Active ingredient: enalapril;
1 tablet contains enalapril maleate in terms of 100% substance 10 mg or 20 mg;
Enalapril tablets - reduce blood pressure, expand the lumen of blood vessels, and have a cardioprotective and natriuretic effect.
Enalapril is the first long-acting ACE inhibitor, and after being tested in numerous studies, these drugs are firmly established as first-line drugs for the treatment of hypertension and heart failure.
Enalapril also has some diuretic effect associated with a moderate inhibition of aldosterone synthesis. Along with lowering arterial blood pressure, the drug reduces pre- and afterload on the myocardium in heart failure, improves pulmonary circulation and respiratory function, and reduces resistance in the vessels of the kidneys, which helps to normalize blood exchange in them.
Has some diuretic effect. The onset of the hypotensive effect when taken orally is 1 hour, reaches a maximum after 4-6 hours and lasts up to 24 hours.
In some patients, therapy is required for several weeks to achieve an optimal blood pressure level. In heart failure, a noticeable clinical effect is observed with long-term use - 6 months or more.
Indications for use Enalapril
- Hypertension;
- Chronic heart failure (as part of combination therapy);
- Renovascular hypertension;
- Prevention of coronary ischemia and heart failure in patients with left ventricular dysfunction.
At what pressure should enalapril be used? The instructions for using enalapril tablets will give a clear answer - for high blood pressure as prescribed by a doctor. Exceeding the required therapeutic dose can lead to an excessive drop in blood pressure (BP).
Is Enalapril a diuretic? The tablets have a diuretic effect, it depends on the dosage of the drug. The higher the dosage, the more pronounced the diuretic effect. Enalapril is a drug for lowering blood pressure and helping the heart (cardioprotector), and not a diuretic in the usual sense.
Instructions for use of Enalapril, dosage
The tablets are taken orally without chewing, with a sufficient amount of water. Chewing or crushing the tablet will accelerate the absorption of the active substance in a higher dose, which may result in an excessive drop in blood pressure.
Standard instructions for use of enalapril
The initial dose for adults is 2.5-5 mg 1 time / day. The average dose is 10-20 mg/day in 2 divided doses.
The maximum daily dosage is 80 mg/day.
For monotherapy of arterial hypertension, the initial dose is 5 mg 1 time per day. If the therapeutic effect is insufficient, after 1-2 weeks the dosage is increased by 5 mg. After taking the initial dose, patients should be under medical supervision until blood pressure stabilizes (1-3 hours).
For the renal-vascular form of arterial hypotension, the initial dose of enalapril is 5 mg, subsequently increasing to 20 mg enalapril per day.
For congestive heart failure, therapy is started in small dosages - 2.5 mg, depending on the effect, the dose is increased to 20 mg (1-2 doses per day).
For heart failure, it is prescribed starting with enalapril 2.5 mg (1/2 or 1/4 tablet), then the dose is gradually increased to 10 - 20 mg (1 - 2 tablets), in one or two doses.
The use of the drug is possible for monotherapy and in combination with other antihypertensive drugs.
For renovascular hypertension, the drug is prescribed in lower doses (due to higher sensitivity to inhibition of angiotensin-converting enzyme). The standard starting dosage of enalapril is 5 mg per day. Then therapy is selected individually, but the daily dose should not exceed 20 mg (once a day). In all cases, if there is an excessive decrease in blood pressure, the dosage is reduced.
In case of asymptomatic disturbances in the activity of the left ventricle of the myocardium, treatment begins with 5 mg of enalapril 2.5 x 2 times a day. If necessary, therapy is adjusted.
In older people, a more pronounced effect of enalapril in lowering blood pressure is often observed, as well as an increase in the duration of action of the drug - this is due to a decrease in the rate of elimination of the active substance of the tablet, therefore the recommended initial dose for elderly people is 1.25 mg.
For asymptomatic dysfunction of the LV function - 2.5 mg 2 times a day. The dose is selected taking into account tolerability up to 20 mg/day, divided into 2 doses.
Sudden cessation of treatment does not lead to withdrawal syndrome (a sharp rise in blood pressure), but it is recommended to reduce the dosage gradually.
Enalapril increases renal blood flow, improves renal function, and prevents the development of diabetic nephropathy. Does not affect the metabolism of glucose and lipoproteins.
Systematic use of enalapril improves quality of life and reduces mortality in congestive heart failure.
If renal dysfunction is detected, the dose of the drug should be reduced depending on creatinine clearance. During the period when hemodialysis is not performed, enalapril doses should be selected taking into account blood pressure levels.
Contraindications Enalapril
Hypersensitivity to any component of the drug or active substance. For angioedema, which is associated with the use of ACE inhibitors or hereditary angioedema.
Pathologies or conditions:
- Bilateral renal artery stenosis.
- Individual intolerance to the components of the drug.
- Pregnancy, breastfeeding period.
- Children's age up to 18 years.
Since hyperkalemia may develop during treatment with enalapril (especially with concomitant chronic renal failure), simultaneous administration of potassium-sparing diuretics is not recommended.
The safety and effectiveness of enalapril in children have not been established. Use in the Russian Federation for children is prohibited.
When used simultaneously with alcohol, the risk of developing arterial hypotension (excessive drop in pressure) increases.
