Enap 5 mg 60 pcs., Pack.

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Product Description

Composition

1 tab. enalapril maleate 5 mg

Excipients: sodium bicarbonate - 2.6 mg, lactose monohydrate - 129.8 mg, corn starch - 22.4 mg, hyprolose - 2.5 mg, talc - 6 mg, magnesium stearate - 1.7 mg.


 

pharmachologic effect

Antihypertensive drug, ACE inhibitor. The mechanism of action is associated with the 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, enalapril, taken orally, is hydrolyzed to enalalrylate, which inhibits ACE. The mechanism of its action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in the plasma blood content of which leads to an increase in the activity of blood plasma renin (due to the elimination of a negative feedback to a change in renin production) and a decrease in aldosterone secretion. Because ACE is identical to kininase II, enalapril can also block the breakdown of bradykinin, a potent vasopressor peptide. The significance of this effect in the mechanism of action of enalapril has not been finally established.

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

Against the background of the use of enalapril, the blood pressure level decreases regardless of body position (both in the supine position and in the standing position) 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 inhibition of ACE activity usually occurs 2-4 hours after a single oral administration of enalapril. The time of the onset of the antihypertensive action when taken orally is usually 1 hour, reaching a maximum after 4-6 hours. The duration of action depends on the dose. When used in 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 the systemic vascular resistance 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, while taking enalapril, albuminuria / proteinuria and IgG excretion by the kidneys decreased.

In patients with chronic heart failure (CHF) during therapy with cardiac glycosides and diuretics
the use of enalapril is accompanied by a decrease in the systemic vascular resistance and blood pressure, 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 pulmonary capillary jamming is also reduced. With long-term use, enalapril increases exercise tolerance and reduces the severity of heart failure (assessed by NYHA criteria). Enalapril in patients with mild to moderate heart failure slows down its progression, as well as slows down the development of left ventricular dilatation. In 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 pectoris).

Indications

- essential hypertension;

- chronic heart failure (as part of combination therapy);

- prevention of the development of clinically severe heart failure in patients with asymptomatic left ventricular dysfunction (as part of combination therapy);

- prevention of coronary ischemia in patients with left ventricular dysfunction in order 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 Quincke's edema or idiopathic angioneurotic edema;

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

- porphyria;

- pregnancy;

- lactation period (breastfeeding);

- age up to 18 years (efficacy and safety have not been established);

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;

- 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 a solitary kidney artery; with primary hyperaldosteronism; hyperkalemia; after kidney transplantation; with aortic stenosis and / or mitral stenosis (with hemodynamic disorders); hypertrophic obstructive cardiomyopathy (GOKMP); with reduced BCC (including with diarrhea, vomiting); with systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus); Ischemic heart disease; with oppression of bone marrow hematopoiesis; cerebrovascular diseases (including cerebrovascular insufficiency); with diabetes mellitus; renal failure (proteinuria - more than 1 g / day); liver failure; in patients on a salt-restricted diet or on hemodialysis; simultaneously with immunosuppressants and diuretics; in elderly patients (over 65 years old).

Side effects

Classification of the incidence of side effects (WHO): very often (≥1 / 10), often (≥1 / 100 and

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

From the side of metabolism:  infrequently - hypoglycemia.

From the nervous system:  very often - dizziness; often - headache, depression; infrequently - confusion, insomnia, drowsiness, paresthesia, irritability, vertigo; rarely - a change in the nature of dreams, sleep disturbances.

From the senses:  often - a change in taste perception; infrequently - tinnitus; very rarely - blurred vision.

From the side of the cardiovascular system:  often - a marked decrease in blood pressure (including orthostatic hypotension), syncope, chest pain, heart rhythm disturbances, angina pectoris; infrequently - palpitations, myocardial infarction or stroke (due to a sharp decrease in blood pressure in high-risk patients); rarely - Raynaud's syndrome.

From the respiratory system:  very often - cough; infrequently - rhinorrhea, sore throat and hoarseness, bronchospasm / bronchial asthma; rarely - shortness of breath, infiltrates in the lungs, 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, dryness of the oral mucosa, peptic ulcer; rarely - impaired liver function and bile secretion, hepatitis (hepatocellular or cholestatic), including liver necrosis, cholestatic jaundice, stomatitis / aphthous ulcers, glossitis; very rarely - intestinal angioedema.

On the part 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, a positive test for antinuclear antibodies. Skin rashes, photosensitivity reactions, or other skin manifestations may occur.

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

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

From the musculoskeletal system:  infrequently - muscle cramps.

On the part of laboratory parameters:  often - hyperkalemia, increased serum creatinine concentration; infrequently - hyponatremia, increased serum urea concentration; rarely - an increase in the activity of hepatic transaminases and the concentration of bilirubin.

