Home Removal Medicinal reference book geotar. Enalaprilat solution: how and when to use? When is intravenous administration necessary?

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Medicinal reference book geotar. Enalaprilat solution: how and when to use? When is intravenous administration necessary?

Instructions for medical use medicine

ENAP ® R

Tradename

International nonproprietary name

Enalaprilat

Dosage form

Solution for intravenous administration, 1.25 mg/ml

Compound

1 ml contains

active substance- enalaprilat 1.25 mg,

Excipients: benzyl alcohol, sodium chloride, sodium hydroxide, water for injection.

Description

Transparent, colorless solution

Pharmacotherapeutic group

Angiotensin converting enzyme (ACE) inhibitors.

ATX code C09AA

Pharmacological properties

Pharmacokinetics

Absorption

Enalaprilat is poorly absorbed after oral administration and is practically inactive, so it is used exclusively intravenously.

Distribution

After intravenous administration, the maximum concentration is reached after 15 minutes, the drug is rapidly distributed among most tissues and reaches high concentrations in the lungs, kidneys and blood vessels. However, there is no evidence that therapeutic doses penetrate the brain. The binding to plasma proteins is about 50-60%. Circulates in the blood unchanged.

Penetrates poorly through the blood-brain barrier.

Metabolism

Enalaprilat is not metabolized; 100% of enalaprilat is excreted in the urine.

Removal

Enalaprilat is excreted primarily through the kidneys (more than 90%). The derivation is a combination glomerular filtration and tubular secretion. The half-life is 4 hours. The half-life is approximately 35 hours.

For renal failure

In patients with renal failure, the duration of action of enalaprilat increases. Elimination is slowed, so doses must be adjusted according to renal function. Enalaprilat can be removed from the systemic circulation by hemodialysis. The clearance of enalaprilat by dialysis is 1.03 ml/sec (62 ml/min), the concentration of enalaprilat in the blood serum after 4-hour hemodialysis is reduced by 45-75%.

Pharmacodynamics

ENAP® P inhibits ACF, which catalyzes the conversion of angiotensin I to the vasoconstrictor form of angiotensin II. Inhibition of ACE leads to a decrease in angiotensin II concentrations, an increase in plasma renin activity, and a decrease in aldosterone secretion.

The hypotensive effect and hemodynamic effects of ENAP® R in patients with high blood pressure are the result of dilation of resistant vessels and a decrease in total blood pressure. peripheral resistance, as a result of which it gradually decreases arterial pressure. At the same time, heart rate and cardiac output usually remain unchanged. After intravenous injection, action of ENAP® P occurs within 5 - 15 minutes, the maximum effect is achieved within 1 - 4 hours and lasts for 6 hours.

Indications for use

hypertensive crisis

arterial hypertension in cases where oral treatment is not possible

hypertensive encephalopathy

Directions for use and doses

The usual dose for the treatment of hypertension is 1.25 mg (1 ampoule) every 6 hours. When switching from enalapril treatment to enalaprilat treatment, the usual dose is 1 ampoule (1.25 mg) every six hours.

Enap® R injection solution is administered intravenously slowly over 5 minutes. It can also be administered with a preliminary dilution in 50 ml of 5% glucose solution, 0.9% sodium chloride solution (saline), 5% glucose solution in 0.9% sodium chloride solution or 5% glucose solution in Ringer's lactate.

For patients taking diuretics, the initial dose is 1/2 ampoule (0.625 mg). If 1 hour after administration therapeutic effect unsatisfactory, the same dose can be re-administered, and after 6 hours treatment with the full dose is continued (1 ampoule every 6 hours).

Treatment with enalaprilat is usually continued for 48 hours. After this, treatment with enalapril should be continued. When switching from parenteral treatment with Enap® R to oral treatment with enalapril, the recommended initial dose is 5 mg per day for patients receiving 1 ampoule (1.25 mg) of enalaprilat every 6 hours. If necessary, the dose can be increased. For patients who received half the dose of enalaprilat (0.625 mg) for treatment, the recommended dose when switching to oral treatment with enalapril is 2.5 mg per day.

Dosage for renal failure

For patients with creatinine clearance above 0.5 ml/s (30 ml/min, plasma creatinine below 265 µmol/l), the initial dose is 1 ampoule (1.25 mg) every 6 hours.

For patients with creatinine clearance below 0.5 ml/s (30 ml/min, plasma creatinine above 265 µmol/l), the initial dose is 1/2 ampoule (0.625 mg). If 1 hour after administration the therapeutic effect is unsatisfactory, the same dose can be re-administered, and after 6 hours treatment with the full dose is continued (1 ampoule every 6 hours).

Dosage for hemodialysis

For patients on hemodialysis, the recommended dose is 1/2 ampoule (0.625 mg) every 6 hours.

Side effects

Very common (≥1/10):

Blurred vision

Dizziness

Dry non-productive cough

Nausea

Asthenia

Often (from ≥1/100 to<1/10):

Headache

Hypotension (including orthostatic hypotension), syncope, chest pain, arrhythmias, angina, bradycardia, tachycardia, acute left ventricular failure

Diarrhea, abdominal pain, changes in food taste

Depression

Rash, hypersensitivity/Quincke's edema

Hypotension (including orthostatic hypotension)

Fatigue

Hyperkalemia, increased plasma creatinine

Uncommon (from ≥1/1,000 to<1/100):

Anemia (including aplastic and hemolytic)

Hypoglycemia

Paresthesia, dizziness

Tinnitus

Cardiopalmus

Rhinorrhea, sore throat and hoarseness, bronchospasm/asthma

Intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation,

anorexia, gastric irritation, dry mouth, peptic ulcer

Confusion, drowsiness, insomnia, nervousness

Sweating, itching, urticaria, alopecia

Renal dysfunction, renal failure, proteinuria

Impotence

Muscle cramps, flushing, tinnitus, general malaise, fever

Increased plasma urea, hyponatremia

Rarely (≥1/10.0000 to<1/1,000):

Neutropenia, decrease in hemoglobin and hematocrit, thrombocytopenia, agranulocytosis, leukopenia, bone marrow suppression, pancytopenia, enlarged lymph nodes, autoimmune diseases

Nightmares, sleep disorders

Pulmonary infiltrates, rhinitis, allergic alveolitis/eosinophilic pneumonia

Stomatitis/aphthous ulcer, glossitis

Liver failure, hepatitis - hepatocellular or cholestatic; hepatitis, including necrosis; cholestasis, including jaundice

Erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma

Oliguria

Gynecomastia

Raynaud's phenomenon

Increased liver enzymes, increased plasma bilirubin

Very rarely (<1/10,000):

Intestinal Quincke's edema

Not known (cannot be estimated based on available data):

A constellation of symptoms have been reported: fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, positive antinuclear antibody (ANA) test, accelerated ESR, eosinophilia and leukocytosis. Rash, photosensitivity and other dermatological manifestations may also occur.

If serious side effects occur, treatment should be stopped.

Contraindications

Hypersensitivity to enalapril, enalaprilat or any excipient or other ACE inhibitors

Angioedema: history associated with previous use of ACE inhibitors; hereditary or idiopathic

Porphyria

Conducting hemodialysis using high-flow membranes (for example, AN 69), LDL apheresis with dextran sulfate, desensitization from wasp or bee venom

Pregnancy (especially in the 2nd and 3rd trimesters) and lactation period

Children and adolescents up to 18 years of age

Drug interactions

Enalaprilat is a metabolite of enalapril. Therefore, during treatment with enalaprilat, the same interactions may occur as during treatment with enalapril.

Potassium-sparing diuretics, potassium supplements

ACE inhibitors reduce potassium loss caused by diuretics. The use of potassium-sparing diuretics (spironolactone, triamterene, or amiloride), other drugs that increase serum potassium levels (eg, heparin), potassium supplements, or potassium-containing salt substitutes may lead to hyperkalemia. Such simultaneous use is therefore not recommended.

If concomitant use is necessary due to hypokalemia, they should be used with caution and with frequent monitoring of plasma potassium levels.

Diuretics (thiazide or loop diuretics)

Pre-treatment with high doses of diuretics may lead to fluid deficiency and increase the risk of hypotension. The hypotensive effect can be reduced by stopping diuretics, increasing salt and fluid intake, or starting therapy with half the dose (1/2 ampoule) of enalaprilat.

Other antihypertensive drugs

The simultaneous use of these drugs may increase the hypotensive effect of enalapril. Concomitant use with nitroglycerin, other nitrates or other vasodilators may lead to a greater decrease in blood pressure

Lithium

Reversible increases in plasma lithium concentrations and toxicity have been reported with concomitant use of lithium and ACE inhibitors. Concomitant use with thiazide diuretics may further increase lithium levels and lead to the risk of lithium toxicity. The simultaneous use of these drugs is not recommended, but if necessary, careful monitoring of plasma lithium levels should be carried out.