Overdose
In case of an overdose of enalapril, the following side effects are possible: a pronounced decrease in blood pressure, up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications; convulsions and stupor.
If an overdose of enalapril is suspected, the patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage and ingestion of saline solution are indicated.
In severe cases, measures aimed at stabilizing blood pressure: intravenous administration of saline, plasma substitutes, if necessary, administration of angiotensin II, hemodialysis (enalaprilat elimination rate - 62 ml/min).
Side effects of the drug Enalapril
Possible dizziness, headache, fatigue, nausea, diarrhea, hypotension, orthostatic reactions, muscle spasms, dry cough, skin rash, angioedema, anemia, thrombocytopenia, leukopenia, agranulocytosis, changes in taste, change in voice timbre.
Rarely - increased levels of urea (gout), creatinine and transaminases in the blood serum, proteinuria, cholestatic jaundice.
Before and during treatment with ACE inhibitors, periodic monitoring of blood pressure, blood counts, and the presence of protein in the urine is necessary.
Analogues of Enalapril, list of drugs
It is possible to use analogues of enalapril based on the active substance. These are the drugs (list):
- Bagopril
- Berlipril
- Vero-Enalapril
- Invoril
- Miopril
- Renipril
- Renitek
- Ednit
- Enalacor
- Enalapril
- Enarenal
- Envipril
Before replacing your prescribed medication with an analogue, you should definitely consult with your doctor. Important - instructions for use, price and reviews of enalapril and analogues may not be the same. This leaflet and other information (reviews, etc.) should not be used for similar medications. They may differ in the concentration of active substances, excipients, etc. When choosing what to replace enalapril with, you must consult your doctor; without this, you cannot replace the drug with an analogue!
Conditions for dispensing from pharmacies
The drug is available with a prescription.
Storage conditions and periods
List B. Store in a dry place, out of reach of children, at a temperature of 15 to 25°C. Shelf life – 3 years.
The site provides reference information for informational purposes only. Diagnosis and treatment of diseases must be carried out under the supervision of a specialist. All drugs have contraindications. Consultation with a specialist is required!
The drug Enalapril
Enalapril– an antihypertensive drug belonging to the class of ACE inhibitors. The action of Enalapril is due to its effect on the renin-angiotensin-aldosterone system, which plays an important role in the regulation of blood pressure. The visible effect of the medicine develops after taking it for 2-4 hours, and the initial effect occurs within an hour. The maximum pressure decreases after 4-5 hours. When Enalapril is taken in recommended doses, its hypotensive effect lasts for about a day.
The drug is quickly absorbed into the gastrointestinal tract with an absorption rate of about 60%. Enalapril is excreted primarily through the kidneys and intestines.
Release forms
Enalapril is available in tablets of 5, 10, 20 mg, packaged in blisters of 10 pieces. There are two or three blisters in a cardboard package.Dutch and English Renitek contains 14 tablets in one package.
Side effects when taking Enalapril are most often reversible. Therefore, if they appear, the drug should be stopped immediately.
Treatment with Enalapril
How to take Enalapril?In accordance with the doctor's prescription, the drug is taken 1-2 times a day, regardless of meals. Combined Enalapril preparations containing diuretics are best taken in the morning. Treatment with the drug is long-term and, if well tolerated, throughout life.
As a result of simultaneous administration of Enalapril with lithium salts, the excretion of lithium may slow down, and its toxic effect increases. Therefore, prescribing these drugs together is not recommended.
Concomitant use of Enalapril with potassium-sparing diuretics can lead to potassium retention and hyperkalemia. Therefore, they can be taken at the same time only under the supervision of laboratory tests.
There is evidence that the simultaneous administration of insulin, as well as other hypoglycemic drugs and Enalapril can lead to hypokalemia. Most often this happens at the beginning of treatment in patients with renal pathology.
Enalapril weakens the effect of Theophylline.
It is safe to prescribe Enalapril with aspirin in a cardiac dosage, with beta-blockers and thrombolytics.
Enalapril's analogs
Analogs (synonyms) of the drug containing Enalapril as the main active ingredient include: - Enap;
- Vazolapril;
- Invoril;
- Berlipril;
- Ednit;
- Enam;
- Bagopril;
- Miopril;
- Enarenal;
- Renitek;
- Envas;
- Corandil;
- Enalacor and others.
Analogs of Enalapril, which have a similar effect, but have a different chemical composition, are the drugs Captopril, Lisinopril, Ramipril, Zofenopril, Perindopril, Trandolapril, Quinapril, Fosinopril.
Enalapril is an angiotensin-converting enzyme (ACE) inhibitor. The human body is a collection of many biochemical reactions that control its vital functions at the cellular level. The renin-angiotensin-aldosterone system is one of these cycles of sequential transformations of biologically active substances, which plays an important role in the regulation of blood pressure and water-salt balance. By inactivating one of the important links in this cycle - angiotensin - enalapril thereby prevents the formation of the adrenal hormone aldosterone, which, in turn, causes a decrease in blood pressure.
Enalapril is an indispensable remedy in the first aid kit for every patient suffering from hypertension. In addition to the hypotensive effect, it also has many positive qualities regarding the cardiovascular system. This includes a reduction in excess vascular tone, a reduction in the load on the heart muscle, and a mild diuretic effect. The pronounced effect of a single dose of the drug is felt 4-6 hours after administration and persists throughout the day. However, one should not expect miracles from it here and now: people with heart failure need to take enalapril for at least 6 months to achieve a clear clinical effect.
