Enap pills 2.5mg 60pcs

Composition

of 1 tab. enalapril maleate 2.5 mg

Auxiliary substances:

sodium bicarbonate-1.3 mg,

lactose monohydrate-64.9 mg,

corn starch-11.2 mg,

hyprolose-1.25 mg,

talc-3 mg,

magnesium stearate-0.85 mg

Pharmacological action

Antihypertensive drug, ACE inhibitor. The mechanism of action is associated with inhibition of ACE activity, which leads to a decrease in the formation of angiotensin II.

Enalapril is a derivative of two amino acids: L-alanine and L-proline. After absorption, oral enalapril is hydrolyzed to enalalrylate, which inhibits ACE.

The mechanism of its action is associated with a decrease in the formation of angiotensin I from angiotensin II, a decrease in the content of which in the blood plasma leads to an increase in the activity of blood plasma renin (by eliminating the negative feedback to changes in renin production) and a decrease in aldosterone secretion.

Since ACE is identical to the enzyme kininase II, enalapril can also block the breakdown of bradykinin, a peptide that has a powerful vasopressor effect. The significance of this effect in the mechanism of action of enalapril has not been definitively established.

The antihypertensive effect of enalapril is primarily associated with the suppression of RAAS activity, which plays an important role in the regulation of blood pressure. Despite this, enalapril has an antihypertensive effect even in patients with arterial hypertension and low renin concentrations.

When using enalapril, the blood pressure level decreases regardless of the body position (both in the supine and standing positions) without a significant increase in heart rate. Symptomatic orthostatic hypotension is rare. In some patients, achieving optimal BP reduction may require several weeks of therapy. Abrupt withdrawal of enalapril was not accompanied by an increase in blood pressure.

Effective ACE inhibition usually occurs 2-4 hours after a single oral dose of enalapril. The time of onset of antihypertensive action when taken orally is usually 1 hour, reaches a maximum – after 4-6 hours. The duration of action depends on the dose. When used at the recommended doses, the antihypertensive effect and hemodynamic effects are maintained for at least 24 hours.

In patients with essential hypertension, a decrease in blood pressure is accompanied by a decrease in OPSS and an increase in cardiac output, while the heart rate does not change or changes slightly. Renal blood flow increases, but the glomerular filtration rate does not change. However, in patients with an initially low glomerular filtration rate, its level usually increased.

In patients with diabetic/non-diabetic nephropathy, enalapril decreased albuminuria / proteinuria and renal excretion of IgG.

In patients with chronic heart failure (CHF) on the background of therapy with cardiac glycosides and diuretics, the use of enalapril is accompanied by a decrease in OPSS and BP, an increase in cardiac output, while the heart rate decreases (usually in patients with chronic heart failure, the heart rate is increased).

The pressure of jamming of pulmonary capillaries is also reduced. Long-term use of enalapril increases exercise tolerance and reduces the severity of heart failure (assessed according to NYHA criteria).

Enalapril in patients with mild to moderate heart failure slows its progression, as well as slows the development of left ventricular dilation. In patients with left ventricular dysfunction, enalapril reduces the risk of major ischemic outcomes (including the incidence of myocardial infarction and the number of hospitalizations for unstable angina).

Indications

essential hypertension;

chronic heart failure (as part of combination therapy);

— prevent the development of symptomatic heart failure in patients with asymptomatic left ventricular dysfunction (as part of combination therapy);

prevention of coronary ischemia in patients with left ventricular dysfunction to reduce the incidence of myocardial infarction and reduce the frequency of hospitalizations for unstable angina.

Contraindications

— a history of angioedema associated with the use of ACE inhibitors;

— hereditary angioedema, or idiopathic angioedema;

— simultaneous use with aliskiren in patients with diabetes or impaired renal function (CC

— porphyria;

— pregnancy;

— lactation (breastfeeding);

— age under 18 years (effectiveness and safety not established);

— lactose intolerance, lactase deficiency, a syndrome of glucose-galactose malabsorption;

— hypersensitivity to enalapril and other components of the drug;

— hypersensitivity to other ACE inhibitors.

