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

Enalapril is an antihypertensive drug from the group of ACE inhibitors. Enalapril is a "prodrug": as a result of its hydrolysis, a enalaprilate, which inhibits ACE. The mechanism of its action is associated with a decrease in the formation of angiotensin I from angiotensin II, a decrease in its content leads to a direct decrease in the release of aldosterone. This reduces the overall peripheral vascular resistance, systolic and diastolic blood pressure (BP), post - and preload on the myocardium.

Expands arteries more than veins, with a reflex increase in heart rate is not noted.

The hypotensive effect is more pronounced with a high level of renin of the blood plasma than at its normal or reduced level. 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 low blood 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 the resistive type decreases, prevents the progression of heart failure and slows down 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.

The time of the onset of an antihypertensive effect with ingestion 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 blood pressure level. With heart failure, a noticeable clinical effect is observed with long-term treatment - 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 - 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 enalaprilata is about 11 hours. enalapril mainly kidneys - 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 enalaprilata).

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

Indications:

- arterial hypertension,

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

Contraindications:

Hypersensitivity to enalapril and other ACE inhibitors, history of angioedema, associated with treatment with ACE inhibitors, 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 hemodynamic disorders),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 a diet restricted salt or in hemodialysis, while reception with immunosuppressants and saluretikami in the elderly (over 65 years), inhibition of bone marrow hematopoiesis, state, accompanied by a decrease in circulating volume (including diarrhea, vomiting).

Dosing and Administration:

Assign inside regardless of the time of ingestion. To ensure the following dosage regimen possible use of enalapril in other dosages.

When monotherapy arterial hypertension - the initial dose of 5 mg 1 time per 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 well tolerated, the dose can be increased to 40 mg / day in 2 divided doses.After 2-3 weeks pass to the maintenance dose - 10-40 mg / day, divided into 1-2 doses. With moderate arterial hypertension, the average daily dose is about 10 mg. The maximum daily dose of the drug is 40 mg / day.

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

Patients with hyponatremia (concentration of sodium ions in the serum of blood less than 130 mmol / l) or serum creatinine concentration in excess of 0.14 mmol / l initial dose - 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 is 2.5 mg once, then the dose is increased by 2.5 to 5 mg every 3-4 days according to the clinical response to the maximum tolerated dose, depending on the 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. 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 the elderly, more pronounced hypotensive effect and lengthening of the drug's action time is more often, which is associated with a decrease in the rate of excretion of enalapril, so the recommended initial dose for the elderly is 1.25 mg.

In chronic renal failure cumulation occurs with a decrease in filtration of less than 10 ml / min. When creatinine clearance (CC) is 80-30 ml / min, the dose is usually 5-10 mg / day, with KK up to 30 -10 ml / min - 2.5-5 mg / day, with 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 the drug is gradually reduced.

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

Side effects:

Enalapril is generally well tolerated and in most cases does not cause side effects requiring the drug to be withdrawn.

From the side of the cardiovascular system: excessive reduction in blood pressure, orthostatic collapse, rarely - chest pain, angina pectoris, myocardial infarction (usually associated with a marked decrease in blood pressure), rarely arrhythmia (atrial brady or tachycardia, atrial fibrillation), palpitation, thromboembolism of the pulmonary artery branches.

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

From the sense organs: violations of the vestibular apparatus, hearing and vision impairment, tinnitus.

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

On the part of the respiratory system, unproductive dry cough, interstitial pneumonitis, bronchospasm, dyspnea, rhinorrhea, pharyngitis.

Allergic reactions: skin rash, itching, urticaria, angioedema, extremely rare dysphonia, polymorphic erythema, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus, photosensitivity, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis.

From the laboratory indicators: hyperkreatininemia, increased urea levels, increased activity of "hepatic" enzymes, hyperbilirubinemia, hyperkalemia, hyponatremia.In some cases, reduced hematocrit, increased ESR, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia.

From the urinary system: impaired renal function, rarely proteinuria.

Other: alopecia, decreased libido, hot flashes.

Overdose:

Symptoms: marked decrease in blood pressure up to the development of collapse, myocardial infarction, acute disturbance of cerebral circulation or thromboembolic complications, convulsions, stupor.

Treatment: the patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage and ingestion of saline are shown, in more severe cases - measures aimed at stabilizing blood pressure: intravenous injection of physiological solution, plasma substitutes, if necessary - the introduction of 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), a decrease in the hypotensive effect of enalapril is possible; with potassium-sparing diuretics (spironolactone, triamterene, 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).

Simultaneous administration with antipyretic and analgesic agents can reduce the effectiveness of the drug. A hypotensive effect reduces estrogens. 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, ethanol, medicines for general anesthesia. Immunosuppressants, allopurinol, cytotoxic drugs increase hematotoxicity. Drugs that cause bone marrow depression, increase the risk of developing neutropenia and / or agranulocytosis.

Special instructions:Care should be taken when prescribing to patients with reduced volume

circulatory blood (as a result of diuretic therapy, with 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 stabilizing blood pressure (BP). In the case of a re-expressed decrease in blood pressure, you should reduce the dose or cancel the drug.

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, periodic monitoring 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, coronary heart disease and cerebrovascular disease, 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 development of the syndrome "rebound" (a sharp rise in blood pressure).

For newborns and infants who have been exposed to the intrauterine effect of ACE inhibitors, it is recommended that careful monitoring be performed to 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 arterial pressure caused by ACE inhibitors.

In oliguria it is necessary to maintain BP and renal perfusion by introducing appropriate fluids and vasoconstrictors. Before examining the functions of parathyroid glands should be discarded. At the beginning of the treatment, before the end of the period, the choice of dose, it is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions. possibly dizziness, especially after the initial dose of an ACE inhibitor in patients taking diuretics. Before surgery (including dentistry), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors.

Form release / dosage:

Tablets of 5 mg and 10 mg.

Packaging:

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

2 contour packs with instructions for use in a pack of cardboard.

Storage conditions:

List B.In a dry, protected from light place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N001443 / 01

Date of registration:19.11.2007

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Enalapril (Enalapril)