decrease in pressure, has a pronounced cardioprotective effect with prolonged use, etc.
Auxiliary components
Milk sugar	The filler of the tablet means is a source of energy
Magnesium carbonate	Thickener, stabilizer, enhance absorption
Gelatin	Thickener
Crospovidone	Allows you to keep the shape, releases the active ingredient
Stearic acid	stabilizer, preservative

What Enalapril tablets look like, what they help with, is written in the instructions for use.

Mechanism of action

Many are concerned about the question of how long the medicine works. The drug Enalapril reduces pressure in about 15-40 minutes. Instructions for use reports that the largest amount of the drug in the blood is found after 3-6 hours.

Table 2. Mechanism of action of Enalapril

Name	the effect	Application of Enalapril
Angiotensin	A special hormone, type II of which leads to narrowing of the lumen of blood vessels and stimulates the production of aldosterone	The process of transformation into a "dangerous" form slows down, the release into the blood is reduced. Arteries and veins dilate, resulting in a decrease in blood pressure
Aldosterone	Increases blood pressure by narrowing the lumen of blood vessels and increasing the volume of circulating blood	Synthesis and release decrease
Bradykinin	Peptide with vasodilating effect. Characterized by rapid decay	Decay time is increasing

Thus, we can conclude what Enalapril is for and what is the result of its use. Thanks to the drug:

blood vessels dilate;
arterial pressure goes down;
heart rate does not increase;
are recovering muscle tissues heart (in particular, leads to regression of hypertrophy), etc.

What helps?

For a full understanding of the action, it is worth familiarizing yourself with the information about what Enalapril is and what the remedy helps with.

Tablets according to the instructions for use are prescribed for:

regular increase in pressure for various reasons over 140–90 mm. mercury column;
as pharmacological treatment a number of heart diseases;
for the prevention of the development of diseases of the heart / blood vessels caused by them lethal outcome.

Enalapril, the dose of which is determined based on the diagnosis, is prescribed exclusively by a specialist.

Indications for use

Establishing an accurate diagnosis is the key to successful treatment. Enalapril, the indications for which are prescribed in the instructions, is recommended for:

arterial hypertension. Enalapril (a prescription can be obtained from a doctor) is effective in the primary form of the disease caused by violations of the system that regulates pressure. It is also prescribed for secondary hypertension resulting from other pathologies. Instructions for use notes that it is effective in the renovascular form of hypertension.
Essential hypertension. A special form of hypertension characteristic feature which is the depletion of renal depressor function.
Chronic HF. Enalapril (instruction for the use of the tablet recommends including complex treatment) is effective in violations of the heart chambers.
Carrying out the prevention of HF and some forms.

A complete source of information about what Enalapril tablets are, from what, and in what cases their use is recommended, is the instruction.

Annotation Enalapril does not specify at what pressure it is optimal to take the drug. The drug must be taken regularly, and not occasionally. Enalapril (pharmacological group - ), has a cardioprotective effect only with a course appointment.

The most common causes of hypertension

Contraindications

Despite the safety of the drug, according to the instructions for use, some patients are forbidden to drink it. Enalapril, contraindications to which are quite extensive, is not recommended for:

anaphylactic shock in history;
arterial stenosis of the only / both kidneys;
an excess of potassium in the body:
various forms of porphyria;
allergies to components;
together with aliskeren;
kidney / liver failure, etc.

The entire list is indicated in the instructions for use.

Instructions for use

Enalapril release form, dosage, time of action and features of the reception are specified in the instructions for use. It also contains information about some categories of patients with additional restrictions:

Children and teenagers. For this category, there are no studies confirming the safety of the product. Under 18 years of age, the drug is not used.
Aged people. Treatment of patients aged 60–65 years requires special care. The first appointment is recommended to be carried out in a hospital.

It is worth drinking in the morning, it does not matter before or after a meal. Enalapril 5 mg instructions for use recommends taking 1 tablet at the initial stages. In some cases, the dose is reduced to 2.5 mg (for the elderly, patients with impaired renal function, etc.). Medium daily dose is 10 or 20 mg (instruction for use involves a double dose).

For emergency pressure reduction, a remedy is used in ampoules. 1.25 mg is administered every 6 hours. After diuretic therapy or with severe impairment of renal function, the dose is reduced to 0.625 mg.

At its core, this is another trade name for the drug. How is it different from Hexal:

Various manufacturers. This tool is produced by the Geksal company, located in Germany, and the second drug is a Russian company. There is no consensus on which manufacturer is better. Both brands have proven themselves on the positive side.
Technologies. The funds are produced according to different specifications and on different equipment.
Compound. The international name is identical, since enalapril maleate is used in the manufacture of both products. However, manufacturers use different excipients.

It is difficult to say which is better, Enalapril or Hexal. The pharmacodynamics and pharmacokinetics of both drugs are similar, so they are interchangeable.

Means are analogues and have identical indications for use. Produced by various companies. Akri is manufactured in Russia by Akrikhin.

The recipe for Enalapril in Latin is the same for both products, but the excipients are slightly different. Before taking it is recommended to read the instructions for use.

The medicine is produced by Moscow pharmaceutical company"Obolensky". The composition and action of the drugs are identical. FPO is also similar in when the remedy begins to act, in which cases the intake is prohibited, when it is necessary to drink tablets with caution. It is quite possible to replace the usual medicine for pressure with FPO without fear.

Recommended for high blood pressure and heart failure. It differs only in the list of additional substances. It belongs to ACE inhibitors and can be used both as part of complex therapy and in monotherapy. It has identical side effects and recommendations for use.

Refers to drugs of complex therapy. It includes two active ingredients at once: the ACE inhibitor enalapril maleate and the diuretic hydrochlorothiazide. It is recommended in cases where monotherapy does not help. Effectively reduces pressure even with severe arterial hypertension.

