Indications for use. Enap - instructions for use Enap n 5 mg instructions for use
Compound
Description of the dosage form
Tablets, 2.5 mg: white or almost white, round, biconvex, chamfered.
Tablets, 5 mg: white or almost white, round, flat-cylindrical, with a risk on one side and a chamfer.
Tablets, 10 mg: red-brown, round, flat-cylindrical, with a risk on one side and a chamfer. White and burgundy inclusions are allowed on the surface and in the mass of the tablet.
Tablets, 20 mg: light orange, round, flat-cylindrical, with a risk on one side and a chamfer. On the surface and in the mass of the tablet, white and brown-burgundy inclusions are allowed.
pharmachologic effect
pharmachologic effect- hypotensive.Pharmacodynamics
Enalapril is an antihypertensive drug, the mechanism of action of which is associated with inhibition of ACE activity, leading 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 enalaprilat, 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 content of which leads to an increase in plasma renin activity (by eliminating the negative feedback on changes in renin production) and a decrease in aldosterone secretion. Since ACE is identical to the enzyme kininase II, enalapril can also block the destruction 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 associated primarily 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 concentration.
Against the background of the use of enalapril, the level of blood pressure decreases regardless of the position of the body (both in the supine position and in the standing position) without a significant increase in heart rate. Symptomatic orthostatic hypotension rarely develops. In some patients, achieving optimal blood pressure reduction may require several weeks of therapy. Abrupt withdrawal of enalapril was not accompanied by a rise in blood pressure.
Effective inhibition of ACE activity usually occurs 2-4 hours after a single oral dose of enalapril. The time of onset of the antihypertensive effect is usually 1 hour when taken orally, reaching a maximum after 4-6 hours. The duration of action depends on the dose. 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 peripheral vascular resistance and an increase in cardiac output, while the heart rate does not change or changes slightly. The renal blood flow increases, but the glomerular filtration rate does not change. However, in patients with initially low glomerular filtration rate, its level usually increased.
In patients with diabetic / non-diabetic nephropathy, while taking enalapril, albuminuria / proteinuria and renal excretion of IgG decreased.
In patients with CHF during therapy with cardiac glycosides and diuretics, the use of enalapril is accompanied by a decrease in peripheral vascular resistance and blood pressure, an increase in cardiac output, while heart rate decreases (usually in patients with CHF, heart rate is increased). The wedge pressure of the pulmonary capillaries also decreases. With long-term use, enalapril increases exercise tolerance and reduces the severity of heart failure, assessed by the criteria NYHA. Enalapril in patients with mild to moderate heart failure slows down its progression, and also slows down the development of left ventricular dilatation.
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 is rapidly absorbed, the degree of absorption of enalapril is approximately 60%. T max enalapril in serum - 1 hour after ingestion. Eating does not affect absorption. Enalapril is rapidly and actively hydrolyzed to form enalaprilat, a potent ACE inhibitor. T max enalaprilat - 3-4 hours after ingestion. T 1/2 of enalapril with repeated use is 11 hours. In patients with normal renal function, C ss of enalaprilat in plasma was achieved on the 4th day of therapy.
Distribution
Communication with proteins of a blood plasma of an enalaprilat in the range of therapeutic doses makes 60%.
Biotransformation (metabolism)
In addition to being converted to enalaprilat, enalapril does not undergo significant biotransformation.
breeding
Enalaprilat is mainly excreted by the kidneys. Enalaprilat (about 40% of the dose) and unchanged enalapril (about 20%) are predominantly determined in the urine.
Special patient groups
Impaired kidney function. In patients with mild to moderate renal insufficiency (Cl creatinine 36-60 ml / min (0.6-1 ml / s) after taking enalapril at a dose of 5 mg 1 time per day, the AUC of enalaprilat is approximately 2 times greater than in patients with normal renal function.In severe renal failure (Cl creatinine ≤30 ml / min): AUC increased by about 8 times.T 1/2 of enalaprilat after repeated use in severe renal failure is extended, and the time to reach an equilibrium state is delayed.Enalaprilat is removed when hemodialysis, excretion rate - 1.03 ml / s (62 ml / min).
Enap ® 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:
Reducing the incidence of myocardial infarction;
Reducing the frequency of hospitalizations for unstable angina.
Contraindications
hypersensitivity to enalapril, other components of the drug or other ACE inhibitors;
history of angioedema associated with previous use of ACE inhibitors, hereditary angioedema angioedema or idiopathic angioedema;
simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (Cl creatinine less than 60 ml / min);
porphyria;
lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (because Enap ® contains lactose);
pregnancy;
breastfeeding period;
age up to 18 years (efficacy and safety have not been established).
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 impaired hemodynamics); hypertrophic obstructive cardiomyopathy (GOKMP); conditions with reduced BCC (including diarrhea, vomiting); systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus); cardiac ischemia; oppression of bone marrow hematopoiesis; cerebrovascular diseases (including cerebrovascular insufficiency); diabetes; renal failure (proteinuria - more than 1 g / day); liver failure; patients on a salt-restricted diet or on hemodialysis; simultaneous reception with immunosuppressants and diuretics; patients over 65 years of age.
Use during pregnancy and lactation
The use of ACE inhibitors, incl. the drug Enap ® in the first trimester of pregnancy is not recommended.
The use of ACE inhibitors, incl. Enap ® is contraindicated in the second and third trimesters of pregnancy.
Epidemiological data on the risk of teratogenic effects of ACE inhibitors during pregnancy do not allow definitive conclusions to be drawn. However, the risk of their development cannot be ruled out. 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 pregnancy is confirmed, Enap ® should be discontinued as soon as possible.
Taking ACE inhibitors in the II and III trimesters can cause fetotoxicity reactions (impaired kidney function, oligohydramnios, slowing down of ossification of the fetal skull bones) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia).
If an ACE inhibitor was taken in the II and III trimesters of pregnancy, it is recommended to conduct an ultrasound scan of the kidneys and bones of the fetal skull.