Tricyclic antidepressants and/or antipsychotics/anaesthetics/narcotics

Concomitant use of certain anesthetics, tricyclic antidepressants and antipsychotic drugs with ACE inhibitors may lead to an additional decrease in blood pressure.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Long-term use of NSAIDs may reduce the antihypertensive effect of ACE inhibitors. NSAIDs and ACE inhibitors have an additive effect on increasing plasma potassium levels, 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 (elderly patients or patients with hypovolemia).

Antidiabetic drugs

Epidemiological studies have shown that the simultaneous use of ACE inhibitors and antidiabetic drugs (insulin, oral hypoglycemic agents) may cause an increased hypoglycemic effect with a risk of hypoglycemia. This phenomenon is more often observed during the first weeks of combination treatment and in patients with renal failure.

Alcohol
Alcohol enhances the hypotensive effect of ACE inhibitors.

Sympathomimetics
Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.

Acetylsalicylic acid, thrombolytics and β-blockers

The simultaneous use of enalapril with acetylsalicylic acid (in cardiac doses), thrombolytics and beta-blockers is safe.

special instructions

Symptomatic hypotension

Symptomatic hypotension is rare in patients with uncomplicated hypertension, but may occur in patients with fluid deficiency (diuretic therapy, salt-restricted diet, hemodialysis, diarrhea or vomiting). Symptomatic hypotension may occur in patients with heart failure with or without associated renal failure. It may also occur in patients with more severe heart failure who are taking high-dose loop diuretics, hyponatremia, or renal failure. In these patients, initiating treatment and changing the dose of enalapril and/or diuretic should be under close medical supervision. Similar precautions should be taken when treating patients with angina or cerebrovascular disease, where an excessive decrease in blood pressure can lead to myocardial infarction or stroke.

Hypotension and its serious consequences occur in rare cases and are transient. They can be avoided by stopping treatment with diuretics and a salt-restricted diet before starting treatment with Enap® R, if possible. In the other conditions mentioned or if discontinuation of diuretic treatment is not possible, treatment with half the dose (1/2 ampoule) of enalaprilat is recommended. If arterial hypotension occurs, the patient should be transferred to a horizontal position lying on his back and, if necessary, plasma volume should be corrected by intravenous administration of a 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication for further use of enalapril. Usually, after normalization of blood pressure and administration of additional volume, further doses of the drug are well tolerated by patients.

Aortic and mitral valve stenosis, hypertrophic cardiomyopathy
Like all vasodilators, ACE inhibitors should be used with caution in the treatment of patients with left ventricular outflow tract obstruction and to avoid cases of cardiogenic shock and hemodynamically significant left ventricular outflow tract obstruction.

Renal dysfunction

In patients with impaired renal function (creatinine clearance<1,33 мл/ сек), начальную дозу следует подбирать в зависимости от клиренса креатинина, затем в зависимости от реакции на лечение.

Plasma creatinine and potassium levels should be monitored regularly.
In patients with severe heart failure or latent kidney disease, including renal artery stenosis, renal failure may occur during treatment with enalapril. With prompt and appropriate treatment, it is usually reversible.

In some patients with invisible but pre-existing kidney disease, minor and transient increases in plasma urea and creatinine levels occurred after taking enalapril concomitantly with diuretics. Therefore, it may be necessary to reduce the dose of the ACE inhibitor and/or discontinue diuretics. This situation provokes the appearance of latent renal artery stenosis.

Renovascular hypertension

There is an increased risk of arterial hypotension and renal failure when treating patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney with ACE inhibitors. Loss of kidney function can occur only with moderate changes in plasma creatinine levels. In such patients, treatment should begin with low doses and under close medical supervision; During treatment, doses should be titrated with caution and renal function monitored.

Kidney transplantation

Due to lack of experience, treatment with enalapril is not recommended for patients who have recently undergone renal transplantation.

Liver failure

During therapy with ACE inhibitors, in rare cases, it is possible to develop a syndrome that begins with cholestatic jaundice and then progresses to fulminant liver necrosis and (sometimes) death. The mechanism of development of this syndrome is unclear. If jaundice or elevated liver enzyme levels occur during treatment with ACE inhibitors, the drug should be discontinued immediately and the patient should be closely monitored and, if necessary, receive adequate therapy.

Neutropenia and agranulocytosis

In patients taking ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported. In patients with normal renal function in the absence of other complications, neutropenia rarely develops.

Enalaprilat should be used very carefully in patients with collagen diseases (for example, systemic lupus erythematosus, scleroderma), simultaneously receiving therapy with immunosuppressants, allopurinolyl procainamide, as well as a combination of these factors, especially with existing renal dysfunction. Some of these patients may develop severe infections that do not respond to intensive antibiotic therapy. When prescribing the drug to such patients, 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 and angioedema

Among patients taking ACE inhibitors, including enalapril or enalaprilat, the development of angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported rarely. It can occur at any time during treatment. In this case, treatment should be stopped and appropriate measures taken to ensure complete resolution of the patient's symptoms.

Angioedema of the face and lips usually does not require treatment; antihistamines can be used to relieve the patient's symptoms.

Angioedema of the larynx can be fatal. If swelling of the tongue, glottis or larynx threatens the development of airway obstruction, it is necessary to carry out emergency treatment as soon as possible - subcutaneous injection of a solution of adrenaline 1:1000 (0.3-0.5 ml) and take measures to ensure airway patency.

Patients with a history of angioedema unrelated to ACE inhibitor therapy are at increased risk of angioedema when taking ACE inhibitors.

Anaphylactoid reactions during desensitization

In patients receiving ACE inhibitors during a course of desensitization with bee or wasp venom, life-threatening anaphylactoid reactions are possible in rare cases. The development of these reactions can be avoided by temporarily withdrawing the ACE inhibitor before each desensitization procedure.

Anaphylactoid reactions during LDL apheresis

In patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis with dextran sulfate, life-threatening anaphylactoid reactions may occur in rare cases. The development of these reactions can be avoided by temporarily discontinuing the ACE inhibitor before each apheresis procedure.

Patients on hemodialysis

The development of hypersensitivity, anaphylactoid reaction, has been reported among patients undergoing hemodialysis using polyacrylonitrile membranes (AN 69) and simultaneously taking ACE inhibitors. If hemodialysis is necessary, a different type of membrane should be used, or the patient should be switched to taking a suitable drug from a different class of antihypertensive drugs.

Patients with diabetes mellitus

In patients with diabetes mellitus receiving oral antidiabetic agents or insulin, blood sugar levels should be carefully monitored during the first month of treatment with ACE inhibitors.

Cough
During treatment with ACE inhibitors, a persistent, dry, nonproductive cough may occur, which resolves after discontinuation of therapy. This should be considered as part of the differential diagnosis of cough.

Surgery and anesthesia

In patients undergoing major surgery or during general anesthesia with antihypertensive drugs, enalapril may block the formation of angiotensin II secondary to compensatory renin release. If the doctor suspects hypotension due to this mechanism, treatment may be aimed at increasing circulating blood volume.

Hyperkalemia
Plasma potassium levels may increase in some patients during treatment with ACE inhibitors, including enalapril and enalaprilat. Patients with renal failure, diabetes mellitus, and patients concomitantly taking potassium-sparing diuretics, potassium supplements, and other drugs that can lead to hyperkalemia (for example, heparin) are at increased risk of developing hyperkalemia. If concomitant use of enalapril with any of the above-mentioned agents is advisable, it is recommended to regularly monitor the level of potassium in the blood plasma.

Lithium
The combined use of lithium and enalapril is not recommended.

Pregnancy and lactation

During pregnancy, the use of ACE inhibitors should not be started. As long as treatment with ACE inhibitors is necessary, patients planning pregnancy should switch to alternative antihypertensive drugs that have an established safety profile for use during pregnancy. If pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately and, if appropriate, alternative treatment initiated. Taking ACE inhibitors in the second and third trimesters of pregnancy is known to cause fetotoxicity (decreased renal function, oligohydramnios, delayed cranial ossification) and neonatal toxicity (renal failure, hypotension, hyperkalemia) in humans. If ACE inhibitors were taken in the second trimester of pregnancy, It is recommended to conduct an ultrasound of the kidneys and skull. Infants whose mothers took ACE inhibitors should be closely monitored for hypotension.

Enap® R is not recommended for use during lactation when breastfeeding premature infants and during the first few weeks after birth, due to the hypothetical risk of cardiovascular and renal effects, as well as due to the lack of sufficient clinical experience. For older newborns, use of Enap® P by a nursing mother may be considered if such treatment is necessary for the mother and baby and is monitored for any side effects.

Ethnic differences

Like other angiotensin-converting enzyme inhibitors, enalaprilat is less effective in lowering blood pressure in black people than in non-black people, possibly due to the high prevalence of low renin status in black people.

Special information about some ingredients
Enap® R injection solution contains benzyl alcohol, which can cause toxic and anaphylactoid reactions in infants and children under 3 years of age. It should not be used in premature or newborn babies.
This medication contains less than 1 mmol sodium (23 mg) per dose and is therefore "sodium free".

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

There are no data on the impact on driving vehicles and operating machinery.

Overdose

Symptoms: excessive decrease in blood pressure up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications, convulsions, stupor.

