ENALAPRIL PILLS 10 MG

Clinico-pharmacological group

ACE inhibitor

Mechanism of action

Enalapril is an antihypertensive drug from the group of ACE inhibitors. Enalapril is a “prodrug”: as a result of its hydrolysis, enalaprilat is formed, which inhibits ACE. The mechanism of its action is associated with a decrease in the formation of angiotensin I from angiotensin II, the reduction of which leads to a direct decrease in the release of aldosterone. At the same time, the total peripheral vascular resistance, systolic and diastolic blood pressure, post- and preload on the myocardium decrease.

Expands the arteries to a greater extent than the veins, while a reflex increase in heart rate is not observed.

The hypotensive effect is more pronounced with a high level of plasma renin than with its normal or reduced level. Reducing blood pressure in therapeutic limits does not affect the cerebral circulation, the blood flow in the vessels of the brain is maintained at a sufficient level and against the background of low blood pressure. Enhances coronary and renal blood flow.

With prolonged use, left ventricular myocardial hypertrophy and myocytes of resistive-type artery walls are reduced, prevents progression of heart failure and slows down the development of left ventricular dilatation. Improves blood supply to ischemic myocardium.Reduces platelet aggregation. It has some diuretic effect.

The time of onset of the 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 an optimal level of blood pressure. With heart failure, a noticeable clinical effect is observed with prolonged use - 6 months or more.

Pharmacokinetics

After ingestion 60% of the drug is absorbed. Eating does not affect the absorption of enalapril. Bioavailability of the drug - 40%. Cmax enalapril in blood plasma is reached after 1 h, enalaprilat after 3-4 h.

Enalapril is up to 50% bound to blood proteins. Enalaprilat easily passes through histohematogenous barriers, excluding BBB, a small amount passes through the placenta and into breast milk.

Enalapril is rapidly metabolized in the liver to form the active metabolite enalaprilat, which is a more active ACE inhibitor than enalapril.

T1/2 enalaprilat - about 11 hours. Enalapril is derived mainly by the kidneys - 60% (20% - as enalapril and 40% - as enalaprilat), through the intestine - 33% (6% - as enalapril and 27% - as enalaprilat). It is removed during hemodialysis (speed - 62 ml / min) and peritoneal dialysis.

Indications for use of the drug

- arterial hypertension;

- with chronic heart failure (as part of combination therapy).

Dosage and administration

Assign inside regardless of meal times.

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

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

In the case of the appointment of patients receiving diuretics at the same time, diuretic treatment should be stopped 2-3 days before the appointment of Enalapril. If this is not possible, then the initial dose of the drug should be 2.5 mg / day.

Patients with hyponatremia (the concentration of sodium ions in the serum is less than 130 mmol / l) or the concentration of creatinine in the serum more than 0.14 mmol / l, the initial dose is 2.5 mg 1 time / day.

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

At chronic heart failure the initial dose is 2.5 mg once, then the dose is increased by 2.5 - 5 mg every 3-4 days in accordance with the clinical response to the maximum tolerated dose, depending on the values ​​of blood pressure, but not more than 40 mg / day once or in 2 doses. In patients with low systolic blood pressure (less than 110 mm Hg), therapy should be started with a dose of 1.25 mg / day. Selection of the dose should be carried out within 2-4 weeks or in a shorter time. The average maintenance dose is 5-20 mg / day for 1-2 doses.

Have the elderly in people more often, a more pronounced hypotensive effect and a prolongation of the drug action time are observed, which is associated with a decrease in the rate of enalapril elimination, therefore the recommended initial dose for the elderly is 1.25 mg.

At chronic renal failure cumulation occurs when filtration decreases below 10 ml / min. When QA is 80-30 ml / min, the dose is usually 5-10 mg / day, with QC up to 30-10 ml / min - 2.5-5 mg / day, with QC less than 10 ml / min - 1.25-2.5 mg / day only in the days of dialysis.