Available in a dosage of 10 mg. It is used as a means to reduce pressure, treat and prevent heart failure. Effectively reduces the number of hospitalizations for unstable angina, the risk of death due to cardiovascular disease.

Available in the form of a solution, which allows the use of the drug in emergency cases. Quickly reduces pressure at risk or onset of a hypertensive crisis. It is used exclusively by an emergency doctor or as part of a hospital. Uncontrolled injections can cause complications or death of the patient.

Manufacturer medicinal product is an Indian company. The drug is available in tablet form at a dosage of 2.5, 10, 20, and 5 mg (indications for use for all forms can be found in the annotation).

The blood pressure lowering drug contains 20 mg of the active substance. Effective 15 minutes after ingestion. The maximum concentration in the blood is found after 3-6 hours. With the right dosage, the hypotensive effect persists for 24 hours. Before use, it is recommended to read the instructions for use.

A single therapeutic effect and a similar composition make it possible to consider the means as synonymous. They are separated:

Excipients. Enap includes several other components used to obtain the required consistency and physico-chemical characteristics.
Manufacturers. Enap is produced in Slovakia and has a high level of protection against falsification.
Price. Enap is 2-3 times more expensive than its counterpart.

On a festive day or on a special occasion, some people want to drink a strong drink. Patients are concerned about the compatibility of the drug with alcohol, the consequences of which are not always predictable. According to the instructions for use:

Alcohol provokes an excessive decrease in pressure. Joint use can cause low scores HELL. It can be dangerous to health and life.
The drug with alcohol leads to an increase in the toxic effects of ethanol.

During pregnancy

Enalapril during pregnancy is very dangerous. It leads to impaired growth and development of the fetus. During pregnancy for early dates detected after the appointment of the remedy, it is worth immediately stopping the use. For women planning to conceive, carrying a child or breastfeeding, the drug is prohibited.

Side effects

Instructions for use describe a number of negative phenomena that can be caused by taking pills.

Table 3. Side effects of Enalapril

The cardiovascular system	Decreased blood pressure, tachycardia, arrhythmia, myocardial infarction
Nervous system	Headache, dizziness, sleep and performance disturbances, irritability
Respiratory system	Dry cough, pneumonia, rhinitis, anaphylactic shock
Skin	Quincke's edema, urticaria, itching, burning, eczema
Gastrointestinal organs	Vomiting, nausea, diarrhea, heartburn, yellowing of the skin
sense organs	Specific taste of metal, the appearance of extraneous sounds
Other	Increased sweating, decreased libido, impotence

Does it affect potency?

Decreased sex drive is on the list of possible side effects. However, if we talk about men, it has been proven that ACE inhibitors increase the production of male hormones, improving potency. In any case, it makes no sense not to treat arterial hypertension. That's why:

in itself leads to impotence due to vasoconstriction and lack of blood supply to the genital organs;
also significantly increases the risk of sudden death.

man with arterial hypertension should be concerned not only with the question of whether the drug affects the potency, but also with the importance of the therapy. Without proper treatment, male power will weaken, and the risk of death will be enormous.

In recent years, an increasing number of people suffer from cardiovascular diseases. Many of them are young. Therefore, it is so important to choose the right treatment.

Enalapril is a drug whose action is aimed at lowering blood pressure. It has an effect on the renin-angiotensin system. The drug has a pronounced hypotensive natriuretic, cardioprotective effect.

Enalapril is prescribed in the treatment of hypertension and as a prophylactic. Rarely causes side effects. The manufacturer is the Serbian pharmaceutical company Hemofarm.

magnesium carbonate;
lactose monohydrate;
magnesium stearate;
gelatin.

Release form - in tablets with round shape. They have a characteristic aroma and a beige hue. The amount of active ingredient per tablet can be 5, 10, 25 mg.

pharmachologic effect

ACE inhibitor. When taking tablets, diastolic and systolic blood pressure decreases. At the same time, afterload decreases, vasodilation occurs, and aldosterone in the adrenal glands decreases.

Long-term treatment reduces the risk of myocardial infarction. Improves coronary and renal blood flow.

The organs of the digestive tract are absorbed quickly. Metabolized in the liver. Active action begins 1-2 hours after taking the pill.

Excretion - unchanged in the urine. 45-50% binds to blood proteins. Bioavailability is about 45%.

It has the ability to pass into breast milk.

Indications for use

in the treatment of arterial hypertension;
after a heart attack;
cardiac ischemia;
with chronic heart failure (as an additional treatment);
with diabetic nephropathy;
dysfunction of the left ventricle.

The drug is prescribed for any indicators of high blood pressure. If more than 120/80 is exceeded, the agent is prescribed in the treatment of the initial stage of the disease.

Enalapril tablets are washed down with a small amount of water. It can be taken before or after meals. Dosing is set individually for each patient, taking into account the stage of the disease and the specifics of the organism.

Moderate hypertension - once a day, 5 mg (half a tablet). If necessary, the dosage is gradually increased, but not more than 40 mg per day.
Severe hypertension - initially taken at 2.5 mg once a day. The dose is gradually increased. At severe course disease, the drug is administered intravenously.
In the treatment of chronic heart failure, the first days it is necessary to take 2.5 drugs. Gradually increase the dose to 5-40 mg.
After a heart attack, the drug is prescribed on the third day of treatment. It is taken three times a day, the dosage is 1/2 tablet (10 mg). Then the dosage is increased to the maximum.
For patients with kidney disease, the drug is prescribed in a dosage of 40 ml (divided into three doses). If the lung disease is severe, the daily dose should not exceed 12.5 mg.