The advantage of enalapril is that there is no need to make allowances for your daily gastronomic routine: it can be taken at any time, regardless of meals. There are many regimens for taking this drug, depending on the disease and the age of the patient. As a general rule, when treating arterial hypertension with enalapril in the “solo” mode, the initial daily dose is 5 mg. If there are no obvious results, after 7-14 days the dose is increased by another 5 mg and so on up to 40 mg, above which you should not rise.
Elderly patients are more susceptible to the action of enalapril, which is manifested in a slightly more pronounced and long-lasting hypotensive effect. This is explained by the reduced rate of excretion of enalapril in older patients. In such cases, the initial daily dose is recommended to be reduced to 1.25 mg.
Enalapril works well both in combination with other antihypertensive drugs and on its own. The timing of taking the drug depends on the observed effect. The dose of the drug at which its clear therapeutic effect was achieved is not an unshakable constant and can subsequently be reduced to maintenance values.
Pharmacology
ACE inhibitor. It is a prodrug from which the active metabolite enalaprilat is formed in the body. It is believed that the mechanism of antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II (which has a pronounced vasoconstrictor effect and stimulates the secretion of aldosterone in the adrenal cortex).
As a result of a decrease in the concentration of angiotensin II, a secondary increase in plasma renin activity occurs due to the elimination of negative feedback during the release of renin and a direct decrease in aldosterone secretion. In addition, enalaprilat appears to have an effect on the kinin-kallikrein system, preventing the breakdown of bradykinin.
Thanks to its vasodilating effect, it reduces roundabout percentage (afterload), wedge pressure in the pulmonary capillaries (preload) and resistance in the pulmonary vessels; increases cardiac output and exercise tolerance.
In patients with chronic heart failure, with long-term use, enalapril increases exercise tolerance and reduces the severity of heart failure (assessed by NYHA criteria). Enalapril in patients with mild to moderate heart failure slows its progression and also slows down the development of left ventricular dilatation. In case of left ventricular dysfunction, enalapril reduces the risk of major ischemic outcomes (including the incidence of myocardial infarction and the number of hospitalizations for unstable angina).
Pharmacokinetics
When taken orally, about 60% is absorbed from the gastrointestinal tract. Concomitant food intake does not affect absorption. Metabolized in the liver by hydrolysis with the formation of enalaprilat, due to the pharmacological activity of which a hypotensive effect is realized. The binding of enalaprilat to plasma proteins is 50-60%.
T1/2 of enalaprilat is 11 hours and increases with renal failure. After oral administration, 60% of the dose is excreted by the kidneys (20% as enalapril, 40% as enalaprilat), 33% is excreted through the intestines (6% as enalapril, 27% as enalaprilat). After intravenous administration of enalaprilat, 100% is excreted unchanged by the kidneys.
Release form
10 pcs. - contour cellular packaging (1) - cardboard packs.
10 pcs. - contour cell packaging (2) - cardboard packs.
10 pcs. - contour cell packaging (3) - cardboard packs.
10 pcs. - contour cell packaging (5) - cardboard packs.
10 pcs. - contour cellular packaging (2) - cardboard packs.
20 pcs. - contour cellular packaging (1) - cardboard packs.
20 pcs. - contour cellular packaging (2) - cardboard packs.
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, patients with sodium deficiency and dehydration due to previous diuretic therapy, patients receiving diuretics, and also with renal failure, administer an initial dose of 625 mg. If the clinical response is inadequate, this dose can be repeated after 1 hour and treatment continued at a dose of 1.25 mg every 6 hours.
The maximum daily dose when taken orally is 80 mg.
Interaction
When used simultaneously with immunosuppressants and cytostatics, the risk of developing leukopenia increases.
With the simultaneous use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium supplements, salt substitutes and dietary supplements containing potassium, hyperkalemia may develop (especially in patients with impaired renal function), because ACE inhibitors reduce the content of aldosterone, which leads to potassium retention in the body while limiting the excretion of potassium or its additional intake into the body.
With the simultaneous use of opioid analgesics and anesthetics, the antihypertensive effect of enalapril is enhanced.
With the simultaneous use of loop diuretics and thiazide diuretics, the antihypertensive effect is enhanced. There is a risk of developing hypokalemia. Increased risk of renal dysfunction.
When used simultaneously with azathioprine, anemia may develop, which is due to inhibition of erythropoietin activity under the influence of ACE inhibitors and azathioprine.
A case of the development of an anaphylactic reaction and myocardial infarction with the use of allopurinol in a patient receiving enalapril is described.
Acetylsalicylic acid in high doses may reduce the antihypertensive effect of enalapril.
It has not been conclusively established whether acetylsalicylic acid reduces the therapeutic effectiveness of ACE inhibitors in patients with coronary artery disease and heart failure. The nature of this interaction depends on the course of the disease.
Acetylsalicylic acid, by inhibiting COX and prostaglandin synthesis, can cause vasoconstriction, which leads to a decrease in cardiac output and worsening of the condition of patients with heart failure receiving ACE inhibitors.
