Enap

Active material: Enalapril
When ATH: C09AA02
CCF: ACE inhibitor
ICD-10 codes (testimony): I10, I50.0
When CSF: 01.04.01.03
Manufacturer: KRKA d.d. (Slovenia)

Pharmaceutical form, composition and packaging

Pills round, lenticular, with a beveled edge, white.

Excipients: natriya carbonate, lactose monohydrate, corn starch, giproloza (hydroksypropyltsellyuloza), talc (magnesium hydrosilicate), magnesium stearate.

10 PC. – blisters (2) – packs cardboard.

Pills round, flat, with a beveled edge and a notch on one side, white.

Excipients: natriya carbonate, lactose monohydrate, corn starch, giproloza (hydroksypropyltsellyuloza), talc (magnesium hydrosilicate), magnesium stearate.

10 PC. – blisters (2) – packs cardboard.

Pills round, flat, with a beveled edge and a notch on one side, red-brown color with a splash of white on the surface and in the weight of the tablet.

Excipients: natriya carbonate, lactose monohydrate, corn starch, talc (magnesium hydrosilicate), magnesium stearate, iron oxide red (Sikofarm red colorant 30, E172).

10 PC. – blisters (2) – packs cardboard.

Pills round, flat, with a beveled edge and a notch on one side, light orange with white patches on the surface and in the weight of the tablet.

Excipients: natriya carbonate, lactose monohydrate, corn starch, talc (magnesium hydrosilicate), magnesium stearate, iron oxide yellow (Sikofarm yellow colorant 10, E172).

10 PC. – blisters (2) – packs cardboard.

Pharmacological action

Antihypertensive drugs, ACE inhibitor. Enalapril is “prodrug”: as a result of hydrolysis is formed enalaprilat. The mechanism of action is associated with inhibition of ACE activity influenced enalaprilate. This reduces the formation of angiotensin II, It is causing a direct reduction in aldosterone secretion. The result is a reduction in systemic vascular resistance, reduced systolic and diastolic blood pressure, office- and preload on the myocardium.

It expands the artery to a greater extent, than veins, with the reflex increase in heart rate were observed.

The hypotensive effect is more pronounced at high plasma renin, than at normal or reduced. Reduction of blood pressure is not within a therapeutic effect on cerebral blood flow, blood flow in the vessels of the brain is maintained at a sufficient level, and due to lower blood pressure. Enhances coronary and renal blood flow.

With prolonged use of reduced left ventricular hypertrophy and myocardial muscle cells of the arterial walls of the resistive type, It prevents the progression of heart failure and slows development of left ventricular dilatation. It improves blood flow to ischemic myocardium.

It inhibits platelet aggregation.

It has some diuretic effect.

When receiving the drug inside the hypotensive effect develops in 1 no, reaches through 4-6 hours and lasts up 24 no. In some patients, to achieve optimal blood pressure needed therapy for a few weeks. In heart failure prominent clinical effect observed with prolonged use – 6 months or more.

Pharmacokinetics

Absorption

After taking the drug inside absorbed about 60% Enalapril. C_max enalapril plasma levels achieved after 1 no. Eating does not affect the absorption.

Distribution and metabolism

In the liver, enalapril is metabolized to the active metabolite enalaprilat, which is a more potent inhibitor of ACE, enalapril. C_max enalaprilat in serum observed through 3-4 no, C_ss – through 4 d.

Enalaprilat binding to plasma proteins – 50-60%.

Enalaprilate readily crosses the blood-tissue barriers, with the exception of the BBB. A small amount crosses the placental barrier and is excreted in breast milk.

Deduction

T_1/2 эnalaprilata – 11 no. Report mostly kidneys – 60% (20% – as enalapril and 40% – as enalaprilat), through the intestine – 33% (6% – as enalapril and 27% – as enalaprilat).

Removed by hemodialysis (speed 62 ml / min) and peritoneal dialysis.

Testimony

- Arterial hypertension;

- Congestive heart failure (in a combination therapy);

- Asymptomatic left ventricular dysfunction (in a combination therapy).

Dosage regimen

The drug is taken orally, regardless of the meal, at the same time of the day. In the event of missed doses, it should be taken as soon as possible. If the reception is to the next few hours, it is necessary to take only the next dose according to the scheme and do not take the missed dose. The dose should never be double. Dose should be adjusted depending on the condition of the patient.

At the treatment of hypertension The recommended starting dose is 5 mg 1 time / day. After receiving the initial dose is required for patients during medical monitoring 2 hours and further 1 h to stabilize blood pressure.

