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

Enalapril is an antihypertensive drug from the group of angiotensin-converting enzyme (ACE) inhibitors. Enalapril is a "prodrug": as a result of its hydrolysis, a enalaprilate, which inhibits the angiotensin-converting enzyme. 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.Reduction of blood pressure within 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 long-term use, myocardial hypertrophy of the left ventricle and myocytes of the walls of arteries of resistive type decrease, 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 onset of an antihypertensive effect with oral administration is 1 hour, 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 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 up to 50 % binds to blood plasma proteins. Enalapril is rapidly metabolized in the liver with the formation of an active metabolite of enalaprilate, which is a more active inhibitor of the angiotensin-converting enzyme 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. Enapaprilat easily passes through the histohematetic 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 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 enalaprilate).

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

Indications:

- arterial hypertension;

- 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, and hereditary or idiopathic angioedema, pregnancy, lactation, age under 18 years (efficacy and safety not established).

Carefully:

Carefully use in 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 / day), liver failure, patients a diet with restriction of salt or on hemodialysis, with simultaneous reception with immunosuppressants and saluretic drugs, in the elderly (over 65), oppression of the medullary gland vetvoreniya; Conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting).

Dosing and Administration:

Assign inside regardless of the time of ingestion. To ensure the following dosing regimen, it is possible to use the drug Enalapril in a dose of 2.5 mg.

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 admission. With moderate arterial hypertension, the average daily dose is about 10 mg.

The maximum daily dose is 40 mg / day.

In the case of appointing patients who are concurrently receiving diuretics, treatment with a diuretic should be discontinued 2-3 days before Enalapril-FPO® is administered. 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 greater than 0.14 mmol / l, the 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 2.5-5 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 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 shorter periods. The average maintenance dose is 5-20 mg / day for 1-2 doses.

In elderly patients, more pronounced hypotensive effect and lengthening of the drug action time are 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 QC up to 30-10 ml / min. - 2.5

- 5 mg / day at a CS 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-FPO® is generally well tolerated and in most cases does not cause side effects requiring the drug to be discontinued.

Co cardiovascular system: excessive reduction of blood pressure, orthostatic collapse, rarely - chest pain, angina, myocardial infarction or stroke (usually associated with a marked decrease in blood pressure), rarely arrhythmias (atrial brady or tachycardia, atrial fibrillation), palpitation, thromboembolism of pulmonary arterial branches, syndrome Reynaud.

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; disturbances 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 rare dysphonia, polymorphic erythema, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus, photosensitivity, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis, intestinal edema rarely).

Co side of laboratory indicators: hypercreatininaemia, increased urea levels, increased activity of "hepatic" enzymes, hyperbilirubinemia, hyperkalemia, hyponatremia, hypoglycemia in patients suffering from diabetes, 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 side of the urinary system: impaired renal function, rarely proteinuria.

Other: alopecia, decreased libido, impotence, 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 enalalrilate 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, 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).

In some patients with impaired renal function, and taking NSAIDs, including cyclooxygenase-2 inhibitors, concomitant use of ACE inhibitors may lead to further impairment of kidney 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. Enalapril strengthens the action of ethanol.

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

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 with the joint use of gold preparations for parenteral use (sodium aurotomy malate) and ACE inhibitors (enalapril).

Special instructions:

Caution should be exercised in appointing patients with reduced circulating blood volume (as a result of diuretic therapy, limiting consumption of table salt, 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, 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 carried out depending on the level of arterial 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.

Care should be taken to monitor patients with severe chronic heart failure, ischemic heart disease and cerebrovascular disease, in whom 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 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 in a timely manner,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.

Before the study of parathyroid gland functions enalapril should be canceled.

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).

Alcohol enhances the hypotensive effect of the drug.

AT Before the completion of the dose selection period, 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.

Effect on the ability to drive transp. cf. and fur:

Form release / dosage:

Tablets of 5 mg, 10 mg and 20 mg.

Packaging:

For 10, 15, 20 or 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered. For 1, 2, 3, 5 or 10 contour mesh packages, together with the instructions for use, are placed in a pack of cardboard.

Storage conditions:

List B. Store in a dry, the dark 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 printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N002143 / 01

Date of registration:14.08.2009

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Information update date: & nbsp18.10.2015

Illustrated instructions

Instructions

Enalapril-FPO® (Enalapril-FPO®)