With the simultaneous use of beta-blockers, methyldopa, nitrates, calcium channel blockers, hydralazine, prazosin, the antihypertensive effect may be enhanced.
When used simultaneously with NSAIDs (including indomethacin), the antihypertensive effect of enalapril is reduced, apparently due to inhibition of the synthesis of prostaglandins under the influence of NSAIDs (which are believed to play a role in the development of the hypotensive effect of ACE inhibitors). The risk of developing renal dysfunction increases; hyperkalemia is rarely observed.
With the simultaneous use of insulin and hypoglycemic agents, sulfonylurea derivatives, hypoglycemia may develop.
With simultaneous use of ACE inhibitors and interleukin-3, there is a risk of developing arterial hypotension.
Syncope has been reported when used concomitantly with clozapine.
When used simultaneously with clomipramine, an increase in the effect of clomipramine and the development of toxic effects are reported.
When used simultaneously with co-trimoxazole, cases of hyperkalemia have been described.
When used simultaneously with lithium carbonate, the concentration of lithium in the blood serum increases, which is accompanied by symptoms of lithium intoxication.
When used simultaneously with orlistat, the antihypertensive effect of enalapril is reduced, which can lead to a significant increase in blood pressure and the development of a hypertensive crisis.
It is believed that with simultaneous use with procainamide, there may be an increased risk of developing leukopenia.
When used simultaneously with enalapril, the effect of drugs containing theophylline is reduced.
There are reports of the development of acute renal failure in patients after kidney transplantation when used simultaneously with cyclosporine.
When used simultaneously with cimetidine, the half-life of enalapril increases and its concentration in the blood plasma increases.
It is believed that the effectiveness of antihypertensive drugs may be reduced when used simultaneously with erythropoietins.
When used simultaneously with ethanol, the risk of developing arterial hypotension increases.
Side effects
From the central nervous system and peripheral nervous system: dizziness, headache, feeling of fatigue, increased fatigue; very rarely when used in high doses - sleep disorders, nervousness, depression, imbalance, paresthesia, tinnitus.
From the cardiovascular system: orthostatic hypotension, fainting, palpitations, pain in the heart; very rarely when used in high doses - hot flashes.
From the digestive system: nausea; rarely - dry mouth, abdominal pain, vomiting, diarrhea, constipation, impaired liver function, increased activity of liver transaminases, increased concentration of bilirubin in the blood, hepatitis, pancreatitis; very rarely when used in high doses - glossitis.
From the hematopoietic system: rarely - neutropenia; in patients with autoimmune diseases - agranulocytosis.
From the urinary system: rarely - renal dysfunction, proteinuria.
From the respiratory system: dry cough.
From the reproductive system: very rarely, when used in high doses - impotence.
Dermatological reactions: very rarely when used in high doses - hair loss.
Allergic reactions: rarely - skin rash, Quincke's edema.
Other: rarely - hyperkalemia, muscle cramps.
Indications
Arterial hypertension (including renovascular), chronic heart failure (as part of combination therapy).
Essential hypertension.
Chronic heart failure (as part of combination therapy).
Prevention of the development of clinically significant heart failure in patients with asymptomatic left ventricular dysfunction (as part of combination therapy).
Prevention of coronary ischemia in patients with left ventricular dysfunction in order to reduce the incidence of myocardial infarction and reduce the frequency of hospitalizations for unstable angina.
Contraindications
History of angioedema, bilateral renal artery stenosis or renal artery stenosis of a single kidney, hyperkalemia, porphyria, simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (KR<60 мл/мин), беременность, период лактации (грудного вскармливания), детский и подростковый возраст до 18 лет, повышенная чувствительность к эналаприлу и другим ингибиторам АПФ.
Features of application
Use during pregnancy and breastfeeding
Contraindicated for use during pregnancy. If pregnancy occurs, enalapril should be stopped immediately.
Enalapril is excreted in breast milk. If it is necessary to use it during lactation, the issue of stopping breastfeeding should be decided.
Use for liver dysfunction
Use with extreme caution in patients with impaired liver function.
Use in children
The safety and effectiveness of enalapril in children have not been established.
Special instructions
Use with extreme caution in patients with autoimmune diseases, diabetes mellitus, liver dysfunction, severe aortic stenosis, subaortic muscular stenosis of unknown origin, hypertrophic cardiomyopathy, and loss of fluid and salts. In the case of previous treatment with saluretics, in particular in patients with chronic heart failure, the risk of developing orthostatic hypotension increases, therefore, before starting treatment with enalapril, it is necessary to compensate for the loss of fluid and salts.
With long-term treatment with enalapril, it is necessary to periodically monitor the peripheral blood picture. Sudden cessation of enalapril does not cause a sharp increase in blood pressure.
During surgical interventions during treatment with enalapril, arterial hypotension may develop, which should be corrected by administering a sufficient amount of fluid.
Before studying the function of the parathyroid glands, enalapril should be discontinued.
Impact on the ability to drive vehicles and operate machinery
Caution is required when driving vehicles or performing other work that requires increased attention, because Dizziness may occur, especially after taking the initial dose of enalapril.