In those rare cases where the use of an ACE inhibitor during pregnancy is considered necessary, periodic ultrasonography should be performed to assess the amniotic fluid index. If oligohydramnios is detected during ultrasound, it is necessary to stop taking the drug. Patients and physicians should be aware that oligohydramnios develops when there is irreversible damage to the fetus.
If ACE inhibitors are used during pregnancy and oligohydramnios develops, then, depending on the week of pregnancy, a stress test, a non-stress test, or a fetal biophysical profile may be necessary 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 crosses the placenta, can be partially removed from the neonatal circulation by peritoneal dialysis, and theoretically it can be removed by exchange transfusion.
Enalapril and enalaprilat are found in breast milk in trace concentrations, therefore, if it is necessary to use the drug Enap ®, breastfeeding should be stopped.
Side effects
Classification of the frequency of development of side effects WHO: very often - ≥1 / 10; often - from ≥1 / 100 to<1/10; нечасто — от ≥1/1000 до <1/100; редко — от ≥1/10000 до <1/1000; очень редко — <1/10000; частота неизвестна — не может быть оценена на основе имеющихся данных. В каждой группе нежелательные эффекты представлены в порядке уменьшения их серьезности.
From the side of the hematopoietic organs: infrequently - anemia (including aplastic and hemolytic); rarely - neutropenia, a decrease in the concentration of hemoglobin and hematocrit in the blood serum, thrombocytopenia, agranulocytosis, inhibition 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, irritability, vertigo; rarely - a change in the nature of dreams, sleep disorders.
From the sense organs: often - changes in taste perception; infrequently - tinnitus; very rarely - blurred vision.
From the CCC: very often - dizziness; often - a pronounced decrease in blood pressure (including orthostatic hypotension), syncope, chest pain, heart rhythm disturbances, angina pectoris; infrequently - 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, bronchospasm / bronchial asthma; rarely - shortness of breath, 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 - impaired liver function 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 side of the skin: often - skin rash, hypersensitivity reactions / angioedema (angioneurotic edema of the face, extremities, lips, tongue, pharynx and / or larynx is described); infrequently - increased sweating, pruritus, 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 ESR, leukocytosis and eosinophilia, a positive test for antinuclear antibodies. Skin rash, photosensitivity reactions, or other skin manifestations may occur.
From the genitourinary system: infrequently - impaired renal function, proteinuria, renal failure, impotence; rarely - oliguria, gynecomastia.
From the musculoskeletal system: infrequently - muscle cramps.
Laboratory indicators: often - hyperkalemia, increased serum creatinine concentration; infrequently - an increase in the concentration of urea in the blood serum, hyponatremia; rarely - an increase in the activity of liver enzymes, an increase in the concentration of bilirubin in the blood serum.
Others: frequency unknown - syndrome of inappropriate ADH secretion.
Adverse events identified during the post-marketing use of the drug, but a causal relationship with the use of the drug has not been established: urinary tract infections, upper respiratory tract infections, bronchitis, cardiac arrest, atrial fibrillation, herpes zoster, melena, ataxia, thromboembolism of the branches of the pulmonary artery and lung infarction, hemolytic anemia, including cases of hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.
Interaction
Double blockade of the 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 the RAAS, i.e. with the simultaneous use of angiotensin II receptor antagonists, ACE inhibitors or aliskiren, in comparison with the use of a drug from one of the listed groups. If necessary, the simultaneous use of drugs is recommended to control blood pressure, kidney function and water and electrolyte balance.
The simultaneous use of enalapril with aliskiren in patients with diabetes mellitus or impaired renal function (Cl creatinine less than 60 ml / min) is contraindicated.
Potassium-sparing diuretics and potassium supplements
ACE inhibitors reduce potassium loss due to diuretics.
The simultaneous use of enalapril and potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing substitutes, as well as the use of other drugs that increase the content of potassium in the blood plasma (for example, heparin) can lead to hyperkalemia.
If necessary, simultaneous use should be careful and regularly monitor the serum potassium content.
Diuretics (thiazide or loop)
Prior therapy with high doses of diuretics may lead to a decrease in BCC and an increased risk of arterial hypotension during the initiation of enalapril therapy. Excessive antihypertensive effect can be reduced by discontinuing the diuretic, increasing water or salt intake, and also by starting treatment with enalapril at a low dose.
Other antihypertensive drugs
Simultaneous with enalapril, the use of beta-blockers, alpha-blockers, ganglion blockers, methyldopa, CCB, nitroglycerin or other nitrates can further reduce blood pressure.
Lithium
With the simultaneous use of ACE inhibitors with lithium preparations, a transient increase in the serum concentration of lithium and the development of lithium intoxication were observed. The use of thiazide diuretics may lead to an additional increase in serum lithium concentration and the risk of lithium intoxication with the simultaneous use of ACE inhibitors. Co-administration of enalapril with lithium is not recommended. Serum lithium concentrations should be carefully monitored if such a combination is required.
Tricyclic antidepressants/antipsychotics (neuroleptics)/anesthetics/narcotics
The simultaneous use of certain anesthetics, tricyclic antidepressants and antipsychotics (neuroleptics) with ACE inhibitors can lead to an additional decrease in blood pressure.
NSAIDs
The simultaneous 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 the increase in serum potassium, which can lead to deterioration of renal function, especially in patients with impaired renal function. This effect is reversible.
In rare cases, acute renal failure may develop, especially in patients with impaired renal function (for example, in elderly patients or with severe hypovolemia, including against the background of the use of diuretics).
Before starting therapy, it is necessary to replenish the BCC. During treatment, it is recommended to monitor kidney function.
Oral hypoglycemic agents and insulin
Epidemiological studies suggest that the simultaneous use of ACE inhibitors and hypoglycemic agents (insulin and oral hypoglycemic agents) may lead to an increase in the hypoglycemic effect with the 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 may reduce the antihypertensive effect of ACE inhibitors.
Acetylsalicylic acid, thrombolytics and beta-blockers
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.
