Enalapril, tablets 5 mg 20 pcs

Pharmgroup:

The ACE inhibitor.

Pharmic action:

The ACE inhibitor is a hypotensive drug and its mechanism of action is related to the reduction of angiotensin I angiotensin II formation, the decrease in the concentration of which leads to a direct reduction of aldosterone secretion. This decreases RPS, systolic and diastolic BP, and post- and preload on the myocardium. It dilates the arteries more than the veins, and there is no reflex increase in heart rate. Reduces bradykinin degradation, increases Pg synthesis. Hypotensive effect is more pronounced at high plasma renin concentration than at normal or reduced.

The decrease of BP within therapeutic limits has no effect on the cerebral blood flow, the blood flow in the brain vessels is maintained at a sufficient level even against the background of reduced BP. It enhances coronary and renal blood flow. Long-term use reduces LV myocardial hypertrophy and myofibrillation of arterial walls of the resistive type, prevents the progression of CHF and slows the development of LV dilatation. It improves blood supply of ischemic myocardium.

Limits platelet aggregation. Prolongs survival in patients with CHF and slows the progression of LV dysfunction in patients who had myocardial infarction without clinical manifestations of CHF.

It has some diuretic effect. It reduces intracolumnar hypertension, slowing down the development of glomerulosclerosis and the risk of CKD.

Enalapril is a “prodrug”: as a result of its hydrolysis enalaprilate is formed, which inhibits ACE.
Time of onset of hypotensive effect when taken orally is 1 hour, it reaches a maximum after 4-6 hours and lasts up to 24 hours. In some patients several weeks therapy is necessary to achieve optimal BP level. With CHF, a noticeable clinical effect is observed with long-term treatment of 6 months or more.

Pharmacokinetics:

After oral administration absorption is 60%. Food intake has no effect on absorption. In the liver it is metabolized to form the active metabolite enalaprilat, which is a more effective ACE inhibitor than enalapril. Binding to plasma proteins of enalaprilat is 50-60%. TCmax of enalapril is 1 h, of enalaprilat – 3-4 h.

Enalaprilat easily passes through the histohematic barriers, excluding the BBB, a small amount passes through the placenta and into breast milk.

T1/2 of enalaprilat is 11 h. It is excreted primarily by the kidneys – 60% (20% as enalapril and 40% as enalaprilat), through the intestine – 33% (6% as enalapril and 27% as enalaprilat).
Removable by hemodialysis (rate 62 ml/min) and peritoneal dialysis.

Indications

Arterial hypertension (symptomatic, renovascular, including with scleroderma, etc.), CHF I-III stages;

Prevention of coronary ischemia in patients with LV dysfunction, asymptomatic LV dysfunction.

Pharmacological effect

Pharmaceutical group:

ACE inhibitor.

Pharmaceutical action:

An ACE inhibitor is an antihypertensive drug, the mechanism of action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in the concentration of which leads to a direct decrease in aldosterone secretion. At the same time, peripheral resistance, systolic and diastolic blood pressure, post- and preload on the myocardium decrease. Dilates arteries to a greater extent than veins, while no reflex increase in heart rate is observed. Reduces bradykinin degradation, increases Pg synthesis. The hypotensive effect is more pronounced at high plasma renin concentrations than at normal or reduced levels.

A decrease in blood pressure within therapeutic limits does not affect cerebral circulation; blood flow in the vessels of the brain is maintained at a sufficient level even against the background of reduced blood pressure. Strengthens coronary and renal blood flow. With long-term use, hypertrophy of the LV myocardium and myofibril of the walls of resistive arteries decreases, prevents the progression of CHF and slows down the development of LV dilatation. Improves blood supply to ischemic myocardium.

Reduces platelet aggregation. Extends life expectancy in patients with CHF, slows the progression of LV dysfunction in patients who have had myocardial infarction without clinical manifestations of HF.

Has some diuretic effect. Reduces intraglomerular hypertension, slowing the development of glomerulosclerosis and the risk of chronic renal failure.

