Enap - instructions for use, dose, side effects, contraindications

Excipients: sodium bicarbonate 1.30 mg, lactose monohydrate 64.90 mg, corn starch 11.20 mg, giprolose 1.25 mg, talc 3.00 mg, magnesium stearate 0.85 mg

1 tablet of 5 mg contains:

Active substance:

Enalapril maleate 5.00 mg

Excipients: sodium hydrogen carbonate 2.60 mg, lactose monohydrate 129,80 mg, corn starch 22,40 mg, giprolose 2,50 mg, talc 6,00 mg, magnesium stearate 1.70 mg

1 tablet of 10 mg contains:

Active substance:

Enalapril maleate 10.00 mg

Excipients: sodium bicarbonate 5,10 mg, lactoses monohydrate 124,60 mg, corn starch 21,40 mg, talc 6.00 mg, magnesium stearate 1.70 mg, ferric iron oxide red (E172) 1.20 mg

1 tablet of 20 mg contains:

Active substance:

Enalapril maleate 20.00 mg

Auxiliary substances: sodium bicarbonate 10,20 mg, lactose monohydrate 117,80 mg, starch corn 13.90 mg, talc 6.00 mg, magnesium stearate 1.70 mg, ferric oxide red oxide (E172) 0.10 mg, dye iron oxide yellow (E172) 0.30 mg

Description:

Tablets 2.5 mg. Tablets are white or almost white, round, biconvex, with a bevel.

Tablets 5 mg. Tablets of white or almost white color, flat-cylindrical, with a risk and a facet.

Tablets 10 mg. Tablets of red-brown color, flat-cylindrical, with a risk and bevel

Tablets of 20 mg. Tablets of light orange color, flat-cylindrical, with a risk and a facet. On the surface and in the mass of the tablet, white and brown-maroon impregnations are allowed

Pharmacotherapeutic group:ACE inhibitor

ATX: & nbsp

C.09.A.A.02 Enalapril

Pharmacodynamics:

Enalapril is an antihypertensive drug whose mechanism of action is associated with inhibition of the activity of the angiotensin-converting enzyme, leading to a decrease in the formation of angiotensin II.

Enalapril is a derivative of two amino acids: L-alanine and L-proline. After suction enalapril, ingested, is hydrolyzed to enalaprilat, which inhibits ACE. The mechanism of its action is associated with a decrease in the formation of angiotensin I angiotensin II, a decrease in the blood plasma which leads to an increase in renin plasma activity (by eliminating the negative feedback reaction to changes in renin production) and a decrease in aldosterone secretion. Because The ACE is identical to the kinase kinase II, enalapril it can also block the destruction of bradykinin, a peptide, which has a powerful vasopressor effect. The significance of this effect in the mechanism of action of enalapril has not been fully established. Antihypertensive the action of enalapril is associated, first of all, with the suppression of the activity of the renin-angiotensin-aldosterone system (RAAS), which plays an important role in the regulation of blood pressure (BP). Despite this, enalapril renders antihypertensive action even in patients with arterial hypertension and low renin concentration.

Against the background of enalapril reduced blood pressure, regardless of position of the body (as in the "lying" position and the "standing") without a significant increase in heart rate (HR). Symptomatic orthostatic hypotension develops rarely. In some patients, achieving optimal BP reduction may require several weeks of therapy. A sharp abolition of enalapril was not accompanied by a rise in blood pressure.

Effective inhibition of ACE activity usually occurs 2-4 hours after a single intake of enalapril inside. Time of approach antihypertensive actions usually when ingested - 1 hour, reaches a maximum - after 4-6 hours. The duration of action depends on the dose. When applying the recommended dosage antihypertensive the effect and hemodynamic effects are maintained for at least 24 hours.

In patients with essential hypertension, blood pressure reduction accompanied by a decrease in peripheral vascular resistance and an increase in cardiac output,at this heart rate does not change or changes insignificantly. Increased renal blood flow, but the rate of glomerular filtration does not change. However, in patients with initially low glomerular filtration rate, its level usually increased.

In patients with diabetic / nondiabetic nephropathy, the albuminuria / proteinuria and renal excretion of IgG decreased with enanapril.