Treatment: ingestion of saline solution, epinephrine (subcutaneous or intravenous), antihistamines, glucocorticosteroids (intravenous), intravenous administration of plasma expanders, angiotensin II, hemodialysis (administration rate - 62 ml/min).

In emergency cases that require urgent and effective relief of dangerous symptoms, it is impossible to get by with such a form of medicine as tablets. For example, a quick effect in a hypertensive crisis is achieved only by intravenous administration of an antihypertensive drug solution such as Enalaprilat.

Let's learn more about its components and application features.

A compound with the chemical name (S) - 1-(N - (1-carboxy-3-phenylpropyl) - L - alanyl) - L - pronil, Enalaprilat is an active metabolite (metabolite product) of the “prodrug” Enalapril. In its pure form, the substance looks like a whitish powder, which has a hygroscopic property (absorbs moisture from the external environment). To prepare a solution of Enalaprilat, the powder is mixed with liquids in different proportions:

with water - 1:200;
with methanol - 1:68;
with dimethylformamide - 1:40;

Enalaprilat powder is very slightly soluble in other liquid compounds.

Enalaprilat is almost insoluble in chloroform. Each ampoule of the drug contains 1.25 mg of enalaprilat per milliliter of solution.

Indications for use

Enalaprilat solution is used to treat hypertension, especially in the acute phase - during a hypertensive crisis. This complication of arterial hypertension is dangerous because it can provoke damage to internal organs, the so-called target organs, which can be the heart, kidneys, brain or central nervous system.

Therefore, injection, which is Enalaprilat (solution), represents the most optimal way to effectively, but smoothly lower pressure when:

hypertension, if oral administration of the medication is not possible;
hypertensive crisis, when a long but reliable antihypertensive effect is required;
with hypertensive encephalopathy - a complication of hypertension, expressed by brain damage.

Instructions for use of Enalaprilat solution

The information contained in the package leaflet for the injection contains several basic guidelines regarding the drug Enalaprilat solution. Instructions for use provide recommendations regarding:

dosage;
method of administration;
contraindications;
overdose;
compatibility with other drugs;
side effects;
special recommendations for use.

Dosage and method of administration

So, in an emergency situation caused by a strong (from 200/110 mm Hg) increase in blood pressure, 1 ampoule (1.25 mg per 1 ml) of Enalaprilat solution is administered intravenously once every 6 hours.

The introduction of the solution should be slow, jet (over 5 minutes) or drip.
Injections should be performed in a hospital setting with careful monitoring of the patient's condition.
If the result is insufficient 1 hour after the injection, it is possible to re-administer the same dose, and after 6 hours switch to the regimen of 1 ampoule every 6 hours.
Hypertensive patients taking diuretics are allowed to administer an initial dose of no more than 625 mcg of Enalaprilat. If the result is unsatisfactory, repeat administration - after 1 hour in the same amount, and after 6 hours you can switch to the full dose - 1.25 mg every 6 hours.

Overdose

The administration of high doses of Enalaprilat solution provokes a sharp drop in pressure (transient hypotension), which can result in collapse or hypoxia of the brain.

Therefore, if hypotonic manifestations are detected (blood pressure below 100 mm Hg), you should:

reduce the dose or completely abandon the drug;
in severe cases, lay the patient on a flat surface without a pillow to ensure blood flow to the brain;
take measures to increase the BCC (circulating blood volume) - introduce saline or other blood-substituting substances;
as symptomatic therapy, it is recommended to administer Epinephrine (intravenously or subcutaneously), one of the antihistamines, intravenous hydrocortisone, angiotensin II, or resort to a dialysis procedure.

Compatibility with other drugs

Does the concomitant use of other medications affect the effect of Enalaprilat solution? The instructions for use contain a list of products that have a special relationship with Enalaprilat.

The likelihood of developing hypotension occurs with the simultaneous use of diuretics, other antihypertensive drugs, opioid analgesics and general anesthetics.
The hypotensive effect of Enalaprilat solution is reduced with parallel use of ethanol, medications that stimulate the renin-angiotensin-aldosterone system, adrenergic stimulants, estrogen-containing drugs, and nonsteroidal anti-inflammatory drugs (NSAIDs).
The risk of severe blood pathologies such as neutropenia and agranulocytosis increases due to the parallel use of allopurinol, immunosuppressants, and cytostatics with Enalaprilat solution.
An increase in the hypoglycemic effect of insulin and sulfonylurea derivatives was found during treatment (synonymous with Enalaprilat).
Reversible lithium poisoning, which occurs during the parallel use of its drugs with Enalaprilat, stops when both the first and the second are discontinued.
With the parallel use of potassium-sparing diuretics, cyclosporines, and potassium supplements, the development of hyperkalemia is likely.

No negative effects were observed with the concurrent use of beta-blockers, prazosin or hydralazine, small calcium channel blockers, nitrates, methyldopa, and digitalis-based medications.

Etiological classification of arterial hypertension

Guidelines for use in serious pathologies

The patient should notify doctors about his treatment with Enalaprilat if he is preparing for surgery. If pathologies are present, the solution should be used with caution or not used at all.

Enalaprilat therapy often provokes the re-development of angioedema.
The use of Enalaprilat should be discontinued if the patient has renal artery stenosis.
Severe heart failure and hyponatremia can provoke arterial hypotension during treatment with Enalaprilat.

Transient, occurring during therapy with an ACE inhibitor, is usually transient. Therefore, with proper regulation of blood volume and blood pressure, further use of this medicine is well tolerated by patients. If symptomatic hypotension occurs, the dosage of the medication is reduced or its use is discontinued.

Contraindications and side effects

The following factors are unconditional contraindications for the use of Enalaprilat solution:

pregnancy and breastfeeding (if a woman needs treatment, feeding should be stopped);
age under 18 years;
various types of porphyria (hereditary pathology of pigment metabolism);
excessive sensitivity to Enalaprilat, including cases of angioedema.

Not contraindicated, but use with caution is recommended in certain cases:

with aortic or mitral stenosis;
with thrombocytopenia and other types of myelosuppression;
renal failure;
obstructive hypertrophic cardiomyopathy;
in diabetics;
in patients with CHF;
with hyponatremia;
cerebrovascular pathologies;
after surgery related to kidney transplantation and other pathologies.

Enalaprilat should not be used by elderly people (over 65 years of age), as well as those on hemodialysis or on a diet that limits salt intake.

Side effects

Sometimes therapy with Enalaprilat leads to the development of side effects:

disorders in the heart and vascular system - hypotension, manifestations of insufficiency, embolism (blockage of blood vessels), angina pectoris and heart attack;
disorders in the nervous system - peripheral neuropathy, anxiety, headaches;
respiratory disorders - bronchospasm, pneumonia, cough;
in the digestive organs - nausea, dysfunction of the pancreas, liver, epigastric pain;
in the epithelium - to exfoliative dermatitis, rashes and other skin pathologies;
in the genitourinary system - to renal failure, oliguria, proteinuria, loss of libido;
others - to angioedema of the larynx, anaphylactoid reactions, convulsions.

At the slightest sign of the development of undesirable effects, the use of Enalaprilat should be suspended.

Enalaprilat and Enalapril - what is the difference?

Despite the similarity in names, the drugs Enalaprilat cannot be called synonyms.

Both medications are called ACE blockers, but they are a prodrug that, as a result of metabolism, forms an active metabolite - actually, Enalaprilat. That is, one remedy is, as it were, a precursor to the next.
Administration of Enalaprilat is possible only intravenously as an injection, since, taken orally, it remains inactive and is poorly absorbed.
Enalapril, on the contrary, has only a tablet form, almost 60% is absorbed through the gastrointestinal tract.
Enalapril is intended for daily use to correct blood pressure, and Enalaprilat is used in emergency cases.

The pharmacological names of Enalapril and Enalaprilat also indicate the difference between the drugs. In the Latin recipe, the first is written as Enalaprilum and the second as Enalaprilatum.

APPROVED

By order of the chairman
Committee for Control of Medical and

Pharmaceutical activities
Ministry of Health

Republic of Kazakhstan

From "_____"_______201__

№ ______________

Instructions for medical use

Medicine

Tradename

International nonproprietary name

Enalaprilat

Dosage form

Solution for intravenous administration, 1.25 mg/ml

Compound

1 ml contains

active substance- enalaprilat 1.25 mg,

Excipients: benzyl alcohol, sodium chloride, sodium hydroxide, water for injection.

Description

Transparent, colorless solution

Pharmacotherapeutic group

Angiotensin converting enzyme (ACE) inhibitors.

ATX code C09AA

Pharmacological properties

Pharmacokinetics

Absorption

Enalaprilat is poorly absorbed after oral administration and is practically

Inactive, therefore used exclusively intravenously.

Distribution

After intravenous administration, maximum concentration is reached after 15 minutes, the drug is rapidly distributed among most tissues and reaches high concentrations in the lungs, kidneys and blood vessels. However, there is no evidence that therapeutic doses penetrate the brain. The binding to plasma proteins is about 50-60%. Circulates in the blood unchanged.

Penetrates poorly through the blood-brain barrier.