The drug should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney; with primary hyperaldosteronism; hyperkalemia; after kidney transplantation; with aortic stenosis and/or mitral stenosis (with hemodynamic disorders); hypertrophic obstructive cardiomyopathy (HOCMP); with reduced BCC (including diarrhea, vomiting); with systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus); IHD; with inhibition of bone marrow hematopoiesis; cerebrovascular diseases (including cerebral circulation insufficiency); diabetes mellitus; renal failure (proteinuria – more than 1 g/day); liver failure; in patients who follow a salt-restricted diet or are on hemodialysis; simultaneously with immunosuppressants and diuretics; in elderly patients (older than 65 years).

Side effects

WHO classification of frequency of side effects: very common (≥1/10), common (≥1/100 and higher).

From the hematopoietic system: infrequently-anemia (including aplastic and hemolytic), rarely-neutropenia, decreased hemoglobin and hematocrit, thrombocytopenia, agranulocytosis, inhibition of bone marrow hematopoiesis, pancytopenia, lymphadenopathy, autoimmune diseases.

From the side of metabolism:  infrequently – hypoglycemia.

Nervous system disorders:  very often – dizziness; often-headache, depression; infrequently-confusion, insomnia, drowsiness, paresthesia, increased excitability, vertigo; rarely-changes in the nature of dreams, sleep disorders.

From the side of the senses: often-changes in taste perception; infrequently-tinnitus; very rarely-blurred vision.

From the cardiovascular system: often – marked decrease in blood pressure (including orthostatic hypotension), syncope, chest pain, cardiac arrhythmias, angina pectoris; infrequently-palpitation, myocardial infarction or stroke (due to a sharp decrease in blood pressure in high-risk patients); rarely – Raynaud’s syndrome.

Respiratory system disorders:  very common-cough; infrequently-rhinorrhea, sore throat and hoarseness, bronchospasm/bronchial asthma; rarely-shortness of breath, lung infiltrates, rhinitis, allergic alveolitis/eosinophilic pneumonia.

From the digestive system:  very often – nausea; often – diarrhea, abdominal pain, flatulence; infrequently – ileitis, intestinal obstruction, pancreatitis, vomiting, constipation, anorexia, dry oral mucosa, peptic ulcer; rarely – liver and biliary dysfunction, hepatitis (hepatocellular or cholestatic), including liver necrosis, cholestatic jaundice, stomatitis/aphthous ulcers, glossitis; very rarely – angioedema of the intestine.

From the side of the skin: often – skin rash; infrequently-increased sweating, pruritus, alopecia; rarely-erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma.

A symptom complex is described, which may include fever, myalgia/myositis, arthralgia/arthritis, serositis, vasculitis, increased ESR, leukocytosis and eosinophilia, and a positive antinuclear antibody test. Skin rash, photosensitization reactions, or other skin manifestations may occur.

From the urinary system:  infrequently-impaired renal function, proteinuria, renal failure; rarely-oliguria.

From the side of the reproductive system: infrequently-decreased potency; rarely-gynecomastia.

Musculoskeletal disorders: infrequently-muscle cramps.

From the side of laboratory parameters: often-hyperkalemia, increased serum creatinine concentration; infrequently-hyponatremia, increased serum urea concentration; rarely-increased activity of hepatic transaminases and bilirubin concentration.

Allergic reactions: often – hypersensitivity reactions/angioedema of the face, lips, tongue, pharynx and / or larynx; infrequently – pruritus, urticaria.

Other services: frequency unknown-syndrome of inadequate ADH secretion.

Adverse events identified in the course of post-marketing use of Enap®, but no causal relationship with the use of the drug has been established:  urinary tract infections, upper respiratory tract infections, bronchitis, cardiac arrest, atrial fibrillation, shingles, melena, ataxia, pulmonary embolism and pulmonary infarction, hemolytic anemia, including cases of hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.