Allopurinol, cytostatics and immunosuppressants (including methotrexate, cyclophosphamide)
Simultaneous use with ACE inhibitors may increase the risk of developing leukopenia. With simultaneous use with allopurinol, the risk of developing an allergic reaction increases, especially in patients with impaired renal function.
Cyclosporine
Simultaneous use with ACE inhibitors may increase the risk of hyperkalemia.
Antacids
Antacids may decrease the bioavailability of ACE inhibitors.
Preparations of gold
When using ACE inhibitors, incl. enalapril, patients receiving an intravenous gold preparation (sodium aurothiomalate), a symptom complex was described, including flushing of the skin of the face, 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.
Dosage and administration
inside, regardless of the time of eating, preferably at the same time of day, drinking a small amount of liquid.
Arterial hypertension
The initial dose is from 5 to 20 mg 1 time per day, depending on the severity of arterial hypertension and the patient's condition. With mild hypertension, the recommended initial dose is 5-10 mg / day.
In patients with severe activation of the RAAS (for example, with renovascular hypertension, salt loss and / or dehydration, decompensated heart failure or severe arterial hypertension), an excessive decrease in blood pressure at the beginning of treatment is possible. 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.
Prior therapy with high doses of diuretics 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. Treatment with diuretics should be discontinued 2-3 days before the start of the use of the drug Enap ® . Caution should be exercised when using the drug Enap ®, monitor kidney function and serum potassium levels.
The usual maintenance dose is 20 mg once daily.
The dosage is selected individually, if necessary, can be increased to a maximum daily dose of 40 mg.
CHF and left ventricular dysfunction
The initial dose of the drug Enap ® is 2.5 mg / day once; treatment in this case must 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, 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, depending on the tolerance of the drug. Dose selection is carried out within 2-4 weeks. The maximum daily dose is 40 mg in 2 divided doses.
1st week: 1-3rd day - 2.5 mg / day in 1 dose; 4-7th day - 5 mg / day in 2 divided doses.
2nd week: 10 mg/day in 1 or 2 doses.
3rd and 4th weeks: 20 mg / day in 1 or 2 doses.
Special precautions should be observed in patients with impaired renal function and taking diuretics.
Given the risk of developing arterial hypotension and renal failure (observed much less frequently), blood pressure and kidney function should be carefully monitored before and after starting the use of the drug Enap ®. In patients taking diuretics, diuretic doses, if possible, should be reduced before taking the drug 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.
Special patient groups
Impaired kidney function. In patients with impaired renal function, the intervals between use should be increased and / or the dose of Enap ® should be reduced.
With Cl creatinine from 30 to 80 ml / min, the initial dose is 5-10 mg / day; from 10 to 30 ml / min - 2.5-5 mg / day; less than 10 ml / min - 2.5 mg on the day of hemodialysis (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 a longer duration of action of the drug are more often observed, which is associated with a decrease in the rate of excretion of enalapril, so the recommended initial dose is 1.25 mg. The dose is selected depending on the function of the kidneys.
Overdose
Symptoms: about 6 hours after ingestion - a pronounced decrease in blood pressure, up to the development of collapse, water and electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough, convulsions, stupor. After oral administration of 300 and 440 mg of enalapril, serum concentrations of enalaprilat in 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 charcoal are indicated, in more severe cases, intravenous infusion of 0.9% sodium chloride solution, plasma substitutes, and, if necessary, intravenous administration of catecholamines. It is possible to remove enalaprilat by hemodialysis, the excretion rate 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 dose 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 doses of diuretics, hyponatremia, or impaired renal function. In these patients, treatment should be started under the supervision of a physician until the optimal dose adjustment of Enap ® and / or diuretic. Similar tactics can be applied to patients with coronary artery disease or cerebrovascular disease, in whom a sharp excessive decrease in blood pressure can lead to the development of myocardial infarction or cerebrovascular accident.
In case of severe arterial hypotension, the patient should be given a horizontal position, legs should be raised and, if necessary, 0.9% sodium chloride solution should be injected intravenously.
Transient arterial hypotension is not 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 may be further reduced when taking Enap ®. This effect is predictable and is not usually a reason to stop therapy. If arterial 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, HOCM
As with all vasodilators, ACE inhibitors should be used cautiously in patients with valvular obstruction and left ventricular outflow tract hypertrophy. It should not be given to patients with cardiogenic shock and hemodynamically significant left ventricular obstruction.
Impaired kidney function
In patients with renal insufficiency (Cl creatinine<80 мл/мин (1,33 мл/с) начальную дозу препарата Энап ® следует подбирать в первую очередь с учетом Cl креатинина и затем — клинического ответа на лечение. У таких пациентов следует регулярно контролировать содержание калия и концентрацию креатинина в сыворотке крови.
In patients with severe heart failure and kidney disease, including renal artery stenosis, renal failure may develop during treatment with Enap ®. Changes were usually reversible after discontinuation of the drug Enap ® .
In some patients with arterial hypertension, in whom no kidney disease was detected before the start of treatment, a slight and transient increase in the concentration of urea and creatinine in the blood serum was observed when using the drug Enap ® simultaneously with a diuretic. In such cases, it may be necessary to reduce the dose of the drug Enap ® and / or 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 the only functioning kidney when treated with ACE inhibitors have an increased risk of arterial hypotension and renal failure. Only minor changes in serum creatinine concentration can indicate a decrease in kidney function. In such patients, treatment should be initiated at 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.
Impaired liver function
In rare cases, therapy with ACE inhibitors was accompanied by the development of a syndrome beginning with cholestatic jaundice and hepatitis up to the development of fulminant liver necrosis. The mechanism by which this syndrome develops is unknown. If jaundice occurs or a significant increase in the activity of liver enzymes, treatment with an ACE inhibitor should be stopped immediately, the patient should be carefully monitored and, if necessary, treated.
Neutropenia/agranulocytosis
In patients treated with ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia, and anemia have been described. Neutropenia rarely develops in patients with normal renal function in the absence of other complications. The drug Enap ® must be used with great caution in patients with connective tissue diseases (including systemic lupus erythematosus, scleroderma), while 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 are not amenable to intensive antibiotic therapy. If patients still take the drug Enap ®, then it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that in case of any signs of infection, it is necessary to immediately consult a doctor.
