Enalapril Hexal, pills 20mg, 20pcs

Composition

1 tablet contains:

Active ingredient:

enalapril malealate 5.0 mg / 10.0 mg/20.0 mg;

excipients:

sodium bicarbonate 2.6 mg/5,1 mg/10.2 mg;

lactose monohydrate 129,8 mg/124,6 mg/to 117.8 mg;

corn starch to 22.4 mg/21,4 mg/13,9 mg;

talc 6.0 mg/mg 6,0/6,0 mg;

hyprolose of 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

Pharmacological action

Pharmacodynamics

Enalapril is an angiotensin-converting enzyme (ACE) inhibitor used to treat arterial hypertension, heart failure, and diabetic nephropathy. The clinical effect of enalapril is due to the suppression of ACE activity and, as a result, 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 the content of potassium and the concentration of renin in blood plasma.

The hemodynamic consequences of these changes are a decrease in total peripheral vascular resistance( OPSS), systolic and diastolic blood pressure, an increase in cardiac output, and a decrease in post – and preload on the myocardium. Enalapril dilates the arteries to a greater extent than the 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 concentrations than at normal or reduced renin levels. The time of onset of the antihypertensive effect when taken orally is 1 hour, which reaches a maximum in 4-6 hours and persists for up to 24 hours.

In some patients, therapy for several weeks is necessary to achieve optimal blood pressure (BP). In chronic heart failure, a noticeable clinical effect is observed with long-term treatment-6 months or more. The duration of therapeutic action is dose-dependent.

The vasodilating and some diuretic effects of enalapril are also provided by blocking 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 muscle. At the same time, there is an increase in coronary and renal blood flow, with prolonged use (from 3-4 weeks of treatment), hypertrophy of the left ventricle and myofibrils of the walls of resistive arteries decreases, dilation of the left ventricle slows down and blood supply to the ischemic myocardium improves, metabolism improves and the frequency of arrhythmias observed after restoration of blood supply to the heart muscle decreases.

Due to the moderate diuretic effect of the drug, intracluvular hypertension decreases, the development of glomerulosclerosis slows down, and the risk of chronic renal failure decreases.

Lowering blood pressure within therapeutic limits (not lower than 110/60 mm Hg) does not affect cerebral circulation: blood flow to the brain is maintained at the proper level and against the background of reduced blood pressure.

Sudden discontinuation of treatment does not lead to a “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, does not change the profile of blood lipoproteins. Enalapril may reduce the hypokalemic effect of thiazide diuretics.

Pharmacokinetics

Suction When taken orally, enalapril is rapidly absorbed, the maximum concentration in blood plasma is reached within 1 hour. Enalapril is well absorbed from the gastrointestinal tract (GIT), within 1 hour (maximum 4-8 hours) after oral use, a therapeutic effect is achieved. Food intake does not affect the absorption of the drug.

Distribution In patients with normal renal function, the steady-state plasma concentration of enalapril is reached 2-3 days after the start of use. It doesn’t accumulate. Binding to plasma proteins is about 50%.

Deduction It undergoes biotransformation in the liver with the formation of an active metabolite – enalaprilate, the maximum concentration of which is determined 4 hours after ingestion. Enalapril is excreted mainly through the kidneys-60% (20% – in the form of enalapril and 40% – in the form of enalaprilat), through the intestine – 33% (6% – in the form of enalapril and 27% – in the form of enalaprilat). The elimination half-life (T 1/2) is 11 hours.

In patients with creatinine clearance (creatinine clearance) less than 30 ml/min, the T 1/2 of enalapril increases. Decreased renal secretion of enalapril may increase hydrolysis to enalaprilate and increase extrarenal excretion of the drug.

The rate of hydrolysis of enalapril may decrease in patients with impaired liver function without reducing the therapeutic effect.

Penetrates the placental barrier. It is excreted in breast milk. Practically does not penetrate the blood-brain barrier. It does not accumulate in any tissues and organs.

Indications

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

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

Due to its vasodilating action, it reduces OPSS (afterload), jamming pressure in the pulmonary capillaries (preload) and resistance in the pulmonary vessels; increases the minute volume of the heart and load tolerance. In patients with chronic heart failure, long-term use of enalapril increases exercise tolerance and reduces the severity of heart failure (evaluated according to NYHA criteria). Enalapril in patients with mild to moderate heart failure slows its progression, and also slows the development of left ventricular dilation. In patients with 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. Simultaneous food intake does not affect absorption. It is metabolized in the liver by hydrolysis to form enalaprilate, due to the pharmacological activity of which a hypotensive effect is realized. The binding of enalaprilate to plasma proteins is 50-60%.

T1 / 2 of enalaprilate is 11 hours and increases in renal failure. After oral use,60% of the dose is excreted by the kidneys (20% in the form of enalapril,40% in the form of enalaprilat),33% is excreted through the intestine (6% in the form of enalapril,27% in the form of enalaprilat). After intravenous use of enalaprilat,100% is excreted unchanged by the kidneys.

Use during pregnancy and lactation

It is contraindicated for use during pregnancy.

If you are pregnant, enalapril should be discontinued immediately.

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

Contraindications

• Hypersensitivity to ACE inhibitors,
• a history of angioedema,
• bilateral renal artery stenosis or stenosis of the renal artery of a single kidney,
• hyperkalemia,
• porphyria,
• concomitant use with aliskiren in patients with diabetes mellitus or impaired renal function,
• pregnancy,
• lactation (breastfeeding),
• children and adolescents under 18 years of age.

Side effects

From the central nervous system and peripheral nervous system: dizziness, headache, fatigue, increased fatigue; very rarely when used in high doses-sleep disorders, nervousness, depression, balance disorders, paresthesia, tinnitus.

From the cardiovascular system: orthostatic hypotension, syncope, 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 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-impaired renal function, proteinuria.

Respiratory system disorders: 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, angioedema.

Other: rarely-hyperkalemia, muscle cramps.

Interaction

When used concomitantly 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 potassium retention 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 anesthesia, the antihypertensive effect of enalapril increases.

With the simultaneous use of “loop” diuretics, thiazide diuretics, the antihypertensive effect increases. There is a risk of hypokalemia. Increased risk of impaired renal function.

When used concomitantly with azathioprine, anemia may develop, which is due to inhibition of erythropoietin activity under the influence of ACE inhibitors and azathioprine.

“

How to take, course of use and dosage

When taken orally, the initial dose is 2.5-5 mg 1 time/ The average dose is 10-20 mg/ day in 2 divided doses.

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

The maximum daily dose when taken orally is 80 mg.

Overdose

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

Treatment: the patient is placed in a horizontal position with a low headboard. In mild cases, gastric lavage and ingestion of saline solution are indicated, in more severe cases-measures aimed at stabilizing blood pressure: intravenous use of saline solution, plasma substitutes, if necessary – use of angiotensin II, hemodialysis (the rate of elimination of enalaprilat on average is 62 ml/min).

Special instructions

Use with extreme caution in patients with autoimmune diseases, diabetes mellitus, impaired liver function, severe aortic stenosis, subaortic muscle stenosis of unknown origin, hypertrophic cardiomyopathy, with loss of fluid and salts. Prior treatment with saluretics, in particular in patients with chronic heart failure, increases the risk of orthostatic hypotension, so 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.

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

Form of production

Light orange biconvex oblong tablets with lighter and darker inclusions 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”).

Storage conditions

List B. Store in a dry place, out of reach of children, at a temperature of 15 to 25°C.

Shelf

life is 3 years.

Active ingredient

Enalapril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as prescribed by a doctor, For adults

Indications

Hypertension, Heart Failure