INN: Enalapril
Manufacturer: Borisov Medical Preparations Plant OJSC
Anatomical-therapeutic-chemical classification: Enalapril
Registration number in the Republic of Kazakhstan: No. RK-LS-5 No. 019608
Registration period: 28.01.2013 - 28.01.2018
Instructions
Trade name
Enalapril
International nonproprietary name
Enalapril
Dosage form
Tablets 5 mg and 10 mg
Compound
One tablet contains
active substance- enalapril maleate 5 mg or 10 mg,
excipients: lactose monohydrate, povidone, potato starch, talc, magnesium stearate.
Description
Tablets are white or white with a yellowish tint, flat-cylindrical, scored and chamfered.
Farmacotherapy group
Drugs affecting the renin-angiotensin system. Angiotensin-angiotensin-converting enzyme (ACE). ACE inhibitors. Enalapril.
ATX code C09AA02
Pharmacological properties
Pharmacokinetics
After oral administration, about 60% of the drug is absorbed; food does not affect the absorption of enalapril. After taking a dose of 10 mg, the time to reach the maximum concentration in the blood plasma is 1 hour, and its level is 200-400 ng/ml. After absorption, it undergoes first-pass metabolism in the liver to form active enalaprilat. Enalaprilat easily passes through histohematic barriers (excluding the blood-brain barrier), penetrates the placenta and is found in fetal tissues. The half-life of enalapril is 2 hours. After use at a dose of 20 mg, the maximum concentration of enalaprilat in the blood plasma is 70-100 ng/ml and is achieved after 3-4 hours. The therapeutic concentration of enalaprilat in the blood plasma is 10-100 ng/ml. 50% bound to plasma proteins. The half-life of enalaprilat is 8-11 hours. 60% of the dose taken is eliminated in the urine (20% as enalapril and 40% as enalaprilat) and through the intestines - 33% (6% as enalapril and 27% as enalaprilat). Within 24 hours, about 90% of the dose taken is eliminated. In severe chronic renal failure (creatine clearance less than 30 ml/min), the elimination of enalaprilat slows down, and its plasma level increases 13 times; drug accumulation occurs when creatine clearance is less than 10 ml/min. It is removed by hemodialysis and peritoneal dialysis.
Pharmacodynamics
Enalapril has hypotensive, vasodilating and cardioprotective effects.
Enalapril inhibits the activity of angiotensin-converting enzyme (ACE). As a result, the formation of angiotensin II is reduced and the secretion of aldosterone is stimulated. Prevents the breakdown of bradykinin and enhances its vasodilatory effect on B2-type bradykinin receptors.
As a result of the use of enalapril in the blood plasma, the level of vasoconstrictor hormones decreases; the level of bradykinin, prostaglandin E2 and prostacyclin, endothelial relaxing factor and atrial natriuric peptide increases.
Enalapril causes dilation of arterial vessels and lowers blood pressure. When enalapril is administered, the hypotensive effect develops 1 hour after administration, reaches a maximum at 6 hours and lasts for about 24 hours. In overweight individuals, it may be necessary to take enalapril for several weeks to achieve an optimal stable blood pressure level. Enalapril slows down the development of hypertrophy and fibrosis of the arterial vessel wall. Due to the vasodilatory effect, enalapril reduces the total peripheral vascular resistance (afterload on the myocardium), wedge pressure in the pulmonary capillaries (preload on the myocardium), resistance in the pulmonary vessels, and increases cardiac output. With long-term use, it reduces the severity of myocardial hypertrophy, prevents the progression of heart failure and slows down the development of left ventricular dilatation (cardioprotective effect).
Indications for use
Arterial hypertension
Chronic heart failure (as part of combination therapy)
Prevention of symptomatic heart failure in patients with asymptomatic left ventricular dysfunction (left ventricular ejection fraction< 35 %)
Directions for use and doses
Use internally regardless of food intake. Patients with high activity of the renin-angiotensin-aldosterone system (for example, renovascular hypertension, salt deficiency and/or dehydration, cardiac decompensation or severe arterial hypertension) may experience a sharp decrease in blood pressure after taking the first dose. Therefore, it is better to take the first dose before bed in a lying position.
For arterial hypertension adults are prescribed an initial dose of 5 mg 1 time per day. If there is no effect, after 1-2 weeks the dose is increased by 5 mg. If well tolerated, the dose can be increased to 20 mg/day in 1 dose. 2-3 weeks after taking enalapril at the maximum dose, they switch to maintenance therapy at a dose of 10-20 mg/day. The maximum daily maintenance dose of enalapril is 40 mg/day (in 2 divided doses).
If diuretics are used, treatment with diuretics should be stopped 2-3 days before enalapril is prescribed, or enalapril should be started at a dose of 2.5 mg/day, slowly increasing the dose by 2.5 mg/week until the optimal effect is achieved.
If the concentration of Na+ in the blood serum is less than 130 mmol/l or the level of creatinine in the serum is more than 0.14 mmol/l, the initial dose of enalapril is 2.5 mg/day.
For renovascular and renal hypertension initial dose is 2.5-5 mg 1 time per day, maintenance dose is 10 mg 1 time per day. The maximum daily dose is 20 mg in 2 divided doses.
At chronic heart failure initial dose of 2.5 mg once with a gradual increase by 2.5-5 mg every 3-4 days to the maximum tolerated (depending on blood pressure level), but not more than 20 mg/day. The average maintenance dose is 5-20 mg/day. The next dose increase is carried out when systolic blood pressure remains stable over 90 mmHg. Art. In patients with low systolic pressure (less than 110 mm Hg), as well as in the elderly, treatment begins with a dose of 1.25 mg/day.