The duration of treatment depends on the effectiveness of the therapy. With too pronounced decrease in blood pressure, the dose of the drug is gradually reduced.

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

Side effect

Enalapril is generally well tolerated and in most cases does not cause side effects requiring discontinuation of the drug.

Since the cardiovascular system: excessive decrease in blood pressure, orthostatic collapse, rarely - chest pain, angina pectoris, myocardial infarction (usually associated with a pronounced decrease in blood pressure), extremely rare - arrhythmias (atrial brady- or tachycardia, atrial fibrillation), palpitations, thromboembolism of pulmonary artery branches.

From the nervous system: dizziness, headache, weakness, insomnia, anxiety, confusion, fatigue, drowsiness (2-3%), very rarely with high doses - nervousness, depression, paresthesia.

From the senses: disorders of the vestibular apparatus, hearing and vision impairment, tinnitus.

From the digestive tract: dry mouth, anorexia, dyspepsia (nausea, diarrhea or constipation, vomiting, abdominal pain), intestinal obstruction, pancreatitis, abnormal liver function and biliary excretion, hepatitis, jaundice.

On the part of the respiratory system: non-productive dry cough, interstitial pneumonitis, bronchospasm, shortness of breath, rhinorrhea, pharyngitis.

Allergic reactions: skin rash, pruritus, urticaria, angioedema, extremely rare - dysphonia, erythema polymorphic, exfoliative dermatitis, Stephen-Johnson syndrome, toxic epidermal necrolysis, pemphigus, photosensitization, serositis, vasculitis, myositis, arthritis, arthritis, stomatitis, photosensitization, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, photosensitization, serositis, vasculitis, myositis, arthritis, arthritis, stomatitis, photosensitization, serositis, vasculitis

From the laboratory indicators: hypercreatininemia, increased urea, increased liver enzymes, hyperbilirubinemia, hyperkalemia, hyponatremia. In some cases, a decrease in hematocrit, increased ESR, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), and eosinophilia are noted.

From the urinary system: renal failure, proteinuria.

Other: alopecia, decreased libido, hot flashes.

Contraindications to the use of the drug

- the presence of a history of angioedema associated with treatment with ACE inhibitors;

- porphyria;

- pregnancy;

- lactation period;

- age up to 18 years (efficiency and safety have not been established);

- Hypersensitivity to enalapril and other ACE inhibitors.

WITH caution use in primary hyperaldosteronism, bilateral renal artery stenosis, single kidney artery stenosis, hyperkalemia, condition after kidney transplantation; aortic stenosis, mitral stenosis (with hemodynamic disorders), idiopathic hypertrophic subaortic stenosis, systemic connective tissue diseases, ischemic heart disease, cerebrovascular diseases, diabetes mellitus, renal failure (proteinuria - more than 1 g / day), liver failure, in dieters with restriction of salt or being on hemodialysis, while taking it with immunosuppressants and saluretics, in the elderly (over 65).

Application for violations of the liver

WITHcaution apply in case of liver failure.

Application for violations of kidney function

At chronic renal failure cumulation occurs when filtration decreases below 10 ml / min. When QA is 80-30 ml / min, the dose is usually 5-10 mg / day, with QC up to 30-10 ml / min - 2.5-5 mg / day, with QC less than 10 ml / min - 1.25-2.5 mg / day only in the days of dialysis.

special instructions

Care must be taken when prescribing Enalapril to patients with reduced BCC (as a result of diuretic therapy, while limiting salt intake, hemodialysis, diarrhea and vomiting) - the risk of sudden and pronounced reduction in blood pressure after the initial dose of the ACE inhibitor has been increased.Transient arterial hypotension is not a contraindication for the continuation of drug treatment after stabilization of blood pressure. In case of repeated pronounced decrease in blood pressure, reduce the dose or discontinue the drug.

The use of highly permeable dialysis membranes increases the risk of an anaphylactic reaction. Correction of the dosing regimen on dialysis-free days should be carried out depending on the level of blood pressure.

