Envas (Tablets) Instructions for Use

ATC Code

C09AA02 (Enalapril)

Active Substance

Enalapril

Clinical-Pharmacological Group

ACE inhibitor

Pharmacotherapeutic Group

ACE blocker

Pharmacological Action

ACE inhibitor. It is a prodrug from which the active metabolite enalaprilat is formed in the body. It is believed that the mechanism of the antihypertensive action is associated with the 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 the decrease in the concentration of angiotensin II, a secondary increase in plasma renin activity occurs due to the elimination of the negative feedback during renin release and a direct decrease in aldosterone secretion. In addition, enalaprilat appears to affect the kinin-kallikrein system by preventing the breakdown of bradykinin.

Due to its vasodilating action, it reduces total peripheral vascular resistance (afterload), pulmonary capillary wedge pressure (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). In patients with mild to moderate heart failure, Enalapril slows its progression and also slows 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).

Pharmacokinetics

When taken orally, about 60% is absorbed from the gastrointestinal tract. Concurrent food intake does not affect absorption. It is metabolized in the liver by hydrolysis to form enalaprilat, through whose pharmacological activity the antihypertensive effect is realized. The binding of enalaprilat to plasma proteins is 50-60%.

The T_1/2 of enalaprilat is 11 hours and increases in 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.

Indications

Arterial hypertension (including renovascular), 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 to reduce the incidence of myocardial infarction and the frequency of hospitalizations for unstable angina.

ICD codes

Dosage Regimen

For arterial hypertension, initiate therapy at 2.5 mg to 5 mg once daily.

Adjust the dose based on individual blood pressure response.

The usual maintenance dose is 10 mg to 20 mg per day, administered as a single dose or in two divided doses.

For chronic heart failure, start with a low initial dose of 2.5 mg once daily under close medical supervision.

In patients at higher risk for hypotension, begin with 1.25 mg once daily.

Titrate the dose gradually to a target maintenance dose of 10 mg to 20 mg daily, given in one or two doses.

The maximum daily dose is 40 mg.

In patients with renal impairment, adjust the dose based on creatinine clearance.

For creatinine clearance greater than 30 mL/min, the initial dose is 5 mg daily.

For creatinine clearance of 30 mL/min or less, the initial dose is 2.5 mg daily.

Subsequent dosing should be titrated according to patient tolerance and therapeutic response.

For patients on diuretic therapy, discontinue the diuretic 2 to 3 days before initiating enalapril if possible to reduce the risk of symptomatic hypotension.

If diuretic therapy cannot be stopped, administer an initial dose of 1.25 mg or 2.5 mg under close medical supervision for at least two hours after the first dose.

Monitor blood pressure and renal function regularly during dose titration and maintenance therapy.

Adverse Reactions

From the nervous system: dizziness, headache, feeling of tiredness, increased fatigue; very rarely when used in high doses – sleep disorders, nervousness, depression, imbalance, paresthesia, tinnitus.

From the cardiovascular system: orthostatic hypotension, fainting, palpitations, chest pain; very rarely when used in high doses – flushing.

From the digestive system: nausea; rarely – dry mouth, abdominal pain, vomiting, diarrhea, constipation, impaired liver function, increased activity of liver transaminases, increased blood bilirubin concentration, 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.

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, angioedema.

Other: rarely – hyperkalemia, muscle cramps.

Contraindications

History of angioedema, bilateral renal artery stenosis or stenosis of the artery of a single kidney, hyperkalemia, porphyria, concurrent use with aliskiren in patients with diabetes mellitus or impaired renal function (creatinine clearance <60 ml/min), pregnancy, lactation period (breastfeeding), children and adolescents under 18 years of age, hypersensitivity to enalapril and other ACE inhibitors.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy. If pregnancy occurs, enalapril should be discontinued immediately.

Enalapril is excreted in breast milk. If its use is necessary during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Use with particular caution in patients with impaired liver function.

Pediatric Use

The safety and efficacy of enalapril in children have not been established.

Special Precautions

Use with particular caution in patients with autoimmune diseases, diabetes mellitus, impaired liver function, severe aortic stenosis, subaortic muscular stenosis of unclear genesis, hypertrophic cardiomyopathy, with loss of fluid and salts. In case of prior treatment with saluretics, particularly in patients with chronic heart failure, the risk of developing orthostatic hypotension increases, so before starting treatment with enalapril, it is necessary to compensate for the loss of fluid and salts.

During long-term treatment with enalapril, it is necessary to periodically monitor the peripheral blood picture. Sudden discontinuation of enalapril does not cause a sharp increase in blood pressure.

During surgical interventions while taking enalapril, arterial hypotension may develop, which should be corrected by administering a sufficient amount of fluid.

Before examining the function of the parathyroid glands, Enalapril should be discontinued.

Effect on the ability to drive vehicles and mechanisms

Caution is required when driving vehicles or performing other work that requires increased attention, because dizziness is possible, especially after taking the initial dose of enalapril.

Drug Interactions

With simultaneous use with immunosuppressants, cytostatics, the risk of developing leukopenia increases.

With simultaneous use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and dietary supplements containing potassium, the development of hyperkalemia is possible (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 limited potassium excretion or its additional intake.

With simultaneous use of opioid analgesics and agents for anesthesia, the antihypertensive effect of enalapril is enhanced.

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

With simultaneous use with azathioprine, the development of anemia is possible, which is due to the suppression of erythropoietin activity under the influence of ACE inhibitors and azathioprine.

A case of anaphylactic reaction and myocardial infarction has been described with the use of allopurinol in a patient receiving Enalapril.

Acetylsalicylic acid in high doses may reduce the antihypertensive effect of enalapril.

It has not been definitively established whether acetylsalicylic acid reduces the therapeutic efficacy 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 in patients with heart failure receiving ACE inhibitors.

With simultaneous use of beta-blockers, methyldopa, nitrates, calcium channel blockers, hydralazine, prazosin, an enhancement of the antihypertensive effect is possible.

With simultaneous use with NSAIDs (including indomethacin), the antihypertensive effect of enalapril is reduced, apparently due to the inhibition of prostaglandin synthesis under the influence of NSAIDs (which are believed to play a certain role in the development of the hypotensive effect of ACE inhibitors). The risk of developing impaired renal function increases; hyperkalemia is rarely observed.

With simultaneous use of insulin, hypoglycemic agents of sulfonylurea derivatives, the development of hypoglycemia is possible.

With simultaneous use of ACE inhibitors and interleukin-3, there is a risk of developing arterial hypotension.

With simultaneous use with clozapine, there are reports of the development of syncope.

With simultaneous use with clomipramine, an enhancement of the action of clomipramine and the development of toxic effects are reported.

With simultaneous use with co-trimoxazole, cases of hyperkalemia have been described.

With simultaneous use with lithium carbonate, the concentration of lithium in the blood serum increases, which is accompanied by symptoms of lithium intoxication.

With simultaneous use 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, the risk of developing leukopenia may increase.

With simultaneous use 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 with simultaneous use with cyclosporine.

With simultaneous use with cimetidine, the T_1/2 of enalapril increases and its concentration in the blood plasma increases.

It is believed that a decrease in the effectiveness of antihypertensive agents is possible with simultaneous use with erythropoietins.

With simultaneous use with ethanol, the risk of developing arterial hypotension increases.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.