In patients with chronic heart failure (CHF) with cardiac glycosides and diuretics, the use of enalapril is accompanied by a decrease in total peripheral vascular resistance and blood pressure, an increase in cardiac output, and a decrease in heart rate (usually in patients with heart failure, heart rate is increased). Similarly, the pressure of wedging of the pulmonary capillaries decreases. With prolonged use enalapril Increases exercise tolerance and reduces the severity of heart failure assessed by NYHA criteria. Enalapril in patients with mild and moderate degree of heart failure slows its progression, as well as slows down the development of dilatation of the left ventricle.

With left ventricular dysfunction enalapril reduces the risk of developing major ischemic outcomes (including the incidence of myocardial infarction and the number of hospitalizations for unstable angina.

Pharmacokinetics:

Suction

After oral administration enalapril quickly absorbed, the degree of absorption of enalapril is approximately 60%. The maximum concentration (Cmax) of enalapril in the serum is observed for 1 hour after ingestion. Eating does not affect absorption.

Enalapril is rapidly and actively hydrolyzed to form enalaprilat, a potent ACE inhibitor. The enalaprilat stasis is observed 3-4 hours after ingestion. The half-life of enalapril (T1 / 2) with repeated use is 11 hours. In patients with normal renal function, the equilibrium enalaprilat concentrations in the blood plasma were reached on the 4th day of therapy.

Distribution

The connection with the proteins of the blood plasma enalaprilata in the range of therapeutic doses is 60%.

Biotransformation (metabolism)

In addition to transformation into enalaprilate enalapril does not undergo significant biotransformation.

Excretion

Enalaprilat is mainly excreted by the kidneys. In the urine, enalaprilate (about 40% of the dose), and unchanged enalapril (about 20 %).

Pharmacokinetics in selected patient groups

Impaired renal function

In patients with mild and moderate renal insufficiency (creatinine clearance (CK) 36-60 ml / min (0.6-1 ml / s)) after enalapril administration at a dose of 5 mg once a day, the area under the concentration-time curve (AUC) of enalaprilat is approximately 2 times greater than in patients with normal renal function. In severe renal failure (CK <30 ml / min): AUC increased by about 8 times. Tx enalaprilata after repeated use in severe renal failure lengthens, and the time to reach the equilibrium state is delayed. Enalaprilat is removed during hemodialysis, the rate of excretion is 1.03 ml / s (62 ml / min).

Indications:

Essential hypertension.

Chronic heart failure (as part of combination therapy).

- Prevention of the development of clinically significant 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:

- decrease in the incidence of myocardial infarction;

- reducing the frequency of hospitalizations for unstable angina

Contraindications:

Hypersensitivity to enalapril, other components of the drug or other andACE inhibitors, angioedema history of edema associated with previous use of ACE inhibitors, hereditary angioedema Quincke or idiopathic angioedema, concomitant use with aliskirenom in patients with diabetes mellitus or renal dysfunction (CC less than 60 ml / min), pregnancy, breastfeeding period, porphyria, age under 18 years (efficacy and safety not established), lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome , t. the composition of Enap ® is lactose.

Carefully:

bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; primary hyperaldosteronism, hyperkalemia, condition after kidney transplantation; aortic stenosis and / or mitral stenosis (with violation of hemodynamics), hypertrophic obstructive cardiomyopathy (GOKMP),conditions with reduced circulating blood volume (bcc) (including diarrhea, vomiting), systemic connective tissue diseases (scleroderma, systemic lupus erythematosus, etc.), ischemic heart disease (IHD), oppression of bone marrow hematopoiesis, cerebrovascular diseases (eg, insufficiency cerebral circulation, etc.), diabetes mellitus, renal failure (proteinuria - more than 1 g / day), liver failure, patients who follow a diet with restriction of table salt or who are on hemodialysis, one Yemen application with immunosuppressive agents and diuretics, age over 65 years

Pregnancy and lactation:

Application in pregnancy

The use of ACE inhibitors, including Enap, in the first trimester of pregnancy is not recommended.

The use of ACE inhibitors, including Enap, in the second and third trimesters of pregnancy is contraindicated.

Epidemiological data on the risk of teratogenic effects of ACE inhibitors during pregnancy do not provide an opportunity to draw definitive conclusions. Nevertheless, one can not exclude the likelihood of risk of their development.If it is necessary to use ACE inhibitors, the patient must be transferred to therapy with another, approved antihypertensive drug with a proven safety profile for pregnant women.