For asymptomatic left ventricular dysfunction apply 2.5 mg 2 times a day. The dose is increased by 2.5 mg every week until optimally tolerated, but not more than 20 mg/day in 2 divided doses.
In patients with impaired renal function the initial dose of enalapril with a creatinine clearance (CL) of 80-30 ml/min is 5-10 mg/day, with a creatinine clearance (CC) of 30-10 ml/min - 2.5-5 mg/day, with a CL of less than 10 ml/min - 1 .25-2.5 mg/day only on dialysis days. The duration of treatment depends on the severity of the effect of the drug; in case of excessive hypotension, the dose of enalapril must be reduced.
Side effects
Very often (≥ 1/10 ):
- visual impairment, in the form of blurred vision
-
dizziness
Often (≥ 1/100- < 1/10 ):
-
diarrhea, abdominal pain, changes in taste perception
skin rash, angioedema of the face, extremities, lips, tongue, glottis and/or larynx
hyperkalemia, increased creatinine levels
hypotension (including orthostatic hypotension), syncope, chest pain, cardiac arrhythmias, angina, tachycardia
headache, depression
fatigue
Sometimes (≥ 1/1 000 - < 1/100 ):
orthostatic hypotension, palpitations, myocardial infarction or cerebral stroke, presumably due to an excessive fall in blood pressure in patients with high risk factors
confusion, drowsiness, insomnia, nervousness, dizziness, paresthesia
heartbeat
intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, lack of appetite, gastric irritation, dry mouth, peptic ulcer
anemia (including aplastic and hemolytic anemia)
rhinorrhea, sore throat and hoarseness, bronchospasm/asthma
sweating, itching, urticaria, alopecia
renal dysfunction, renal failure, proteinuria
impotence
muscle cramps, hot flashes, tinnitus, malaise, fever
increased urea levels, hyponatremia, hypoglycemia
Rarely (≥ 1/10 000 - < 1/1000 ):
liver failure, hepatitis, cholestasis, jaundice, increased activity of “liver” transaminases, hyperbilirubinemia
neutropenia, decreased hemoglobin and hematocrit, thrombocytopenia, agranulocytosis, bone marrow depression, pancytopenia, enlarged lymph nodes, autoimmune diseases
changes in the nature of dreams, sleep disturbances
Raynaud's syndrome
pulmonary infiltrates, rhinitis, allergic alveolitis/eosinophilic pneumonia
stomatitis/aphthous ulcers, glossitis
liver failure, hepatitis - hepatocellular or cholestatic, including hepatic necrosis, cholestasis (including jaundice)
erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma
oliguria
gynecomastia
increased liver enzyme levels, increased serum bilirubin levels
Very rarely (< 1/10 000 ):
angioedema of the intestine
Frequency unknown:
Parhon's syndrome (syndrome of inappropriate antidiuretic hormone secretion)
A symptom complex has been reported that may be accompanied by some or all of the following side effects: fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, increased antinuclear antibody (ANA) titer, increased ESR, eosinophilia and leukocytosis. Skin rash, photosensitivity, or other skin manifestations may occur.
Contraindications
Hypersensitivity to enalapril, the components of the drug or other ACE inhibitors
Hereditary or angioedema occurring after
use of angiotensin-converting enzyme inhibitors in
medical history
Porphyria
Primary hyperaldosteronism
Hyperkalemia (more than 6 mmol/l)
Aortic stenosis or low-output hypertrophic cardiomyopathy
Leukopenia or thrombocytopenia
Bilateral renal artery stenosis or stenosis of the artery of a solitary kidney
Hereditary fructose intolerance, Lapp-lactase enzyme deficiency, glucose-galactose malabsorption
Pregnancy and lactation
Children and adolescents up to 18 years of age
Drug interactions
Eating does not affect the absorption of enalapril.
With simultaneous use of enalapril and potassium-sparing diuretics (spironolactone, triamterene, amiloride) or potassium supplements hyperkalemia may develop. When using enalapril simultaneously with diuretics, beta-blockers, methyldopa, nitrates, calcium channel blockers, hydralazine, prazosin the hypotensive effect may be enhanced. When used simultaneously with non-steroidal anti-inflammatory drugs(including acetylsalicylic acid) may reduce the effect of enalapril and increase the risk of developing renal dysfunction. Enalapril weakens the effect of drugs containing theophylline. With the simultaneous use of enalapril and lithium preparations, the excretion of lithium slows down and its effect increases (monitoring the concentration of lithium in the blood plasma is indicated). With simultaneous use of enalapril and cimetidine, the half-life of enalapril is prolonged.
Concomitant use of ACE inhibitors and antidiabetic drugs(insulin, oral hypoglycemic agents) can cause a decrease in blood glucose levels, which is accompanied by a risk of developing hypoglycemia. This effect is more often observed during the first weeks of combination treatment, as well as in patients with impaired renal function.
Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors. Nitritoid reactions (facial flushing, nausea, vomiting and hypotension) have been rarely reported in patients receiving gold injection (sodium aurothiomalate) and concomitant ACE inhibitors, including enalapril.