Metabolism

Enalaprilat is not metabolized; 100% of enalaprilat is excreted in the urine.

Removal

Enalaprilat is excreted primarily through the kidneys (more than 90%). Excretion is a combination of glomerular filtration and tubular secretion. The half-life is 4 hours. The half-life is approximately 35 hours.

For renal failure

In patients with renal failure, the duration of action of enalaprilat is prolonged. Elimination is slowed, so doses must be adjusted according to renal function. Enalaprilat can be removed from the systemic circulation by hemodialysis. The clearance of enalaprilat by dialysis is 1.03 ml/sec (62 ml/min), the concentration of enalaprilat in the blood serum after 4-hour hemodialysis is reduced by 45-75%.

Pharmacodynamics

The hypotensive effect and hemodynamic effects of ENAP® R in patients with high blood pressure are the result of dilation of resistant vessels and a decrease in total peripheral resistance, resulting in a gradual decrease in blood pressure. However, heart rates and cardiac output usually remain unchanged. After intravenous injection, the effect of ENAP® R occurs within 5 - 15 minutes, the maximum effect is achieved within 1 - 4 hours and lasts for 6 hours.

Indications for use

Hypertensive crisis

Arterial hypertension in cases where oral treatment

Impossible

Hypertensive encephalopathy

Directions for use and doses

For patients taking diuretics, the initial dose is 1/2 ampoule (0.625 mg). If 1 hour after administration the therapeutic effect is unsatisfactory, the same dose can be re-administered, and after 6 hours treatment with the full dose is continued (1 ampoule every 6 hours).

Dosage for renal failure

For patients with creatinine clearance above 0.5 ml/s (30 ml/min, plasma creatinine below 265 µmol/l), the initial dose is 1 ampoule (1.25 mg) every 6 hours.

Dosage for hemodialysis

Side effects

Very common (≥1/10):

Blurred vision

Dizziness

Dry non-productive cough

Nausea

Asthenia

Often (from ≥1/100 to<1/10):

Headache

Hypotension (including orthostatic hypotension), syncope, chest pain,

Rhythm disturbances, angina pectoris, bradycardia, tachycardia, acute left ventricular

Daughter failure

Diarrhea, abdominal pain, changes in food taste

Depression

Rash, hypersensitivity/Quincke's edema

Hypotension (including orthostatic hypotension)

Fatigue

Hyperkalemia, increased plasma creatinine

Uncommon (from ≥1/1,000 to<1/100):

Anemia (including aplastic and hemolytic)

Hypoglycemia

Paresthesia, dizziness

Tinnitus

Cardiopalmus

Rhinorrhea, sore throat and hoarseness, bronchospasm/asthma

Intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation,

Anorexia, gastric irritation, dry mouth, peptic ulcer

Confusion, drowsiness, insomnia, nervousness

Sweating, itching, urticaria, alopecia

Renal dysfunction, renal failure, proteinuria

Impotence

Muscle cramps, flushing, tinnitus, general malaise,

Fever

Increased plasma urea, hyponatremia

Rarely (≥1/10.0000 to<1/1,000):

Neutropenia, decrease in hemoglobin and hematocrit, thrombocytopenia,

Agranulocytosis, leukopenia, bone marrow suppression,

Pancytopenia, enlarged lymph nodes, autoimmune diseases

Nightmares, sleep disorders

Pulmonary infiltrates, rhinitis, allergic alveolitis/eosinophilic

Pneumonia

Stomatitis/aphthous ulcer, glossitis

Liver failure, hepatitis - hepatocellular or

Cholestatic; hepatitis, including necrosis; cholestasis, including jaundice

Erythema multiforme, Stevens-Johnson syndrome, exfoliative

Dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma

Oliguria

Gynecomastia

Raynaud's phenomenon

Increased liver enzymes, increased plasma bilirubin

Very rarely (<1/10,000):

Intestinal Quincke's edema

Not known (cannot be estimated based on available data):

If serious side effects occur, treatment should be stopped.

Contraindications

Hypersensitivity to enalapril, enalaprilat or any

Excipient or other ACE inhibitors

Angioedema: history related to previous

The use of ACE inhibitors; hereditary or idiopathic

Porphyria

Conducting hemodialysis using high-flow membranes

(for example, AN 69), LDL apheresis with dextran sulfate, desensitization

From wasp or bee venom

Pregnancy (especially in the 2nd and 3rd trimesters) and lactation period

Children and adolescents up to 18 years of age

Drug interactions

Enalaprilat is a metabolite of enalapril. Therefore, during treatment with enalaprilat, the same interactions as during treatment with enalapril may occur.

Potassium-sparing diuretics, potassium supplements

If simultaneous use is necessary due to hypokalemia, they should be used with caution and with frequent monitoring of plasma potassium levels.

Diuretics (thiazide or loop diuretics)

Other antihypertensive drugs

Tricyclic antidepressants and/or antipsychotics/anaesthetics/narcotics

Concomitant use of certain anesthetics, tricyclic antidepressants and antipsychotic drugs with ACE inhibitors may lead to an additional decrease in blood pressure.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Antidiabetic drugs

Epidemiological studies have shown that the simultaneous use of ACE inhibitors and antidiabetic drugs (insulin, oral hypoglycemic agents) may cause an increased glucose-lowering effect with a risk of hypoglycemia. This phenomenon is more often observed during the first weeks of combination treatment and in patients with renal failure.

Alcohol

Alcohol enhances the hypotensive effect of ACE inhibitors.

Sympathomimetics

Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.

Acetylsalicylic acid, thrombolytics and ß-blockers

Concomitant use of enalapril with acetylsalicylic acid

(in cardiac doses), thrombolytics and beta-blockers are safe.

special instructions

Symptomatic hypotension

Symptomatic hypotension is rare in patients with uncomplicated hypertension, but may occur in patients with fluid deficiency (diuretic therapy, salt-restricted diet, hemodialysis, diarrhea or vomiting). Symptomatic hypotension may occur in patients with heart failure with or without associated renal failure. It may also occur in patients with more severe heart failure who are taking high-dose loop diuretics, hyponatremia, or renal failure. In these patients, initiating treatment and changing the dose of enalapril and/or diuretic should be done under close medical supervision. Similar precautions should be taken when treating patients with angina or cerebrovascular disease, where an excessive decrease in blood pressure can lead to myocardial infarction or stroke.

Aortic and mitral valve stenosis, hypertrophic cardiomyopathy

Like all vasodilators, ACE inhibitors should be used with caution in the treatment of patients with left ventricular outflow tract obstruction and to avoid cases of cardiogenic shock and hemodynamically significant left ventricular outflow tract obstruction.

Renal dysfunction

Plasma creatinine and potassium levels should be monitored regularly.

In patients with severe heart failure or latent kidney disease, including renal artery stenosis, renal failure may occur during treatment with enalapril. With prompt and appropriate treatment, it is usually reversible.

In some patients with invisible but pre-existing kidney disease,

After taking enalapril simultaneously with diuretics, slight and transient increases in plasma urea and creatinine levels appeared. Therefore, it may be necessary to reduce the dose of the ACE inhibitor and/or discontinue diuretics. This situation provokes the appearance of latent renal artery stenosis.

Renovascular hypertension

Kidney transplantation

Due to lack of experience, treatment with enalapril is not recommended for patients who have recently undergone renal transplantation.

Liver failure

Neutropenia and agranulocytosis

Enalaprilat should be used very carefully in patients with collagen diseases (for example, systemic lupus erythematosus, scleroderma), concomitantly receiving immunosuppressant therapy, allopurinol or procainamide, as well as a combination of these factors, especially with existing renal impairment. Some of these patients may develop severe infections that do not respond to intensive antibiotic therapy. When prescribing the drug to such patients, 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 and angioedema

Angioedema of the face and lips usually does not require treatment; antihistamines can be used to relieve the patient's symptoms.

Patients with a history of angioedema unrelated to ACE inhibitor therapy are at increased risk of angioedema when taking ACE inhibitors.

Anaphylactoid reactions during desensitization

Anaphylactoid reactions during LDL apheresis

Life-threatening anaphylactoid reactions have rarely occurred in patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis with dextran sulfate. The development of these reactions can be avoided by temporarily discontinuing the ACE inhibitor before each apheresis procedure.

Patients on hemodialysis

Patients with diabetes mellitus

In patients with diabetes mellitus receiving oral antidiabetic agents or insulin, blood sugar levels should be carefully monitored during the first month of treatment with ACE inhibitors.

During treatment with ACE inhibitors, a persistent, dry, nonproductive cough may occur, which resolves after discontinuation of therapy. This should be considered as part of the differential diagnosis of cough.

Surgery and anesthesia

Hyperkalemia

Plasma potassium levels may increase in some patients during treatment with ACE inhibitors, including enalapril and enalaprilat. Patients with renal failure, diabetes mellitus, and patients concomitantly taking potassium-sparing diuretics, potassium supplements, and other drugs that can lead to hyperkalemia (such as heparin) are at increased risk of developing hyperkalemia. If concomitant use of enalapril with any of the above-mentioned agents is advisable, it is recommended to regularly monitor plasma potassium levels.

