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. in scleroderma, etc.), CHF I-III stages;

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

Active ingredient

Composition

One tablet contains:

Active substance:

Enalapril maleate – 5 mg.

Associates:

Cellulose microcrystalline – 73 mg;

Corn starch pregelatinized – 30 mg;

Talc – 3 mg;

Colloidal silica – 1 mg;

Magnesium stearate – 1 mg.

How to take, the dosage

Overly, regardless of meals.

In monotherapy of arterial hypertension, the initial dose is 5 mg once daily. If there is no effect, after 1-2 weeks the dose is increased by 5 mg. After the initial dose, patients should be under medical supervision for 2 hours and an additional 1 hour until BP stabilizes. If necessary and tolerated well enough, the dose can be increased to 40 mg/day at 1-2 doses. After 2-3 weeks, switch to a maintenance dose of 10-40 mg/day divided into 1-2 doses. In moderate hypertension, the average daily dose is about 10 mg. The maximum daily dose of the drug is 40 mg.
If prescribed to patients simultaneously receiving diuretics, diuretic treatment should be discontinued 2-3 days before enalapril administration. If this is not possible, the starting dose of enalapril should be 2.5 mg/day.

Patients with hyponatremia (serum Na+ concentration less than 130 mmol/L) or serum creatinine concentration greater than 0.14 mmol/L have a starting dose of 2.5 mg once daily.

Renovascular hypertension: initial dose is 2.5-5 mg/day. The maximum daily dose is 20 mg.

In severe arterial hypertension, IV administration is possible (see Enalaprilat), conducted only in a hospital setting.

In CHF, the initial dose is 2.5 mg once, then the dose is increased by 2.5-5 mg every 3-4 days according to clinical response to the maximum tolerated dose (depending on BP), but no more than 40 mg/day, once, or in 2 doses. In patients with low systolic blood pressure (less than 110 mmHg), therapy should be started with a dose of 1.25 mg. The dose should be adjusted over 2-4 weeks or at shorter intervals. The average maintenance dose is 5-20 mg/day with 1-2 doses.
A more pronounced hypotensive effect and prolonged time of action of the drug are more often observed in elderly people due to decreased elimination rate of enalapril, therefore the recommended initial dose for elderly people is 1.25 mg.

In asymptomatic LV dysfunction, 2.5 mg twice daily. The dose is adjusted for tolerance to 20 mg/day, divided into 2 doses.

In CKD, cumulation occurs when filtration is less than 10 ml/min. For CK 80-30 mL/min, the dose is usually 5-10 mg/day, CK 30-10 mL/min is 2.5-5 mg/day, and less than 10 mL/min is 1.25-2.5 mg/day on dialysis days only.

The duration of treatment depends on the effectiveness of therapy. If BP decreases too markedly, the dose of the drug is gradually reduced.

Interaction

Concomitant use with immunosuppressants, cytostatics increases the risk of leukopenia.

Concomitant use of potassium-saving diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and food supplements containing potassium may lead to hyperkalemia (especially in patients with renal impairment).Because ACE inhibitors decrease the content of aldosterone, which leads to potassium retention in the body against the background of potassium excretion restriction or its additional intake.

The simultaneous use of opioid analgesics and drugs for anesthesia increases the antihypertensive effect of enalapril.

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

In concomitant use with azathioprine, anemia may occur due to inhibition of erythropoietin activity caused by ACE inhibitors and azathioprine.

A case of anaphylactic reaction and myocardial infarction has been described in a patient receiving enalapril when using allopurinol.

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

It is not conclusively established whether acetylsalicylic acid reduces the therapeutic efficacy of ACE inhibitors in patients with CHF and heart failure. The nature of this interaction depends on the course of the disease.

Acetylsalicylic acid, by inhibiting COX and prostaglandin synthesis, may cause vasoconstriction, resulting in decreased cardiac output and worsening of heart failure patients receiving ACE inhibitors.

The simultaneous use of beta-adrenoblockers, methyldopa, nitrates, calcium channel blockers, hydralazine, prazosin may increase the antihypertensive effect.

In concomitant use with NSAIDs (including indomethacin) antihypertensive effect of enalapril decreases, probably due to inhibition of prostaglandin synthesis (which is believed to play a role in development of hypotensive effect of ACE inhibitors) under the influence of NSAIDs. There is an increased risk of renal dysfunction; hyperkalemia is rarely observed.

