The instruction for use
of medicine for experts
the Trade name
the International unlicensed
name Enalapril Dosage Form
of the Tablet of 2.5 mg, 5 mg, 10 mg, 20 mg No. 10 in the blister, 2 or 3 blisters in a cardboard box.
One tablet contains
active agent – enalapril a maleate of 2.5 mg, 5 mg, 10 mg or 20 mg,
excipients: silicone, colloidal anhydrous, magnesium stearate, sodium hydroxide, povidone, talc, krospovidon, cellulose mikrokristellichesky, lactose monohydrate.
Inhibitor of the Angiotensin-converting Enzyme (ACE) of Automatic Telephone Exchange group C09AA02 code
Pharmacokinetics Later properties of intake is soaked up about 60% of enalapril. Meal does not influence absorption. Is exposed to metabolism in a liver about formation of an active metabolite of enalaprilat which is more APF active inhibitor, than enalapril. Communication with proteins of plasma of enalaprilat – 50 – 60%. The maximum concentration of enalaprilat in serum are observed in 3 – 4 hour, enalapril – in 1 hour. Stable concentration in serum are established in 4 days. Enalaprilat easily passes through gistogematichesky barriers, excepting a blood-brain barrier, a small amount gets through a placenta and into breast milk.
Elimination half-life of enalaprilat – 11 hours. It is removed mainly by kidneys – 60% (20% – in the form of enalapril and 40% – in the form of enalaprilat), through intestines – 33% (6% – in the form of enalapril and 27% – in the form of enalaprilat).
Is removed at a hemodialysis (speed of 62 ml/min.) and peritoneal dialysis.
The maximum effect of drug is noted in 6-8 hours. The effect remains within 24 hours. The maximum clinical effect is reached in 2-4 weeks.
Enalapril is pro-medicine which in an organism is quickly metabolized in the enalaprilat having expressed the inhibiting activity concerning angiotensin-converting enzyme. Oppression of activity of the turning enzyme leads to decrease in concentration of angiotensin II, increase in activity of renin in plasma and to decrease in secretion of Aldosteronum. Antihypertensive and hemodynamic effects of Ednit at patients with the increased arterial blood pressure develop at the expense of dilatation of vessels and decrease in peripheric resistance that leads to a lowering of arterial pressure. Heart rate and minute volume usually do not change. Ednit reduces vascular resistance of kidneys, increases a renal blood stream, glomerular filtration, excretion of sodium and water, keeps potassium, reduces protein excretion.
Ednit’s use after a myocardial infarction can prevent development of dysfunction of a left ventricle and heart failure. Ednit renders also favorable effect on cerebral circulation at patients with hypertensia and a chronic disease of brain vessels. The termination of therapy does not cause direct increase in arterial blood pressure.
– essential hypertensia of any severity
– secondary hypertensia in diseases of kidneys (also in the renal failure caused by diabetes)
– heart failure
– prevention of ischemia of a myocardium and symptomatic heart failure at patients with dysfunction of a left ventricle.
The route of administration and doses
As meal does not influence absorbability of drug, the drug can be taken to, in time or after a meal.
Usual daily dose: 10-20 mg in one or two receptions (in the morning and in the evening). The maximum daily dose – 40 mg. Considering a possibility of development of hypotonia from the first dose, it is reasonable to begin therapy by Ednit with low dosed
the Initial dose – 5 mg. If necessary the specified dose can be increased. Dose adjustment of Ednit should be carried out in 2-4 weeks of treatment.
If the patient received previously diuretic therapy, intake of diuretics needs to be stopped in 2-3 days prior to Ednit’s appointment. If it is impossible, then it is recommended to begin with a dose 2.5 mg under observation of the doctor.
the Recommended initial dose of Ednit – 2.5 mg, with the subsequent gradual increase to a maintenance dose depending on individual reaction of the patient. The maintenance dose makes 10-20 mg a day. For the best shipping this dose can be divided into two receptions. The maximum daily dose makes 20 mg.
In heart failure of Ednit it is quite often applied together with drugs of a foxglove and diuretics. The patient has to be in such cases under observation of the doctor and also it is necessary to reduce a diuretic dose previously.
Hypotension of treatment does not serve in the beginning as a contraindication to drug use further in adequate doses.
The renal failure
In a renal failure is required reduction of a dose and/or lengthening of intervals between administrations of drug.
At clearance of creatinine of 30-80 ml/min. the initial dose makes 2.5 mg. A usual maintenance dose – 5-10 mg a day. The daily dose should not exceed 20 mg.
At clearance of creatinine of 30 ml/min. and below (serum creatinine level> 3 mg/dl) therapy should be begun with 2.5 mg of Ednit. A usual maintenance dose – 5 mg a day. The daily dose should not exceed 10 mg.
At the patients who are on a hemodialysis, the usual dose makes 2.5 mg, but it must be kept in mind that enalapril passes through the dialyzing membranes.