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

Others:  frequency unknown - syndrome of inappropriate secretion of ADH.

Adverse events identified during the post-marketing use of Enap®, however, a causal relationship with the drug intake has not been established: urinary tract infections, upper respiratory tract infections, bronchitis, cardiac arrest, atrial fibrillation, shingles, melena, ataxia, thromboembolism of the pulmonary branches arteries and pulmonary infarction, hemolytic anemia, including cases of hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.

Interaction

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

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

ACE inhibitors reduce potassium loss from diuretics. The simultaneous use of enalapril and potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing table salt substitutes, as well as the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin) can lead to hyperkalemia. If necessary, the simultaneous use should be careful and regularly monitor the serum potassium content.

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

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

With the simultaneous use of ACE inhibitors with lithium preparations, a transient increase in serum lithium concentration and the development of lithium intoxication were observed. The use of thiazide diuretics can lead to an additional increase in serum lithium concentration and the risk of lithium intoxication with the simultaneous use of ACE inhibitors. The simultaneous use of enalapril with lithium is not recommended. If it is necessary to use such a combination, serum lithium concentrations should be carefully monitored.

The simultaneous use of certain anesthetics, tricyclic antidepressants and antipsychotics (neuroleptics) with ACE inhibitors can lead to an additional decrease in blood pressure.

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

In rare cases, the development of acute renal failure is possible, 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. It is recommended to monitor kidney function during treatment.

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

Ethanol enhances the antihypertensive effect of ACE inhibitors.

Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors.

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

Weakens the effect of drugs containing theophylline.

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

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

Antacids can reduce the bioavailability of ACE inhibitors.

When using ACE inhibitors, incl. enalapril, in patients receiving iv gold preparations (sodium aurothiomalate), a symptom complex was described, including flushing of the facial skin, nausea, vomiting, arterial hypotension.

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

With simultaneous use with propranolol, the concentration of enalaprilat in the blood serum decreases, but this effect is clinically insignificant.

How to take, course of administration and dosage

The drug is taken orally, regardless of food intake, preferably at the same time of day. The tablets should be taken 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 hypertension. For mild arterial hypertension, the recommended initial dose is 5-10 mg / day.

In patients with severe activation of the RAAS (for example, with renovascular hypertension, electrolyte loss and / or dehydration, decompensated heart failure, or severe hypertension), an excessive decrease in blood pressure is possible at the beginning 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 physician.

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

The usual maintenance dose is 20 mg 1 time / day.

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

Chronic heart failure and left ventricular dysfunction

The initial dose is 2.5 mg 1 time / day, while treatment should be started under the close supervision of a physician.

The drug Enap® for the treatment of heart failure can be used simultaneously with diuretics and / or beta-blockers, and, if necessary, with cardiac glycosides. In the absence of symptomatic arterial 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, in depending on the tolerability of the drug. The dose selection is carried out within 2-4 weeks. The maximum daily dose is 40 mg in 2 divided doses.

Week Dose in mg / day Week 11-3 days: 2.5 mg / day * in 1 dose
4-7 days: 5 mg / day in 2 doses Week 210 mg in 1-2 doses Week 3 and 420 mg in 1-2 doses

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

Given the risk of arterial hypotension and renal failure (observed much less often), blood pressure and renal function should be carefully monitored before and after the start of the use of Enap®. In patients taking diuretics, the dose of the latter, if possible, should be reduced before taking Enap®. The development of arterial hypotension after taking 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.

CC Initial daily dose from 80 ml / min to 30 ml / min 5 mg-10 mg from 30 ml / min to 10 ml / min 2.5-5 mg less than 10 ml / min 2.5 mg on dialysis days *

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

Elderly patients

In elderly patients, a more pronounced antihypertensive effect and an increase in the duration of the drug's action are more often observed, which is associated with a decrease in the rate of elimination of enalapril, therefore 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 pronounced decrease in blood pressure up to the development of collapse, disturbances in water-electrolyte balance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough, convulsions, stupor. After oral administration 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 ingestion of activated carbon are indicated; in more serious cases - intravenous infusion of 0.9% sodium chloride solution, plasma substitutes, if necessary - intravenous administration of catecholamines. Possible elimination of enalaprilat by hemodialysis, the rate of elimination is 62 ml / min. Patients with bradycardia, resistant to therapy, are shown setting a pacemaker. Serum electrolytes and serum creatinine should be closely monitored.

Special instructions

Arterial hypotension

Symptomatic arterial hypotension rarely develops in patients with uncomplicated arterial hypertension. Arterial hypotension with all clinical manifestations can be observed after the first administration of Enap® in patients with hypovolemia, as a result of diuretic therapy, salt-free diet, diarrhea, vomiting or hemodialysis. The development of symptomatic arterial 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 started under the supervision of a physician until the optimal dose adjustment of Enap® and / or a diuretic. A similar tactic can be applied to patients with coronary artery disease or cerebrovascular diseases,

In case of severe arterial hypotension, it is necessary to transfer 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 stabilization of blood pressure and BCC, therapy can be continued.

