Enalapril, tablets 10 mg, 20 pcs.

Pharmaceutical group:

The ACE inhibitor.

Pharmic action:

The ACE inhibitor is a hypotensive drug, the mechanism of action is related to the reduction of formation from angiotensin I of angiotensin II, a 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 decreases 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 to ischemic myocardium. Decreases 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.

Limits intracochlear hypertension, slowing the development of glomerulosclerosis and the risk of CKD. Enalapril is a “prodrug”: its hydrolysis produces enalaprilate, which inhibits ACE.

The 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, therapy for several weeks is necessary to achieve optimal BP level. With CHF a notable clinical effect is observed with long-term treatment – 6 months or more.

Indications

Arterial hypertension (symptomatic, renovascular, including in scleroderma, etc.), CHF stage I-III; prevention of coronary ischemia in patients with LV dysfunction, asymptomatic LV dysfunction.

Active ingredient

How to take, the dosage

Enalapril can be taken with plenty of fluids and without meals. Daily doses are usually taken in the morning, however, the drug may be divided into 2 times – morning and evening. Increased hypotensive effect is possible with concomitant use of diuretics.

Arterial hypertension:

The initial dose is 5 mg in the morning (1 tablet of 5 mg enalapril maleate). If blood pressure does not normalize at this dose, the daily dose may be increased to 10 mg. The interval between dose increases should be at least 3 weeks. The maintenance dose is usually 10 mg enalapril maleate. The maximum daily dose should not exceed 40 mg per day (2 times 20 mg of enalapril maleate).

Chronic heart failure:

The initial dose is 2.5 mg in the morning. The dose should be increased gradually, depending on the patient’s condition. The maintenance dose is usually 5 – 10 mg (1 – 2 tablets of 5 mg, or 1 tablet of 10 mg enalapril maleate). The maximum daily dose should not exceed 20 mg (2 tablets of 10 mg, or 1 tablet of 20 mg).

Left ventricular dysfunction:

The starting dose is 2.5 mg of enalapril maleate 2 times daily, dose adjustment is possible depending on the patient’s condition. The average maintenance dose is 10 mg 2 times daily.

Patients with moderate renal impairment (creatinine clearance 30 – 60 ml/minute) and patients aged over 65 years: The initial dose is 2.5 mg in the morning. The maintenance dose is usually 5 to 10 mg (1 to 2 tablets of 5 mg or 1 tablet of 10 mg) of enalapril maleate per day. The maximum daily dose should not exceed 20 mg (2 tablets of 10 mg or 1 tablet of 20 mg) of enalapril.

Patients with significant renal impairment (creatinine clearance less than 30 ml/min) and those on hemodialysis: The starting dose is 2.5 mg enalapril maleate daily.

Patients on hemodialysis should take the drug after dialysis. The maintenance dose is usually 5 mg (1 5 mg tablet) of enalapril per day. The maximum daily dose should not exceed 10 mg (1 10-mg tablet or 2 5-mg tablets) per day.

The drug may be used as monotherapy, or in combination with other antihypertensive agents, especially diuretics.

Interaction

In concomitant use with immunosuppressants, cytostatics, the risk of leukopenia increases. 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 aldosterone content, which leads to potassium retention in the body against restricted potassium excretion or its additional intake into the body. When concomitant use of opioid analgesics and drugs for anesthesia, the antihypertensive effect of enalapril increases. When concomitant use of “loop” diuretics, thiazide diuretics, the antihypertensive effect increases. There is a risk of hypokalemia.

The risk of impaired renal function is increased. In concomitant use with azathioprine development of anemia is possible due to inhibition of erythropoietin activity under influence of 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. Whether acetylsalicylic acid reduces the therapeutic efficacy of ACE inhibitors in patients with CHD and heart failure has not been definitively determined.

The nature of this interaction depends on the course of the disease. Acetylsalicylic acid, by inhibiting COX and prostaglandin synthesis, may cause vasoconstriction, which leads to decreased cardiac output and worsening in patients with heart failure receiving ACE inhibitors.

Concomitant use of beta-adrenoblockers, methyldopa, nitrates, calcium channel blockers, hydralazine, prazosin may increase the antihypertensive effect. When concomitant use with NSAIDs (including indomethacin), the antihypertensive effect of enalapril decreases, apparently due to inhibition of prostaglandin synthesis (which is believed to play a role in the development of hypotensive effect of ACE inhibitors) under the influence of NSAIDs. The risk of renal dysfunction increases; hyperkalemia is rarely observed. Concomitant use of insulin and hypoglycemic agents of sulfonylurea derivatives may cause hypoglycemia.

In concomitant use of ACE inhibitors and interleukin-3 there is a risk of arterial hypotension. When concomitant use with clozapine there are reports about the development of syncope. Increased effect of clomipramine and development of toxic effects have been reported when concomitant use with clomipramine. When 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. When concomitant use with orlistat the antihypertensive effect of enalapril decreases, which may lead to a significant increase in BP, development of hypertensive crisis. It is believed that concomitant use with procainamide may increase the risk of leukopenia. When concomitant use with enalapril the effect of drugs containing theophylline is reduced. There are reports about the development of acute renal failure in patients after kidney transplantation when concomitant use with cyclosporine.

Concomitant use with cimetidine increases T1/2 of enalapril and increases its plasma concentrations. It is believed that the effectiveness of antihypertensive agents may decrease when concomitant use with erythropoietins. When concomitant use with ethanol the risk of arterial hypotension increases.

Special Instructions

Particular caution is used in patients with autoimmune diseases, diabetes mellitus, liver dysfunction, severe aortic stenosis, subaortic muscle stenosis of unclear genesis, hypertrophic cardiomyopathy, loss of fluid and salts.

In prior saluretic treatment, particularly in patients with chronic heart failure, the risk of orthostatic hypotension increases, so fluid and salt loss should be compensated before starting enalapril treatment. During long-term treatment with enalapril, peripheral blood counts should be periodically monitored.

Sudden discontinuation of enalapril does not cause a sharp increase in BP. Surgical interventions during enalapril treatment may cause arterial hypotension, which should be corrected by administration of sufficient fluids. Enalapril should be discontinued before parathyroid function study.

Impact on driving and operating machinery

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

Contraindications

A history of angioedema associated with treatment with ACE inhibitors; porphyria; pregnancy; lactation; under 18 years of age (efficacy and safety not established); 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.

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

Urinary system disorders: 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.

Other: rarely – hyperkalemia, muscle cramps.

Overdose

Symptoms: marked decrease of blood pressure, up to the development of collapse, myocardial infarction, acute cerebral circulation disorder 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 administration of saline solution, plasma substitutes, if necessary – angiotensin II administration, hemodialysis (elimination rate of enalaprilat is on average 62 ml/minute).

Similarities