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

Clinical and pharmacological group: & nbsp

ACE Inhibitors

Included in the formulation

Enap®R

solution in / in

KRKA, dd, Novo mesto, AO

АТХ:

C.09.A.A ACE Inhibitors

Pharmacodynamics:

Inhibitor of ACE, metabolite of enalapril. Reduces the formation of angiotensin II from angiotensin I, reduces the concentration of aldosterone in the blood, increases the release of renin, stimulates the release of prostaglandins and endothelial relaxing factor of veins, depresses the sympathetic nervous system. Reduces the overall peripheral resistance of blood vessels, blood pressure, pre- and postnagruzku on the myocardium, dilates the arteries to a greater extent than the veins.

The antihypertensive 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. Improves the blood supply of the ischemic myocardium.

The therapeutic effect after intravenous administration occurs after 5-15 minutes, reaches a maximum after 1-4 hours, remains about 6 hours.

Pharmacokinetics:

Enalaprilat poorly absorbed after ingestion and almost inactive, so it is administered only intravenously. Maximum concentrationafter intravenous administration is achieved after 15 minutes. Binding to plasma proteins is 50-60%. Circulates in the blood in unchanged form.Poorly penetrates the blood-brain barrier. Not exposed to metabolism. Half-lifeis 4 hours. It is excreted from the body in unchanged form, more than 90% - with urine. The clearance of enalaprilat in hemodialysis is 38-62 ml / min, the enalaprilat concentration in the blood serum after a 4-hour hemodialysis is reduced by 45-75%.

Indications:

Hypertensive crisis; Arterial hypertension in cases when taking the drug inside is not possible; hypertensive encephalopathy.

ICD-10

IX.I10-I15.I15 Secondary Hypertension

IX.I10-I15.I10 Essential [primary] hypertension

Contraindications:

Hypersensitivity, including angioedema in the treatment of ACE in history, porphyria, pregnancy, breast-feeding, children's age (safety and efficacy not determined).

Carefully:

With caution should be used for primary hyperaldosteronism, aortic stenosis, mitral stenosis, hyperkalemia, condition after kidney transplantation, systemic connective tissue diseases, cerebrovascular diseases, diabetes mellitus, chronic heart failure, hypertrophic obstructive cardiomyopathy,myelosuppression (leukopenia, thrombocytopenia), ischemic heart disease, renal insufficiency (proteinuria more than 1 g per day), hyponatremia, as well as patients who maintain a diet with restriction of table salt or who are on hemodialysis, elderly patients (over 65 years).

Pregnancy and lactation:

Contraindicated in pregnancy.

Action category for the fetus by FDA - C (I trimester).

Action category for the fetus by FDA - D (II and III trimesters).

For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

Enter in a dose of 1.25 mg every 6 hours intravenously struino slowly (for 5 minutes) or drip, including patients who have taken earlier enalapril inside. Treatment is carried out only in a hospital.

If, after 1 hour after the administration, the therapeutic effect is unsatisfactory, the administration can be repeated at a dose of 1.25 mg, and after 6 hours the treatment is continued according to the usual scheme (1.25 mg every 6 hours).

In patients taking diuretics, the initial dose of enalaprilat should be reduced to 625 μg. If, after 1 hour after the administration, the therapeutic effect is unsatisfactory, the same dose can be reintroduced, and after 6 hours the complete dose (1.25 mg every 6 hours) is continued.

For chronic renal insufficiency of moderate degree with creatinine clearance> 30 ml / min (serum creatinine does not exceed 265.2 μmol / L), dose adjustment is not required. When creatinine clearance <30 ml / min (serum creatinine exceeds 265.2 μmol / L), the initial dose is 625 μg, followed by monitoring for 1 hour to detect excessive blood pressure lowering. In the absence of effect after 1 hour, the dose of 625 μg is repeated and the treatment is continued at a dose of 1.25 mg every 6 hours. For patients on hemodialysis, the dose of enalaprilate is 625 μg every 6 hours for 48 hours.

When switching to oral administration, the recommended initial dose of enalapril is 5 mg per day for patients who were previously given enalaprilate intravenously at a dose of 1.25 mg / ml. If necessary, the dose for oral intake can be increased.

For patients who are enalaprilate injected intravenously at an initial dose of 625 μg, the recommended dose of the drug when switching to ingestion is 2.5 mg per day.