When confirming pregnancy, Enap® should be discontinued as soon as possible.

Application in the second and third trimesters of pregnancy can cause fetotoxic effects (renal dysfunction, oligohydramnios, deceleration of the fossil skull bones) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia).

If the ACE inhibitor was taken in the second and third trimesters of pregnancy, it is recommended to perform ultrasound examination of the kidneys and bones of the fetal skull.

In those rare cases when the use of an ACE inhibitor during pregnancy is considered necessary, periodic ultrasound (ultrasound) should be performed to assess the amniotic fluid index. In case of detection during an ultrasound of oligohydramnion, it is necessary to stop taking the drug. Patients and the physician should be aware that the oligohydramnion develops with irreversible damage to the fetus.If ACE inhibitors are used during pregnancy and the development of oligohydramnion is observed, depending on the week of pregnancy, it may be necessary to perform a stress test, a stress test, or a biophysical profile of the fetus to assess the functional state of the fetus.

Newborns whose mothers took ACE inhibitors during pregnancy should be monitored, given the risk of developing arterial hypotension. Enalapril, which penetrates the placenta, can be partially removed from the bloodstream of a newborn by peritoneal dialysis, in theory it can be removed by exchange blood transfusion.

Application in the period of breastfeeding

Enalapril and enalaprilate are determined in breast milk in trace concentrations, therefore, if Enap® is needed, breastfeeding should be discontinued.

Dosing and Administration:

Inside, regardless of the time of ingestion, it is desirable at the same time of day, squeezed with a small amount of liquid.

Arterial hypertension

The initial dose is 5 to 20 mg once a day, depending on the severity of the arterial hypertension and the patient's condition. With mild hypertension, the recommended initial dose is 5-10 mg / day.

Have patients with a pronounced activation of RAAS (eg, with renal vascular hypertension, loss of salt and / or dehydration, decompensation of heart failure or severe hypertension), there may be an excessive decrease in blood pressure at the beginning of treatment. In such situations it is recommended to start therapy with a low initial dose - 5 mg / day or less under the supervision of a doctor.

Prior therapy with high doses of diuretics may lead to dehydration and an increased risk of developing arterial hypotension at the beginning of therapy with Enap®; the recommended initial dose is 5 mg / day. Treatment with diuretics should be discontinued 2-3 days before application of Enap®. Care should be taken with Enap®, monitoring kidney function and potassium in the blood serum.

Usually the maintenance dose is 20 mg once a day.

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

Chronic heart failure and left ventricular dysfunction

The initial dose of Enap® is 2.5 mg once a day; treatment in this case it is necessary to begin under the close supervision of a doctor.

The drug Enap ® for the treatment of heart failure can be used simultaneously with diuretics and / or beta-adrenoblockers, 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 divided 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.

A week	Dose, mg / day
1st week	1-3 day: 2.5 mg / day * in one dose 4-7 days: 5 mg / day in two doses
2nd week	10 mg in one or two doses
3rd and 4th weeks	20 mg in one or two doses

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

Given the risk of developing arterial hypotension and (there is much less frequent) renal failure, you should carefully monitor blood pressure and kidney function before and after the Enap® application.In patients taking diuretics, the dose of diuretics, if possible, should be reduced before the start of 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 the use of the drug.

Impaired renal function

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

Creatinine clearance (CC)	Initial dose, mg / day
Creatinine clearance from 30 ml / min to 80 ml / min	5 mg-10 mg
Creatinine clearance from 10 ml / min to 30 ml / min	2.5-5 mg
Creatinine clearance less than 10 ml / min	2.5 mg per day of hemodialysis *

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

Elderly patients Older patients more often have a more pronounced antihypertensive effect and lengthening the duration of the drug, which is associated with a decrease in the rate of excretion of enalapril, so the recommended initial dose is 1.25 mg.

In elderly patients, the dose is selected depending on the function of the kidneys

Side effects:

Classification of the incidence of adverse events of the World Health Organization (WHO);

very often> or = 1/10

often from> or = 1/100 to <1/10

infrequently from> or = 1/1000 to <1/100

rarely from> or = 1/10000 to <1/1000

very rarely from <1/10000

frequency unknown: can not be estimated from the available data.