– the excessive lowering of arterial pressure, orthostatic collapse, is rare – a retrosternal pain stenocardia, a myocardial infarction (are usually connected with the significant decrease in the ABP), arrhythmias (submedian bradi- or tachycardia, atrial fibrillation), heartbeat, a thrombembolia of branches of a pulmonary artery, pain in heart, a faint
– dizziness, a headache, weakness, increased fatigue, drowsiness, very seldom confusion of consciousness, increased fatigue, is very rare at use of high doses – nervousness, a depression, paresthesias
– disturbances of a vestibular mechanism, hearing and sight, sonitus
– dryness in a mouth, anorexia, dispepsichesky disorders (nausea, diarrhea or a constipation, vomiting, pains in a stomach), intestinal impassability, pancreatitis, an abnormal liver function and a zhelchevydeleniya, hepatitis, jaundice
– unproductive dry cough, an interstitial pneumonitis, a bronchospasm, an asthma, a rhinorrhea, pharyngitis
– skin rash, a Quincke’s disease of the face, extremities, lips, language, a glottis and/or throat, a dysphonia, a polymorphic erythema, exfoliative dermatitis, a toxic epidermal necrolysis, a pempigus, an itching, a small tortoiseshell, a photosensitization, a serositis, a vasculitis, a miositis, an arthralgia, arthritis, stomatitis, a glossitis
– a hypercreatinemia, increase in content of urea, activity of hepatic transaminases, a hyperbilirubinemia, a hyperpotassemia, a hyponatremia, decrease in a hemoglobin content and a hematocrit, increase SOE, thrombocytopenia, a neutropenia, an agranulocytosis (at patients with autoimmune diseases), an eosinophilia
– a renal failure, a proteinuria
– an alopecia, decrease in a libido, inflows.
The arising by-effects are easy and reversible, and usually do not demand the termination of a course of treatment.
– hypersensitivity to enalapril, other components of drug or other APF inhibitors
– a porphyria
– the Quincke’s disease in the anamnesis connected with the previous use of APF inhibitors (allergic reaction with sharp hypostasis of lips, persons, necks and, perhaps hands and legs, followed by suffocation and hoarseness of a voice)
– the period of pregnancy and a lactation.
of Ednit should be applied with care:
– with other hypotensive drugs (synergism), especially concerning thiazide diuretics
– with lithium (the clearance of lithium decreases, frequent control of its level is required)
– with the drugs causing hypotension (the hypotensive effect amplifies)
– with alcohol (combined use enhances hypotensive effect).
To avoid combined use
– with kaliysoderzhashchy drugs and kaliysberegayushchy diuretics (Triamterenum, amiloride) (as potassium level in serum can increase considerably, especially in a renal failure). The combination to Spironolactonum is allowed only at frequent control of level of potassium in serum.
– with non-steroidal anti-inflammatory drugs (including with acetylsalicylic acid) decrease in effect of Ednit and increase in risk development of arterial hypotension is possible
– with ethanol and also means for the general anesthesia the risk of developing arterial hypotension increases
– with the drugs containing theophylline the easing their action takes place.
At patients who received previously treatment by diuretics or were exposed to other action causing liquid loss (for example, strong sweating, long vomiting, a diarrhea, salt loss) and also in the heart failure and a hypertension which is followed by the increased renin level at Ednit’s reception the symptomatic hypotonia can develop.
Possible sudden falling of arterial blood pressure can lead to a loss of consciousness, the extra care is required in the presence of coronary heart disease and cerebrovascular pathology (stenocardia, a myocardial infarction, cardiac arrest, a cerebrovascular stroke can develop).
At patients with heart failure it is necessary to control arterial blood pressure and renal function to and during treatment.
The extra care is required at Ednit’s appointment to patients who in the anamnesis have instructions on the postponed Quincke’s disease.
In a bilateral stenosis of renal arteries of Ednit it is possible to apply only in the conditions of careful control of function of kidneys (can cause increase in level of creatinine in serum).
Though enalapril does not worsen function of kidneys, the lowering of arterial pressure under the influence of inhibitor of angiotensin-converting enzyme can aggravate already available renal failure. At such patients even the acute renal failure which in most cases is reversible can develop. At some patients with a hypertension without damage of kidneys the moderate increase in level of creatinine and urea in serum is noted, especially at simultaneous use of diuretics.
At surgical interventions and also when carrying out anesthesia the drugs causing hypotension, enalapril prevents secondary formation of angiotensin II after compensatory release of renin. In such cases in a lowering of arterial pressure the input of the fluid is recommended.
Pregnancy and a lactation
Administration of drug during pregnancy is contraindicated.
Inhibitors of angiotensin-converting enzyme, in particular enalapril, can have teratogenic effect (hypotension, a renal failure, a hyperpotassemia, a neonatal hypoplasia of a skull, pre-natal death) in case of their use during the second and third trimester of pregnancy. At use of drugs during the first trimester of pregnancy, the above-stated undesirable effects it was not revealed. After pregnancy identification Ednit’s use should be stopped as soon as possible.
Use of drug when feeding by a breast is not recommended because a small amount of enalapril is distinguished with maternal milk.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms
At certain patients drug can cause the profound arterial hypotension and dizziness, especially in an initiation of treatment, rendering, thus, indirect and passing influence on ability to run motor transport and the machine equipment.
Symptoms: hypotonia, up to development of collapse, a myocardial infarction, an acute disorder of cerebral circulation or tromboembolic episodes, spasms, a stupor.
Treatment: to lay the patient in horizontal position with a low headboard, to wash out a stomach and to appoint intake of activated carbon, in more serious cases – the actions directed to stabilization of arterial blood pressure by intravenous administration of normal saline solution, plasma substitutes, if necessary – intravenous administration of angiotensin II, a hemodialysis (enalaprilat clearance rate – 62 ml/min.).
The release form
On 10 tablets in the blister, 2 or 3 blisters in cardboard packing
to Store Storage conditions in original packing at a temperature of 15-30 °C.
To store out of children’s reach.
not to use an expiration date after expiry date.
According to the prescription.
The producer Gideon Richter A.O.
of 1103 Budapest, Djemrei St., 19-21, Hungary