Enalapril tablets 5 mg 20 pcs.

Enalapril is an antihypertensive drug from the ACE inhibitor group. Enalapril is a “prodrug”: as a result of its hydrolysis enalaprilat is formed, which inhibits ACE. Its mechanism of action is related to the reduction of angiotensin I and angiotensin II, the reduction of which leads to a direct reduction of aldosterone secretion. This decreases total peripheral vascular resistance, systolic and diastolic BP, post- and preload on myocardium.

Dilates the arteries to a greater extent than the veins, and there is no reflex increase in heart rate.

The hypotensive effect is more pronounced at high plasma renin levels than at normal or reduced levels. 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 blood pressure. It enhances coronary and renal blood flow.

Long-term use reduces hypertrophy of the left ventricular myocardium and myocytes of the resistive arterial walls, prevents the progression of heart failure and slows the development of left ventricular dilatation. Improves blood supply to ischemic myocardium. Reduces platelet aggregation. It has some diuretic effect.

The time of the onset of hypotensive effect when taken orally is 1 hour, reaches a maximum after 4-6 hours and lasts up to 24 hours. In some patients, therapy for several weeks is necessary to achieve optimal BP levels. In cardiac insufficiency noticeable clinical effect is observed with long-term use – 6 months or more.

Indications

Active ingredient

Composition

Active ingredient:

Enalapril maleate – 5 mg.

Auxiliary substances:

Lactose monohydrate – 106,000 mg,

Magnesium carbonate – 71,645 mg,

gelatin – 7,800 mg,

crospovidone – 7,800 mg,

magnesium stearate – 1,755 mg.

How to take, the dosage

Appoint orally regardless of the time of meals.

In monotherapy of arterial hypertension, the initial dose is 5 mg once daily.
In the absence of clinical effect the dose is increased by 5 mg in 1-2 weeks. After the initial dose, patients should be under medical supervision for 2 hours and additional 1 hour until BP stabilizes. If necessary and tolerated well enough, the dose can be increased to 40 mg/day in 2 doses. After 2-3 weeks, switch to a maintenance dose of 10-40 mg/day divided into 1-2 doses. In moderate arterial hypertension, the average daily dose is about 10 mg.

The maximum daily dose of the drug is 40 mg/day.

If patients are prescribed concomitantly receiving diuretics, diuretic treatment should be discontinued 2-3 days before administration of enalapril. If this is not possible, the initial dose of the drug should be 2.5 mg/day.
Patients with hyponatremia (serum concentration of sodium ions less than 130 mmol/l) or serum creatinine concentration more than 0.14 mmol/l should take the initial dose of 2.5 mg once daily.

In renovascular hypertension the initial dose is 2.5-5 mg/day. The maximum daily dose is 20 mg.

In chronic heart failure the initial dose is 2.5 mg once and then the dose is increased by 2.5-5 mg every 3-4 days according to the clinical response up to maximum tolerated dose depending on the value of BP, but not more than 40 mg/day once or in 2 doses. Patients with low systolic blood pressure (less than 110 mmHg) should start therapy with a dose of 1.25 mg. The dose should be adjusted for 2-4 weeks or for shorter periods. The average maintenance dose is 5-20 mg/day in 1-2 doses.

The elderly more often have a more pronounced hypotensive effect and prolonged time of action of the drug, which is associated with decreased elimination rate of enalapril, so the recommended initial dose for the elderly is 1.25 mg.
In chronic renal failure, cumulation occurs when filtration is less than 10 ml/min. In creatinine clearance (CK) 80-30 ml/min, the dose is usually 5-10 mg/day, in CK up to 30-10 ml/min, 2, 5- 5 mg/day, in CK less than 10 ml/min, 1.25-2.5 mg/day on dialysis days only.

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

The drug is used both in monotherapy and in combination with other antihypertensive agents.

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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

An history of angioedema, bilateral renal artery stenosis or renal artery stenosis of the sole kidney, hyperkalemia, porphyria, concomitant use with aliskiren in patients with diabetes or impaired renal function (CK < 60 ml/min), pregnancy, lactation (breastfeeding), childhood and adolescence under 18 years of age, hypersensitivity to enalapril and other ACE inhibitors.

Side effects

CNS and peripheral nervous system disorders: dizziness, headache, fatigue, increased fatigue; very rarely with high doses – sleep disorders, nervousness, depression, balance disorders, paresthesias, tinnitus.

Cardiovascular system disorders: orthostatic hypotension, fainting, palpitations, heart pain; very rare with high doses – hot flashes.

The digestive system: nausea; rarely – dry mouth, abdominal pain, vomiting, diarrhea, constipation, liver disorders, increased liver transaminases activity, increased blood bilirubin concentration, hepatitis, pancreatitis; very rare in high doses – glossitis.

The hematopoietic system: rarely – neutropenia; in patients with autoimmune diseases – agranulocytosis.

Additional disorders of the urinary system: rarely – renal dysfunction, proteinuria.

Respiratory system disorders: dry cough.

Reproductive system disorders: very rare when used in high doses – impotence.

Dermatological reactions: very rare in high doses – hair loss.

Allergic reactions: rare – skin rash, Quincke’s edema.

Others: rarely – hyperkalemia, muscle cramps.

Overdose

Symptoms: pronounced BP decrease up to the development of collapse, myocardial infarction, acute cerebral circulation disorder or thromboembolic complications, convulsions, stupor.

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

Similarities