Enalapril is a “prodrug”: as a result of its hydrolysis, enalaprilat is formed, which inhibits ACE.
The onset of the hypotensive effect when taken orally is 1 hour, it 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 CHF, a noticeable clinical effect is observed with long-term treatment – 6 months or more.

Pharmacokinetics:

After oral administration, absorption is 60%. Eating does not affect absorption. It is metabolized in the liver to form the active metabolite enalaprilat, which is a more effective ACE inhibitor than enalapril. The binding of enalaprilat to plasma proteins is 50-60%. TCmax of enalapril – 1 hour, enalaprilat – 3-4 hours

Enalaprilat easily passes through histohematic barriers, excluding the blood-brain barrier; a small amount penetrates the placenta and into breast milk.

T1/2 of enalaprilat – 11 hours. Excreted mainly by 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).
It is removed by hemodialysis (rate 62 ml/min) and peritoneal dialysis.

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.

Active ingredient

Enalapril

Composition

1 tablet contains:

Active substance:

Enalapril maleate – 5 mg.

Excipients:

Microcrystalline cellulose – 73 mg;

Pregelatinized corn starch – 30 mg;

Talc – 3 mg;

Colloidal silicon dioxide – 1 mg;

Magnesium stearate – 1 mg.

Contraindications

Hypersensitivity to enalapril or other ACE inhibitors;

Pregnancy, lactation period.

With caution:

History of angioedema during therapy with ACE inhibitors, hereditary or idiopathic angioedema;

Aortic stenosis;

Cerebrovascular diseases (including cerebrovascular insufficiency);

IHD;

Coronary insufficiency;

Severe autoimmune systemic connective tissue diseases (including SLE, scleroderma);

Inhibition of bone marrow hematopoiesis;

Diabetes mellitus;

Hyperkalemia;

Bilateral renal artery stenosis;

Stenosis of the artery of a single kidney;

Condition after kidney transplantation;

Renal and/or liver failure;

Na+ restricted diet;

Conditions accompanied by a decrease in blood volume (including diarrhea, vomiting),

Elderly age, age under 18 years (safety and effectiveness of use have not been studied).

Side Effects

From the cardiovascular system: excessive decrease in blood pressure, orthostatic collapse, rarely – chest pain, angina pectoris, myocardial infarction (usually associated with a pronounced decrease in blood pressure), arrhythmias (atrial brady- or tachycardia, atrial fibrillation), palpitations, thromboembolism of the branches of the pulmonary artery.

From the nervous system: dizziness, fainting, headache, weakness, insomnia, anxiety, confusion, fatigue, drowsiness (2-3%), very rarely when used in high doses – nervousness, depression, paresthesia.

From the senses: disorders of the vestibular apparatus, hearing and vision impairment, tinnitus.

From the digestive system: dryness of the oral mucosa, loss of appetite, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, abdominal pain), intestinal obstruction, pancreatitis, impaired liver function and biliary excretion, hepatitis, jaundice.

From the respiratory system: nonproductive “dry” cough, interstitial pneumonitis, bronchospasm, shortness of breath, rhinorrhea, pharyngitis.

Allergic reactions:
skin rash, angioedema of the face, small intestine (very rarely), limbs, lips, tongue, glottis and/or larynx, dysphonia, exfoliative dermatitis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), pemphigus (pemphigus), pruritus, urticaria, photosensitivity, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis.

From laboratory parameters: hypercreatininemia, increased urea concentration, increased activity of “liver” transaminases, hyperbilirubinemia, hyperkalemia, hyponatremia, decreased Hb and hematocrit, increased ESR, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia.

From the urinary system: impaired renal function, proteinuria.

Other: alopecia, decreased libido, flushing of the face. Cases of hypoglycemia have been reported in patients with diabetes mellitus who took insulin and oral hypoglycemic drugs.

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, increased effects 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 when used simultaneously 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.

Overdose

Symptoms: excessive 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 saline solution are indicated; in more serious cases, measures aimed at stabilizing blood pressure are indicated: intravenous administration of a 0.9% NaCl solution, plasma substitutes, if necessary, intravenous administration of angiotensin II, hemodialysis (enalaprilat excretion rate – 62 ml/min).

Manufacturer

Izvarino Pharma, Russia