Enalapril - instructions for use, dose, side effects, contraindications

Description:white tablets from yellowish hue of color flat-cylindrical form with a bevel for a dosage of 5 mg and with a facet and a risk for a dosage of 20 mg.

Pharmacotherapeutic group:Angiotensin-converting enzyme (ACE) inhibitor.

ATX: & nbsp

C.09.A.A.02 Enalapril

Pharmacodynamics:

The ACE inhibitor is an antihypertensive agent, the mechanism of action of theIt is associated with a decrease in the formation of angiotensin I from atyotensin II, whose concentration decreases to a direct reduction in secretion aldosterone.

At the same time, the total peripheral resistance of blood vessels, systolic and diastolic arterial pressure (BP), post-, and preload on the myocardium. Expands arteries in larger degree than the veins, with a reflex increase in the frequency of cardiac no abbreviations are noted. Reduces the degradation of bradykinin, increases synthesis prostaglandins. The hypotensive effect is more pronounced at high concentration renin in the blood plasma than with normal or decreased. Reduction of blood pressure within the therapeutic limits does not affect cerebral blood circulation, blood flow in the vessels of the brain is maintained on sufficient level and against a background of lowered blood pressure.Strengthens coronary and renal blood flow. When prolonged use decreases myocardial left ventricular hypertrophy and mof wall iocytesof arteries of resistive type, prevents progression chronic heart failure and slows down the development ofleft ventricular dilation. Improves the blood supply of the ischemic myocardium. Reduces the aggregation of platelets. Lengthens life expectancy in patients with chronic heart failure, slows the progression of left ventricular dysfunction in patients who underwent myocardial infarction, without clinical manifestations of heart failure. Has some diuretic effect.

Reduces intra-cerebral hypertension, slowing the development of glomerulosclerosis and the risk of chronic renal failure.

Enalapril is a "prodrug": as a result of its hydrolysis, enaLaprilat, which also inhibits APF.

The time of onset of an antihypertensive effect with oral administration is 1 hour, reaches a maximum after 4-6 hours and lasts up to 24 hours. Some patients need therapy for several weeks to achieve the optimal level of blood pressure.In chronic heart failure, a visible clinical effect is observed with long-term treatment - 6 months or more.

Pharmacokinetics:

After ingestion, absorption is 60%. Eating does not affect absorption. In the liver is metabolized to form an active metabolite of enalaprilat, which is a more effective ACE inhibitor than enalapril. The connection with the proteins of the blood plasma enalaprilata - 50-60%. Time to reach the maximum concentration in the blood plasma enalapril - 1 hour, enalaprilata - 3-4 hours. Enalaprilat easily passes through the histohematological barriers, excluding the blood-brain barrier, a small amount penetrates through the placenta and into breast milk. The half-life of enalaprilat is 1 h. It is mainly excreted by the kidneys - 60% (20% in the form of enalapril and 40% in the form of enalaprilate), 33% through the intestine (6% in the form of enalapril and 27% in the form of enalaprilate).

It is removed during hemodialysis (rate 62 ml / min) and peritoneal dialysis.

Indications:

- arterial hypertension;

- chronic heart failure (as part of combination therapy);

- prevention of coronary ischemia in patients with left ventricular dysfunction;

- asymptomatic dysfunction of the left ventricle.

Contraindications:

Hypersensitivity to enalapril and other ACE inhibitors, history of angioedema, associated with treatment with ACE inhibitors, and hereditary or idiopathic angioedema, porphyria, pregnancy, lactation, age under 18 years (efficacy and safety not established).

Carefully:Be wary of primary hyperaldosteronism, bilateral renal artery stenosis, stenosis of the artery to a solitary kidney, hyperkalemia, condition after kidney transplantation; aortic stenosis, mitral stenosis (with impaired hemodynamics), idiopathic hypertrophic subaortic stenosis, systemic connective tissue diseases, ischemic heart diseases, cerebrovascular diseases, diabetes, renal disease (proteinuria greater than 1 g / d.), liver failure, patients complying diet with restriction of salt or hemodialysis, while admission to immunosuppressants and saluretikami in the elderly (over 65 years)oppression of bone marrow hematopoiesis; Conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting).

