Enalapril

Active material: Enalapril
When ATH: C09AA02
CCF: ACE inhibitor
When CSF: 01.04.01.03
Manufacturer: HEMOFARM A.D. (Serbia)

Pharmaceutical form, composition and packaging

Pills white, round, lenticular, scored on one side.

[Ring] lactose monohydrate, magnesium carbonate, gelatin, krospovydon, magnesium stearate.

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

Pills white, round, lenticular, scored on one side.

Excipients: lactose monohydrate, magnesium carbonate, gelatin, krospovydon, magnesium stearate.

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

Pills white, round, lenticular, scored on one side.

[Ring] lactose monohydrate, magnesium carbonate, gelatin, krospovydon, magnesium stearate.

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

DESCRIPTION OF ACTIVE SUBSTANCES.

Pharmacological action

ACE inhibitor. It is a prodrug, from which the body produces an active metabolite ènalaprilat. It is believed, antigipertenzivnogo mechanism of action is related to the competitive inhibition of ENZYME activity, which leads to a decrease in the speed of making angiotenzina I angiotenzin II (which has a strong vasoconstrictive effect and stimulates the secretion of aldosterone in the adrenal cortex).

As a result of the decrease in the concentration of angiotensin II occurs secondary increase of plasma Renin activity by eliminating negative feedback when released Renin and aldosterone secretion reduced direct. Besides, Enalaprilat, apparently, It affects the kallikrein-kinin system, preventing the breakdown of bradykinin.

Thanks vasodilator action, reduces round (afterload), wedge pressure in the pulmonary capillaries (preload) and pulmonary vascular resistance; improves cardiac output and exercise tolerance.

Pharmacokinetics

The ingestion of about 60% absorbed from the gastrointestinal tract. Simultaneous eating does not affect the skin. Metabolised in the liver by hydrolysis with the formation of englaprilata, Thanks to pharmacological activity which implements gipotenzivne effect. Linking plasma protein is englaprilata 50-60%.

T_1/2 englaprilata is 11 hr and increased in renal failure. Once inside 60% dose appears kidneys (20% in the form of enalapril, 40% as enalaprilat), 33% displayed through the intestines (6% in the form of enalapril, 27% as enalaprilat). After the on/in the englaprilata 100% excreted by the kidneys in unchanged form.

Testimony

Arterial hypertension (incl. renovascular), congestive heart failure (in a combination therapy).

Dosage regimen

When administered an initial dose – 2.5-5 mg 1 time / day. The average dose – 10-20 mg / day 2 admission.

The on / in the introduction – by 1.25 mg every 6 no. To identify excessive hypotension in patients with the deficiency of sodium and dehydration, resulting from previous therapy dioretikami, patients, receiving diuretics, as well as renal failure injected initial dose 625 mg. Depending on clinical response, the dose may be repeated after 1 h and continue treatment in a dose 1.25 mg every 6 no.

The maximum dose: ingestion – 80 mg / day.

Side effect

From the central and peripheral nervous system: dizziness, headache, feeling tired, fatigue; very rarely when used in high doses – sleep disorders, nervousness, depression, disequilibrium, paresthesia, noise in ears.

Cardio-vascular system: orthostatic hypotension, fainting, heartbeat, precordialgia; very rarely when used in high doses – tides.

From the digestive system: nausea; rarely – dry mouth, stomach ache, vomiting, diarrhea, constipation, abnormal liver function, increase in liver transaminases, increasing the concentration of bilirubin in the blood, hepatitis, pancreatitis; very rarely when used in high doses – glossitis.

From the hematopoietic system: rarely – neutropenia; in patients with autoimmune diseases – agranulocytosis.

From the urinary system: rarely – renal dysfunction, proteinuria.

The respiratory system: dry cough.

Reproductive system: very rarely when used in high doses – impotence.

Dermatological reactions: very rarely when used in high doses – hair loss.

Allergic reactions: rarely – skin rash, angioedema.

Other: rarely – hyperkalemia, muscle cramps.

Contraindications

Swelling angioneuroticeski in history, stenoses bilateral renal artery stenosis or renal artery only kidney, hyperkalemia, pregnancy, hypersensitivity to ènalaprilu or other ACE inhibitors.