Hypersensitivity/angioedema
In patients treated with ACE inhibitors, including enalapril, there have been reports of the development of angioedema of the face, extremities, lips, vocal cords and / or larynx at any time after the start of treatment. You should immediately stop the drug Enap ® and observe the patient until the symptoms disappear completely. Even in the case of swelling of the tongue only, when there is only difficulty in swallowing without respiratory distress syndrome, patients may require long-term observation, because. 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 cords, or larynx can lead to airway obstruction, especially after a history of airway surgery. In the presence of swelling of the tongue, vocal cords or larynx, appropriate therapy is indicated, which may include: s / c injection of a 0.1% solution of epinephrine (adrenaline) (0.3-0.5 ml) and / or measures aimed at recovery airway patency (intubation or tracheostomy).
Among black patients receiving therapy with an ACE inhibitor, the incidence of angioedema is higher than among patients of other races.
Patients with a history of angioedema unrelated to ACE inhibitors have an increased risk of developing angioedema when taking any ACE inhibitor.
Anaphylactoid reactions during desensitization with hymenoptera (hymenoptera) venom
Patients treated with ACE inhibitors during desensitization with hymenoptera venom have rarely developed life-threatening anaphylactoid reactions. To prevent such reactions, it is necessary to temporarily stop taking the ACE inhibitor during desensitization procedures.
Anaphylactoid reactions during LDL apheresis
Patients treated with ACE inhibitors during LDL apheresis with dextran sulfate have rarely developed life-threatening anaphylactoid reactions. It is necessary to temporarily replace the drugs of another group.
Hemodialysis
Due to the increased risk of anaphylactoid reactions, the drug should not be used in patients on hemodialysis using high-flow polyacrylonitrile membranes (AN69 ®) undergoing LDL apheresis with dextran sulfate. 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 diabetic patients receiving oral hypoglycemic agents or insulin, blood glucose levels should be closely monitored during the first month of treatment with an ACE inhibitor.
Cough
When using the drug Enap ®, a dry, unproductive, prolonged cough may occur, which disappears after discontinuation 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 surgery (including dental procedures), it is necessary to warn the surgeon / anesthetist about the use of the drug Enap ®. During major surgery or general anesthesia with the use of drugs that cause arterial hypotension, 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
May develop during treatment with ACE inhibitors, incl. and drug Enap ® . Risk factors for the development of hyperkalemia are renal failure, advanced age (over 70 years), diabetes mellitus, some concomitant conditions (decrease in BCC, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous 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 content of potassium in the blood plasma (for example, heparin). The use of potassium supplements, potassium-sparing diuretics and salt substitutes containing potassium can lead to a significant increase in serum potassium, especially in patients with impaired renal function. Hyperkalemia can lead to serious heart rhythm disturbances, sometimes fatal. The simultaneous use of the above drugs should be carried out with caution under the control of the content of potassium in the blood serum.
Lithium
The simultaneous use of lithium salts and the drug Enap ® is not recommended.
Ethnic features
The drug Enap ® , like other ACE inhibitors, has a less pronounced antihypertensive effect in patients of the Negroid race compared to representatives of other races.
Special information on excipients
The drug Enap ® contains lactose, so the drug is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.
Influence on the ability to perform potentially hazardous activities that require special attention and speed of reactions (for example, driving vehicles, working with mechanisms). When using the drug Enap ®, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require 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 ).
Release form
1. Production at JSC "Krka, d.d., Novo Mesto". Slovenia.
Tablets, 2.5 mg, 5 mg, 10 mg and 20 mg. In a blister of combined material OPA/Al/PVC and aluminum foil, 10 pcs. 2, 3, 6 or 9 blisters in a carton pack.
Tablets, 10 mg and 20 mg. In a blister, 10 pcs. 10, 20, 50 or 100 blisters in a carton pack (for hospitals).
Packing and / or packaging at the Russian enterprise KRKA-RUS LLC.
Compound
Each tablet contains 10 mg or 20 mg of enalapril maleate.
Tablets 10 mg
Excipients: sodium bicarbonate, lactose monohydrate, maize starch, iron oxide red E 172, talc, magnesium stearate.
Tablets 20 mg
Excipients: sodium bicarbonate, lactose monohydrate, maize starch, iron oxide red E172, iron oxide yellow E172, talc, magnesium stearate.
Description
Tablets 10 mg: round, flat reddish-brown tablets, with a bevelled edge and a notch on one side, with separate white patches on the surface and in the mass of the tablet. The notch is not designed to break the tablet.
Tablets 20 mg: round, flat tablets of light orange color with a bevelled edge and a notch on one side, with separate white patches on the surface and in the mass of the tablet. The notch is not designed to break the tablet.
Pharmacotherapeutic group
Pharmacotherapeutic group: Angiotensin-converting enzyme (ACE) inhibitors. ATX code: C09AA02.
Pharmacological properties
Pharmacodynamics
Enalapril maleate is a salt of maleic acid and enalapril, a derivative of two amino acids (L-alanine and L-proline). After absorption, enalapril undergoes hydrolysis to enalaprilat, which inhibits ACE, which leads to a decrease in the plasma concentration of the angiotensin II pressor compound and, as a result, to an increase in plasma renin activity and a decrease in aldosterone secretion. The drug can also block the breakdown of bradykinin, a powerful vasodepressor (vasodilator) peptide.
Although the mechanism by which enalapril exerts its hypotensive effect is primarily through the suppression of the renin-angiotensin-aldosterone system, which plays the most important role in the regulation of blood pressure, the drug also exerts an antihypertensive effect in patients with low renin levels. The use of enalapril in patients with hypertension leads to a decrease in blood pressure in both the supine and standing positions without an increase in heart rate. Symptomatic postural hypotension is rare. In some patients, reaching the level of blood pressure reduction may require several weeks of therapy. Abrupt withdrawal of enalapril is not accompanied by a rapid increase in blood pressure.