Dosing and Administration:

Inside, regardless of food intake.

When monotherapy arterial hypertension - the initial dose of 5 mg 1 time per day.

In the absence of a therapeutic 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 a fairly good tolerability dose can be increased to 40 mg / day. for l-2 reception. After 2-3 weeks pass to the maintenance dose - 10-40 mg / day, divided into 1-2 admission.

With a moderate degree of arterial hypertension, the average daily dose is about 10 mg. The maximum daily dose of the drug is 40 mg. In case of appointment to patients receiving diuretics at the same time, treatment with a diuretic should be stopped 2-3 days before. Enalapril administration. If this is not possible, the initial dose of Enalapril should be 2.5 mg / day. Patients with hyponatremia (serum sodium concentration below 130 mmol / L) or serum creatinine concentration greater than 0.14 mmol / L initial dose of 2.5 mg once a day.

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

In elderly patients, more pronounced hypotensive effect and lengthening of the drug action time are more frequent, which is associated with a decrease in the rate of enalapril elimination, therefore the recommended initial dose for elderly patients is 1.25 mg.

With asymptomatic violations of the function of the left ventricle - 2.5 mg 2 times a day. The dose is selected taking into account the tolerance to 20. mg / day, divided, into 2 doses. In chronic renal failure cumulation occurs with a decrease in filtration of less than 10 ml / min. With a creatinine clearance of 80-30 ml / min, the dose is usually 5-10 mg / day, the creatinine clearance is 30-10 ml / min. - 2.5-5 mg / day, less than 10 ml / min - 1.25-2.5 mg / day.only during dialysis days.

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

Side effects:

From the cardiovascular system: excessive decrease in blood pressure, orthostatic collapse, rarely - chest pain, angina, myocardial infarction or stroke (usually associated with a marked decrease in blood pressure), rarely arrhythmia (atrial brady or tachycardia, atrial fibrillation), palpitations , thromboembolism of the branches of the pulmonary artery, Raynaud's syndrome.

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

Co sensory side: violations of the vestibular apparatus, hearing and vision impairment, tinnitus.

Co the sides of the digestive system: dry mouth, anorexia, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, abdominal pain), intestinal obstruction, pancreatitis, liver and biliary dysfunction, hepatitis (hepatocellular or cholestatic), jaundice.

Co of the respiratory system: unproductive dry cough, sore throat, hoarseness, pulmonary infiltrates, interstitial pneumonitis, bronchospasm, dyspnea, rhinorrhea, pharyngitis.

Allergic reactions: skin rash, itching, urticaria, angioedema, extremely rarely dysphonia, polymorphic erythema, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus,

photosensitivity, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis, intestinal angioedema (very rarely).

Co side of laboratory indicators: hyperkreatinipaemia, increased urea levels, increased activity of "hepatic" enzymes, hyperbilirubinemia, hyperkalemia, hyponatremia, hypoglycemia in patients suffering from diabetes mellitus receiving hypoglycemic agents for ingestion or insulin.

In some cases, a decrease in the concentration of hemoglobin and hematocrit, increased ESR, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia are noted.

Co the side of the urinary system: violation kidney function, rarely proteinuria.

Other: alopecia, decreased libido, impotence, hot flashes.

Overdose:

Symptoms: excessive reduction of blood pressure, up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications; convulsions, stupor.

Treatment: patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage and ingestion of saline are shown, in more serious cases, measures aimed at stabilizing blood pressure: intravenous administration of a 0.9% solution NaCl, plasma substitutes, if necessary - intravenous angiotensin II, hemodialysis (the rate of excretion of enalaprilate is 62 ml / min).

Interaction:

With concomitant administration of enalapril with non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2 inhibitors), the hypotensive effect of enalapril may be reduced; with potassium-sparing diuretics (spironolactone, triamterep, amiloride) can lead to hyperkalemia; with lithium salts - to slow down the excretion of lithium (shown control of the concentration of lithium in blood plasma).