Contraindications

hypersensitivity of the body;
lung disease, accompanied by shortness of breath;
pregnancy;
severe exhaustion;
porphyria;
breastfeeding;
with impaired kidney function;
stenosis of the aortic mouth;
liver disease in the acute stage;
children under 18 years of age;
with obstructed outflow of blood from the left ventricle;
angioedema;
hyperkalemia;
after kidney transplant;
with lactose intolerance.

The treatment is carried out under medical supervision for the elderly, with disturbed stools, after a chronic intervention. Dosage per day should not exceed 40 mg.

Reception during pregnancy and lactation

Enalapril is contraindicated in pregnancy at any time. Studies have shown that taking an ACE inhibitor disrupts the course of pregnancy and causes pathologies in the development of the fetus. If the pregnant woman took the drug, it is necessary to carry out a complete clinical trial and ultrasound to assess the condition of the body of a woman and a child.

Active during breastfeeding active substance enters the baby's body. The result is a violation of the stool, nausea, colic, fainting, low blood pressure and other complications.

Possible adverse reactions

tachycardia;
gagging;
tide;
allergy;
depressed state;
swelling of the larynx;
stool disorder;
soreness of the abdomen;
skin redness;
decreased vision;
nausea;
fatigue;
fainting state;
soreness in the chest area;
increase in calcium concentration;
angina;
a sharp increase in blood pressure;
rash;
increased sensitivity to the sun;
headache;
with problems with falling asleep;
bronchospasm;
dry mouth;
violation of taste sensations;
peptic ulcer;
sharp weight loss;
pneumonia;
circulatory disorders in the brain;
bleeding gums;
stomatitis;
drowsiness.

When side effects the drug is stopped.

Overdose

With an overdose, there is a sharp decrease in pressure, sudden weakness, confusion. Gastric lavage is performed antihistamines. In severe cases, hospitalization is necessary.

Interaction with other medicines

The absorption of Enalapril while taking diuretics, beta-blockers begins to increase.

It is forbidden to take other drugs together, the action of which is aimed at reducing pressure.
With the simultaneous use of NSAIDs, the effect of Enalapril is reduced.

Simultaneous treatment with immunosuppressants leads to a violation of the hematological type.

The drug increases the therapeutic effect of agents containing potassium, which causes negative reactions.

Hepatotoxicity increases with the simultaneous use of cytostatics.

If the patient is taking other drugs, a doctor's consultation is necessary.

special instructions

If tablets are prescribed regularly or for a long time, it becomes necessary to conduct a study of the kidneys.

If a dry cough develops after ingestion, the intake should be discontinued. Otherwise, it can cause pneumonia.

The drug in high dosages can cause an anaphylactic reaction.

It is forbidden to take it simultaneously with alcohol.

The drug can cause dizziness, confusion, a tendency to fall asleep. Therefore, it is forbidden to engage in activities that require increased alertness and drive cars.

Storage

The product is stored in a dry place, at a temperature not higher than +25 degrees. Shelf life - three years from the date indicated by the manufacturer on the package.

The drug is dispensed by prescription.

Analogues

Enarenal;
Golten;
Renitek;
Sandoz;
Blockordil;
Kaptopres;
Envas;
Vasolapril;
Norton;
Korandil;
Epistron;
Biosynthesis.

What do hypertensive patients write on the forums

Maria Semyonovna
Enalapril is good effective remedy. It can be taken at any elevated pressure. The main thing is to follow the recommended dosages in the instructions. Quickly helps to return to normal. The cost is cheap. I have tried many others before medicines, in the treatment of hypertension helped only this. The drug is well tolerated. A proven tool, I have been taking it for many years.

Alexandra
I never thought I would have high blood pressure. I have always suffered from hypotension. And then it suddenly became ill, the pain in my head was such that I thought I couldn’t stand it, it darkened in my eyes. I went to the clinic, it turned out that my blood pressure was 180 to 120. The doctor immediately prescribed Enalapril. Start with the lowest dosage. The condition immediately improved, literally after 10 minutes. I drank it in a course, the pressure no longer bothers me. But if anything, I know which drug will help me now.

People, don't drink this stuff! Enalapril leads to asthma, coughing and bouts of bronchospasm within a month and a half after taking! Checked on myself.

Aset Sarapalova

For two months, with a break of 10 days, I drank Enalapril 1-2 times a day, half a tablet. The result - suffocation at night, because of which I practically did not sleep and the inability to take a full breath - a cough began and, more interestingly, it was almost impossible to cough, dryness instantly appeared in the throat, followed by suffocation. I suffered for six months, the doctors did not help, they only prescribed an inhaler. Now I take everything from pressure, but not pills. I did not use an inhaler - folk remedies helped.

C09AA02 (Enalapril)
C09BA02 (enalapril and diuretics)

Analogues of the drug according to ATC codes:

You should consult with your doctor before using ENALAPRIL. These instructions for use are for informational purposes only. For more complete information please refer to the manufacturer's instructions.

Clinical and pharmacological groups

01.024 (ACE inhibitor)
01.048 (Antihypertensive drug)

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 vasoconstrictive effect and stimulates the secretion of aldosterone in the adrenal cortex).

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

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

Pharmacokinetics

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

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 by the kidneys unchanged.

ENALAPRIL: 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.

With intravenous administration - 1.25 mg every 6 hours. To detect excessive hypotension in patients with sodium deficiency and dehydration due to previous diuretic therapy, patients receiving diuretics, as well as in renal failure, an initial dose of 625 mg is administered. In case of inadequate clinical response, this dose can be repeated after 1 hour and continue treatment at a dose of 1.25 mg every 6 hours.

The maximum daily dose for oral administration is 80 mg.

drug interaction

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

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

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

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

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

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

Acetylsalicylic acid in high doses may reduce the antihypertensive effect of enalapril.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

With simultaneous use with cimetidine, T1 / 2 of enalapril increases and its concentration in blood plasma increases.