In each group, undesirable effects are presented in order of decreasing severity.

From the hemopoiesis: infrequently: anemia (including aplastic and hemolytic);

rarely: neutropenia, a decrease in hemoglobin and hematocrit in the serum, thrombocytopenia, agranulocytosis, oppression of bone marrow hematopoiesis, pancytopenia, lymphadenopathy, autoimmune diseases.

From the side of metabolism: infrequently: hypoglycemia.

From the nervous system:

often: headache, depression;

infrequently: confusion, insomnia, drowsiness, paresthesia, increased excitability, vertigo;

rarely: a change in the nature of dreams, sleep disorders.

From the sense organs:

often: a change in taste perception;

infrequently: noise in the ears;

very rarely: blurred vision.

From the cardiovascular system:

very often: dizziness;

often: marked decrease in blood pressure (including orthostatic hypotension), syncope, chest pain, heart rhythm disturbances, angina pectoris;

infrequent: heart palpitations, myocardial infarction, or stroke, possibly due to a sharp drop in blood pressure in patients at high risk;

rarely: Raynaud's syndrome.

From the respiratory system: very often: cough;

infrequently: rhinorrhea, sore throat and hoarseness of the voice, bronchospasm / bronchial asthma; rarely: dyspnea; pulmonary infiltrates, rhinitis, allergic alveolitis / eosinophilic pneumonia;

From the digestive system:

very often: nausea;

often: diarrhea, abdominal pain, flatulence;

infrequently: ileitis, intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation,

anorexia, dryness of the oral mucosa, peptic ulcer;

rarely: a violation of the liver and bile secretion, hepatitis (hepatocellular or cholestatic), including hepatic necrosis, cholestasis (including jaundice),

stomatitis / aphthous ulcers, glossitis;

very rarely: angioedema of the intestine;

From the skin:

often: skin rash,hypersensitivity reactions / angioedema (described angioedema, facial, extremities, lips, tongue, pharynx and / or throat), infrequent: increased sweating, itching, urticaria, alopecia; rarely: erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus (pemphigus), erythroderma.

A symptom complex is described, which may include: fever, myalgia / myositis, arthralgia / arthritis, serositis, vasculitis, increased erythrocyte sedimentation rate (ESR), leukocytosis and eosinophilia, positive antinuclear antibody test. There may be: skin rash, photosensitivity reactions or other skin manifestations. From the genitourinary system:

infrequently: impaired renal function, proteinuria, renal failure, impotence;

rarely: oliguria, gynecomastia;

From the side of the musculoskeletal system: infrequently: muscle cramps;

Laboratory indicators:

often: hyperkalemia, increased serum creatinine concentration; infrequently: increased urea concentration in blood serum, hyponatremia;

rarely: increased activity of "hepatic" enzymes, increased serum bilirubin concentration;

Other:

frequency unknown: syndrome of inadequate secretion of antidiuretic hormone;

The undesirable phenomena revealed during the postmarketing use of the drug, but the cause-There is no evidence of a drug-related complication: urinary tract infection, upper respiratory tract infection, bronchitis, cardiac arrest, atrial fibrillation, herpes zoster, melena, ataxia, pulmonary artery thromboembolism and pulmonary infarction, hemolytic anemia, including hemolysis in patients with deficiency glucose-6-phosphate dehydrogenase

Overdose:

Symptoms: approximately 6 hours after ingestion, a marked decrease in blood pressure, up to the development of collapse, disturbance of the water-electrolyte balance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, coughing, convulsions, stupor. After ingestion of 300 and 440 mg of enalapril, the serum concentrations of enalaprilate in the blood plasma exceeded the usual therapeutic concentrations of 100 and 200 times, respectively.

Treatment: the patient should be moved to a horizontal position with a low headboard.

In mild cases, gastric lavage and ingestion of activated carbon are shown, in more severe cases, intravenous infusion of 0.9% sodium chloride solution, plasma substitutes, if necessary intravenous catecholamines. It is possible to excrete enalaprilate by hemodialysis; the rate of excretion is 62 ml / min. Patients with a bradycardia that is resistant to therapy are shown staging the pacemaker. Serum content of electrolytes and serum creatinine concentration should be carefully monitored.