Dose adjustment is carried out depending on the therapeutic effect (BP reduction). In the absence of clinical effect, increase the dose by 1-2 weeks 5 mg. Usually, the maintenance dose is between 10 mg 20 mg, if necessary, at a sufficiently well tolerated dose could be increased to 40 mg / day. The maximum daily dose is 40 mg. The high dose should be divided into 2 admission.

To patients, who continue to take diuretics the initial dose is 2.5 mg 1 time / day.

To patients with hyponatremia (sodium ion concentration in the blood serum of less than 130 mmol / l) or the content of serum creatinine 140 mmol / l the initial dose is - 2.5 mg 1 time / day.

To Patients with kidney disease Enap dose^® is determined depending on renal function and / or QA. If more QC 30 ml / min starting dose is 5 mg / day; at least QC 30 ml / min starting dose is 2.5 mg / day and gradually increased until clinical effect.

Patients, hemodialysis, the day of the procedure, the drug is prescribed in a dose 2.5 mg, other days the doctor adjusts the dose according to blood pressure rates.

In elderly patients often there is a more pronounced antihypertensive effect and lengthening the time of the drug, which is associated with a decrease in the rate of excretion of enalapril, therefore, the recommended starting dose is 1.25 mg.

At the treatment of chronic heart failure The recommended starting dose is 2.5 mg 1 time / day. Enap The dose should be increased gradually up to the maximum clinical effect, usually via 2-4 of the week. The usual maintenance dose is from 2.5 mg 10 mg 1 time / day; The maximum maintenance dose is on 20 mg 2 times / day.

At treatment of asymptomatic left ventricular dysfunction The recommended starting dose - 2.5 mg 2 times / day. Correction of the dose depends on the tolerability. Usually maintenance dose - 10 mg 2 times / day.

Treatment Enap^® long, usually lifelong, unless circumstances arise, requiring its cancellation.

The tablets should be swallowed whole, drinking a small amount of liquid.

Side effect

Cardio-vascular system: excessive reduction of blood pressure, Orthostatic hypotension, rarely – chest pain, angina, myocardial infarction (usually associated with a marked decrease in blood pressure), Arrhythmia (Beards- or tachycardia, auricular fibrillation), heartbeat, thromboembolism pulmonary artery branches, precordialgia, fainting, Raynaud's syndrome.

From the central and peripheral nervous system: dizziness, headache, insomnia, weakness, fatigue, drowsiness (2-3%), rarely confusion, fatigue, very rarely when used in high doses – hypererethism, depression, paresthesia.

From the senses: violation of the vestibular apparatus, hearing and visual impairment, noise in ears.

The respiratory system: nonproductive cough, interstitial pneumonitis, bronchospasm / asthma, breathlessness, rhinorrhea, pharyngitis, sore throat, hoarseness.

From the digestive system: dry mouth, anorexia, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, abdominal pains), ileus, pancreatitis, liver and biliary excretion, hepatitis (hepatocellular or cholestatic), jaundice, increase in liver transaminases, giperʙiliruʙinemija.

From the urinary system: impairment of renal function, proteinuria, giperkreatininemiя.

Metabolism: increase of urea, hyperkalemia, giponatriemiya.

From the hematopoietic system: reduction of the concentration of hemoglobin and hematocrit, thrombocytopenia, neutropenia, agranulocytosis (patients with autoimmune diseases), eozinofilija.

Dermatological reactions: photosensitivity, pemphigus, alopecia.

Allergic reactions: skin rash, angioneurotic edema of the face, limbs, lips, language, glottis and / or larynx, disfonija, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, itch, hives, photosensitivity, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis, increased perspiration.

Other: decreased libido, tides, reduced potency, increased erythrocyte sedimentation rate.

Perhaps the development of a complex of symptoms, which may include some or all of the following symptoms of: fever, serositis, vasculitis, myalgia / myositis, arthralgia / arthritis, a positive test for antinuclear antibodies, increased erythrocyte sedimentation rate, eozinofilija, leukocytosis.

Side effects, observed with Enap^®, usually, have mild, transient in nature and do not require discontinuation of the drug.

Contraindications

- A history of angioedema (incl. associated with the use of ACE inhibitors);

- Porphyria;

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to enalapril and other ingredients;

- Hypersensitivity to other ACE inhibitors.

Do not use the drug in patients with a history of angioedema, related to previous ACE inhibitor (allergic reaction to sudden swelling of the lips, person, neck and, possible hands and feet, accompanied by dyspnea and hoarseness) or other reasons, in children and adolescents under the age of 18 years (efficacy and safety have not been established).