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

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

Pregnancy and lactation

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

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

ENALAPRIL SIDE EFFECTS

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

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

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

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

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

From the side 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, angioedema.

Others: rarely - hyperkalemia, muscle cramps.

Indications

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

Contraindications

History of angioedema, bilateral renal artery stenosis or stenosis renal artery solitary kidney, hyperkalemia, pregnancy, hypersensitivity to enalapril and other ACE inhibitors.

special instructions

Use with extreme caution in patients with autoimmune diseases, diabetes, impaired liver function, severe aortic stenosis, subaortic muscular stenosis of unknown origin, hypertrophic cardiomyopathy, with 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.

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

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

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

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

Influence on the ability to drive vehicles and control mechanisms

Caution required when driving vehicles or other work that requires heightened attention, because dizziness is possible, especially after taking the initial dose of enalapril.

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Characteristics of the substance Enalapril

ACE inhibitor, related to drugs that affect the RAAS. It is a derivative of the amino acids L-alanine and L-proline.

Pharmacology

pharmachologic effect- hypotensive, vasodilating, natriuretic, cardioprotective.

Pharmacodynamics

An antihypertensive drug used to treat essential hypertension (primary arterial hypertension of any severity) and renovascular hypertension, both in monotherapy and in combination with other antihypertensive drugs, in particular diuretics. Enalapril is also used to treat or prevent heart failure.

After oral administration, enalapril is rapidly absorbed and hydrolyzed to enalaprilat, which is a highly specific and long-acting ACE inhibitor that does not contain a sulfhydryl group.

ACE (peptidyl dipeptidase A) catalyses the conversion of angiotensin I to the vasopressor peptide angiotensin II. ACE inhibition leads to a decrease in the concentration of angiotensin II in blood plasma, which entails an increase in plasma renin activity (due to the elimination of negative feedback in response to renin release) and a decrease in aldosterone secretion. At the same time, SBP and DBP, OPSS decrease, post- and preload on the myocardium decrease.

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

ACE is identical to the enzyme kininase II, so enalapril can also block the destruction of bradykinin, a peptide with a pronounced vasodilatory effect. The significance of this effect in the therapeutic action of enalapril requires clarification. The main mechanism of the antihypertensive action of enalapril is considered to be the suppression of RAAS activity, which plays an important role in the regulation of blood pressure, but enalapril exhibits an antihypertensive effect even in patients with arterial hypertension and with reduced plasma renin activity. The antihypertensive effect is more pronounced with a high concentration of renin than with normal or reduced.

The use of enalapril by patients with arterial hypertension leads to a decrease in blood pressure both in the standing position and in the supine position without a significant increase in heart rate. Symptomatic orthostatic (postural) hypotension in the treatment of enalapril rarely develops.

Effective inhibition of ACE activity usually develops 2-4 hours after a single oral dose of enalapril. The antihypertensive effect develops within 1 hour, the maximum decrease in blood pressure is observed 4-6 hours after taking enalapril. The duration of action depends on the dose. When using the recommended doses, the antihypertensive effect and hemodynamic effects persist for 24 hours after administration.

In some patients, achieving optimal blood pressure reduction may require several weeks of therapy. Interruption of enalapril therapy does not cause a sharp rise in blood pressure.

Antihypertensive therapy with enalapril leads to a significant regression of left ventricular hypertrophy and preservation of its systolic function.

In patients with essential hypertension, a decrease in blood pressure is accompanied by a decrease in TPVR and an increase in cardiac output, while the heart rate does not change or changes slightly.

After taking enalapril, an increase in renal blood flow is observed. At the same time, GFR does not change, there are no signs of sodium or fluid retention. However, in patients with initially reduced glomerular filtration rate, its rate usually increases.

Enalapril reduces intraglomerular hypertension, slowing down the development of glomerulosclerosis and the risk of developing chronic renal failure.

Long-term use of enalapril in patients with essential hypertension and kidney failure may lead to an improvement in kidney function, as evidenced by an increase in GFR.

In patients with renal insufficiency and diabetes mellitus or without it, there is a decrease in albuminuria, excretion of IgG by the kidneys, as well as a decrease in total protein in the urine after taking enalapril.

With the simultaneous use of enalapril and thiazide diuretics, a more pronounced antihypertensive effect is observed. Enalapril reduces or prevents the development of hypokalemia caused by taking thiazide diuretics.

Therapy with enalapril is usually not associated with an undesirable effect on the concentration of uric acid in the blood plasma.

Therapy with enalapril is accompanied by a favorable effect on the ratio of lipoprotein fractions in blood plasma and no effect or a favorable effect on the concentration of total cholesterol.

In patients with CHF during therapy with cardiac glycosides and diuretics, enalapril causes a decrease in peripheral vascular resistance and blood pressure. Cardiac output increases while heart rate (usually elevated in patients with CHF) decreases. The wedge pressure in the pulmonary capillaries also decreases. Exercise tolerance and NYHA heart failure severity are improving. These effects are observed during long-term therapy with enalapril.

In patients with mild to moderate heart failure, enalapril slows down the progression of heart dilatation and heart failure, as evidenced by a decrease in diastolic and systolic volumes and an improvement in left ventricular ejection fraction.

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

Enalapril reduces the incidence of ventricular arrhythmias in patients with heart failure, although the underlying mechanisms and clinical significance of this effect are not known.

In CHF, a noticeable clinical effect is observed with long-term treatment for 6 months or more.

Pharmacokinetics

Suction. After oral administration, enalapril is rapidly absorbed from the gastrointestinal tract. C max enalapril in serum is achieved within 1 hour after ingestion. The degree of absorption when taken orally is approximately 60%. Simultaneous food intake does not affect the absorption of enalapril.