Interaction

The risk of developing hypotension, hyperkalemia, and impaired renal function (including acute renal failure) is higher in the case of double blockade of the RAAS, i. e. with simultaneous use of angiotensin II receptor antagonists, ACE inhibitors, or aliskiren, compared with the use of one of the listed groups of drugs. If necessary, simultaneous use of drugs is recommended to monitor blood pressure, kidney function and water-electrolyte balance.

Concomitant use of enalapril with aliskiren in patients with diabetes mellitus or impaired renal function (CC

ACE inhibitors reduce potassium loss due to diuretics. Concomitant use of enalapril and potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing substitutes for table salt, as well as the use of other drugs that increase the potassium content in blood plasma (for example, heparin) may lead to hyperkalemia. If concomitant use is necessary, caution should be exercised and the serum potassium content should be monitored regularly.

Previous therapy with high-dose diuretics may lead to a decrease in BCC and an increased risk of hypotension during the initiation of enalapril therapy. Excessive antihypertensive effects can be reduced by discontinuing the diuretic, increasing the intake of water or table salt, as well as by starting treatment with enalapril in a low dose.

Concomitant use of beta-blockers, alpha-blockers, ganglion blockers, methyldopa, slow calcium channel blockers, nitroglycerin, or other nitrates with enalapril may further reduce blood pressure.

When ACE inhibitors were co-administered with lithium preparations, a transient increase in serum lithium concentrations and the development of lithium intoxication were observed. The use of thiazide diuretics may lead to an additional increase in serum lithium concentrations and the risk of lithium intoxication with simultaneous use of ACE inhibitors. Concomitant use of enalapril with lithium is not recommended. If this combination is necessary, serum lithium concentrations should be carefully monitored.

Concomitant use of certain anaesthetic agents, tricyclic antidepressants, and antipsychotics (neuroleptics) with ACE inhibitors may lead to an additional decrease in blood pressure.

Concomitant use of NSAIDs (including selective COX-2 inhibitors) may weaken the antihypertensive effect of ACE inhibitors or angiotensin II receptor antagonists. NSAIDs and ACE inhibitors have an additive effect on increasing serum potassium, which can lead to reversible deterioration of renal function, especially in patients with existing renal impairment.

In rare cases, acute renal failure may occur, especially in patients with impaired renal function (for example, in elderly patients or with severe hypovolemia, including with the use of diuretics). Before starting therapy, it is necessary to replenish the BCC. During treatment, it is recommended to monitor kidney function.

Epidemiological studies suggest that the simultaneous use of ACE inhibitors and hypoglycemic agents (insulin and hypoglycemic drugs for oral use) may lead to an increased hypoglycemic effect with the risk of hypoglycemia. More often, hypoglycemia develops in the first weeks of therapy in patients with impaired renal function.

Ethanol enhances the antihypertensive effect of ACE inhibitors.

Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.

Concomitant use of enalapril with acetylsalicylic acid (as an antiplatelet agent), thrombolytics and beta-blockers is safe.

Weakens the effect of drugs containing theophylline.

Concomitant use of allopurinol, cytostatics, and immunosuppressants (including methotrexate, cyclophosphamide) with ACE inhibitors may increase the risk of leukopenia. Concomitant use with allopurinol increases the risk of an allergic reaction, especially in patients with impaired renal function.

Concomitant use of cyclosporine with ACE inhibitors may increase the risk of hyperkalemia.

Antacids may reduce the bioavailability of ACE inhibitors.

When using ACE inhibitors, including enalapril, in patients receiving intravenous gold preparations (sodium aurothiomalate), a symptom complex was described, including facial skin hyperemia, nausea, vomiting, and hypotension.

There was no clinically significant pharmacokinetic interaction of enalapril with hydrochlorothiazide, furosemide, digoxin, timolol, methyldopa, warfarin, Indometacin, sulindac and cimetidine.

When used concomitantly with propranolol, the concentration of enalaprilate in the blood serum decreases, but this effect is clinically insignificant.

How to take, course of use and dosage

The drug is taken orally, regardless of food intake, preferably at the same time of day. Tablets should be washed down with a small amount of liquid.