The combined use of lithium and enalapril is not recommended.

Pregnancy and lactation

During pregnancy, the use of ACE inhibitors should not be started. As long as treatment with ACE inhibitors is necessary, patients planning pregnancy should switch to alternative antihypertensive drugs that have an established safety profile for use during pregnancy. If pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately and, if appropriate, alternative treatment initiated. Taking ACE inhibitors in the second and third trimesters of pregnancy is known to cause fetotoxicity (decreased renal function, oligohydramnios, delayed cranial ossification) and neonatal toxicity (renal failure, hypotension, hyperkalemia) in humans. If ACE inhibitors were taken in the second trimester of pregnancy, it is recommended to perform an ultrasound of the kidneys and skull. Infants whose mothers took ACE inhibitors should be closely monitored for hypotension.

Ethnic differences

Special information about some ingredients

Enap® R injection solution contains benzyl alcohol, which can cause toxic and anaphylactoid reactions in infants and children up to

3 years. It should not be used in premature or newborn babies.

This medication contains less than 1 mmol sodium (23 mg) per dose and is therefore "sodium free".

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

There are no data on the impact on driving vehicles and operating machinery.

Overdose

Symptoms: excessive decrease in blood pressure up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications, convulsions, stupor.

Treatment: ingestion of saline solution, epinephrine (subcutaneously or intravenously), antihistamines, glucocorticosteroids (intravenously), intravenous administration of plasma expanders, angiotensin II, hemodialysis (administration rate - 62 ml/min).

Representative office of “KRKA, tovarna zdravil, d.d., Novo mesto” in the Republic of Kazakhstan

Even many hypertensive patients who take the drug of the same name in tablet form do not know about Enap injection solution. But in the form of a solution, the medicine is not often used, only to provide emergency medical care. But when are Enap injections given? What effect does the medicine have on the body with this method of administration?

A colorless transparent solution for injection from the group of ACE inhibitors is available in ampoules of 1 ml and contains 25 mg of the main active ingredient enalapril. When the medication enters the bloodstream, it enters into a chemical reaction with blood components. The reaction occurs in several stages:

Enap, entering the blood, is transformed by an enzyme into enalaprilat;

then Enaprylat is converted into inactive Angiotensin;
the following enzymatic reaction activates the action of the substance Angiotensin.

Active Angiotensin affects vascular tone, causing relaxation of the vessel wall, and helps to lower A/D. The drug administered by injection acts quickly, all chemical reactions in the blood take place in a few minutes and already 5-7 minutes after administration the patient feels an improvement in well-being.

Additional substances

In addition to the main active ingredient Enalapril, the medical solution contains:

Benzyl alcohol. It does not have any effect on the adult body and after Enap injections it is not prohibited to work with moving mechanisms or drive. But benzyl alcohol is toxic to young children and to the fetus during fetal development.
Sodium chloride. The sodium content in the solution is minimal and does not have any effect on the body.

Additional components are taken into account only when prescribing the drug to pregnant women, lactating women or for certain diseases. But not only benzyl alcohol affects the fetus or newborn child; the influence of ACE inhibitors is also dangerous for the child’s body, and pregnant women are prescribed the medicine only when it is impossible to stabilize hypertension with a drug that is safer for the fetus.

Effect on the body

The medication is administered intravenously and begins to act 3 minutes after entering the bloodstream and reaches its maximum therapeutic effect after an hour. Under its influence:

blood pressure decreases;
coronary blood flow is stabilized and blood supply to the myocardium is improved;
metabolism in cardiac muscle cells is stimulated;
myocardial contractility increases;
pressure in the pulmonary vessels decreases;
signs of left ventricular hypertrophy decrease;
kidney performance increases.

However, the medicine does not affect:

heart rate;
glucose metabolism;
functioning of the reproductive system.

After intravenous administration, the drug is completely eliminated from the body through the urinary system within 6 hours.

The contents of the ampoule are diluted with a 5% glucose solution or 0.9% sodium chloride solution (saline). The instructions for use indicate that the diluted drug should be administered very slowly and only qualified medical personnel should do this in a hospital setting. 2 administration options are allowed:

Intravenously slowly. The contents of the ampoule are diluted in 2 ml of one of the above solutions and slowly injected into a vein over 5 minutes.
Intravenous drip. The product is diluted into a bottle with glucose or saline and dripped into the patient at a moderate speed for 30-40 minutes.

When providing first aid, if improvement does not occur within an hour, the medication is re-administered in the same dosage. But the daily dose of the active substance enalapril, unless there are special restrictions, should not be more than 5 mg (2 ampoules) per day.

Restrictions on the use of the product

With caution, Enap injection is prescribed to hypertensive patients in the following cases:

constant use of diuretics;
chronic renal failure (for this pathology, the dosage is selected individually taking into account serum createnine levels).
hemodialysis;
any kidney disease, if the patient has only one;
bilateral renal artery stenosis;
condition after kidney surgery;
aortic or mitral stenosis;
heart failure;
cardiomyopathy;
blood diseases;
systemic connective tissue lesions;
diabetes;
insufficiency of liver function (use of the drug by injection can cause hemolytic jaundice);
elderly age.

In all of these cases, injection administration of the medication is not prohibited, but the dosage is selected individually and will be much lower than the instructions for use indicate.

When is intravenous administration necessary?

Enap tablets are well absorbed from the gastrointestinal tract and reach their maximum concentration in the blood plasma after 4 hours. Thanks to such successful use of the tablet form, the medication is used in injections extremely rarely. Indications for intravenous administration will be:

high hypertension;
encephalopathy that developed against the background of hypertension;
inability to take medication in tablets.

Injections are given only in the acute period of the disease, then the patient is gradually transferred to taking medications in tablets.

Absolute contraindications

Despite the fact that Enap successfully reduces A/D and improves heart and kidney function, its use is prohibited in the following cases:

angioedema;
acute renal failure;
a bee or wasp sting that occurred within the last 3 days (enalapril is temporarily contraindicated in the presence of the poison of these insects in the body);
porphyria;
pregnancy and lactation;
individual intolerance to the drug;
children under 18 years of age;
the use of certain types of membranes during hemodialysis.

The use of Enap in childhood has a negative effect on the development of the cardiovascular and urinary systems. Children whose mothers received Enap injections during pregnancy or lactation for emergency reasons are carefully monitored by doctors for timely disruption of organ function.

If a nursing woman needs to take Enalapril injections to maintain her health, she is advised to stop breastfeeding for the duration of treatment.

Overdose or rapid administration of medication

Exceeding a single dose of the drug can happen if the patient was unconscious or, when collecting anamnesis, did not indicate that he has diseases that prohibit the use of Enap in a standard therapeutic dosage, as well as if he had previously taken tablets from this group. In case of an overdose of the drug, a person may develop the following complications:

collapse, in severe cases may be complicated by cardiac arrest;
heart attack;
convulsive syndrome (it will differ from epileptic syndrome in the absence of warning signs);
thromboembolism of large arteries (usually pulmonary);
confusion.

The same complications can develop in humans with rapid administration of a medicinal solution. If one of the above signs appears, the patient needs to be administered ACE antidotes and undergo hemodialysis (purification of plasma from the active Angiotensin contained in it). Next, you need to carry out treatment to help relieve the symptoms that have arisen.

Symptomatic therapy is prescribed depending on how the developed complication manifests itself and what disturbances have occurred in the functioning of the organs.

Side effects when using the medicine

If the rules for intravenous administration are followed, then with a single use of the medication, side effects occur very rarely.

In some cases, you may develop:

Cardiac dysfunction. Usually various rhythm disturbances (arrhythmias, tachy and bradycardia) occur, and pulmonary embolism develops less frequently. Cardiovascular disorders are one of the most common adverse reactions with Enap injections.
Neurological disorders can be different. The most commonly observed are cerebral signs (migraine-like headaches, loss of coordination, dizziness, vision problems), less commonly observed sleep disturbances (insomnia or, conversely, increased drowsiness), confusion and various parasthesias. If sensitivity to the components of the drug is increased, the person may develop depressive syndrome.
Disorders of the gastrointestinal tract are manifested by nausea, vomiting, and intestinal dyspepsia. If the medicine is not stopped in a timely manner, the person will experience a loss of appetite and may develop an aversion to food.
The respiratory system may, in response to the administration of the medication, give a reaction such as the development of a dry non-productive cough, increased breathing, or the appearance of signs of rhinitis. Some patients experience hoarseness and sometimes aphonia.
Renal dysfunction may be manifested by changes in the filtration of the renal tubules. In this case, in a biochemical blood test, an increase in urea and createnine will be noted, and there may be pronounced proteinuria in the urine. Oliguria or anuria may develop, which will cease after discontinuation of the medication. If urinary retention continues for a long time, drug treatment may be required.
A change in the water-salt balance is possible when the sodium content in the plasma decreases or the amount of potassium increases.
With a side effect on the musculoskeletal system, pain and limited joint mobility occur; in addition, pain in the bones may occur. In case of individual hypersensitivity to the active component, symptoms of acute arthritis may appear.
Allergic reactions may include hives, swelling, or hemorrhagic rash. In severe cases, anaphylactic shock or the development of swelling of the larynx and glottis is possible.
Decreased sexual function. There is a decrease in attraction to the opposite sex, but the functioning of the reproductive system and hormonal levels are not disturbed. Impotence in men can develop only if sexual dysfunction has previously been observed when taking tablets with Enalapril.
Violation of thermoregulation. You may feel very hot or sweaty. It is noted that the side effect of hot flashes is more often observed in middle-aged women, and sweating in men.

