1 tablet contains:
enalapril malealate 5.0 mg / 10.0 mg / 20.0 mg;
sodium bicarbonate 2.6 mg / 5.1 mg / 10.2 mg;
lactose monohydrate 129.8 mg / 124.6 mg / 117.8 mg;
corn starch 22.4 mg / 21.4 mg / 13.9 mg;
talc 6.0 mg / 6.0 mg / 6.0 mg;
hyprolosis 2.5 mg / - / -;
magnesium stearate 1.7 mg / 1.7 mg / 1.7 mg;
iron oxide red - / 1.2 mg / 0.1 mg;
iron oxide yellow - / - / 0.3 mg.
Enalapril is an angiotensin-converting enzyme (ACE) inhibitor used to treat hypertension, heart failure, diabetic nephropathy. The clinical effect of enalapril is due to the suppression of ACE activity and, as a consequence, a decrease in the formation of angiotensin II from angiotensin I in tissues and circulating blood. A decrease in the concentration of angiotensin II, in turn, leads to vasodilation, a decrease in the secretion of aldosterone, an increase in potassium and renin concentration in the blood plasma.
The hemodynamic consequences of these changes are a decrease in total peripheral vascular resistance (OPSR), systolic and diastolic blood pressure, an increase in cardiac output, and a decrease in post- and preload on the myocardium. Enalapril dilates arteries to a greater extent than veins, while there is no reflex increase in heart rate (HR). Reduces the degradation of bradykinin, increases the synthesis of prostaglandins. The antihypertensive effect is more pronounced at high renin levels than at normal or reduced levels. The time of onset of the antihypertensive effect when taken orally is 1 hour, which reaches a maximum after 4-6 hours and lasts up to 24 hours.
Some patients need therapy for several weeks to achieve optimal blood pressure (BP). In chronic heart failure, a noticeable clinical effect is observed with prolonged treatment - 6 months or more. The duration of the therapeutic effect is dose-dependent.
The vasodilating and some diuretic effect of enalapril is also provided by the blockade of the destruction of bradykinin, which, in turn, stimulates the synthesis of vasodilating and renal prostaglandins. An increase in the content of bradykinin, both in the blood plasma and locally in the organs and tissues of the body, blocks the pathological processes that occur in chronic heart failure in the myocardium, kidneys, and vascular smooth muscles. At the same time, an increase in coronary and renal blood flow is observed, with prolonged use (from 3-4 weeks of treatment), hypertrophy of the left ventricle and myofibrils of the walls of resistive type arteries decreases, dilatation of the left ventricle slows down and blood supply to the ischemic myocardium improves, metabolism improves and the frequency of arrhythmias decreases,
Due to the moderate diuretic effect of the drug, intraglomerular hypertension decreases, the development of glomerulosclerosis slows down and the risk of chronic renal failure decreases.
A decrease in blood pressure within the therapeutic range (not lower than 110/60 mm Hg) does not affect cerebral circulation: blood supply to the brain is maintained at the proper level and against the background of reduced blood pressure.
Abrupt withdrawal of treatment does not result in withdrawal syndrome (a sharp rise in blood pressure).
Enalapril does not cause metabolic disorders, does not affect glucose metabolism, does not increase the concentration of uric acid, and does not change the blood lipoprotein profile. Enalapril can reduce the hypokalemic effect of thiazide diuretics.
When taken orally, enalapril is rapidly absorbed, the maximum plasma concentration is reached within 1 hour.
Enalapril is well absorbed from the gastrointestinal tract (GIT), within 1 hour (maximum 4-8 hours) after oral administration, a therapeutic effect is achieved. Food intake does not affect the absorption of the drug.
In patients with normal renal function, the equilibrium concentration of enalapril in the blood plasma is reached 2-3 days after the start of administration. Does not cumulate. The connection with blood plasma proteins is about 50%.
Biotransformation in the liver with the formation of an active metabolite - enalaprilat, the maximum concentration of which is determined 4 hours after administration. Enalapril is excreted mainly through the kidneys - 60% (20% - in the form of enalapril and 40% - in the form of enalaprilat), through the intestines - 33% (6% - in the form of enalapril and 27% - in the form of enalaprilat). The half-life (T1 / 2) is 11 hours.
In patients with creatinine clearance (CC) less than 30 ml / min, T1 / 2 of enalapril increases. Decreased renal secretion of enalapril can increase hydrolysis to enalaprilat and increase extrarenal excretion of the drug.
The rate of hydrolysis of enalapril can be reduced in patients with impaired liver function without reducing the therapeutic effect.
Penetrates the placental barrier. Excreted in breast milk. Practically does not penetrate the blood-brain barrier. Does not accumulate in any tissues and organs.
Enalapril is an 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.
Due to the vasodilating action, it reduces the OPSS (afterload), the pressure of wedging in the pulmonary capillaries (preload) and resistance in the pulmonary vessels; increases cardiac output and exercise tolerance.