FROM caution should use the drug in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney; with primary hyperaldosteronism, hyperkalemia, after kidney transplantation, with aortic stenosis, mitralynыm stenozom (violations of hemodynamics), idiopathic hypertrophic stenosis subaortal, systemic connective tissue disorders, CHD, cerebrovascular diseases, diabetes, renal failure (proteinuria – more 1 g / day), hepatic insufficiency, patients, a diet with salt restriction, or on hemodialysis; simultaneously with immunosuppressants and saluretikami; in elderly patients (senior 65 years).

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation (breast-feeding). If pregnancy occurs during treatment with Enap^® immediately remove the drug.

Cautions

In the treatment of Enap^® It requires regular medical examinations, especially at the beginning of treatment and / or the selection of the optimal dose. The frequency of medical examinations determined by the attending physician.

Keep in mind the possibility of hypotension (even a few hours after the first dose) in patients with severe heart failure, severely impaired renal function, as well as in patients with impaired water and electrolyte balance, caused by diuretic treatment, bessolevoy dyetoy, diarrhea, vomiting, and in patients, hemodialysis.

Marked decrease in blood pressure is usually manifested by nausea, an increase in heart rate, swoon. In the case of hypotension the patient should be transferred to a horizontal position with a low headboard, at the same time necessary to monitor the doctor.

Hypotension and its serious consequences are rare and have a transitory nature. Transient hypotension is not a contraindication to further treatment drug. Once the blood pressure has stabilized, drug therapy can be continued in the medium recommended doses. Hypotension can be avoided, interrupting treatment with diuretics and abandoning salt-free diet before treatment Enap^®, if possible. Patients should be warned about, if relapse hypotension, accompanied by nausea, an increase in heart rate and fainting, it is necessary to consult a doctor.

Before treatment and during therapy should be monitoring of renal function.

During treatment Enap^® possible to increase the content of potassium in blood serum, especially in patients with chronic renal failure, diabetes, while the appointment of potassium-sparing diuretics (such as spironolactone, amiloride and triamterene) potassium or drugs. Such patients should be informed of the need to resort to the doctor if you have muscle weakness and arrhythmias.

Patients, receiving Enap^®, should not drink alcohol because of the risk of hypotension.

In case of side effects or angioedema (rapid swelling of the lips, person, Neck, hands and feet, accompanied by dyspnea and hoarseness) Enap^® should be discontinued and appropriate treatment.

It should stop the drug before the study of the function of the parathyroid glands.

Before the planned surgery should notify the anesthesiologist, that the patient receives Enap^®, because of the risk of arterial hypotension during general anesthesia.

It will be appreciated, that the treatment of Enap^® may develop allergic reactions due to the use of certain types of filter membranes, It is applied in hemodialysis or other kinds of blood filtering.

During the treatment of allergies (desensitization) a wasp or bee venom in patients, receiving Enap^®, may develop hypersensitivity reactions.

Use in Pediatrics

It should appoint a drug to children, tk. efficacy and safety of its use in pediatrics not established.

Effects on ability to drive vehicles and management mechanisms

In some cases, the drug can cause severe hypotension and dizziness, especially at the beginning of treatment, providing, thus, indirect and transient effect on the ability to drive vehicles and operate machinery.

Overdose

Symptoms: excessive reduction of blood pressure until the development of collapse, myocardial infarction, acute stroke and thromboembolic complications, convulsions, stupor.

Treatment: the patient should be transferred to a horizontal position with a low headboard. In mild cases showing a gastric lavage and ingestion of saline; in more severe cases, – Events, to stabilize blood pressure, in / in a saline solution, plasma expanders, if necessary – in / with the introduction of angiotensin II, hemodialysis (rate of excretion enalaprilate – 62 ml / min).

Drug Interactions

The simultaneous use of enalapril and diuretics or other, antihypertensives increases the effectiveness of these drugs.

Interaction with Drug, used to treat heart failure (cardiac glycosides) no clinical significance.

With simultaneous use of enalapril and NSAIDs, incl. acetylsalicylic acid, may decrease the effectiveness of enalapril and an increased risk of renal dysfunction.

With simultaneous use of certain diuretics (spironolactone, amiloride or triamterene) and / or supplemental potassium preparations , may increase the level of potassium in blood serum (hyperkalemia).

Enalapril reduces the effect of funds, containing theophylline. Concomitant use of drugs lithium may enhance the side effects of lithium.

Preparations, soderzhashtie cimetidine, Increases the effect of enalapril.

Patients, receiving enalapril, there is a risk of arterial hypotension during general anesthesia.

Ethanol enhances the hypotensive effect of enalapril.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dry place at temperatures no higher than 25 ° C. Shelf life – 3 year.