Pregnancy and lactation

Contraindicated during pregnancy. When pregnancy reception should cease immediately enalapril.

Enalapril is secreted in breast milk. If necessary, its use during lactation should decide on the termination of breastfeeding.

Cautions

With the utmost care use in patients with autoimmune diseases, diabetes, impaired liver function, severe aortic stenosis, subaortal′nym muscle stenosis ambiguous Genesis, hypertrophic cardiomyopathy, in the event of loss of fluids and salts. In the case of previous treatment saluretikami, in particular in patients with chronic heart failure, increases the risk of orthostatic hypotension, Therefore, before starting treatment englaprilom it is necessary to compensate for the loss of fluids and salts.

In long-term care englaprilom should be periodically monitored picture peripheral blood. Sudden cessation of receiving enalapril is not causing skyrocketing HELL.

When surgical procedures during treatment englaprilom may develop arterial hypotension, that should be corrected with the introduction of enough liquid.

Before examining the function of the parathyroid glands enalapril should be discontinued.

Safety and efficacy of enalapril children have not been established.

Effects on ability to drive vehicles and management mechanisms

Care should be taken when driving or performing other work, requiring greater attention, tk. dizziness, especially after taking initial dose enalapril.

Drug Interactions

While the use of immunosuppressants, cytostatics increases the risk of leukopenia.

While applying kalisberegath dioretikov (incl. spironolactone, triamteren, amilorida), potassium products, Salt substitutes and food supplements, containing potassium, may develop hyperkalemia (especially in patients with impaired renal function), tk. ACE inhibitors reduce aldosterone, which leads to a delay of potassium in the body amid restrictions potassium excretion or additional intake of.

Together with the use of opioid analgesics and means to narcosis is enhanced antihypertensive enalapril.

In an application “loop” diuretics, thiazide diuretic antihypertensive effect is enhanced. There is a risk of hypokalemia. Increased risk of kidney function.

While the use of azathioprine may develop anemia, due to inhibition of the activity of erythropoietin under the influence of ACE inhibitors and azathioprine.

Describes a case of anaphylactic reaction and development of myocardial infarction in the application of allopurinol in patients, receiving enalapril.

Acetylsalicylic acid in high doses may reduce antihypertensive activity enalapril.

Definitively not set, whether aspirin reduces the therapeutic efficacy of ACE inhibitors in patients with coronary artery disease and heart failure. The nature of this interaction depends on the course of the disease.

Acetylsalicylic acid, inhibiting the synthesis of prostaglandins and COX, can cause vasoconstriction, which leads to reduced cardiac output and deterioration in heart failure patients, receiving ACE inhibitors.

Together with the use of beta-adrenoblokatorov, methyldopa, nitrates, calcium channel blockers, gidralazina, prazosine may increase antigipertenzivnogo actions.

In an application with NSAIDs (incl. with indomethacin) diminishes antihypertensive activity enalapril, apparently, influenced by inhibiting prostaglandin synthesis NSAIDS (that, believed, play a role in the development of hypotensive effect of ACE inhibitors). Increases the risk of renal dysfunction; rarely observed hyperkalemia.

While applying insulin, gipoglikemicakih funds derived sulfonylureas may develop hypoglycemia.

With simultaneous use of ACE inhibitors and interleukin-3, there is the risk of hypotension.

Together with the use of klozapinom there are reports on the development of sinkope.

Together with the use of claumipraminom reported on reinforcement of actions and development of Clomipramine toxic effects.

Together with the use of co-trimoksazolom are the cases of giperkaliemii.

Together with the use of lithium carbonate lithium concentration increases in serum, accompanied by symptoms of lithium intoxication.

Together with the use of orlistatom decreases the antihypertensive enalapril, that can lead to a significant improvement in HELL, development gipertoniceski kriza.

It is believed, that together with the application prokainamidom may increase the risk of hemorrhagic.

Together with the use of englaprilom decreases the activity of drugs, containing theophylline.

There are reports on the development of acute renal failure in patients after kidney transplantation with ziklosporinom.

Together with the use of cimetidine increases T_1/2 enalapril and increases its concentration in the blood plasma.

It is believed, that may decrease the effectiveness of antihypertensive drugs, while the application with erythropoietin.

Together with the use of ethanol increases the risk of arterial hypotension.