Before and during treatment with ACE inhibitors, periodic monitoring of blood pressure, blood parameters (hemoglobin, potassium, creatinine, urea, liver enzyme activity), and protein in the urine is necessary.

Patients with severe heart failure, coronary heart disease and vascular diseases of the brain, in whom a sharp decrease in blood pressure can lead to myocardial infarction, stroke or impaired renal function, should be carefully monitored.

Sudden cancellation of treatment does not lead to the syndrome of "cancellation" (a sharp rise in blood pressure).

Newborns and infants who have been exposed to intrauterine effects of ACE inhibitors are recommended to be closely monitored to timely detect a pronounced decrease in blood pressure, oliguria, hyperkalemia and neurological disorders, possibly due to a decrease in renal and cerebral blood flow while reducing blood pressure caused by ACE inhibitors. In oliguria, it is necessary to maintain blood pressure and renal perfusion by injecting appropriate fluids and vasoconstrictor agents.In the presence of renal failure, a decrease in the elimination of the active metabolite is possible, leading to an increase in its concentration in the blood plasma. Such patients may require the appointment of smaller doses of the drug.

In patients with arterial hypertension and unilateral or bilateral stenosis of the renal arteries, an increase in serum urea and creatinine levels is possible.

In these patients, renal function must be monitored during the first few weeks of therapy. May require reduced dosage of the drug.

The balance of risk and potential benefit should be considered when prescribing enalapril to patients with coronary and cerebrovascular insufficiency, due to the danger of increased ischemia in patients with excessive arterial hypotension.

The drug should be prescribed with caution in patients with diabetes due to the risk of hyperkalemia.

Patients with a history of indications of angioedema may have an increased risk of developing angioedema due to treatment with enalapril.

In patients with severe autoimmune diseases, such as systemic lupus erythematosus or scleroderma, the risk of developing neutropenia or agranulocytosis with enalapril is increased.

It is recommended to exercise caution when prescribing Enalapril for the treatment of chronic heart failure in patients receiving cardiac glycosides and / or diuretics.

Before the study of the functions of the parathyroid glands, the drug should be canceled. Alcohol enhances the hypotensive effect of the drug.

Before surgery (including dentistry) it is necessary to warn the surgeon / anesthesiologist about the use of ACE inhibitors.

Influence on ability to drive motor transport and control mechanisms

At the beginning of treatment, before the end of the dose selection period, it is necessary to refrain from driving vehicles and practicing potentially hazardous activities that require increased concentration and psychomotor speed, as dizziness is possible, especially after the initial dose of the ACE inhibitor in patients taking diuretic drugs.

Overdose

Symptoms: pronounced decrease in blood pressure up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications, convulsions, stupor.

Treatment: the patient is transferred to a horizontal position with a low head. In mild cases, gastric lavage and ingestion of a saline solution are shown, in more severe cases, measures aimed at stabilizing blood pressure: intravenous saline, plasma substitutes, if necessary, angiotensin II administration, hemodialysis (enalaprylate elimination rate averages 62 ml / min ).

Drug interaction

With the simultaneous appointment of enalapril with NSAIDs, a hypotensive effect may be reduced; with potassium-sparing diuretics (spironolactone, triamteren,amiloride) can lead to hyperkalemia; with lithium salts - to slow the removal of lithium (shown to control the concentration of lithium in the blood plasma).

Simultaneous use with antipyretic and analgesic drugs can reduce the effectiveness of enalapril.

Enalapril reduces the effect of drugs containing theophylline.

The hypotensive effect of enalapril is enhanced by diuretics, beta-blockers, methyldopa, nitrates, Calcium channel blockers, hydralazine, prazozin.

Immunosuppressants, Allopurinol, cytotoxic drugs enhance hematotoxicity.

Drugs that cause bone marrow depression increase the risk of developing neutropenia and / or agranulocytosis.

Terms and conditions of storage

List B. Store in a dry place inaccessible to children at a temperature of from 15 to 25 ° C.