Enalapril, tablets 10 mg 20 pcs

Pharmgroup:

A ACE inhibitor.

Pharm action:

The ACE inhibitor is a hypotensive drug; its mechanism of action is related to reduction of formation from angiotensin I of angiotensin II, reduction of concentration of which leads to direct reduction of aldosterone secretion.

This decreases RPS, systolic and diastolic BP, post- and preload on myocardium.

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

Decreases bradykinin degradation, increases Pg synthesis. Hypotensive effect is more pronounced at high plasma renin concentration than at normal or reduced concentration.

The decrease of BP within therapeutic limits has no effect on cerebral blood flow; blood flow in cerebral vessels is maintained at a sufficient level even against the background of reduced BP.

Enhances coronary and renal blood flow. With prolonged use it decreases LV myocardial hypertrophy and myofibrillar resistance arterial walls, prevents the progression of CHF and slows the development of LV dilatation.

It improves blood supply to 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”: its hydrolysis produces enalaprilate, which inhibits ACE.

The time of onset of hypotensive effect with oral administration 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 levels. In patients with CHF, a significant clinical effect is seen 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.

The 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.

The T1/2 of enalaprilat is 11 h. It is excreted mainly 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 stage I-III; prevention of coronary ischemia in patients with LV dysfunction, asymptomatic LV dysfunction.

Active ingredient

Composition

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, the dose is increased by 5 mg after 1-2 weeks.

After the initial dose, patients should be under medical supervision for 2 hours and an additional 1 hour until BP stabilizes. If necessary and sufficiently well tolerated, the dose can be increased to 40 mg/day in 1-2 doses.

After 2-3 weeks, a maintenance dose of 10-40 mg/day, divided into 1-2 doses, is switched to. 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 receiving diuretics at the same time, the diuretic treatment should be stopped 2-3 days before prescribing enalapril. 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 forms of arterial hypertension, IV administration is possible (see Enalaprilat), carried out only under hospital conditions.

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 maximum tolerated doses (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 in 1-2 doses.

The elderly are more likely to have a more pronounced hypotensive effect and prolonged time of action of the drug due to decreased elimination rate of enalapril, so the recommended starting dose for the elderly 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 significantly, the dose of the drug is gradually reduced.

Interaction

Enhances the effect of ethanol, slows excretion of Li+.

Limits the effect of drugs containing theophylline.

Hypotensive effect is decreased by NSAIDs including selective COX-2 inhibitors, estrogens; it is increased by diuretics, other hypotensive drugs (beta-adrenoblockers, methyldopa, nitrates, BMCC, hydralazine, prazosin), drugs for general anesthesia, ethanol.

Potassium-saving diuretics and potassium-containing drugs increase the risk of hyperkalemia.
Drugs that cause bone marrow suppression increase the risk of neutropenia and/or agranulocytosis.

When concomitant use of ACE inhibitors and gold drugs for parenteral use (sodium aurothiomalate) a symptom complex including facial hyperemia, nausea, vomiting and decrease in blood pressure has been described.

Simultaneous use with insulin and oral hypoglycemic drugs increases the risk of hypoglycemia.

Immunosuppressants, allopurinol, cytostatics increase hematotoxicity.

Special Instructions

Caution should be exercised when prescribing in patients with decreased blood pressure (as a result of diuretic therapy, restriction of table salt intake, hemodialysis, diarrhea and vomiting) – the risk of a sudden and pronounced BP decrease after using even the initial dose of ACE inhibitor is increased.

Transient hypotension is not a contraindication to continue treatment with the drug after BP stabilization. In case of repeated pronounced BP decrease, the dose should be reduced or the drug should be discontinued.

In case of development of excessive BP decrease, the patient should be placed in horizontal position with low headrest; if necessary, 0.9% NaCl solution and plasma exchange drugs should be administered.

The use of high-flow dialysis membranes (including AN69) increases the risk of anaphylactic reaction. Adjustment of the dosing regimen on days free of dialysis should be made depending on BP.

Before and during treatment with ACE inhibitors, BP, blood parameters (Hb, concentration of K+, creatinine, urea, activity of “liver” enzymes), urine protein should be controlled.

Patients with decompensated CHF, CHD, and cerebrovascular disease in whom a rapid decrease of BP may result in myocardial infarction, stroke, or impaired renal function should be closely monitored.

The abrupt withdrawal of treatment does not result in “withdrawal” syndrome (a rapid rise in BP).

Patients with a history of angioedema have an increased risk of developing it when taking ACE inhibitors.

In newborns and infants who have had intrauterine exposure to ACE inhibitors should be closely monitored for early detection of significant decreases in BP, oliguria, hyperkalemia, and neurologic impairment due to decreased renal and cerebral blood flow with ACE inhibitor-induced BP reduction.

In oliguria, it is necessary to maintain BP and renal perfusion by administration of appropriate fluids and vasoconstrictors.

In patients with reduced renal function, the single dose should be reduced or the intervals between doses should be increased.

Enalapril should be stopped before parathyroid function tests.

Cautions should be taken when exercising or in hot weather (risk of dehydration and excessive lowering of BP due to decreased RBC).

Warn the surgeon/anesthesiologist about the use of ACE inhibitors before surgical procedures (including dentistry).

At the time of treatment, caution should be exercised when driving a vehicle and engaging in other potentially dangerous activities requiring increased concentration and rapid psychomotor reactions (dizziness is possible, especially after taking the initial dose of ACE inhibitor in patients taking diuretic drugs).

Contraindications

Side effects

Cardiovascular system disorders: excessive BP decrease, orthostatic collapse, rarely – chest pain, angina pectoris, myocardial infarction (usually associated with a pronounced BP decrease), 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, paresthesia.

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

Digestive system disorders: dry mouth, decreased appetite, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, abdominal pain), intestinal obstruction, pancreatitis, disorders of liver function and biliary excretion, hepatitis, jaundice.

Respiratory system: non-productive “dry” cough, interstitial pneumonitis, bronchospasm, dyspnea, 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-Johnson syndrome).Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), pemphigus, pruritus, urticaria, photosensitization, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis.

Laboratory values: hypercreatininemia, increased concentration of urea, increased “hepatic” transaminases activity, hyperbilirubinemia, hyperkalemia, hyponatremia, decreased Hb and hematocrit, increased sedimentation rate, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia.

Urinary system disorders: impaired renal function, proteinuria.

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

Overdose

Symptoms:

The excessive decrease in BP, up to the development of collapse, myocardial infarction, acute cerebral circulation disorder or thromboembolic complications; seizures, 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 stabilization of BP:

injection of 0.9% NaCl solution, plasma substitutes, if necessary – intravenous angiotensin II, hemodialysis (elimination rate of enalaprilat 62 ml/min).

Similarities