Side effects:

From the side cardiovascular system and blood (hematopoiesis, hemostasis): hypotension (including orthostatic), angina pectoris,myocardial infarction, palpitation, rhythm disturbance (atrial tachycardia or bradycardia, atrial fibrillation), acute left ventricular heart failure, pulmonary artery embolism, cerebrovascular disorders, lowering of hemoglobin or hematocrit, neutro- and thrombocytopenia, myelodepression.

From the side nervous system and sense organs: fatigue, fatigue, asthenia, headache, dizziness, drowsiness, anxiety, syncope, depression, ataxia, peripheral neuropathy (paresthesia, dysesthesia).

From the side organs of the digestive tract: nausea, abdominal pain, pancreatitis, impaired liver function (cholestatic jaundice, fulminant liver necrosis with fatal outcome), change in the level of transaminases.

From the side skin integument: rash, exfoliative dermatitis, toxic epidermal necrosis, Stevens-Johnson syndrome, erythema multiforme.

From the side genitourinary system: edema, proteinuria, oliguria, renal failure, anuria, impotence, decreased libido.

From the side respiratory system: cough, dyspnea, inflammation of the respiratory tract, pneumonia, bronchospasm, lung infarction.

Other: convulsions, anaphylactoid reactions, angioedema, swelling of the face, neck, tongue, throat and larynx.

Overdose:

Symptoms: hypotension.

Treatment: reduction of dose or complete withdrawal of the drug; gastric lavage, transfer of the patient to a horizontal position, carrying out measures to increase the volume of circulating blood (introduction of physiological solution, transfusion of other blood-substituting fluids), symptomatic therapy: epinephrine (subcutaneously or intravenously), antihistamines, hydrocortisone (intravenously), the introduction of angiotensin II, hemo- or peritoneal dialysis.

Interaction:

Simultaneous use of enalaprilat with diuretics, other antihypertensive drugs, opioid analgesics, means for general anesthesia increases the risk of arterial hypotension.

NSAIDs, estrogens, adrenostimulators, drugs that activate the renin-angiotensin-aldosterone system, the intake of salt in excess, ethanol with simultaneous use weaken the hypotensive effect of enalaprilat.

Potassium preparations, potassium-sparing diuretics (spironolactone, amiloride, triamterene), ciclosporin with simultaneous use with enalaprilat increase the risk of hyperkalemia.

Simultaneous administration of enalaprilat and lithium preparations can lead to reversible intoxication with lithium, which occurs after the discontinuation of the use of both drugs.

Enalaprilat enhances the hypoglycemic effect of derivatives of sulfonylurea, insulin.

With the simultaneous use of enalaprilat with allopurinol, cytostatic agents, immunosuppressants, procainamide, the risk of developing neutropenia and / or agranulocytosis increases.

Special instructions:

Do not use enalaprilate in patients with bilateral stenosis of the renal arteries or artery of a single kidney, as this can lead to impaired renal function and even acute renal failure, which is usually reversible.

It is not recommended to apply enalaprilate simultaneously with potassium-sparing diuretics (spironolactone, amiloride, triamterene), since during the treatment with enalaprilat, an increase in potassium in the blood is possible, especially in patients with chronic renal insufficiency.

Arterial hypotension can be observed (even a few hours after the first dose) in patients with severe chronic heart failure and hyponatremia, as well as in patients with severe renal insufficiency and in patients with hypertension, especially against the background of hypovolemia as a result of treatment with diuretics, salt-free diets, diarrhea, vomiting or hemodialysis.

Treatment of patients with an increased risk of developing arterial hypotension after the first dose should be started with half the dose of enalaprilate (625 μg). With arterial hypotension, the patient should be given a horizontal position with a low head and if necessary adjust the volume of plasma by infusing 0.9% sodium chloride solution. Arterial hypotension and its effects are rare and transient. Transient arterial hypotension is not a contraindication to further treatment with enalaprilate. After correction of blood pressure and the volume of circulating blood, the subsequent administration of enalaprilat is usually well tolerated. In case of symptomatic arterial hypotension, the dose of enalaprilat should be reduced or discontinued.

If there is an angioedema in the anamnesis (even if not associated with the intake of ACE inhibitors), there is an increased risk of its re-development against the background of enalaprilat treatment.

Before surgery (including dentistry), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors.

Enalaprilat can be used concomitantly with digitalis preparations, beta-adrenoblockers, methyldopa, nitrates, slow calcium channel blockers, hydralazine and prazosin.

Instructions

Enalaprilat (Enalaprilatum)