Interaction:

Double blockade of angiotensin-aldosterone system (RAAS)

The risk of developing arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) is higher in the case of a double blockade of RAAS, i.e. with simultaneous use of angiotensin II receptor antagonists, (ARA II), ACE inhibitors or aliskiren, in comparison with the use of a drug of one of the listed groups.

If it is necessary to simultaneously use drugs, it is recommended to monitor blood pressure, kidney function and water-electrolyte balance. The simultaneous use of enalapril with aliskiren in patients with diabetes mellitus or renal dysfunction (KC less than 60 ml / min) is contraindicated.

Potassium-sparing diuretics and potassium preparations

ACE inhibitors reduce potassium loss by diuretics.

Simultaneous use of enalapril and potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), potassium or potassium substitute preparations, and the use of other drugs that increase the potassium level in the blood plasma (eg, heparin) can lead to hyperkalemia.

If simultaneous application is necessary, care should be taken and the serum potassium content is regularly monitored.

Diuretics (thiazide or loop)

Prior therapy with high doses of diuretics can lead to a decrease in the volume of circulating blood (BCC) and an increased risk of developing arterial hypotension during the initiation of enalapril therapy. Excessive antihypertensive effects can be reduced by eliminating the diuretic, increasing water intake or table salt, as well as starting treatment with enalapril at a low dose.

Other antihypertensive drugs

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

Lithium

With 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 simultaneous use of ACE inhibitors. Simultaneous use of enalapril with lithium is not recommended. If this combination is necessary, the serum concentrations of lithium should be carefully monitored.

Tricyclic antidepressants / antipsychotics (antipsychotics) / anesthetics / drugs

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

Non-steroidal anti-inflammatory drugs (NSAIDs)

Simultaneous application of NSAIDs (including selective inhibitors of cyclooxygenase-2) can weaken the antihypertensive effect of ACE inhibitors or APA II.

NSAIDs and ACE inhibitors have an additive effect on potassium levels in the blood serum, which can lead to impaired renal function, especially in patients with impaired renal function. This effect is reversible.

In rare cases, the development of acute renal failure, especially in patients with impaired renal function (for example, in elderly patients or with pronounced hypovolemia, including with the use of diuretics) is possible.

Before the start of therapy, it is necessary to replenish the BCC. During treatment, it is recommended to monitor kidney function.

Hypoglycemic agents for oral administration and insulin

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

Ethanol

Ethanol enhances the antihypertensive effect of ACE inhibitors.

Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors. Acetylsalicylic acid, thrombolytics and beta-blockers

Safe simultaneous use of enalapril with acetylsalicylic acid (as an antiplatelet agent), thrombolytics and beta-blockers. Relieves the effect of medications containing theophylline.

Allopurinol, cytostatics and immunosuppressants (incl. methotrexate, cyclophosphamide) Simultaneous use with ACE inhibitors may increase the risk of developing leukopenia. With simultaneous application with allopurinol, the risk of developing an allergic reaction increases, especially in patients with impaired renal function.

Cyclosporin

Simultaneous use with ACE inhibitors may increase the risk of developing hyperkalemia.

Antacids

Antacids can reduce the bioavailability of ACE inhibitors.

Preparations of gold

With the use of ACE inhibitors, including enalapril, patients receiving an intravenous drug of gold (sodium aurotomy malate), a symptom complex including facial flushing, nausea, vomiting, and arterial hypotension was described.

There was no clinically significant pharmacokinetic interaction of enalapril with hydrochlorothiazide, furosemide,digoxin, timolol, methyldopa, warfarin, indomethacin, sulindac and cimetidine. With concomitant use with propranolol, the enalaprilat concentration in the blood serum decreases, but this effect is clinically insignificant.

Special instructions:

Arterial hypotension

Symptomatic arterial hypotension develops rarely 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. Development of symptomatic arterial hypotension more likely in patients with severe heart failure due to the use of high doses of diuretics, hyponatremia or impaired renal function. In these patients, treatment should be started under the supervision of a physician, up to an optimal dose adjustment of Enap and / or a diuretic. Similar tactics can be applied to patients with (IHD) or cerebrovascular diseases, in whom a sharp excessive decrease in blood pressure can lead to the development of myocardial infarction or cerebral circulation disorders.