In patients with chronic heart failure, long-term use of enalapril increases exercise tolerance and reduces the severity of heart failure (assessed by NYHA criteria). Enalapril in patients with mild to moderate heart failure slows down its progression, and also slows down the development of left ventricular dilatation. In 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 pectoris).
When taken orally, about 60% is absorbed from the gastrointestinal tract. Simultaneous food intake does not affect absorption. It is metabolized in the liver by hydrolysis with the formation of enalaprilat, due to the pharmacological activity of which the hypotensive effect is realized. Plasma protein binding of enalaprilat is 50-60%.
T1 / 2 of enalaprilat is 11 hours and increases with renal failure. After oral administration, 60% of the dose is excreted by the kidneys (20% as enalapril, 40% as enalaprilat), 33% is excreted through the intestines (6% as enalapril, 27% as enalaprilat). After intravenous administration of enalaprilat, 100% is excreted by the kidneys unchanged.
Application during pregnancy and lactation
Contraindicated in pregnancy.
With the onset of pregnancy, enalapril should be stopped immediately.
Enalapril is excreted in breast milk. If necessary, its use during lactation should decide on the termination of breastfeeding.
- Hypersensitivity to ACE inhibitors,
- a history of angioedema,
- bilateral stenosis of the renal arteries or stenosis of the renal artery of a solitary kidney,
- simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function,
- lactation period (breastfeeding),
- children and adolescents up to 18 years old.
From the side of the central nervous system and peripheral nervous system: dizziness, headache, fatigue, increased fatigue; very rarely when used in high doses - sleep disorders, nervousness, depression, imbalance, paresthesia, tinnitus.
From the side of the cardiovascular system: orthostatic hypotension, fainting, palpitations, pain in the region of the heart; very rarely when used in high doses - hot flashes.
From the digestive system: nausea; rarely - dry mouth, abdominal pain, vomiting, diarrhea, constipation, abnormal liver function, increased activity of hepatic transaminases, increased concentration of bilirubin in the blood, hepatitis, pancreatitis; very rarely when used in high doses - glossitis.
From the hematopoietic system: rarely - neutropenia; in patients with autoimmune diseases - agranulocytosis.
From the urinary system: rarely - renal dysfunction, proteinuria.
From the respiratory system: dry cough.
On the part of the reproductive system: very rarely, when used in high doses, impotence.
Dermatological reactions: very rarely, when used in high doses, hair loss.
Allergic reactions: rarely - skin rash, Quincke's edema.
Others: rarely - hyperkalemia, muscle cramps.
When used simultaneously with immunosuppressants, cytostatics, the risk of developing leukopenia increases.
With the simultaneous use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and dietary supplements containing potassium, hyperkalemia may develop (especially in patients with impaired renal function), because ACE inhibitors reduce the content of aldosterone, which leads to a retention of potassium in the body against the background of limiting the excretion of potassium or its additional intake into the body.
With the simultaneous use of opioid analgesics and anesthetics, the antihypertensive effect of enalapril is enhanced.
With the simultaneous use of "loop" "diuretics, thiazide diuretics increases the antihypertensive effect. There is a risk of hypokalemia. Increased risk of renal dysfunction.
With simultaneous use with azathioprine, anemia may develop, which is due to inhibition of the activity of erythropoietin under the influence of ACE inhibitors and azathioprine.
How to take, course of administration and dosage
When taken orally, the initial dose is 2.5-5 mg 1 time / Average dose is 10-20 mg / 2 divided doses.
When administered intravenously - 1.25 mg every 6 hours. To detect excessive hypotension in patients with sodium deficiency and dehydration caused by previous diuretic therapy, in patients receiving diuretics, as well as in renal failure, an initial dose of 625 mg is administered. If there is an inadequate clinical response, this dose can be repeated after 1 hour and treatment can be continued at a dose of 1.25 mg every 6 hours.
The maximum daily dose for oral administration is 80 mg.
Symptoms: a pronounced decrease in blood pressure, up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications, convulsions, stupor.
Treatment: the patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage and ingestion of a saline solution are indicated, in more severe cases, measures aimed at stabilizing blood pressure: intravenous administration of saline, plasma substitutes, if necessary, administration of angiotensin II, hemodialysis (the rate of elimination of enalaprilat is on average 62 ml / min).
It is used 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 picture of peripheral blood. Sudden discontinuation of enalapril does not cause a sharp increase in blood pressure.
With surgical interventions during the period of treatment with enalapril, arterial hypotension may develop, which should be corrected by the introduction of a sufficient amount of fluid.
Light orange biconvex oblong tablets with lighter and darker specks with a smooth surface with a notch on one side and the inscription “EN 20” and a notch on the opposite side at an angle of 140 degrees (“Snap-tab”).