After absorption, enalapril is rapidly hydrolyzed to form the active metabolite enalaprilat, a strong ACE inhibitor. C max enalaprilat in serum is observed approximately 4 hours after taking a dose of enalapril inside. The duration of absorption and hydrolysis of enalapril is similar for various recommended therapeutic doses. In healthy volunteers with normal function kidney C ss enalaprilat in serum is reached by day 4 from the start of enalapril.

Distribution. In the range of therapeutic doses, the binding of enalaprilat to plasma proteins does not exceed 60%.

Enalaprilat easily penetrates the blood-tissue barriers, excluding the BBB, a small amount penetrates the GPB and into breast milk.

Metabolism. There are no data on other significant pathways of metabolism of enalapril, except for hydrolysis to enalaprilat. The rate of hydrolysis of enalapril may be reduced in patients with impaired liver function without reducing the therapeutic effect.

Withdrawal. Excretion of enalaprilat is carried out mainly by the kidneys - 60% (20% - unchanged and 40% - in the form of enalaprilat), through the intestines - 33% (6% - unchanged and 27% - in the form of enalaprilat). The main metabolites determined in the urine are enalaprilat, which is approximately 40% of the dose taken, and unchanged enalapril. There are no data on other metabolites of enalapril. The plasma concentration profile of enalaprilat has a long end phase, apparently due to its binding to ACE. T 1/2 enalaprilat about 11 hours.

Special patient groups

Impaired kidney function. The AUC of enalapril and enalaprilat is increased in patients with renal insufficiency.

In patients with mild to moderate renal insufficiency (Cl creatinine 40-60 ml / min), after taking enalapril at a dose of 5 mg 1 time per day, the equilibrium value of enalaprilat AUC is approximately 2 times higher than in patients with unchanged renal function.

In patients with severe renal insufficiency (Cl creatinine ≤30 ml / min), after repeated use of enalapril, the AUC value of enalaprilat increases by approximately 8 times, T 1/2 increases, the achievement of C ss is delayed.

Enalaprilat can be removed from the general circulation using a hemodialysis procedure. Clearance during hemodialysis is 62 ml / min (1.03 ml / s).

Breast-feeding. After a single oral administration of enalapril at a dose of 20 mg in patients in the postpartum period, the average Cmax of enalapril in breast milk is 1.7 μg / l (0.54-5.9 μg / l) 4-6 hours after administration. The average C max of enalaprilat is 1.7 μg / l (1.2-2.3 μg / l) and is observed at various times within 24 hours after administration. Taking into account data on maximum concentrations in breast milk, the estimated maximum consumption of enalapril by a child who is on full breastfeeding, is 0.16% of the dose, calculated taking into account the body weight of the mother.

After taking enalapril orally at a dose of 10 mg 1 time per day for 11 months, Cmax of enalapril in breast milk is 2 μg / l 4 hours after administration, enalaprilat - 0.75 μg / l approximately 9 hours after administration. The average concentration in breast milk within 24 hours after taking enalapril is 1.44 mcg / l and enalaprilat - 0.63 mcg / l.

The use of the substance Enalapril

Essential hypertension of any severity; renovascular hypertension; heart failure of any severity (in patients with clinical manifestations of heart failure, enalapril is also indicated to increase patient survival, slow the progression of the disease, and reduce the frequency of hospitalizations for heart failure); prevention of the development of clinically significant heart failure (in patients without clinical symptoms heart failure with left ventricular dysfunction, enalapril is indicated to slow the development clinical manifestations diseases, reducing the frequency of hospitalizations for heart failure); prevention of coronary ischemia in patients with left ventricular dysfunction to reduce the incidence of myocardial infarction, reduce the frequency of hospitalizations for unstable angina.

Contraindications

Hypersensitivity to enalapril or other ACE inhibitors; history of angioedema associated with previous use of ACE inhibitors, as well as hereditary or idiopathic angioedema; simultaneous use with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and / or impaired renal function (GFR<60 мл/мин/1,73 м 2) (см. «Взаимодействие»); возраст до 18 лет (безопасность и эффективность применения не изучены); беременность и период грудного вскармливания; наследственная непереносимость лактозы, дефицит лактазы, синдром глюкозо-галактозной мальабсорбции.

Application restrictions

Bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; condition after kidney transplantation; aortic or mitral stenosis (with impaired hemodynamic parameters); hypertrophic obstructive cardiomyopathy; ischemic heart disease; cerebrovascular diseases (including cerebrovascular insufficiency); renal failure (Cl creatinine<80 мл/мин); угнетение костномозгового кроветворения; системные заболевания соединительной ткани (в т.ч. склеродермия, системная красная волчанка), иммуносупрессивная терапия, лечение с применением аллопуринола или прокаинамида или комбинация указанных осложняющих факторов; печеночная недостаточность; сахарный диабет; гиперкалиемия; одновременное применение калийсберегающих диуретиков, препаратов калия, калийсодержащих заменителей поваренной соли и препаратов лития; проведение процедуры афереза ЛПНП с использованием декстрана сульфата; отягощенный аллергологический анамнез или ангионевротический отек в анамнезе; состояния, сопровождающиеся снижением ОЦК (в т.ч. при терапии диуретиками, соблюдении диеты с ограничением поваренной соли, диализе, диарее или рвоте); проведение десенсибилизации аллергеном из яда перепончатокрылых; у пациентов, находящихся на диализе с применением высокопроточных мембран (таких как AN 69 ®); после больших хирургических вмешательств или при проведении общей анестезии; у пациентов негроидной расы; пожилой возраст (>65 years old); primary aldosteronism.

Use during pregnancy and lactation

When pregnancy occurs, enalapril should be discontinued immediately, unless it is considered vital for the mother.

