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

Enalapril is an antihypertensive drug whose mechanism of action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in its content leads to a direct decrease in the release of aldosterone. At the same time, the overall peripheral vascular resistance decreases, systolic and diastolic arterial pressure (BP), post- and preloading on myocardium. Expands arteries to a greater extent, than a vein, thus refractory increase in frequency of intimate or cardiac reductions is not marked or celebrated. Reduces the degradation of bradykinin, increases the synthesis of prostaglandin.

The hypotensive effect is more pronounced with a high plasma renin level than at a normal or reduced level of plasma.

Decrease in blood pressure within the therapeutic limits does not affect cerebral circulation, blood flow in the vessels of the brain is maintained at a sufficient level and against a background of reduced pressure. Strengthens coronary and renal blood flow. With prolonged use, hypertrophy of the left ventricle of the myocardium and myocytes of the walls of arteries of resistive type decreases,prevents the progression of heart failure and slows the development of dilatation of the left ventricle. Improves the blood supply of the ischemic myocardium.

Reduces the aggregation of platelets. Has some diuretic effect. Enalapril is a "prodrug": as a result of its hydrolysis, a enalaprilate, which inhibits the angiotensin-converting enzyme (ACE).

The time of onset of an antihypertensive effect with ingestion is 1 hour, it reaches a maximum after 4-6 hours and lasts up to 24 hours. In some patients, in order to achieve the optimal level of blood pressure, therapy is needed for several weeks. 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.

Enalapril binds up to 50% with plasma proteins. Enalapril is rapidly metabolized in the liver to form an active metabolite of enalaprilate, which is a more active ACE inhibitor than enalapril. Bioavailability of the drug is 40%.

The maximum concentration of enalapril in the blood plasma is achieved after 1 hour, enalaprilata after - 3-4 hours. Enalaprilat easily passes through the histohematological barriers, excluding the blood-brain barrier, a small amount penetrates the placenta and into the breast milk.

The half-life of enalaprilat is about 11 hours. Displayed enalapril mainly through the kidneys of 60% (20% in the form of enalapril and 40% in the form of enalaprilata), through the intestine 33% (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:

Enalapril is prescribed for various forms of hypertension, including renovascular hypertension. Chronic heart failure (as part of combination therapy).

Contraindications:

Enalapril is contraindicated in cases of increased sensitivity to enalapril and other ACE inhibitors, with a history of angioedema, associated with treatment with ACE inhibitors, porphyria, pregnancy, lactation, under the age of 18 years (efficacy and safety not established).

Carefully:Caution should be applied Enalapril with primary hyperaldosteronism, bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, hyperkalemia, a condition after kidney transplantation, aortic stenosis, mitral stenosis (with violations hemodynamics) idiopathic hypertrophic subaortal stenosis, systemic connective tissue diseases, ischemic heart disease, cerebrovascular diseases, diabetes mellitus, renal insufficiency (proteinuria more than 1 g / day), liver failure, in patients with salt restriction or hemodialysis simultaneous reception with immunosuppressants and saluretic, in the elderly (over 65 years).

Dosing and Administration:

Enalapril is administered orally regardless of the time of ingestion. At monotherapy of an arterial hypertensia the initial dose - 5 mg once a day. If there is no 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 BP stabilizes. If necessary and fairly good tolerability, the dose can be increased to 40 mg per day for 1-2 doses.After 2-3 weeks pass to a maintenance dose of 10-40 mg per day, divided into 1-2 doses. With moderate arterial hypertension, the average daily dose is about 10 mg. The maximum daily dose is 40 mg.

In the event that you want to assign Enalapril For a patient who takes diuretics, treatment with diuretics should be discontinued 2-3 days before enalapril is started. If this is not possible, the initial dose of Enalapril should be 2.5 mg / day.

Patients with hyponatremia (concentration of sodium ions in the blood serum of less than 130 mmol / l) or with an increase in serum creatinine concentration greater than 0.14 mmol / l are prescribed Enalapril in an initial dose of 2.5 mg once a day.

With 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 of Enalapril 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 the values of 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 at a dose of 1.25 mg / day.Selection of the dose should be carried out within 2-4 weeks or if necessary and the opportunity in a shorter time. The average maintenance dose is 5-20 mg / day for 1-2 doses.

In elderly people, more pronounced hypotensive effect and lengthening of the action time of Enalapril are more common, which is associated with a decrease in the rate of excretion of the drug, therefore the recommended initial dose for elderly patients is 1.25 mg / day.

In chronic renal failure, cumulation of Enalapril occurs with a decrease in filtration of less than 10 ml / min. When creatinine clearance (CC) is 80-30 ml / min, the dose of enalapril should be 5-10 mg / day, with a decrease in CK to 30-10 ml / min-2.5-5 mg / day, with a CC less than 10 ml / min - 1,25-2,5 mg / day only on dialysis days.