In some patients with impaired renal function, and taking NSAIDs, including COX-2 inhibitors, the concomitant use of ACE inhibitors may lead to further impairment of renal function. These changes are reversible. Simultaneous administration with antipyretic and analgesic agents can reduce the effectiveness of the drug.

Enalapril weakens the effect of drugs containing theophylline.

The hypotensive effect of enalapril is enhanced by diuretics, beta-blockers, methyldopa, nitrates, blockers of "slow" calcium channels dihydropyridine series, hydralazine, prazozin.

Immunosuppressants, allopurinol, cytotoxic drugs increase hematotoxicity. Drugs that cause bone marrow depression, increase the risk of developing neutropenia and / or agranulocytosis.

The combined use of ACE inhibitors and hypoglycemic agents (insulin, hypoglycemic agents for oral administration) can enhance the hypoglycemic effect of the latter with the risk of developing hypoglycemia. This is most often observed during the first weeks of joint use, as well as in patients with renal insufficiency.In patients with diabetes, receiving hypoglycemic agents for ingestion and insulin, blood glucose control is necessary, especially during the first month of joint use with ACE inhibitors.

ACE inhibitors reduce the excretion of lithium by the kidneys, and increase the risk of developing lithium intoxication. If it is necessary to prescribe lithium salts, it is necessary to control the level of lithium in the blood serum.

Symptomocomplex, which includes facial flushing, nausea, vomiting and arterial hypotension, is described in rare cases when gold is used together for parenteral use (sodium aurotomy malate) and ACE inhibitors (enalapril).

Special instructions:

Caution should be exercised when prescribing, patients with reduced circulating blood volume (as a result of diuretic therapy, restriction of salt intake, hemodialysis, diarrhea and vomiting) - the risk of a sudden and pronounced decrease in blood pressure after applying even an initial dose of an ACE inhibitor is increased. Transient arterial hypotension is not a contraindication for continuing treatment with the drug after BP stabilization.In the case of a re-expressed decrease in blood pressure should reduce the dose or cancel the drug.

With the development of excessive reduction in blood pressure, the patient is transferred to a horizontal position with a low headboard, if necessary, 0.9% solution is administered NaCl and plasma-substituting drugs.

The use of high-flow dialysis membranes increases the risk of developing an anaphylactic reaction. Correction of the dosing regimen on days free from dialysis should be performed depending on the level of blood pressure.

Before and during treatment with ACE inhibitors, control of blood pressure, blood counts (hemoglobin, potassium, creatinine, urea, activity of "liver" enzymes) and protein in the urine is necessary.

Care should be taken to monitor patients with decompensated chronic heart failure, coronary heart disease and cerebrovascular diseases, in which a sharp decrease in blood pressure can lead to myocardial infarction, stroke, or renal dysfunction. Sudden abolition of treatment does not lead to the syndrome of "withdrawal" (a sharp rise in blood pressure).

Patients with an indication of angioedema development in the anamnesis have an increased risk of its development with the administration of ACE inhibitors.For newborns and infants who have been exposed to the intrauterine effect of ACE inhibitors, careful monitoring is recommended to detect a marked decrease in blood pressure, oliguria, hyperkalemia, and and neurological disorders, which are possible due to a decrease in renal and cerebral blood flow with a decrease in blood pressure caused by ACE inhibitors. In oliguria it is necessary to maintain blood pressure and renal perfusion by introducing appropriate fluids and vasoconstrictive drugs.

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

Before the study of parathyroid function, eialapril should be discontinued. Caution should be exercised when performing physical exercises or in hot weather (risk of dehydration and excessive blood pressure lowering due to decreased circulating blood volume).

Before surgery (including dentistry), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors. During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions (possibly dizziness, especially after taking the initial dose of an ACE inhibitor in patients taking diuretics).

Form release / dosage:

Tablets 5 mg and 20 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinyl chloride film, and aluminum foil printed lacquered.

2 contour mesh packs together with instructions for use are placed in a pack of cardboard.

Storage conditions:

List B. In dry the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003189 / 01

Date of registration:15.12.2008

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

Shchelkovo Vitamin Plant, OJSC Russia

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Enalapril (Enalapril)