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

Aortic or mitral stenosis, GOKMP

As with all vasodilators, ACE inhibitors should be used with caution in patients with valve obstruction and left ventricular outflow tract hypertrophy. Should not be administered to patients with cardiogenic shock and hemodynamically significant left ventricular obstruction.

Impaired renal function

In patients with renal insufficiency (CC® should be selected, first of all, taking into account the CC and, then, the clinical response to treatment. In such patients, the potassium content and serum creatinine concentration should be regularly monitored.

In patients with severe heart failure and kidney disease, including renal artery stenosis, during treatment with Enap®, renal failure may develop. Changes were usually reversible after discontinuation of Enap®.

In some patients with arterial hypertension, who had no kidney disease before starting treatment, there was a slight and transient increase in the concentration of urea and creatinine in the blood serum when using the drug Enap®. In such cases, it may be necessary to reduce the dose of Enap® and / or withdraw the diuretic. This situation indicates the possibility of latent renal artery stenosis.

Renovascular hypertension

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

Kidney transplant

There is no experience with the use of Enap® in patients who have recently undergone kidney transplantation. Therefore, the treatment of such patients with Enap® is not recommended.

Liver dysfunction

In rare cases, therapy with ACE inhibitors was accompanied by the development of a syndrome starting with cholestatic jaundice and hepatitis up to the development of fulminant necrosis of the liver. The mechanism for the development of this syndrome is unknown. If jaundice appears or a significant increase in the activity of hepatic enzymes occurs, treatment with an ACE inhibitor should be stopped immediately, the patient should be carefully monitored and, if necessary, treated.

Neutropenia / agranulocytosis

Cases of neutropenia / agranulocytosis, thrombocytopenia, and anemia have been described in patients using ACE inhibitors. In patients with normal renal function in the absence of other complications, neutropenia is rare. Enap® should be used with great caution in patients with connective tissue diseases (including systemic lupus erythematosus, scleroderma), who are simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as with a combination of these factors, especially with existing impaired renal function ... These patients may develop severe infections that do not respond to intensive antibiotic therapy. If patients still take Enap®, it is recommended to periodically monitor the number of leukocytes in the blood. The patient must be warned about

Hypersensitivity / angioedema

In patients receiving ACE inhibitors, including Enap®, there have been reports of the development of angioedema of the face, extremities, lips, vocal folds and / or larynx at any time after the start of treatment. You should immediately cancel the drug Enap® and observe the patient until the symptoms disappear completely. Even in the presence of swelling of the tongue, when only difficulty in swallowing occurs without respiratory distress syndrome, patients may need to be monitored for a long time. the use of antihistamines and GCS may be insufficient.

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 administration of 0.1% epinephrine (adrenaline) solution (0.3 ml-0.5 ml) and / or measures aimed at restoring airway patency (intubation or tracheostomy).

Among patients of the Negroid race, receiving therapy with an ACE inhibitor, the incidence of angioedema is higher than among patients of other races.

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

Anaphylactoid reactions during desensitization with hymenoptera venom (hymenoptera)

Rarely, life-threatening anaphylactoid reactions have developed in patients taking ACE inhibitors during hymenoptera venom desensitization. To prevent such reactions, it is necessary to temporarily stop taking an ACE inhibitor during desensitization procedures.

Anaphylactoid reactions during LDL apheresis

Rarely, life-threatening anaphylactoid reactions have developed in patients taking ACE inhibitors during LDL apheresis with dextran sulfate. The drug should be temporarily replaced with drugs of another group.

Hemodialysis

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

Hypoglycemia

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

Cough

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

Surgery / general anesthesia

Before surgical intervention (including dental procedures), it is necessary to warn the surgeon / anesthesiologist about the use of Enap®. During major surgery or general anesthesia with hypotensive agents, ACE inhibitors can block the formation of angiotensin II in response to compensatory renin release. If at the same time a pronounced decrease in blood pressure develops, explained by a similar mechanism, it can be corrected by the introduction of plasma substitutes.

Hyperkalemia

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

The use of potassium preparations, potassium-sparing diuretics and potassium-containing salt substitutes can lead to a significant increase in serum potassium, especially in patients with impaired renal function. Hyperkalemia can lead to serious, sometimes fatal, heart rhythm disturbances. The simultaneous use of the above drugs should be carried out with caution under the control of serum potassium.

Lithium

The simultaneous 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 Negroid race than in other races.

Specific information on excipients

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

Influence on the ability to drive vehicles and use mechanisms

When using Enap®, care must be taken when driving vehicles and performing other potentially hazardous 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

3 years.