The simultaneous use of insulin and hypoglycemic agents of sulfonylurea derivatives may lead to hypoglycemia.

The simultaneous use of ACE inhibitors and interleukin-3 may lead to a risk of hypotension.

In concomitant use with clozapine, there have been reports of syncope.

In concomitant use with clomipramine there have been reports of increased effects of clomipramine and development of toxic effects.

In concomitant use with co-trimoxazole cases of hyperkalemia have been described.

Concomitant use with lithium carbonate leads to increased serum lithium concentration accompanied by symptoms of lithium intoxication.

Concomitant use with orlistat decreases antihypertensive effect of enalapril, which may cause significant increase in BP, development of hypertensive crisis.

It is believed that concomitant use with procainamide may increase the risk of leukopenia.

Concomitant use with enalapril decreases the effect of drugs containing theophylline.

There have been reports of acute renal failure in patients after renal transplantation when concomitant use with cyclosporine.

Concomitant use with cimetidine increases the T1/2 of enalapril and increases its plasma concentrations.

It is believed that the effectiveness of antihypertensive agents may be reduced when used concomitantly with erythropoietins.

Concomitant use with ethanol increases the risk of arterial hypotension.

Special Instructions

Particular caution is used in patients with autoimmune diseases, diabetes mellitus, hepatic dysfunction, severe aortic stenosis, subaortic muscle stenosis of unclear genesis, hypertrophic cardiomyopathy, loss of fluid and salts. In case of previous saluretic treatment, particularly in patients with chronic heart failure, the risk of orthostatic hypotension increases, therefore the loss of fluids and salts should be compensated before starting enalapril treatment.

In long-term treatment with enalapril, peripheral blood counts should be monitored periodically. Sudden discontinuation of enalapril does not cause a sudden increase in BP.

In surgical interventions during enalapril treatment, arterial hypotension may occur, which should be corrected by administration of adequate fluid.

Enalapril should be stopped before parathyroid function study.

Influence on driving and operating machinery

Cautious driving or other work requiring increased attention is necessary because dizziness may occur, especially after taking the initial dose of enalapril.

Contraindications

Hypersensitivity to enalapril or other ACE inhibitors;

Pregnancy, lactation.

With caution:

Anhyoneurotic edema in the history of therapy with ACE inhibitors, hereditary or idiopathic angioedema;

Aortic stenosis;

Cerebrovascular disease (including.ч. Cerebrovascular failure);

IBS;

Coronary artery disease;

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

Inhibition of medullary hematopoiesis;

Diabetes mellitus;

Hyperkalemia;

Bilateral renal artery stenosis;

Stenosis of the artery of the sole kidney;

Post renal transplant condition;

Renal and/or hepatic insufficiency;

Na+ restricted diet;

CRC-reducing conditions (including

Elderly age, age under 18 years (safety and effectiveness not studied).

Side effects

Cardiovascular disorders: excessive decrease in BP, orthostatic collapse, rarely – chest pain, angina pectoris, myocardial infarction (usually associated with a pronounced decrease in BP), arrhythmias (atrial bradycardia or tachycardia, atrial fibrillation), palpitation, pulmonary artery thromboembolism.

Nervous system disorders:dizziness, fainting, headache, weakness, insomnia, anxiety, confusion, increased fatigue, somnolence (2-3%), very rarely with high doses – nervousness, depression, paresthesias.

Sensory organs:vestibular disorders, hearing and vision disorders, tinnitus.

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

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

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

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

Urinary system disorders: renal dysfunction, proteinuria.

Others: alopecia, decreased libido, “rushes” of blood to the face. Cases of hypoglycemia have been reported in patients with diabetes mellitus who were taking insulin and oral hypoglycemic drugs.

Overdose

Symptoms: excessive decrease in BP, up to the development of collapse, myocardial infarction, acute stroke or thromboembolic complications; convulsions, stupor.

Treatment: the patient is transferred to a horizontal position with a low headboard. In mild cases gastric lavage and oral administration of saline solution are indicated, in more severe cases – measures aimed at BP stabilization: intravenous infusion of 0.9% NaCl solution, plasma substitutes, if necessary – intravenous angiotensin II, hemodialysis (elimination rate of enalaprilat 62 ml/min).

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