Effective suppression of ACE activity usually develops within 2-4 hours after ingestion of an individual dose of enalapril. The onset of antihypertensive activity is usually observed within an hour, the maximum reduction in blood pressure is achieved within 4-6 hours after administration. The duration of action depends on the dose. However, in the recommended amounts, the antihypertensive and hemodynamic effects persist for at least 24 hours.
In hemodynamic studies in patients with essential hypertension, a decrease in blood pressure was accompanied by a decrease in peripheral resistance in the arteries with an increase in cardiac output and little or no change in heart rate. After the introduction of enalapril, there was an increase in renal blood flow; glomerular filtration rate did not change; no signs of sodium or water retention were observed. However, in patients with reduced glomerular filtration, an increase in this indicator was noted.
In short-term clinical studies of patients with kidney disease with or without diabetes mellitus, a decrease in albuminuria and a decrease in urinary excretion of IgG and total protein were observed after taking enalapril.
When combined with thiazide-type diuretics, the hypotensive effect is additive. At the same time, enalapril can reduce or prevent the development of hypokalemia caused by taking thiazides.
In patients with heart failure during therapy with digitalis and diuretics, enalapril reduces peripheral resistance and blood pressure. Cardiac output increases while heart rate (usually elevated in patients with heart failure) decreases; the wedge pressure in the pulmonary capillaries (DZLK) decreases. Therapy with enalapril normalizes the condition in heart failure and improves exercise tolerance. These effects persist throughout therapy. In patients with mild or moderate heart failure, the drug slows down the progression of heart dilatation and heart failure (decrease in the end diastolic and systolic volume of the left ventricle and improve the ejection fraction (ejection)).
In patients with left ventricular dysfunction, enalapril reduces the risk of major cardiovascular events, myocardial infarction and the number of hospitalizations for unstable angina.
Pharmacokinetics
Suction
Enalapril is rapidly absorbed from the gastrointestinal tract; the maximum concentration in blood serum is reached within one hour. The degree of absorption is about 60%, while eating does not affect absorption. After absorption, enalapril is rapidly and completely hydrolyzed to enalaprilat, an active ACE inhibitor. The peak concentration of enalaprilat in the blood serum is observed 4 hours after taking enalapril inside. The effective half-life for accumulation of enalaprilat after repeated oral administration of enalapril is 11 hours. In patients with normal renal function, a stable serum concentration of enalaprilat is achieved four days after the start of treatment.
Distribution
In the range of therapeutically significant concentrations, the binding of enalaprilat to serum proteins is 60%.
Metabolism
With the exception of conversion to enalaprilat, there are no signs of significant metabolism of enalapril.
breeding
Enalaprilat is excreted mainly by the kidneys. The main components in the urine are enalaprilat, which accounts for 40% of the dose, and unchanged enalapril (about 20%).
Impaired kidney function
Exposure to enalapril and enalaprilat is increased in patients with renal insufficiency. In patients with mild or moderate renal insufficiency (creatinine clearance 0.6-1 ml / s), after taking the drug 5 mg once a day, the AUC value of enalaprilat is approximately two times higher than in patients with normal renal function; whereas in severe renal insufficiency (creatinine clearance 0.5 ml / s), the AUC value increases by approximately eight times. At this level of renal failure, the effective half-life of enalaprilat is prolonged and the time to steady state is increased.
Enalaprilat can be removed from the circulatory system by hemodialysis. Enalaprilat dialysis clearance is 1.03 ml/sec.
Children and teenagers
Significant differences in pharmacokinetics in children compared with adults have not been established. The data show an increase in AUC (standardized for dose per body weight) with increasing age; however, no increase in AUC was observed when data were standardized for body surface area. At steady state, the mean effective half-life of accumulated enalaprilat was 14 hours.
Indications for use
Treatment of arterial hypertension.
Treatment of symptomatic heart failure.
Prevention of symptomatic heart failure in patients with asymptomatic left ventricular dysfunction (ejection fraction< 35 %).
Contraindications
Hypersensitivity to enalapril, other components of the drug or other ACE inhibitors.
A history of angioedema caused by the use of ACE inhibitors.
Hereditary or idiopathic angioedema.
Second and third trimester of pregnancy.
The simultaneous use of Enap and aliskiren-containing drugs is contraindicated in patients with diabetes mellitus or renal insufficiency (GFR< 60мл/мин/1,73 м2).
Dosage and administration
The dose is selected individually depending on the patient's condition. hypertension
The initial dose is 5 mg - 20 mg, depending on the degree of hypertension and the patient's condition. The drug is taken once a day. For moderate hypertension, the recommended starting dose is 5 mg to 10 mg per day. In patients with marked activity of the renin - angiotensin - aldosterone system (for example, renovascular hypertension, loss of water and / or salts, cardiac decompensation or severe hypertension), an excessive drop in blood pressure may occur at the beginning of treatment. In such patients, it is recommended to start treatment under medical supervision with a dose of 5 mg or less. Prior treatment with high doses of diuretics may lead to hypovolemia and the risk of hypotension at the start of treatment. In such patients, the recommended starting dose is 2.5 mg. If possible, 2-3 days before the start of treatment with enalapril, diuretic therapy should be canceled. During treatment, it is necessary to monitor kidney function and potassium levels.
The usual maintenance dose is 10-20 mg per day. The maximum maintenance dose is 40 mg per day.
Heart failure/ asymptomatic left ventricular dysfunction
The initial dose of enalapril maleate in patients with symptomatic heart failure or asymptomatic left ventricular dysfunction is 2.5 mg once daily. The initial effect on blood pressure should be carefully monitored.
For the treatment of symptomatic heart failure, enalapril maleate is usually used in combination with diuretics and beta-blockers and, if necessary, also with digitalis glycosides.
If, after initiation of treatment for heart failure, symptomatic hypotension is absent or effectively eliminated, then the dose should be gradually increased to the usual maintenance dose of 20 mg, taken once or divided into two doses (depending on patient tolerance).