If adverse reactions occur, the administration of the medication should be stopped and the patient should be given ACE antidotes. In case of laryngeal edema or anaphylactic shock, resuscitation measures should be started immediately.

The danger of injections lies in the fact that if side effects almost always develop slowly when taking tablets, then if they enter the bloodstream directly, the medication can provoke the development of an acute reaction that is dangerous for human life; this feature makes intravenous administration of Enap possible only in hospital conditions.

Interaction with other substances

Like any chemical compound, the active ingredient of the drug, when combined with other medications or products, can act stronger or weaker in the fight against a hypertensive crisis:

Diuretics. They enhance the hypotensive effect of Enap and contribute to a strong decrease in fluid in the bloodstream. If the patient takes diuretic drugs for a long time, the single therapeutic dose of the antihypertensive drug is reduced.
Analgesics from the group of opiates. Opium-type narcotic analgesics enhance the effect of active Angiotensin on blood vessels. The combined administration of enalapril and opiates can provoke the development of collapse.
Hormonal drugs. The effect of hormones, especially those used to correct the hormonal background of the reproductive system of men and women, has an inhibitory effect on the reaction of transformation of Enap into active Angiotensin and the therapeutic effect of the administration of the drug is greatly reduced.
Salt. In hypertensive patients who abuse salty foods, A/D after the administration of the medication decreases poorly or does not decrease at all.
Potassium-containing medications. When Enap is used together with medications containing potassium, the risk of hyperkalemia increases.
Medications containing lithium, when taken simultaneously with Enalapril, can cause intoxication with lithium salts. Lithium intoxication is reversible and disappears after stopping both medications.
Antihyperglycemic drugs. Angiotensin, which appears during enzymatic transformations in the blood, increases the hypoglycemic effect of drugs. For diabetes mellitus, Enap is prescribed intravenously with caution, monitoring blood glucose levels.
Simultaneous administration of cytostatics or immunosuppressants with Enalapril can suppress the function of hematopoiesis in the bone marrow.
Non-steroidal anti-inflammatory drugs in combination with Enap provoke the development of acute heart or kidney failure.
Anesthesia. Some drugs for intravenous anesthesia prevent the full flow of chemical blood and inactive Angiotensin does not turn into active. The medication simply does not have a therapeutic effect.
Alcohol enhances the effect of Enalapril. If Enap is administered intravenously to a hypertensive patient who has taken a little alcohol, this can cause collapse.

But most medications that are used in the treatment of diseases associated with hypertension can be combined with Enap injections. The medicine can be administered if the patient has taken:

cardiac glycosides;
beta blockers;
nitrates (used to relieve angina attacks);
calcium channel blockers;
aspirin;
anticoagulants;
thrombolytic agents.

These drugs do not affect the therapeutic effect of Enalapril.

Drug analogues

Analogues of Enap can be divided into 2 groups:

contain substances that have a similar effect on the human body as Enalapril (prescribed when Enap cannot be used for treatment).

Drugs in this group are produced by various companies and may differ from Enap in the amount of active substance and the presence of additional components in the solution. Before using them, you should always clarify the therapeutic dosage for the patient. The most commonly used analogues for treatment are:

Berlipril;
Enam;
Enalapril-Acri;
Enoloside mono;
Renitek.

As mentioned above, they all have a similar effect to Enap and can replace each other during treatment. But, when replacing a drug, you must always take into account the content of the active component in the solution. It cannot exceed a single therapeutic dose for administration, but can be reduced. Some pharmacological companies produce separate ampoules with the dosage recommended for heart and kidney pathologies (it is much lower).

Analogues of other groups

They are used to treat patients when the use of Enalapril is prohibited or adverse reactions have occurred after administration of the medication. The following can be used for treatment:

Vitopril;
Diraton;
Irumed;
Lisinopril;
Lizoril;
Ramizes.

The list of drugs that have an effect similar to Enap is large, but only a doctor can select an analogue for a replacement, taking into account the general condition of the patient and laboratory test data.

Enap, an injection solution, is not used often, only for the treatment of severe conditions. Injection therapy does not last long, no more than 48 hours, after which the patient is transferred to the tablet form of the drug. But those who want to be treated at home, even if they have friends who know how to give intravenous injections, should remember that injections should only be carried out under strict medical supervision. Complications caused by an overdose or rapid administration of a medication without timely resuscitation measures can be fatal.

active substance: enalaprilat;

1 ml contains 1.25 mg of enalaprilat;

Excipients: benzyl alcohol, sodium chloride, sodium hydroxide, water for injection.

Dosage form

Injection.

Pharmacological group

Agents acting on the renin-angiotensin system. ACE inhibitors.

ATC code C09A A02.

Indications

Arterial hypertension, hypertensive crisis.

Enalaprilat is indicated for the treatment of hypertension in cases where oral treatment is not possible.

Contraindications

Hypersensitivity to enalapril, enalaprilat, other ACE inhibitors or to any components of the drug;
A history of angioedema associated with previous treatment with ACE inhibitors;
Hereditary or idiopathic angioedema.

Directions for use and doses

For use by adults.

Enap ® solution for injection should be administered intravenously in a slow stream over at least 5 minutes. It can also be administered diluted in 50 ml of 5% glucose, 0.9% sodium chloride (saline), 5% glucose in 0.9% sodium chloride, or 5% glucose in lactated Ringer's solution.

The recommended dose for the treatment of arterial hypertension and hypertensive crises (acute increase in blood pressure) is 1.25 mg of enalaprilat (1 ampoule) every 6:00. When switching from enalapril treatment to enalaprilat treatment, the usual dose is 1 ampoule (1.25 mg) every 6:00.

Treatment with enalaprilat usually lasts 48 hours. After this, the patient should be transferred to therapy with enalapril tablets. When switching from parenteral enalaprilat treatment to oral enalapril treatment, the recommended starting dose is 5 mg once daily for patients who have already been administered 1 ampoule (1.25 mg) of enalaprilat every 6 hours. If necessary, the dose can be increased. For patients who were initially treated with half the usual dose of enalaprilat (0.625 mg), the recommended dose when switching to oral treatment is 2.5 mg enalapril per day.

Kidney failure.

Doses of enalaprilat for patients with chronic renal failure depend on creatinine clearance.

For patients with a creatinine clearance of more than 0.5 ml/sec (serum creatinine - up to 265 µmol/l), prescribe the usual doses of enalaprilat 1.25 mg (1 ml) every 6:00. For patients with creatinine clearance below 0.5 ml/sec (serum creatinine greater than 265 µmol/L), an initial dose of 0.625 mg (0.5 ml) is prescribed. If the clinical effect is unsatisfactory after an hour, the same dose should be re-administered. Continue treatment at the full dose of 1.25 mg every 6:00.

Dosing for hemodialysis.

Dosage for patients treated with diuretics.

For patients treated with diuretics, the recommended starting dose is 0.625 mg (0.5 ml). If the clinical effect is unsatisfactory after an hour, the dose of 0.625 mg (0.5 ml) can be repeated. Subsequent doses of 1.25 mg are given every 6:00.

Adverse reactions

Enalaprilat is a metabolite of enalapril. Therefore, during treatment with Enap ® injection solution, the same side effects may occur as during treatment with Enap ® tablets or other ACE inhibitors.

In controlled clinical trials of enalaprilat, the most common adverse effect in hypersensitivity patients was hypotension (1.8%). Side effects that occurred in more than 1% of patients also included headache (2.9%) and nausea (1.1%). Less common side effects, occurring in 0.5% to 1% of patients, were myocardial infarction, fatigue, dizziness, fever, skin rash and constipation.

From the blood and lymphatic system:

anemia (including aplastic and hemolytic), neutropenia, decreased hemoglobin, decreased hematocrit, thrombocytopenia, agranulocytosis, suppression of bone marrow function, pancytopenia, lymphadenopathy, autoimmune diseases.

From the endocrine system:

syndrome of impaired ADH secretion.

Metabolism:

hypoglycemia.

From the nervous system and mental disorders:

headache, depression, confusion, drowsiness, insomnia, nervousness, paresthesia, dizziness, abnormal dreams, sleep disturbances.

From the organs of vision:

blurred vision.

From the heart and vascular systems:

dizziness, hypotension (including orthostatic hypotension), syncope, myocardial infarction or stroke, possibly due to severe hypotension in patients at increased risk, chest pain, cardiac arrhythmias, angina pectoris, tachycardia, orthostatic hypotension, tachycardia, Raynaud's phenomenon.