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

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

Side effects:

Co hand cardiovascular system: excessive decline HELL, orthostatic collapse, rarely - retrosternal pain, angina pectoris, myocardial infarction (usually associated with marked decrease in blood pressure), arrhythmias (atrial brady or tachycardia, atrial fibrillation), palpitations,thromboembolism of the branches of the pulmonary artery, pain in the region of the heart, fainting.

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

Co side of the senses: disturbances of the vestibular apparatus, hearing and vision impairment, tinnitus.

From the digestive tract: dry mouth, anorexia, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, abdominal pain), intestinal obstruction, pancreatitis, impaired liver function and bile secretion, hepatitis, jaundice.

Co the respiratory system: unproductive dry cough, interstitial pneumonitis, bronchospasm, dyspnea, rhinorrhea, pharyngitis.

Allergic reactions: skin rash, angioedema, facial edema, extremities, lips, tongue, glottis and / or larynx, dysphonia, polymorphic erythema, exfoliative dermatitis, Stephen-Johnson syndrome, toxic epidermal necrolysis, pemphigus, pruritus, urticaria, photosensitivity, serositis, vasculitis, myositis , arthralgia, arthritis, stomatitis, glossitis.

Co side of laboratory indicators: hypercreatinemia, increased urea levels, increased activity of "hepatic" transaminases, hyperbilirubinemia, hyperkalemia, hyponatremia. In some cases, a decrease in hematocrit and hemoglobin content, an increase in ESR, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia are noted.

From the urinary system: impaired renal function, proteinuria. Other: alopecia, decreased libido, hot flashes.

Overdose:

Symptoms: marked decrease in blood pressure up to the development of collapse, myocardial infarction, acute impairment of cerebral circulation 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 indicated. In more severe cases, measures aimed at stabilizing blood pressure are recommended: intravenous injection of physiological solution, plasma substitutes, and if necessary - angiotensin II, hemodialysis (the rate of enalapril removal is on the average 62 ml / min).

Interaction:

With the simultaneous administration of enalapril with non-steroidal anti-inflammatory drugs, hypotensive effect can be reduced. Use of the drug in conjunction with potassium-sparing diuretics (spironolactone, triamterene, amiloride), as well as with potassium-containing drugs increase the risk of hyperkalemia, with lithium salts - to slowing the excretion of lithium (shown control of the concentration of lithium in blood plasma). Simultaneous reception of enalapril with antipyretic and analgesic medicines can reduce the effectiveness of enalapril. Enalapril weakens the effect of medicines containing theophylline.

The hypotensive effect of enalapril is enhanced by diuretics, beta-blockers, methyldopa, nitrates, blockers of "slow" calcium channels, hydralazine, prazozin. Immunodepressants, allopurinol, cytotoxic drugs increase hematotoxicity. Drugs that cause bone marrow depression, increase the risk of developing neutropenia and / or agranulocytosis up to death.

Special instructions:

Caution should be exercised in prescribing the drug to the Nazis with reduced circulating blood volume (as a result of diuretic therapy, with restriction consumption of salt, hemodialysis, diarrhea and vomiting) - increased risk of sudden and pronounced blood pressure lowering after applying even the initial dose of the inhibitor AG1F. Treading hypotension is not a contraindication for the continuation of treatment with the drug after stabilization of blood pressure, in the case of a repeated pronounced decrease in blood pressure, you 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, the physiological solution and plasma-substituting drugs.

The use of high permeability dialysis membranes increases risk development of an anaphylactic reaction. Correction of the dosing regimen in days. Free from dialysis, should be carried out depending on the level of blood pressure.

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

It should be carefully monitored for patients with severe heart failure, ischemic heart disease and cerebrovascular disease, in which a sharp decrease in blood pressure can lead to myocardial infarction,stroke or impaired renal function. Sudden abolition of treatment does not lead to the syndrome of "withdrawal" (a sharp rise in blood pressure).

Patients with an angioedema history in history, there is an increased risk of developing it with the intake of inhibitors AG1F.

For newborns and infants who have undergone intrauterine exposure to ACE inhibitors, careful monitoring is recommended to timely detect a marked decrease in blood pressure, oliguria, hyperkalemia and neurological disorders, possibly 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 BP and renal perfusion by introducing appropriate fluids and vasoconstrictors.

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

Before the study of parathyroid function Enalapril should be canceled.

During the period of treatment it is not recommended to drink alcoholic beverages, since alcohol enhances the hypotensive effect of the drug. During the treatment period it is necessary to refrain from driving motor vehicles and classes potentially dangerous activities that require increased concentration and speed of psychomotor reactions, since dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretics.

Caution should be exercised when performing physical exercises or 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.

Form release / dosage:Tablets of 5 and 10 mg.

Packaging:

10 tablets per contour cell pack. On 20 tablets in cans polymeric. Each jar or 2 contour squares, together with the instructions for use, are placed in a pack of cardboard.

Storage conditions:List B. In a dry, sheltered from the world.

Shelf life:2 of the year. Do not use after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003374 / 01

Date of registration:23.03.2009

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Information update date: & nbsp18.10.2015

Illustrated instructions

Instructions

Enalapril (Enalapril)