* Patients with impaired renal function or who are treated with diuretics should be especially careful
Blood pressure and renal function should be monitored before and after initiation of treatment with enalapril maleate, as hypotension and (less commonly) subsequent renal failure have been reported. In patients taking diuretics, the dose should be reduced if possible before starting treatment with enalapril. The appearance of hypotension at the beginning of treatment does not mean that such a reaction will also occur during long-term therapy with enalapril, and does not preclude further use of the drug. During treatment, it is necessary to monitor kidney function and serum potassium levels.
Dosage in renal failure
In patients with renal insufficiency, the intervals between taking enalapril should be extended and / or the dosage reduced.
* On non-dialysis days, the dose should be adjusted according to blood pressure readings.
Use in elderly patients
The dose should be adjusted according to the patient's renal function. Use in children
Clinical experience with enalapril maleate in children with hypertension is limited.
For patients who can swallow tablets, the dose should be adjusted individually depending on the patient's condition and response from blood pressure. For patients weighing 20 to 50 kg, the recommended starting dose is 2.5 mg enalapril maleate per day; for patients weighing 50 kg or more - 5 mg of enalapril maleate once a day. The dosage should be selected depending on the needs of the patient. The maximum recommended dose of enalapril maleate for patients weighing 20-50 kg is 20 mg per day; for patients weighing 50 kg or more - 40 mg of enalapril maleate per day.
Treatment with Enap is long-term, usually throughout life, unless circumstances arise that require its cancellation.
Side effect
Side effects that may occur during treatment with Enap are classified into groups depending on the frequency of occurrence:
Very common (≥ 1/10), frequent (≥ 1/100 to< 1/10), нечастые (>1/1000 to< 1/100), редкие (≥ 1/10000 до < 1/1000) очень редкие (< 1/10000), частота неизвестна (не могут быть оценены по доступным данным).
Within each group, side effects of the drug are presented in order of decreasing significance.
Side effects observed during treatment with Enap are usually mild, transient in nature and do not require discontinuation of the drug.
The frequency of side effects is listed by individual organ systems.
Research:
Frequent - hyperkalemia, hypercreatininemia;
Infrequent - increase in serum urea, hyponatremia;
Rare - increased liver enzymes, increased serum bilirubin.
Cardiovascular disorders:
Very common - dizziness;
Frequent - hypotension (including orthostatic hypotension);
Infrequent - orthostatic hypotension, palpitations;
Rare - syncope, myocardial infarction or stroke, possibly due to excessive hypotension in high-risk patients, chest pain, arrhythmias, angina pectoris, bradycardia or tachycardia, atrial fibrillation, hemodynamic vertebrobasilar insufficiency, Raynaud's phenomenon.
Blood and lymphatic system disorders:
Infrequent - anemia (including aplastic and hemolytic);
Rare - neutropenia, decreased hemoglobin, decreased hematocrit, thrombocytopenia, agranulocytosis, bone marrow suppression, pancytopenia, lymphadenopathy, autoimmune diseases.
Endocrine system disorders:
The frequency is not known - syndrome of inappropriate secretion of antidiuretic hormone (SIADH).
Nervous system disorders:
Frequent - headache, drowsiness;
Infrequent - insomnia, dizziness;
Rare - confusion, nervousness, depression, paresthesia, sleep anomaly, sleep disturbances.
Violations of the organ of vision:
Frequent - blurred vision.
Respiratory, thoracic and mediastinal disorders:
Very common - unproductive dry cough;
Frequent - shortness of breath;
Infrequent - rhinorrhea, pharyngitis, hoarseness, bronchospasm / asthma;
Rare - inflammation of the upper respiratory tract, lung infiltrates; rhinitis, allergic alveolitis/eosinophilic pneumonia.
Gastrointestinal disorders:
Very common - nausea;
Frequent - diarrhea, abdominal pain, change in taste;
Infrequent - intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, anorexia, gastric irritation, dry mouth, gastric and duodenal ulcers;
Rare - stomatitis / aphthous ulceration, glossitis;
Very rare, frequency unknown - intestinal angioedema. Renal and urinary tract disorders:
Infrequent - renal dysfunction, renal failure, proteinuria;
Rare - oliguria.
Skin and subcutaneous tissue disorders:
Frequent - rash, hypersensitivity / angioedema;
Infrequent - increased sweating, itching, urticaria, alopecia;
Rare - exudative erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrosis, pemphigus, erythroderma, photosensitivity.
Metabolic and nutritional disorders:
Infrequent - hypoglycemia.
Complications of a general nature and reactions at the injection site:
Frequent - asthenia, fatigue;
Infrequent - muscle cramps, hyperemia, tinnitus, malaise, fever.
Liver and biliary tract disorders:
Rare - liver failure, hepatocellular or cholestatic hepatitis, including hepatic necrosis, cholestasis, including jaundice.
Reproductive system and mammary gland disorders:
Infrequent - impotence;
Rare - gynecomastia.
Mental disorders:
Frequent - depression.
A complex of symptoms has been reported: fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, positive ANF, elevated ESR, eosinophilia, and leukocytosis.
In the event of severe side effects, treatment should be discontinued.
Overdose
Data regarding overdose in humans are limited.
Main symptom overdose is hypotension, starting six hours after taking the tablets and accompanied by blockade of the renin-angiotensin system and stupor.
Other symptoms: circulatory shock, electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.
Treatment: intravenous infusion of saline. If necessary, it is also possible to carry out treatment with infusion of angiotensin II and/or catecholamines intravenously. If the tablets have been taken recently, then measures should be taken to eliminate enalapril maleate (for example, vomiting, gastric lavage, administration of absorbents and sodium sulfate).
Enalaprilat can be removed from the general circulation by hemodialysis (62 ml/min). For bradycardia that does not respond to treatment, treatment with a pacemaker is indicated. Vital signs, electrolyte levels and serum creatinine concentration should be constantly (long-term) monitored.
