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, enalalylate is formed, which also 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 myocyte walls of arteries of resistive type, 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 the hypotensive effect with oral administration - 1 hour reaches the maximum after 4-6. h and persists up to 24 hours. In some patients to achieve The optimal level of blood pressure requires therapy for several weeks. With heart failure, a noticeable clinical effect is observed with long-term treatment - 6 months or more.

Pharmacokinetics:

After ingestion, 60 % preparation. 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 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, porphyria, pregnancy, lactation, age under 18 years (efficacy and safety not established).

Carefully:

Dosing and Administration:

Assign inside regardless of the time of ingestion. To ensure the following dosing regimen, it is possible to use enalapril in other dosages: 2.5 mg, 5 mg, 10 mg.

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

In the absence of clinical effect through 1-2 pedules, 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 / day. in 2 admission. After 2-3 weeks pass to a maintenance dose of 10-40 mg / day, divided into 1 to 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 psihotraemia (concentration of sodium ions in the blood serum of 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 to 5 mg every 3-4 days according to the clinical response to the maximum tolerable 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.

The elderly are more likely to have a more pronounced hypotensive effect and lengthening the duration of the drug, 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, with KK 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.

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

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.

On the part of the digestive system: dry mouth, anorexia, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, abdominal pain), intestinal obstruction, pancreatitis, liver and bile secretion, hepatitis (hepatocellular or cholestatic), jaundice.

On the part 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 angioedema (rarely).

On the part of laboratory indicators: hypercreatininaemia, increased urea levels, increased activity of "liver" 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.

On the part of the urinary system: a violation of kidney 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 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, triamterene, amiloride) can lead to hypercapia; 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 with the joint use of gold preparations for parenteral use (sodium aurotomy malate) and ACE inhibitors (enalapril).

Special instructions:

Caution should be exercised when prescribing to 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 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-strength 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, careful monitoring is recommended in order to timely detect a marked decrease in blood pressure, oliguria, hyperkalemia and neurological disorders that are possible due to a decrease in renal and cerebral blood flow while lowering the 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.

Alcohol enhances the hypotensive effect of the drug.

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 20 mg.

Packaging:

For 10, 20, 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

According to 1,2, 3,4, 5, 6 contour cell packs of 10 tablets or 1,2, 3 contour packs of 20 tablets or 1, 2 circuit packs of 30 tablets together 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:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009718/08

Date of registration:05.12.2008

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)