Concomitant use of other antihypertensive drugs or vasodilators may enhance the hypotensive effect of enalapril.
Alcohol enhances the hypotensive effect of ACE inhibitors.
Special instructions
Symptomatic hypotension
In uncomplicated arterial hypertension, hypotension is rare.
With a lack of fluid in the body, for example, due to diuretic therapy, a salt-depleted diet, dialysis, diarrhea or vomiting in patients suffering from arterial hypertension, symptomatic hypotension develops more often during treatment with Enalapril. Symptomatic hypotension has been observed in patients with heart failure, with or without renal failure. This may particularly apply to patients with severe heart failure whose disease severity is reflected in high doses of loop diuretics, hyponatremia or decreased renal function. Treatment of such patients - if a new dose of Enalapril and/or a diuretic is to be selected - must be started and carried out under the supervision of a physician. The same applies to patients with coronary heart disease or cerebrovascular disease, in whom an excessive drop in blood pressure can lead to myocardial infarction or cerebral stroke.
If hypotension develops, the patient should be placed in a horizontal position and, if necessary, given an intravenous infusion of sodium chloride solution. A transient hypotonic reaction is not a contraindication for further treatment, which can usually be carried out without problems after normalization (by replenishing the circulating blood volume) of blood pressure.
In some patients with heart failure whose blood pressure is normal or low, a further decrease in systemic blood pressure may occur under the influence of Enalapril. This far from unexpected effect is usually not a reason to discontinue the drug. If the decrease in blood pressure becomes symptomatic, i.e. will be accompanied by symptoms, it may be necessary to reduce the dose of Enalapril and/or diuretic and/or discontinue Enalapril.
Aortic or mitral stenosis/hypertrophic cardiomyopathy
As with other vasodilators, special caution is recommended when using ACE inhibitors in patients who have left ventricular valve obstruction and outflow tract obstructions. In case of shock accompanied by circulatory failure and a hemodynamically obvious obstruction in the outflow tract, the use of these drugs should be avoided.
Renal dysfunction
In patients with decreased renal function (creatinine clearance< 80 мл/мин) начальную дозу эналаприла малеата следует подбирать в зависимости от клиренса креатинина у пациента.
The maintenance dose is selected depending on the patient's response to treatment. In these patients, monitoring of serum potassium and creatinine is routine as part of their usual medical management.
In particular, renal failure has been reported in association with the use of enalapril maleate in patients with severe heart failure or underlying renal disease, including renal artery stenosis. With timely diagnosis and appropriate treatment, renal failure during therapy with enalapril maleate is usually reversible.
In some hypertensive patients who do not have renal disease, the combination of enalapril maleate with a diuretic may result in increased serum urea and creatinine levels. In such cases, it may be necessary to reduce the dose of enalapril maleate and/or discontinue the diuretic. In this case, one must think about possible stenosis of the renal arteries as the cause of these phenomena.
Renovascular hypertension
In patients with bilateral renal artery stenosis or renal artery stenosis of a single functioning kidney, treatment with ACE inhibitors poses a particular risk of a drop in blood pressure or the development of kidney failure. Loss of renal function may occur, often resulting in only mild changes in serum creatinine. Treatment of these patients should be started with low doses and under strict medical supervision, carefully titrating the dose and monitoring renal function.
Kidney transplantation
There is no experience with the use of Enalapril in patients who have recently undergone kidney transplantation. Therefore, treatment of such patients with this drug is not recommended.
Liver failure
During treatment with ACE inhibitors, a syndrome has rarely been observed, starting with cholestatic jaundice and progressing to fulminant hepatic necrosis (sometimes with fatal outcome). The pathogenesis of this syndrome is unclear. In patients who develop jaundice or a marked increase in liver enzyme levels during treatment with an ACEI, discontinuation of the ACEI and appropriate treatment are necessary.
Neutropenia/agranulocytosis
Neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and without special risk factors, neutropenia rarely occurs. In patients suffering from collagenosis with vascular involvement, as well as those being treated with immunosuppressants, allopurinol, procainamide, or in patients with the presence of several of these risk factors, enalapril maleate should be used with extreme caution, especially if there is a decrease in renal function. Some of these patients developed severe infections that in some cases did not respond to intensive antibiotic therapy. If these patients are taking enalapril maleate, they are advised to have their white blood cell count regularly monitored and are encouraged to report any signs of any infection to their doctor.
Hypersensitivity/angioedema
Angioedema involving the face, extremities, lips, tongue, vocal folds and/or larynx has been reported in patients treated with ACEIs, including Enalapril. They may appear at any time during treatment. In these cases, Berlipril® should be discontinued immediately. To ensure complete reversal of symptoms before discharge from the hospital, the patient must be closely monitored. Even if angioedema affects only the tongue in the absence of respiratory failure, long-term observation is still necessary, since the administration of antihistamines and corticosteroids may not be sufficient.
Extremely rare cases of death due to the development of angioedema of the larynx or tongue have been reported. Swelling of the tongue, epiglottis, or larynx increases the risk of airway obstruction, especially in patients who have had airway surgery. Angioedema involving the larynx can be fatal. If the tongue, vocal folds or larynx are involved and there is a risk of airway obstruction, appropriate treatment should be started immediately (for example, subcutaneous injection of 0.3-0.5 ml of epinephrine solution [1:1,000 dilution]) and/or measures should be taken to ensure airway patency .