Interaction with other drugs, as well as other types of interaction
Potassium-sparing diuretics, potassium supplements
ACE inhibitors reduce diuretic-induced potassium loss. Potassium-sparing diuretics (eg, spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes can lead to hyperkalemia. If combined use is indicated due to proven hypokalemia, then it should be used with caution and with regular monitoring of potassium in the blood serum.
Diuretics (thiazide or loop diuretics)
Prior treatment with high doses of diuretics may lead to hypovolemia and the risk of severe hypotension. The hypotensive effect can be reduced by discontinuing diuretics, compensating for the lack of salts and fluids in the body, or taking low doses of enalapril at the initial stage of treatment.
Other antihypertensive agents
The simultaneous use of enalapril and other antihypertensive drugs may increase the antihypertensive effect of enalapril. Simultaneous use with nitroglycerin, other nitrates or vasodilators may also lead to a decrease in blood pressure.
Double renin blockade- angiotensin -aldosterone system
Dual blockade of the renin-angiotensin-aldosterone system with combined use of angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with an increased risk of side effects such as hypotension, hyperkalemia, and decreased renal function (including acute renal failure) compared with the use of one of the agents that affect the renin-angiotensin-aldosterone system (see section "Precautions").
Lithium
A reversible increase in the concentration of lithium in the blood serum and its toxic effect have been reported with the combined use of lithium and ACE inhibitors. The simultaneous use of ACE inhibitors and thiazide diuretics can lead to an increase in lithium levels and increase the risk of lithium toxicity. Therefore, the co-administration of enalapril and lithium is not recommended. If this combination is still necessary, then careful monitoring of the level of lithium in the blood serum should be carried out.
Tricyclicantidepressants / antipsychotics / anesthetics / drugs
The simultaneous use of certain anesthetics, tricyclic antidepressants and neuroleptics with ACE inhibitors can lead to an additional decrease in blood pressure.
Non-steroidal anti-inflammatory drugs (NSAIDs)
Chronic use of NSAIDs may reduce the antihypertensive effect of ACE inhibitors. NSAIDs and ACE inhibitors have an additive effect on increasing serum potassium, which can lead to deterioration of kidney function. This effect is usually reversible. In rare cases, acute renal failure may occur, especially in patients with impaired renal function (eg, elderly or dehydrated patients).
Antidiabetic agents
Epidemiological studies suggest that the concomitant use of ACE inhibitors and antidiabetic drugs (insulin or oral antidiabetic drugs) may lead to hypokalemia. This symptom is most likely to occur in patients with kidney damage during the first weeks of combined treatment.
Alcohol
Alcohol enhances the hypotensive effect of ACE inhibitors. Sympathomimetics
Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.
Acetylsalicylic acid, thrombolytics andβ- blockers
Enalapril can be safely administered concomitantly with acetylsalicylic acid (in cardiac dosage), thrombolytics and β-blockers.
cardiac glycosides
The simultaneous use of Enap and cardiac glycosides does not have a clinically significant adverse interaction.
Cimetidine
With the joint administration of Enap and cimetidine, the half-life of Enap may be lengthened. If the patient is already taking the above drugs, he should inform the doctor that he is taking Enap.
Precautionary measures
Symptomatic hypotension
Symptomatic hypotension is rare in uncomplicated hypertension. It is most likely to occur in hypertensive patients with hypovolemia, for example, due to diuretic treatment, a salt-depleted diet, dialysis, diarrhea, or vomiting. Symptomatic hypotension may also occur in patients with heart failure with or without concomitant renal failure. More likely to occur in patients with more severe heart failure due to high doses of loop diuretics, hyponatremia, or kidney damage. In such patients, treatment should be started under medical supervision, with strict adherence to selected doses of enalapril and / or diuretic. A similar principle can be applied to patients with ischemic heart disease or cerebrovascular disease, in whom a sudden drop in blood pressure can lead to myocardial infarction or stroke. If hypotension develops, the patient should be placed in the supine position and, if necessary, intravenous infusion of 0.9% sodium chloride solution should be given to replenish plasma volume. Transient hypotension is not a contraindication for enalapril treatment. After adjusting blood pressure and plasma volume, patients subsequently generally tolerate treatment well.
In some patients with heart failure with normal or low blood pressure, enalapril may cause an additional decrease in blood pressure. This effect is predictable and is usually not a reason to stop treatment. If hypotension becomes symptomatic, dose reduction and/or discontinuation of the diuretic and/or enalapril is required.
Double blockade of renin-angiotensin-aldosterone system (RAAS)
The simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia, impaired renal function (including acute renal failure).
Due to the dual blockade of the RAAS, the combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended.
The appointment of therapy for dual blockade of the RAAS, due to its absolute necessity, should occur only under the supervision of a specialist and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
Stenosis of the aortic or mitral valve of the heart / hypertrophiccardiomyopathy
As with all vasodilators, ACE inhibitors should be used with extreme caution in patients with left ventricular outflow tract obstruction. In cases of cardiogenic shock and severe hemodynamic obstruction of the outflow tract of the left ventricle, the use of these drugs should be avoided.
Impaired kidney function
In patients with impaired renal function (creatinine clearance< 1,33 мл/сек) начальную дозу следует подбирать согласно клиренсу креатинина. Поддерживающие дозы назначают в соответствии с реакцией пациента на лечение. При этом регулярно следует контролировать уровни креатинина и калия в сыворотке крови.
In patients with severe heart failure or underlying kidney disease, including renal artery stenosis, renal failure may occur during treatment with enalapril. With timely diagnosis and appropriate treatment, this disease is usually reversible.
Some patients with overt pre-existing kidney disease have developed minimal and transient increases in serum urea and creatinine levels when enalapril was given concomitantly with a diuretic. In such cases, it may be necessary to reduce the dosage of ACE inhibitors and / or cancel diuretics. This situation should increase the likelihood of predisposing renal artery stenosis.