From the respiratory system, chest and mediastinum:

cough, shortness of breath, rhinorrhea, sore throat, dysphonia, bronchospasm/asthma, pulmonary infiltration, rhinitis, allergic alveolitis/eosinophilic pneumonia.

From the digestive tract:

nausea, diarrhea, abdominal pain, change in taste, intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, anorexia, stomach irritation, dry mouth, peptic ulcers, stomatitis/canker sores, glossitis, edema.

From the liver and gallbladder:

liver failure, hepatitis - hepatocellular or cholestatic, hepatonecrosis, cholestasis, including jaundice.

For the skin and subcutaneous tissues:

rash, hypersensitivity/angioedema Angioedema of the face, extremities, lips, tongue, glottis and/or larynx, sweating, pruritus, urticaria, alopecia, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxicodermal necrolysis, pemphigus, erythroderma have been reported .

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

Exanthema, photosensitivity and other skin changes may occur.

From the kidneys and urinary tract:

renal dysfunction, renal failure, proteinuria, oliguria.

From the reproductive system and mammary glands:

impotence, gynecomastia.

General violations:

asthenia, fatigue, muscle cramps, hot flashes, ringing in the ears, discomfort, fever.

Laboratory indicators:

hyperkalemia, increased serum creatinine, increased blood urea levels, hyponatremia, increased liver enzymes, serum bilirubin.

If severe side effects occur, treatment should be stopped.

Overdose

The most likely manifestation of an overdose is arterial hypotension. If hypotension develops, the patient should be placed in the supine position and, if necessary, the patient's plasma volume should be adjusted with an infusion of isotonic sodium chloride solution.

During treatment of overdose, the patient's blood pressure, respiratory rate, blood potassium concentration, and diuresis should be monitored.

Temporary hypotension is not a contraindication for treatment with enalaprilat. Once blood pressure and plasma volume have stabilized, patients usually tolerate this dose (1 ml/1.25 mg). In severe cases, the use of angiotensin II is recommended.

Enalaprilat can be removed from the general circulation using hemodialysis. During hemodialysis, the clearance of enalaprilat is 38-62 ml/min; after four hours of hemodialysis, serum enalaprilat concentrations are reduced by 45-57%.

Use during pregnancy or breastfeeding.

When planning pregnancy or if pregnancy is diagnosed, the drug should be discontinued as soon as possible, unless its use is considered vital for the mother.

A retrospective epidemiological study found that neonates whose mothers used an ACE inhibitor during the first trimester of pregnancy had an increased risk of developing major birth defects compared with neonates who were not exposed to an ACE inhibitor during the first trimester. The incidence of birth defects is small and the data from this study have not been re-validated. In addition, prematurity, intrauterine growth restriction, and patent ductus arteriosus have been reported; however, a definitive relationship with ACE inhibitor use has not been established.

ACE inhibitors can cause disease and death of the fetus or newborn when used by women during the second and third trimesters of pregnancy.

The use of ACE inhibitors during this period was associated with adverse effects on the fetus and newborn, including hypotension, renal failure, hyperkalemia, and/or neonatal calvarial hypoplasia. As a result of decreased fetal renal function, oligohydramnios may develop. This complication can lead to contracture of the limbs, deformation of the craniofacial region and pulmonary hypoplasia.

When prescribing Enap ®, it is necessary to inform the patient about the potential harm to the fetus.

In cases where the administration of the drug during pregnancy is considered necessary, periodic ultrasound examinations should be performed to assess the intra-amniotic space. If oligoamnion is detected, Enap ® should be discontinued, except in cases where its use is considered vital for the mother. However, both doctors and patients need to be aware that oligoamnion can develop after irreversible damage has occurred in the fetus.

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

Infants whose mothers took ACE inhibitors should be carefully monitored for hypotension, oliguria, and hyperkalemia. Enalapril, which has the ability to penetrate the placenta, can be partially eliminated from the newborn's body by peritoneal dialysis; theoretically it can be removed by exchange transfusion, although there is no experience with the latter procedure.

Enalapril and enalaprilat pass into breast milk, but their effect on the infant receiving breast milk is uncertain. Mothers are not advised to breastfeed during treatment with ACE inhibitors.

Children

Enap ® injection solution should not be used in children due to insufficient data regarding the effectiveness and safety of use.

Features of application

Parenteral enalaprilat rapidly reduces high blood pressure and improves heart function.

Symptomatic hypotension.

Hypertensive patients with severe heart failure, hyponatremia and/or hypovolemia through diuretic therapy, as a result of salt-free diet and dialysis, or through diarrhea and vomiting constitute a subgroup of patients whose blood pressure is dependent on renin and activation of the renin-angiotensin system.

In such patients, as well as in elderly patients and patients with impaired renal function, hypotension with all clinical consequences (from dizziness and nausea to acute renal failure, stroke or myocardial infarction) may occur even several hours after taking the first dose of enalaprilat.

Arterial hypotension and its severe consequences are isolated and reversible phenomena. They can be avoided by stopping treatment with diuretics and eating a low-salt diet before starting Enap ® treatment, if possible.

If treatment with enalaprilat cannot be stopped in all these patients, it is recommended to begin diuretic treatment cautiously, with a low dose (0.625 mg).

Aortic or mitral valve stenosis/hypertrophic cardiomyopathy

Use this medication with caution in patients with aortic stenosis or idiopathic hypertrophic subaortic stenosis and atherosclerosis. Hypotension in such patients can lead to hypoperfusion and ischemia of the heart, brain and kidneys. Patients with peripheral vascular disease or atherosclerosis may have renal vascular disease without clinical manifestation. Treatment of such patients with enalaprilat should be started very carefully, with a lower dose (0.625 mg).

ACE inhibitors should be administered cautiously to patients with left ventricular outflow tract obstruction and avoided in cases of cardiogenic shock and hemodynamically significant left ventricular outflow tract obstruction.

Renal dysfunction.

Patients with impaired renal function (creatinine clearance

In patients with severe heart failure or impaired renal function, including renal artery stenosis, renal failure may occur when treated with enalapril. If a diagnosis is made quickly and appropriate treatment is prescribed, the phenomenon is usually reversible.

In some patients, in the absence of clear symptoms of kidney disease, a slight and transient increase in serum urea and creatinine levels may be observed when enalapril is administered concomitantly with diuretics. A dose reduction of ACE inhibitors and/or discontinuation of diuretics may be required. This situation may indicate the possibility of renal artery stenosis.

Renovascular arterial hypertension.

Patients with bilateral renal artery stenosis, vasodilation of postglomerular efferent arterioles may have temporary renal dysfunction or even acute renal failure.

Patients with solitary kidney stenosis may experience temporary renal dysfunction or even acute renal failure in the affected kidney. Therefore, the assessment of a patient with hypertension should always include an assessment of renal function. Treatment of renovascular hypertension should only be carried out by an experienced specialist.

kidney transplant

There is insufficient data on the treatment of patients with recent kidney transplantation with enalapril, therefore treatment with enalapril in patients in this group is not recommended.

Liver failure.

If jaundice or marked increases in liver enzyme levels occur during treatment with ACE inhibitors, treatment should be stopped immediately, the patient should be closely monitored and treatment should be prescribed if necessary.

Neutropenia/agranulocytosis.

The possibility of developing neutropenia or agranulocytosis cannot be completely excluded, so it is recommended to regularly do a complete blood count. Enalapril should be used very cautiously in patients with collagen vascular disease (eg, systemic lupus erythematosus, scleroderma), concomitantly with antidepressants, allopurinol or procainamide, or a combination of these factors, especially if there is already impaired renal function. Some of these patients may develop a serious infection that sometimes does not respond to intensive antibiotic therapy. If enalapril/enalaprilat is used in such patients, periodic analysis of the white blood cell count is recommended.

Hypersensitivity/angioedema.

In rare cases, during treatment with enalaprilat, angioedema of the face, extremities, lips, tongue, glottis and/or larynx develops. This can happen at any time during treatment. In such cases, treatment should be discontinued, antihistamines should be prescribed and the patient should be monitored appropriately to ensure that all symptoms of hypersensitivity have completely disappeared. For angioedema of the tongue without respiratory failure, patients may require long-term observation as treatment with antihistamines and corticosteroids may not be sufficient.

Patients with a history of angioedema associated with ACE inhibitor therapy are at increased risk of developing angioedema while taking ACE inhibitors. Patients with angioedema of the tongue, glottis, and/or larynx are at increased risk for airway obstruction, especially with airway surgery.

Angioedema of the tongue, glottis and/or larynx can lead to airway obstruction, therefore it is necessary to carry out appropriate therapy as soon as possible, which may include subcutaneous administration of a solution of adrenaline 1: 1000 (0.3 ml to 0.5 ml) and measures to ensure patency of the upper respiratory tract.

Black patients who receive ACE inhibitors have been reported to have a higher incidence of tongue angioedema compared with other patients.

Patients with a history of angioedema associated with ACE inhibitor therapy are at increased risk of developing angioedema while taking ACE inhibitors.