Epidemiological data indicate a possible teratogenic effect on the fetus of ACE inhibitors in the first trimester of pregnancy. If therapy with an ACE inhibitor is not life-saving, then women planning a pregnancy should use other antihypertensive drugs that are approved during pregnancy and have proven safety.

ACE inhibitors can cause disease or death of the fetus or newborn when used in the II and III trimesters of pregnancy. The use of ACE inhibitors during these periods was accompanied by negative effects on the fetus and newborn, including the development of arterial hypotension, renal failure, hyperkalemia and / or hypoplasia of the skull bones in the newborn. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, but it is not clear whether these cases were associated with the action of ACE inhibitors. In 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, enalapril should be discontinued, unless its use is considered life-saving for the mother. However, both the patient and the doctor must be aware that oligohydramnios develops with irreversible damage to the fetus. If ACE inhibitors are used during pregnancy and oligohydramnios develops, then, depending on the gestational age, a stress test, a non-stress test, or a biophysical profile of the fetus may be necessary to assess the functional state of the fetus.

Perhaps the development of oligohydramnios occurs due to a decrease in fetal kidney function. This complication can lead to contracture of the limbs, deformities of the bones of the skull, including the facial part, and hypoplasia of the lungs. When using enalapril, it is necessary to inform the patient about the potential risk to the fetus. Newborns whose mothers took enalapril should be carefully monitored for hypotension, oliguria and hyperkalemia.

Enalapril, which crosses the placenta, may be partially removed from the neonatal circulation by peritoneal dialysis; theoretically, it can be removed by exchange transfusion.

Enalapril and enalaprilat are excreted in breast milk in trace concentrations. If it is necessary to use enalapril during lactation, breastfeeding should be discontinued.

Side effects of Enalapril

The frequency of manifestation of adverse reactions is given in accordance with the WHO classification: very often (> 1/10); often (>1/100,<1/10); нечасто (>1/1000, <1/100); редко (>1/10000, <1/1000); очень редко (<1/10000, включая отдельные сообщения); частота неизвестна (определить частоту возникновения по имеющимся данным невозможно).

From the blood and lymphatic system: infrequently - anemia (including aplastic and hemolytic); rarely - neutropenia, decreased hemoglobin and hematocrit, thrombocytopenia, agranulocytosis, inhibition of bone marrow hematopoiesis, pancytopenia, lymphadenopathy, autoimmune diseases.

From the side of metabolism and malnutrition: infrequently - hypoglycemia (see "Precautions").

From the side of the central nervous system: very often - dizziness; often - headache, depression; infrequently - confusion, drowsiness, insomnia, irritability, paresthesia, vertigo; rarely - unusual dreams, sleep disturbances.

On the part of the organ of hearing and labyrinth disorders: infrequently - tinnitus.

From the side of the organ of vision: rarely - blurred vision.

From the CCC: often - a pronounced decrease in blood pressure, fainting, chest pain, heart rhythm disturbance, angina pectoris, tachycardia; infrequently - orthostatic hypotension, palpitations, myocardial infarction or stroke (possibly due to a sharp decrease in blood pressure in high-risk patients) (see "Precautions"); rarely - Raynaud's syndrome.

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

From the digestive system: very often - nausea; often - diarrhea, pain in the abdomen, taste disturbance; infrequently - intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, anorexia, stomach irritation, dryness of the oral mucosa, gastric and duodenal ulcers; rarely - stomatitis / aphthous ulcers, glossitis; very rarely - intestinal edema.

From the side of the liver and biliary tract: rarely - liver failure, hepatitis (hepatocellular or cholestatic), including hepatic necrosis, cholestasis (including jaundice).

From the skin and subcutaneous tissues: often - hypersensitivity reactions / angioedema of the face, limbs, lips, tongue, vocal folds and / or larynx, skin rash; infrequently - increased sweating, pruritus, urticaria, alopecia; rarely - erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, pemphigus, erythroderma.

A symptom complex has been reported that may be accompanied by some and / or all of the following symptoms: fever, serositis, vasculitis, myalgia / myositis, arthralgia / arthritis, positive antinuclear antibody test, increased ESR, eosinophilia and leukocytosis. Skin rash, photosensitivity, or other skin reactions may also occur.

From the side of the kidneys and urinary tract: infrequently - impaired renal function, renal failure, proteinuria; rarely - oliguria.

From the endocrine system: frequency unknown - syndrome of inappropriate ADH secretion.

From the genitals and breast: infrequently - erectile dysfunction; rarely - gynecomastia.

Deviations of data from laboratory and instrumental studies: often - hyperkalemia, an increase in the concentration of creatinine in the blood serum; infrequently - hyponatremia, an increase in the concentration of urea in the blood; rarely - an increase in the activity of hepatic transaminases, an increase in the concentration of bilirubin in the blood serum.

General disorders: very often - asthenia; often - increased fatigue; infrequently - muscle cramps, flushing of the skin of the face, discomfort, fever.

In rare cases, with the simultaneous use of ACE inhibitors (including enalapril) and intravenous administration of gold preparations (sodium aurothiomalate), a symptom complex is described, including facial redness, nausea, vomiting, and arterial hypotension.

Adverse events that were observed during the post-marketing use of enalapril (a causal relationship has not been established): urinary tract infection, upper respiratory tract infection, bronchitis, cardiac arrest, atrial fibrillation, herpes zoster, melena, ataxia, pulmonary embolism and pulmonary infarction, hemolytic anemia, including cases of hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.

Interaction

Other antihypertensive drugs. With the simultaneous use of enalapril and other antihypertensive therapy, an additive effect may be observed.

When using enalapril simultaneously with other antihypertensive drugs, especially diuretics, there may be an increase in the antihypertensive effect.