In the case of development of severe arterial hypotension, the patient should be given a horizontal position, legs Raise and, if necessary, intravenously introduce 0.9% solution of sodium chloride.

Transient arterial hypotension is a contraindication to further treatment with Enap after stabilization of blood pressure and bcc

In some patients with heart failure and normal or low blood pressure, it is possible to reduce it further when taking Enap. This effect is predictable and usually does not constitute a reason for discontinuing therapy. If hypotension is accompanied by clinical symptoms, dosage and / or diuretic and / or Enap® should be reduced.

Aortic or mitral stenosis, GOKMP

Like all vasodilators, ACE inhibitors should be used cautiously in patients with valvular obstruction and hypertrophy of the outflow tract of the left ventricle. Do not prescribe to patients with cardiogenic shock and hemodynamically significant obstruction of the left ventricle.

Impaired renal function

In patients with renal insufficiency (CC <80 ml / min (1.33 ml / s)) the initial dose of Enap should be selected, first of all, taking into account the QC and, then, the clinical response to treatment.Such patients should regularly monitor the potassium content and serum creatinine concentration.

In patients with severe heart failure and kidney disease, including renal artery stenosis, the development of renal failure may occur with Enap. The changes were usually reversible after the drug Enap was discontinued.

In some patients with hypertension who did not have renal disease before treatment, there was a slight and transient increase in serum urea and creatinine levels with Enap® concurrently with the diuretic. In such cases, it may be necessary to reduce the dose of Enap® and / or to cancel the diuretic. This situation indicates the possibility of latent stenosis of the renal artery. Renovascular hypertension Patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney in the treatment of ACE inhibitors have an increased risk of developing arterial hypotension and renal failure. To reduce the function of the kidneys can indicate only minor changes in serum creatinine concentration.In such patients, treatment should begin with small doses under the close supervision of a physician. It is necessary to carefully titrate the dose and monitor the function of the kidneys. Kidney transplantation Experience with Enap in patients who have recently undergone kidney transplantation is not available. Therefore, the treatment of such patients with Enap is not recommended. Impaired Hepatic Function In rare cases, treatment with ACE inhibitors was accompanied by the development of the syndrome that starts with cholestatic jaundice and hepatitis until the development of fulminant hepatic necrosis. The mechanism of development of this syndrome is unknown. When the jaundice, or a significant increase in activity of "liver" enzymes should immediately discontinue treatment with an ACE inhibitor, carefully observe the patient and, if necessary, to carry out the necessary treatment.

Neutropenia / agranulocytosis

In patients treated with ACE inhibitors, described cases of neutropenia / agranulocytosis, thrombocytopenia and anemia. In patients with normal renal function in the absence of other complications, neutropenia develops rarely. The drug Enap® must be used with great care in patients with connective diseasestissue (including systemic lupus erythematosus, scleroderma), simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as a combination of these factors, especially with existing violations of kidney function. These patients can develop severe infections that are not amenable to intensive antibiotic therapy. If patients still take Enap®, then it is recommended to periodically monitor the number of white blood cells in the blood. The patient should be warned that if there are any signs of infection, you should immediately consult a doctor.

Hypersensitivity / angioedema

Patients receiving ACE inhibitors, including Enap®, have been reported to develop angioedema, facial, extremities, lips, vocal folds and / or larynx at any time after initiation of treatment. It is necessary to immediately cancel the drug Enap® and monitor the patient until the symptoms disappear completely. Even if there is only tongue edema, when there is only difficulty swallowing without respiratory distress syndrome, patients may need long-term follow-up, since the use of antihistamines and glucocorticosteroids may not be sufficient.

Angioedema of the larynx or tongue can be fatal in very rare cases. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction, especially after an operation on the airway in an anamnesis. 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 (epinephrine) solution (0.3 ml - 0.5 ml) and / or measures aimed at restoring the patency respiratory tract (intubation or tracheostomy).

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

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

Anaphylactoid reactions during desensitization with Hepaticoptera (Hymenoptera)

In patients who took ACE inhibitors during desensitization with Hepaticoptera, rare life-threatening anaphylactoid reactions developed.To prevent such reactions, it is necessary to temporarily stop the use of an ACE inhibitor during desensitization procedures.