A higher incidence of angioedema has been reported with ACEI therapy in black patients compared with non-black patients.
Patients with a history of angioedema not caused by ACEIs may have an increased risk of developing it when taking ACEIs.
Anaphylactic reactions during desensitization therapy against hymenoptera venom
Occasionally during desensitization therapy directed against venom insects, and the simultaneous use Life-threatening anaphylactic reactions have been observed with ACE inhibitors. If specific immunotherapy (desensitization) directed against the venom is indicated insects, then ACE inhibitors must be temporarily replaced with other drugs for the treatment of arterial hypertension or heart failure.
Anaphylactic reactions during LDL apheresis (low-density lipoprotein plasmapheresis)
During LDL apheresis using dextran sulfate, life-threatening anaphylactic reactions have occurred rarely during concomitant use of ACE inhibitors. If LDL apheresis is indicated, then ACE inhibitors should be temporarily replaced with other drugs for the treatment of arterial hypertension or heart failure.
Patients undergoing hemodialysis treatment
When using high-flux membranes (for example, “AN 69”) during dialysis and simultaneous use of ACE inhibitors, anaphylactoid reactions have been reported. In such patients, consideration should be given to using a different type of dialysis membrane or prescribing a different class of antihypertensive drug.
Hypoglycemia
Patients with diabetes mellitus who are being treated with oral antidiabetic drugs or insulin should be advised at the beginning of treatment with ACE inhibitors of the need to carefully monitor blood glucose levels, especially in the first month of simultaneous use of these drugs.
Cough
Cough has been reported in association with the use of ACEIs. The absence of sputum is typical, the cough is persistent and disappears after discontinuation of treatment. Cough caused by ACEI therapy should also be considered in the differential diagnosis of cough.
Surgical procedures/anesthesia
In patients undergoing major surgery or anesthesia with drugs that lower blood pressure, enalapril maleate inhibits, in response to compensatory secretion of renin, the production of angiotensin II. If hypotension develops on this basis, it can be corrected by replenishing the volume of circulating blood.
Hyperkalemia
Increases in serum potassium concentrations have been observed in some patients treated with ACE inhibitors, including enalapril. Risk factors for the development of hyperkalemia are: renal failure, impaired renal function, advanced age (over 70 years), diabetes mellitus, intercurrent factors such as dehydration, acute cardiac decompensation, metabolic acidosis and concomitant treatment with potassium-sparing diuretics (eg, spironolactone, eplerenone, triamterene or amiloride), taking potassium supplements or potassium-containing salt substitutes, as well as concomitant treatment with other drugs that can lead to an increase in serum potassium levels (eg, heparin). When using potassium supplements, potassium-sparing diuretics and salt substitutes containing potassium in patients with impaired renal function, a significant increase in the concentration of potassium in the blood is possible. Hyperkalemia can cause the development of severe arrhythmia, including death. If the use of the above drugs simultaneously with enalapril is still considered appropriate, then treatment should be carried out with caution, regularly monitoring the concentration of potassium in the blood serum.
Lithium
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
There is evidence that the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of arterial hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, double blockade of the RAAS when taking ACE inhibitors, angiotensin II receptor blockers or aliskiren together is not recommended.
If dual blockade therapy is absolutely necessary, it should only be carried out under specialist supervision, as well as careful monitoring of renal function, electrolytes and blood pressure.
The combined use of ACE inhibitors and angiotensin II receptor blockers is contraindicated in patients with diabetic nephropathy.
Lactose
Enalapril contains lactose. Therefore, patients suffering from rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not take this drug. The lactose content in one Enalapril tablet does not exceed 200 mg.
Ethnic differences
The severity of the hypotensive effect of enalapril - as in the case of other ACE inhibitors - in black patients, obviously, may be less than in non-black patients; this is presumably due to the fact that black patients with hypertension often have reduced plasma renin levels.
Pregnancy and lactation.
The drug is not prescribed during pregnancy, since ACE inhibitors can cause illness or death of the fetus or newborn, including arterial hypotension, renal failure, hyperkalemia, hypoplasia of the newborn's skull, and the development of oligohydramnios (contracture of the limbs, deformation of the facial bones of the skull, pulmonary hypoplasia).
The drug is excreted in trace concentrations in breast milk. If it is necessary to use it during lactation, breastfeeding should be stopped.
Features of the effect of the drug on the ability to drive a vehicle and other potentially dangerous mechanisms.
During the period of use of the drug, you should, if possible, refrain from any activity related to driving a vehicle or potentially dangerous mechanisms, due to the possible development of side effects such as dizziness.
Overdose
Symptoms: arterial hypotension. Taking enalapril at a dose of 300-400 mg leads to a level of the drug in the blood 100-200 times higher than the therapeutic level. The development of acute arterial hypotension up to collapse, cerebrovascular accident, myocardial infarction, thromboembolism or angioedema is characteristic; the development of stupor and convulsions is also possible.
Treatment: discontinuation of the drug, gastric lavage with activated charcoal, prescription of saline laxatives, transfer of the patient to a horizontal position with raised legs, replenishment of circulating blood volume with isotonic sodium chloride solution and plasma-substituting solutions, supportive and symptomatic therapy. In severe cases, hemodialysis is performed.