Simultaneous use with beta-blockers, methyldopa or CCB increases the severity of the antihypertensive effect.

Simultaneous use with alpha-, beta-blockers and ganglionic blockers should be carried out under close medical supervision.

Simultaneous use with nitroglycerin, other nitrates or vasodilators enhances the antihypertensive effect.

Serum potassium. In patients with arterial hypertension who took enalapril in monotherapy for more than 48 weeks, there was an increase in serum potassium by an average of 0.2 mmol / l.

With the simultaneous use of enalapril with diuretics that cause the loss of potassium ions (thiazide or loop diuretics), hypokalemia caused by the action of diuretics is usually weakened due to the effect of enalapril.

Risk factors for the development of hyperkalemia are renal failure, diabetes mellitus, concomitant use of potassium-sparing diuretics (eg spironolactone, eplerenone, triamterene or amiloride), as well as potassium-containing supplements and salts. The use of potassium supplements, potassium-sparing diuretics or potassium-containing salts, especially in patients with impaired renal function, can lead to a significant increase in serum potassium. If necessary, the simultaneous use of the above potassium-containing or potassium-increasing drugs should be careful and regularly monitor the content of potassium in the blood serum.

Hypoglycemic agents. The simultaneous use of ACE inhibitors and hypoglycemic agents (insulin, hypoglycemic drugs for oral administration) may enhance the hypoglycemic effect of the latter with the risk of developing hypoglycemia. This effect is usually most often observed during the first weeks of combination therapy, as well as in patients with impaired renal function. In patients with diabetes mellitus taking hypoglycemic drugs for oral administration or insulin, the concentration of glucose in the blood should be regularly monitored, especially during the first month of simultaneous use with ACE inhibitors.

lithium preparations. Like other drugs that affect sodium excretion, ACE inhibitors can reduce the excretion of lithium by the kidneys, therefore, with the simultaneous use of lithium preparations and ACE inhibitors, it is necessary to regularly monitor the concentration of lithium in the blood serum.

Tricyclic antidepressants/neuroleptics/general anesthetics. The simultaneous use of certain anesthetic drugs, tricyclic antidepressants and neuroleptics with ACE inhibitors can lead to a further decrease in blood pressure (see "Precautions").

Ethanol. Ethanol enhances the antihypertensive effect of ACE inhibitors.

Acetylsalicylic acid, thrombolytics and beta-blockers. Enalapril can be used simultaneously with acetylsalicylic acid (as an antiplatelet agent), thrombolytics and beta-blockers.

Sympathomimetics. Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.

NSAIDs. NSAIDs, including selective COX-2 inhibitors, may reduce the effect of diuretics and other antihypertensive drugs. As a result, the antihypertensive effect of ARA II or ACE inhibitors may be weakened when used simultaneously with NSAIDs, incl. with selective COX-2 inhibitors.

In some patients with impaired renal function (for example, in elderly patients or patients with dehydration, including those taking diuretics) receiving NSAID therapy, including selective COX-2 inhibitors, the simultaneous use of ARA II or ACE inhibitors may cause further deterioration of kidney function, including the development of acute renal failure. These effects are usually reversible, so the simultaneous use of these drugs should be carried out with caution in patients with impaired renal function.

Double blockade of the RAAS. Double blockade of the RAAS using ARA II, ACE inhibitors or aliskiren (a renin inhibitor) is associated with an increased risk of arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy. Regular monitoring of blood pressure, kidney function and electrolytes in the blood is necessary in patients taking enalapril and other drugs at the same time that affect the RAAS. Enalapril should not be co-administered with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and/or impaired renal function (GFR).<60 мл/мин/1,73 м 2).

The simultaneous use of ACE inhibitors with ARA II in patients with diabetic nephropathy is contraindicated.

Preparations of gold. In rare cases, with the simultaneous use of gold preparations for parenteral administration (sodium aurothiomalate) and ACE inhibitors, including enalapril, a symptom complex (nitrate-like reactions) is observed, including a rush of blood to the skin of the face, nausea, vomiting and arterial hypotension.

mTOR inhibitors. In patients taking both an ACE inhibitor and an enzyme inhibitor mTOR (mammalian target of rapamycin Mammalian target of rapamycin) (e.g. temsirolimus, sirolimus, everolimus), therapy may be associated with an increased risk of angioedema.

Allopurinol, cytostatics and immunosuppressants. Simultaneous use with ACE inhibitors may increase the risk of developing leukopenia.

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

Antacids. May reduce the bioavailability of ACE inhibitors.

Theophylline. Enalapril weakens the effect of drugs containing theophylline.

Other medicines. There is no clinically significant pharmacokinetic drug interaction between enalapril and the following drugs: hydrochlorothiazide, furosemide, digoxin, timolol, methyldopa, warfarin, indomethacin, sulindac and cimetidine. With the simultaneous use of enalapril and propranolol, the concentration of enalaprilat in the blood serum decreases, but this effect is not clinically significant.

Overdose

Symptoms: a pronounced decrease in blood pressure (begins approximately 6 hours after ingestion), up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications, impaired water and electrolyte balance, renal failure, increased respiration, tachycardia, palpitations, bradycardia, dizziness, anxiety, fear, convulsions, cough, stupor. Enalaprilat plasma concentrations 100-200 times higher than after therapeutic doses were observed after oral administration of 300 and 440 mg of enalapril, respectively.

Treatment: move the patient to a horizontal position with a low headboard. In mild cases, gastric lavage and ingestion of activated charcoal are indicated, in more serious cases, measures aimed at normalizing blood pressure (in / in the introduction of 0.9% sodium chloride solution, plasma substitutes, if necessary, in / in the introduction of catecholamines), hemodialysis (rate of excretion enalaprilat - 62 ml / min). Patients with bradycardia resistant to therapy are shown setting a pacemaker.