Anaphylactoid reactions during desensitization

Patients taking ACE inhibitors during desensitization to aspen or bee venom may rarely experience allergic-like (pseudoanaphylactic) reactions that are life-threatening. Such reactions can be avoided by temporarily suspending ACE inhibitor therapy before each desensitization.

Anaphylactoid reactions during low-density lipoprotein apheresis

Patients taking ACE inhibitors during low-density lipoprotein apheresis from dextrin sulfate may rarely experience allergic-like (pseudoanaphylactic) reactions that are life-threatening. Such reactions can be avoided by temporarily suspending ACE inhibitor therapy before each apheresis.

Patients undergoing hemodialysis sessions

There have been reports of hypersensitivity, reactions similar to allergic (pseudoanaphylactic) in patients undergoing dialysis sessions using polyacrylonitrile membranes (for example AN 69) and concomitantly taking ACE inhibitors. For such patients, the use of other types of dialysis membranes or a different class of antihypertensive agents should be considered.

hypoglycemia

In diabetic patients taking oral antidiabetic agents or insulin, careful glycemic control is necessary, especially during the first few months of concomitant treatment with ACE inhibitors.

cough

A continuous dry non-productive cough that stops when treatment is stopped may occur during treatment with ACE inhibitors. This should be considered as part of the differential diagnosis of cough.

Surgery/anesthesia

In patients undergoing major surgery or anesthesia with drugs that cause hypotension, enalapril may block the formation of angiotensin II due to compensatory renin release.

If hypotension occurs and is thought to be due to this mechanism, adjustment should be made by increasing blood volume.

hyperkalemia

During treatment with ACE inhibitors, including enalapril, blood potassium levels may increase in some patients. Risk factors for hyperkalemia include renal failure or decreased renal function, age (70 years), diabetes mellitus, intercurrent conditions such as dehydration, acute heart failure, metabolic acidosis, and concomitant use of potassium-sparing diuretics (eg, spironolactone, eplerenone, triamterene, or amiloride). ), food additives containing potassium, or its salts with potassium; or other drugs that cause an increase in serum potassium concentrations (for example, heparin). The use of potassium supplements, potassium-sparing diuretics, or potassium salt substitutes, especially in patients with impaired renal function, may result in significant increases in serum potassium levels. Hyperkalemia can cause serious, sometimes fatal arrhythmias. If concomitant use of these drugs is considered necessary, regular monitoring of serum potassium levels is recommended.

lithium

Pregnancy or breastfeeding

Taking ACE inhibitors should not be started during pregnancy. If continued ACE inhibitor therapy is considered important, patients planning pregnancy should be switched to an alternative antihypertensive treatment that has an established safety profile for use during pregnancy. If pregnancy is detected, treatment with ACE inhibitors should be discontinued immediately and, if possible, alternative therapy should be initiated.

ethnic characteristics

Like all ACE inhibitors, enalapril is less effective in lowering blood pressure in black patients than in non-black patients, possibly due to the greater prevalence of low-renin conditions among black patients with hypertension.

Special warnings regarding inactive ingredients

Enap ® contains benzyl alcohol, which can cause toxic and anaphylactoid reactions in infants and children under 3 years of age. It is contraindicated for premature babies and newborns.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, which is essentially sodium-free.

The ability to influence the reaction rate when driving a vehicle or working with other mechanisms.

Considering the possibility of developing adverse reactions such as dizziness, fainting, hypotension, muscle cramps, confusion, drowsiness, blurred vision, you should be vigilant during activities that require attentiveness.

Interaction with other drugs and other types of interactions

With the simultaneous use of enalaprilat with digitalis, beta-adrenergic receptors, methyldopa, nitrates, calcium channel blockers, hydralazine and prazosin, a slight synergistic effect is observed.

Thus, enalaprilat can be used simultaneously with any other medicines for the treatment of arterial hypertension. Concomitant use with nitroglycerin, other nitrates or other vasoconstrictors may further reduce blood pressure. Enalapril can be safely administered concomitantly with acetylsalicylic acid (in doses according to cardiac indications) and thrombolytics.

Pre-treatment with diuretics in high doses may lead to a decrease in circulating blood volume and an increased risk of excessive hypotension. The hypotonic effect can be reduced by stopping the diuretic or starting therapy with a lower dose (0.625 mg) of enalaprilat. If this dose reduction is insufficient, the potential for hypotension can be minimized by administering a saline infusion before starting enalaprilat treatment. If it is necessary to continue treatment with a diuretic, the patient should be closely monitored for at least 1 hour after the enalaprilat injection.

ACE inhibitors reduce potassium loss caused by diuretics. Potassium-sparing diuretics (eg, spironolactone, triamterene, or amiloride), potassium supplements, or salt substitutes containing potassium may lead to hyperkalemia. If ACE inhibitors and potassium-sparing diuretics are concomitantly used due to overt hypokalemia, they should be used with great caution and serum potassium concentrations should be monitored frequently.

Concomitant use of ACE inhibitors and lithium may result in a temporary increase in serum lithium levels and lithium toxicity. Concomitant use of ACE inhibitors and thiazide diuretics may further increase plasma lithium levels and the risk of lithium toxicity.

Concomitant use of ACE inhibitors and NSAIDs may lead to impaired renal function and/or congestive heart failure and a dry, nonproductive cough. It is believed that the mechanism of this effect is the inhibition of the action of prostaglandins.

It is necessary to monitor renal function and use caution when using enalaprilat and cyclosporine simultaneously.

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

There are also reports of anaphylactic-type reactions in patients treated with enalapril and simultaneously receiving immunotherapy (desensitization) with bee venom.

Thus, enalaprilat should be avoided in patients who are allergic to wasp and bee venom and who are undergoing specific desensitization.

In patients undergoing major surgery or during anesthesia with agents that cause hypotension, enalaprilat may block the formation of angiotensin II from the compensatory release of renin. If there is arterial hypotension that occurs for this reason, it can be corrected by increasing plasma volume.

Concomitant use of ACE inhibitors and antidiabetic drugs (insulin or oral antidiabetic drugs) may cause hypoglycemia. The appearance of this phenomenon is possible during the first weeks of combined treatment and in patients with impaired renal function.

Chronic use of NSAIDs may reduce the antihypertensive effect of ACE inhibitors.

Reactions to nitrites (symptoms include flushing, nausea, vomiting and hypertension) have been rarely reported in patients prescribed gold injection (sodium once) and concomitant ACE inhibitors, including enalapril.

Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.

There are no contraindications for the combination of enalapril maleate with acetylsalicylic acid (in cardiac doses), thrombolytic agents and beta-blockers.

Alcohol enhances the hypotensive effect of ACE inhibitors.

Pharmacological properties.

Pharmacodynamics.

Enalaprilat inhibits ACE, which catalyzes the conversion of angiotensin I to angiotensin II. Suppression of ACE leads to a decrease in angiotensin II concentrations, an increase in plasma renin activity and a decrease in aldosterone secretion.

The antihypertensive effect and hemodynamic effects of enalaprilat in patients with high blood pressure are the result of dilation of resistant vessels and a decrease in overall peripheral resistance, gradually lowering blood pressure. Systolic and diastolic pressure and pressure in the main pulmonary artery decrease, coronary blood flow increases, cardiac index and stroke volume of the heart increase (with a constant heart rate).

After injection, the effect of the drug occurs within 5-15 minutes, the maximum effect occurs after 1-4 hours, and its effect lasts for approximately 6:00.

Enalaprilat does not affect the metabolism of glucose, lipoproteins, uric acid and cholesterol. The drug can be prescribed to patients suffering from diabetes, chronic obstructive pulmonary diseases, angina pectoris, and congestive heart failure.

Pharmacokinetics.

After oral administration, enalaprilat is poorly absorbed and practically inactive, so it should only be administered intravenously.

After injection, the drug is quickly distributed in most tissues of the body with high concentrations in the lungs, kidneys and blood vessels, and is observed in plasma for 96 hours. The drinking period is 4:00, and the maximum concentration in the blood plasma is reached after 3-5 hours. 50-60% of enalaprilat binds to blood plasma proteins.

Isn't enalaprilat converted? 100% of enalaprilat is excreted in the urine.

Enalaprilat is excreted mainly through the kidneys, using glomerular filtration and tubular secretion. The conclusion consists of several stages and is explained by strong binding to serum ACE. The half-life in the initial phase is approximately 11:00, and in the final phase it is 35 hours. The clinical effect is observed approximately 15 minutes after administration of enalaprilat, and the maximum hypotensive effect is observed 4:00 after administration and lasts approximately 6:00.

Basic physical and chemical properties

transparent colorless liquid without visible mechanical impurities.

Incompatibility

The drug should not be mixed with amphotericin B and phenytoin due to turbidity of the solution and the formation of a precipitate.

Best before date

Storage conditions

Store at a temperature not exceeding 25 o C out of the reach of children.

Package

1 ml solution for injection in ampoules, 5 ampoules in a cardboard box.

Vacation category

On prescription.

Manufacturer

KRKA, d.d., Novo Mesto, Slovenia /

KRKA, dd, Novo mesto, Slovenia.

Location

Šmarješka cesta 6, 8501 Novo Mesto, Slovenia /

ENAP ® R

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