Arterial hypertension

The initial dose is from 5 to 20 mg 1 time / day, depending on the severity of arterial hypertension. In patients with mild hypertension, the recommended starting dose is 5-10 mg / day.

Patients with severe RAAS activation (e. g., renovascular hypertension, loss of electrolytes and/or dehydration, decompensated heart failure, or severe arterial hypertension) may experience an excessive decrease in blood pressure at the start of treatment. In such situations, it is recommended to start therapy with a low initial dose of 5 mg / day or less, under the supervision of a doctor.

Previous high-dose diuretic therapy may lead to dehydration and an increased risk of hypotension at the start of Enap therapy; the recommended starting dose is 5 mg/day. Treatment with diuretics should be discontinued 2-3 days before the start of Enap®use. Caution should be exercised when using Enap®, and renal function and serum potassium levels should be monitored.

Usually, the maintenance dose is 20 mg 1 time/day.

The dose is selected individually, if necessary, it can be increased to the maximum daily dose of 40 mg

. Chronic heart failure and left ventricular dysfunction

The initial dose is 2.5 mg 1 time / day, and treatment should be started under the careful supervision of a doctor.

Enap® for the treatment of heart failure can be used simultaneously with diuretics and / or beta-blockers, if necessary – with cardiac glycosides. In the absence of symptomatic hypotension at the beginning of therapy or after its correction, the dose should be increased gradually (by 2.5-5 mg every 3-4 days) to the usual maintenance dose of 20 mg / day, which is prescribed either once or in 2 doses, depending on the tolerability of the drug. The dose is selected within 2-4 weeks. The maximum daily dose is 40 mg in 2 divided doses.

Weekly dose in mg/dayweeks 11-3 day: 2.5 mg / day* in 1 reception 4-7 day: 5 mg/day in 2 receptionsweeks 210 mg in 1-2 receptionsweeks 3 and 420 mg in 1-2 receptions

*Special precautions should be observed in patients with impaired renal function taking diuretics.

Given the risk of developing hypotension and renal failure (which is much less common), blood pressure and renal function should be carefully monitored before and after starting Enap®. In patients taking diuretics, the dose of the latter, if possible, should be reduced before taking Enap®. The development of arterial hypotension after the first dose does not mean that arterial hypotension will persist with prolonged use, and does not indicate the need to stop using the drug.

Impaired renal function

In patients with impaired renal function, the intervals between doses should be increased and / or the dose of Enap should be reduced.

KK The initial daily dose is 80 ml / min to 30 ml / min 5 mg-10 mg 30 ml / min to 10 ml/min 2.5-5 mg less than 10 ml / min 2.5 mg on dialysis days*

* Enalaprilat is eliminated during hemodialysis. In the interval between hemodialysis sessions, the dose of the drug should be selected under the control of blood pressure.

Elderly patients

Elderly patients often have a more pronounced antihypertensive effect and prolongation of the drug’s action time, which is associated with a decrease in the rate of elimination of enalapril, so the recommended initial dose is 1.25 mg.

In elderly patients, the dose is selected depending on renal function.

Overdose

Symptoms: approximately 6 hours after ingestion – a marked decrease in blood pressure up to the development of collapse, impaired water-electrolyte balance, renal failure, hyperventilation, tachycardia, palpitation, bradycardia, dizziness, anxiety, cough, convulsions, stupor.

After oral use of enalapril at a dose of 300 and 440 mg, serum concentrations of enalaprilat in blood plasma exceeded the usual therapeutic concentrations by 100 and 200 times, respectively.

Treatment: the patient should be placed in a horizontal position with a low headboard. In mild cases, gastric lavage and oral use of activated charcoal are indicated; in more serious cases, intravenous infusion of 0.9% sodium chloride solution, plasma substitutes, and, if necessary, intravenous use of catecholamines.

It is possible to remove enalaprilat by hemodialysis, the rate of elimination is 62 ml / min. Patients with therapy-resistant bradycardia should have a pacemaker installed. Serum electrolytes and serum creatinine concentrations should be carefully monitored.