Routes of administration

inside.

Enalapril substance precautions

Symptomatic arterial hypotension. Symptomatic arterial hypotension is rarely observed in patients with uncomplicated arterial hypertension. In patients with arterial hypertension taking enalapril, arterial hypotension develops more often against the background of dehydration, which occurs, for example, as a result of diuretic therapy, restriction of salt intake, in patients on dialysis, as well as in patients with diarrhea or vomiting (see. " Side effects", "Interaction"). Symptomatic arterial hypotension is also observed in patients with heart failure with or without renal failure.

Arterial hypotension develops more often in patients with more severe heart failure with hyponatremia or impaired renal function, in whom higher doses of loop diuretics are used. In these patients, treatment with enalapril should be started under medical supervision, which should be especially careful when changing the dose of enalapril and / or diuretic. Similarly, patients with coronary artery disease or cerebrovascular disease should be monitored, in whom an excessive decrease in blood pressure can lead to the development of myocardial infarction or stroke.

With the development of arterial hypotension, the patient should be laid down and, if necessary, injected with a 0.9% solution of sodium chloride. Transient arterial hypotension while taking enalapril is not a contraindication to further use and dose increase, therapy can be continued after replenishment of fluid volume and normalization of blood pressure.

In some patients with heart failure and normal or low blood pressure, enalapril may cause an additional decrease in blood pressure. This reaction to enalapril is expected and is not a reason to stop treatment. In cases where arterial hypotension becomes stable, the dose should be reduced and / or treatment with a diuretic and / or enalapril should be discontinued.

Aortic or mitral stenosis/hypertrophic obstructive cardiomyopathy. As with all drugs with a vasodilatory effect, ACE inhibitors should be used with caution in patients with obstruction of the outflow tract from the left ventricle.

Impaired kidney function. In some patients, arterial hypotension that develops after the start of treatment with ACE inhibitors can lead to a further deterioration in renal function. In some cases, the development of acute renal failure, usually reversible, has been reported.

In patients with renal insufficiency, a dose and / or frequency reduction of enalapril may be required. In some patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney, an increase in the concentration of urea in the blood and creatinine in the blood serum was observed. Changes were usually reversible, and indicators returned to baseline values after treatment was stopped. This pattern of changes is most likely in patients with renal insufficiency.

In some patients who did not have kidney disease before treatment, enalapril in combination with diuretics usually caused a slight and transient increase in the concentration of urea in the blood and serum creatinine. In such cases, it may be necessary to reduce the dose and / or cancel the diuretic and / or enalapril.

Kidney transplant. Treatment with enalapril is not recommended in kidney transplant patients due to lack of experience with this use.

Liver failure. The use of ACE inhibitors is rarely associated with the development of a syndrome that begins with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis, sometimes with a fatal outcome. The mechanism of this syndrome has not been studied. With the appearance of jaundice or a significant increase in the activity of hepatic transaminases against the background of the use of ACE inhibitors, enalapril should be discontinued and appropriate adjuvant therapy should be prescribed; the patient should be under appropriate supervision.

Neutropenia/agranulocytosis. Neutropenia/agranulocytosis, thrombocytopenia and anemia have been observed in patients taking ACE inhibitors. Neutropenia occurs rarely in patients with normal renal function and no other complicating factors.

Enalapril should be used with extreme caution in patients with systemic connective tissue disease (systemic lupus erythematosus, scleroderma, etc.) who are receiving immunosuppressive therapy, allopurinol or procainamide, or a combination of these complicating factors, especially if there is already existing renal dysfunction. Some of these patients develop serious infectious diseases, which in some cases do not respond to intensive antibiotic therapy. If enalapril is used in such patients, regular monitoring of the number of leukocytes and lymphocytes in the blood is recommended and patients should be warned to report any signs of an infectious disease.

Hypersensitivity reactions / angioedema. With the use of ACE inhibitors, including enalapril, rare cases of angioedema of the face, extremities, lips, tongue, vocal cords and / or larynx that occurred at different periods of treatment were observed. In very rare cases, intestinal edema may develop. In such cases, you should immediately stop taking enalapril and carefully monitor the patient's condition in order to control and correct clinical symptoms. Even in cases where there is only swelling of the tongue without the development of respiratory distress syndrome, patients may require long-term observation, since therapy with antihistamines and corticosteroids may not be sufficient.

Very rarely, a fatal outcome has been reported due to angioedema associated with swelling of the larynx or tongue. Swelling of the tongue, vocal cords, or larynx may lead to airway obstruction, especially in patients who have undergone respiratory surgery. In cases where edema is localized in the region of the tongue, vocal cords or larynx and can cause airway obstruction, appropriate treatment should be immediately prescribed, which may include subcutaneous injection of a 0.1% solution of epinephrine (0.3-0.5 ml ) and/or maintain airway patency.

In patients of the black race taking ACE inhibitors, angioedema is observed more often than in patients of other races.

Patients with a history of angioedema unrelated to ACE inhibitors may be at greater risk of developing angioedema during therapy with ACE inhibitors (see "Contraindications").

Anaphylactoid reactions during desensitization with an allergen from Hymenoptera venom. In rare cases, patients taking ACE inhibitors develop life-threatening anaphylactoid reactions during desensitization with allergen from hymenoptera venom. Adverse reactions can be avoided by temporarily stopping the ACE inhibitor before starting desensitization.

Anaphylactoid reactions during LDL apheresis. Life-threatening anaphylactoid reactions rarely occur in patients taking ACE inhibitors during LDL apheresis using dextran sulfate. The development of these reactions can be avoided if the ACE inhibitor is temporarily discontinued before each LDL apheresis procedure.