Anaphylactoid reactions during apheresis of LDL

In patients taking ACE inhibitors during apheresis of low-density lipoprotein (LDL) by dextran sulfate, in rare cases, life-threatening anaphylactoid reactions developed. It should be temporarily replaced with drugs from another group.

Hemodialysis

Due to the increased risk of anaphylactoid reactions, the drug should not be used for patients on hemodialysis using high-flux polyacrylonitrile membranes (AN69®) undergoing low-density lipoprotein apheresis using dextran sulfate. If hemodialysis is necessary, it is advisable to use dialysis membranes of a different type, or hypotensive drugs of another group.

Hypoglycaemia

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

Cough

With Enap®, a "dry", unproductive, prolonged cough may occur that disappears after the cessation of the use of ACE inhibitors, which must be taken into account in the differential diagnosis of coughing with the use of an ACE inhibitor.

Surgery / general anesthesia

Before surgery (including dental procedures), the surgeon / anesthesiologist must be warned about the use of Enap®.

With extensive surgical intervention or general anesthesia with the use of agents that cause arterial hypotension, ACE inhibitors can block the formation of angiotensin II in response to compensatory release of renin. If this results in a pronounced decrease in blood pressure, explained by a similar mechanism, it can be corrected by introducing plasma substitutes.

Hyperkalemia

It can develop during treatment with ACE inhibitors, including enalapril. Risk factors for hyperkalemia include: renal failure, elderly age (over 70 years), diabetes mellitus, certain concomitant conditions (decreased BCC, acute heart failure in 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 potassium content in the blood plasma (for example, heparin). The use of potassium preparations, potassium-sparing diuretics and substitutes for edible salt containing potassium can lead to a significant increase in serum potassium content, especially in patients with impaired renal function. Hyperkalemia can lead to serious heart rhythm disturbances, sometimes with a fatal outcome. Simultaneous use of the above drugs should be done with caution under the control of potassium in the blood serum.

Lithium

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

Ethnic Features

The Enap® preparation, like other ACE inhibitors, has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races.

Special information on excipients

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

Effect on the ability to drive transp. cf. and fur:

When using Enap®, care must be taken when driving vehicles and engaging in other potentially dangerous activities requiring increased concentration 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 ).

Form release / dosage:Tablets of 2.5 mg, 5 mg, 10 mg and 20 mg.

Packaging:

In production at JSC "Krka, dd .. Novo mesto", Slovenia:

Tablets of 2.5 mg, 5 mg, 10 mg and 20 mg.

For 10 tablets in a blister of the combined material OPA / A1 / PVC (polyamide / aluminum foil / PVC) and aluminum foil.

2, 3 or 6 blisters together with instructions for use are placed in a cardboard pack. For hospitals (for tablets 10 mg and 20 mg):

For 10, 20, 50 or 100 blisters together with instructions for use are put in a cardboard pack.

When packaging and / or packaging at the Russian company LLC "Krka-RUS":

Tablets of 2.5 mg, 5 mg, 10 mg and 20 mg.

For 10 tablets in a blister of the combined material OPA / A1 / PVC (polyamide / aluminum foil / PVC) and aluminum foil.

2, 3 or 6 blisters together with instructions for use are placed in a cardboard pack.

At packing on the Russian enterprise of Joint-Stock Company "Vector-medica":

Tablets of 2.5 mg, 5 mg, 10 mg and 20 mg.

2 blisters together with instructions for use are placed in a cardboard pack.

When produced at OOO Krka-Rus, Russia:

Tablets of 2.5 mg, 5 mg, 10 mg and 20 mg.

For 10 tablets in a contour mesh package made of combined material OPA / A1 / PVC (polyamide / aluminum foil / PVC) and aluminum foil.

2, 3 or 6 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

For hospitals (for tablets 10 mg and 20 mg):

For 10, 20, 50 or 100 contour mesh packages together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In a place protected from moisture, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N013165 / 02

Date of registration:12.10.2011

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, dd, Novo mesto, AO Slovenia

KRKA-RUS, LLC Russia

VECTOR-MEDICA, CJSC Russia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp23.10.2015

Illustrated instructions

Instructions

Enap® (Enap®)