Special instructions

Arterial hypotension

Symptomatic hypotension is rare in patients with uncomplicated hypertension. Hypotension with all clinical manifestations may occur after the first use of Enap® in patients with hypovolemia, as a result of diuretic therapy, salt-free diet, diarrhea, vomiting or hemodialysis.

The development of symptomatic hypotension is more likely in patients with severe heart failure due to the use of high-dose diuretics, hyponatremia, or impaired renal function.

In such patients, treatment should be initiated under the supervision of a doctor until optimal dose adjustment of Enap® and / or a diuretic. Similar tactics can be applied to patients with CHD or cerebrovascular diseases, in which a sharp excessive decrease in blood pressure can lead to the development of myocardial infarction or impaired cerebral circulation.

In case of severe hypotension, it is necessary to move the patient to a horizontal position with a low headboard and, if necessary, inject 0.9% sodium chloride solution intravenously.

Transient arterial hypotension is not a contraindication for further treatment with Enap®. After blood pressure and BCC have stabilized, therapy can be continued.

In some patients with heart failure and normal or low blood pressure, an additional decrease in blood pressure may occur with Enap. This effect is predictable and does not warrant discontinuation of therapy. If hypotension is accompanied by clinical symptoms, the dose should be reduced and/or the diuretic and / or Enap should be discontinued.

Aortic or mitral stenosis, HOCMP

Like all vasodilators, ACE inhibitors should be used with caution in patients with valvular obstruction and hypertrophy of the left ventricular outflow tract. It should not be used in patients with cardiogenic shock and hemodynamically significant left ventricular obstruction.

Impaired renal function

In patients with renal insufficiency, creatinine clearance should be selected primarily based on creatinine clearance and, subsequently, clinical response to treatment. These patients should be regularly monitored for potassium and serum creatinine levels.

Patients with severe heart failure and kidney disease, including renal artery stenosis, may develop renal failure when treated with Enap®. The changes were usually reversible after discontinuation of Enap.

Some patients with arterial hypertension who did not develop kidney disease prior to treatment showed a slight and transient increase in serum urea and creatinine concentrations when Enap®was used. In such cases, it may be necessary to reduce the dose of Enap® and / or discontinue the diuretic. This situation indicates the possibility of latent renal artery stenosis.

Renovascular hypertension

Patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are at increased risk of developing hypotension and renal failure when treated with ACE inhibitors. Only minor changes in the serum creatinine concentration can indicate a decrease in renal function. In such patients, treatment should be started with small doses under close medical supervision. Carefully titrate the dose and monitor renal function.

Kidney transplantation

There is no experience of using Enap® in patients who have recently undergone a kidney transplant. Therefore, treatment of such patients with Enap® is not recommended.

Impaired liver function

In rare cases, ACE inhibitor therapy was accompanied by the development of a syndrome beginning with cholestatic jaundice and hepatitis up to the development of fulminant liver necrosis. The mechanism of development of this syndrome is unknown. If jaundice occurs or there is a significant increase in the activity of liver enzymes, treatment with an ACE inhibitor should be stopped immediately, the patient’s condition should be carefully monitored and, if necessary, treatment should be carried out.

Neutropenia/agranulocytosis

Neutropenia/agranulocytosis, thrombocytopenia, and anemia have been reported in patients treated with ACE inhibitors. Neutropenia is rare in patients with normal renal function in the absence of other complications. Enap® should be used with great caution in patients with connective tissue diseases (including systemic lupus erythematosus, scleroderma), simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as with a combination of these factors, especially with existing renal dysfunction. These patients may develop severe infections that do not respond to intensive antibiotic therapy. If patients are still taking Enap®, it is recommended to periodically monitor the number of white blood cells in the blood. The patient should be warned that if any signs of infection appear, you should immediately consult a doctor.

Hypersensitivity/angioedema

Angioedema of the face, extremities, lips, vocal folds, and/or larynx has been reported at any time after initiation of treatment in patients treated with ACE inhibitors, including Enap. Enap should be discontinued immediately and the patient should be monitored until symptoms disappear completely. Even in the case of tongue edema, when only difficulty swallowing occurs without respiratory distress syndrome, patients may need long-term follow-up, as the use of antihistamines and corticosteroids may not be sufficient.

Angioedema of the larynx or tongue can be fatal in very rare cases. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction, especially after a history of airway surgery. In the presence of edema of the tongue, vocal folds or larynx, appropriate therapy is indicated, which may include: subcutaneous use of 0.1% epinephrine (epinephrine)solution (0.3 ml-0.5 ml) and/or measures aimed at restoring airway patency (intubation or tracheostomy).

Among black patients receiving ACE inhibitor therapy, the incidence of angioedema is higher than among patients of other races.

Patients with a history of angioedema that is not associated with ACE inhibitors have an increased risk of developing angioedema when using any ACE inhibitor.

Anaphylactoid reactions in hymenoptera venom desensitization

Patients treated with ACE inhibitors during hymenopteran venom desensitization have rarely experienced life-threatening anaphylactoid reactions. To prevent such reactions, it is necessary to temporarily stop taking an ACE inhibitor during desensitization procedures.

Anaphylactoid reactions during LDL apheresis

Patients treated with ACE inhibitors during LDL apheresis with dextran sulfate rarely developed life-threatening anaphylactoid reactions. The drug should be temporarily replaced with drugs of a different group.

Hemodialysis

Due to the increased risk of anaphylactoid reactions, the drug should not be used in patients undergoing hemodialysis using high-flow polyacrylonitrile membranes (AN69®). If hemodialysis is necessary, it is advisable to use dialysis membranes of a different type or antihypertensive drugs of a different group.

Hypoglycemia

In patients with diabetes mellitus receiving oral hypoglycemic drugs or insulin, blood glucose concentrations should be carefully monitored during the first month of treatment with an ACE inhibitor.

Cough

When using Enap®, a dry, unproductive, prolonged cough may occur, which disappears after the use of ACE inhibitors is discontinued, which should be taken into account in the differential diagnosis of cough against the background of the use of an ACE inhibitor.

Surgical intervention/general anesthesia

Before surgical intervention (including dental procedures), the surgeon/anesthesiologist should be warned about the use of Enap®. During extensive surgery or general anesthesia with hypotensive agents, ACE inhibitors can block the formation of angiotensin II in response to the compensatory release of renin. If a marked decrease in blood pressure occurs due to such a mechanism, it can be corrected by the introduction of plasma substitutes.

Hyperkalemia

It may develop during treatment with ACE inhibitors, including Enap. Risk factors for hyperkalemia include renal failure, advanced age (over 70 years), diabetes mellitus, certain concomitant conditions (decreased BCC, acute heart failure in the decompensation stage, metabolic acidosis), concomitant use of potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing substitutes, and the use of other drugs that increase the potassium content in blood plasma (for example, heparin).

The use of potassium supplements, potassium-sparing diuretics, and dietary salt substitutes containing potassium can lead to significant increases in serum potassium levels, especially in patients with impaired renal function. Hyperkalemia can lead to serious cardiac arrhythmias, sometimes fatal. Concomitant use of the above drugs should be carried out with caution under the control of the potassium content in the blood serum.

Lithium

Concomitant use of lithium salts and Enap® is not recommended.

Ethnic features

Enap®, like other ACE inhibitors, has a less pronounced antihypertensive effect in patients of the black race compared to representatives of other races.

Special information on excipients

Enap ® contains lactose, so the drug is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

Influence on the ability to drive motor vehicles and manage mechanisms

When using Enap®, care should be taken when driving vehicles and performing other potentially dangerous types of work that require increased concentration of attention and speed of psychomotor reactions (dizziness may develop due to a sharp decrease in blood pressure, especially after taking the initial dose of Enap® in patients taking diuretics).

Storage conditions

The drug should be stored out of the reach of children, protected from moisture at a temperature not exceeding 25°C.

Shelf

life is 3 years.

Active ingredient

Enalapril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Heart Failure, Hypertension