Renovascular hypertension
Patients with bilateral renal artery stenosis or stenosis of the artery of one functioning kidney, who are treated with ACE inhibitors, have an increased risk of developing hypotension and renal failure. In this case, a decrease in kidney function can be manifested only by minor changes in the level of creatinine in the blood serum. In such patients, treatment should begin at low doses and under medical supervision; during treatment, careful titration and monitoring of renal function is necessary.
kidney transplant
Due to lack of experience with enalapril, treatment with enalapril is not recommended in patients with a recent kidney transplant.
Liver failure
During treatment with ACE inhibitors, in rare cases, a syndrome may occur that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is unknown. If jaundice or a marked increase in liver enzymes develop during treatment with ACE inhibitors, treatment should be discontinued immediately and the patient should be closely monitored and treated if necessary.
Neutropenia/agranulocytosis
Neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. Neutropenia rarely occurs in patients with normal renal function and no other complications. Enalapril should be used with extreme caution in patients with vascular collagenosis (eg, systemic lupus erythematosus, scleroderma), as well as in patients treated with immunosuppressive drugs, allopurinol or procainamide, or in patients with a combination of these factors, especially with pre-existing impaired renal function. Some of these patients may develop serious infections, in some cases not responding to intensive antibiotic therapy. If enalapril is used in such patients, then periodic monitoring of the number of leukocytes is recommended. Patients should be instructed to report any signs of infection.
Hypersensitivity/ angioedema
During treatment with ACE inhibitors, including enalapril, in rare cases, angioedema of the face, extremities, lips, tongue, pharynx and / or larynx may develop at any stage of treatment. In such cases, enalapril should be discontinued immediately. Appropriate monitoring should be carried out to ensure that all symptoms have disappeared before the patient is discharged from the hospital.
Angioedema of the face and lips usually does not require treatment; antihistamines may be used to relieve symptoms. Angioedema of the larynx can be fatal. In case of angioedema of the tongue, pharynx or larynx, which can cause airway obstruction, it is necessary to immediately prescribe epinephrine (0.3-0.5 ml subcutaneous adrenaline solution in a ratio of 1:1000) and ensure free airway patency.
Patients with a history of angioedema unrelated to treatment with ACE inhibitors have an increased risk of developing angioedema while receiving ACE inhibitors.
Anaphylactoid reaction during desensitization
In patients taking ACE inhibitors, life-threatening anaphylactoid (allergic type) reactions may occur in rare cases during desensitization against wasp or bee venom. These reactions can be avoided by temporarily stopping treatment with ACE inhibitors before each desensitization.
Anaphylactoid reactions during LDL apheresis
In patients receiving ACE inhibitors, during low-density lipoprotein (LDL) apheresis with dextran sulfate, life-threatening anaphylactoid (allergic-type) reactions may occur in rare cases. These reactions can be avoided by temporarily stopping treatment with ACE inhibitors before each apheresis.
Patients on hemodialysis treatment
There have been reports of hypersensitivity reactions and allergic-type reactions (anaphylactoid reactions) in patients undergoing dialysis using high flux density membranes (eg AN 69) and concomitantly treated with ACE inhibitors. If hemodialysis is necessary, the patient should be transferred to another class of drugs, or another type of membrane should be used for dialysis.
Patients with diabetes
In diabetic patients treated with oral antidiabetic drugs or insulin, blood glucose levels should be carefully monitored during the first few months of concomitant treatment with ACE inhibitors. Cough
During treatment with ACE inhibitors, a persistent, dry, non-productive cough may occur, which stops after discontinuation of treatment. This should be included in the differential diagnosis.
Surgicalintervention/ anesthesia
In patients undergoing major surgery or during anesthesia with drugs that cause hypotension, enalapril may block the formation of angiotensin II secondary to compensatory renin release. Hypotension associated with this mechanism can be corrected by increasing blood volume.
Hyperkalemia
During treatment with ACE inhibitors, including enalapril, the level of potassium in the blood may increase in some patients. The risk of developing hyperkalemia is higher in patients with renal insufficiency, diabetes mellitus, who are simultaneously taking potassium-sparing diuretics, potassium supplements, or other drugs that can cause hyperkalemia (eg, heparin). In cases where the simultaneous use of the above-mentioned agents is considered appropriate, it is recommended to regularly monitor the level of potassium in the blood serum. Lithium
The appointment of a combination of lithium and enalapril is usually not recommended. Use in children
There is limited, effective and safe experience in children over 6 years of age with hypertension. There is no experience with other indications. Limited pharmacokinetic data are available for children over 2 months of age. Enalapril is recommended for use in children only for the treatment of hypertension.
Ethnic features
Like other ACE inhibitors, enalapril is less effective in lowering blood pressure in dark-skinned patients; a possible cause is the predominance of a state of reduced renin secretion in dark-skinned hypertensive patients.
Special precautions regarding excipients
Enap contains lactose. Patients with a rare hereditary disorder of galactose intolerance, lactose intolerance and malabsorption of glucose - galactose should not take this drug.
Pregnancy and lactation
Pregnancy
Epidemiological data regarding the risk of teratogenesis due to the use of ACE inhibitors during the first trimester of pregnancy are not conclusive, however, a slight increase in risk cannot be ruled out. Unless continued treatment with ACE inhibitors is deemed necessary, patients planning pregnancy should switch to an alternative antihypertensive treatment that has an established safety profile for use during pregnancy.
If pregnancy is established, then ACE inhibitors should be stopped immediately and, if necessary, treatment with alternative means should be started.
It is known that the use of ACE inhibitors in women during the second and third trimesters of pregnancy has a fetotoxic effect (decrease in renal function, oligohydramnios, delayed ossification of the skull) and neonatal toxic effect (renal failure, hypotension, hyperkalemia).
If the use of ACE inhibitors occurred in the second trimester of pregnancy, it is recommended to conduct ultrasound monitoring of the function of the kidneys and skull.
Newborns whose mothers have taken ACE inhibitors should be carefully monitored for hypotension.
lactation period
Pharmacokinetic data indicate a very low concentration in breast milk. Despite the fact that these concentrations are considered clinically insignificant, the use of Enap is not recommended for breastfeeding premature babies and in the first weeks after birth due to the hypothetical risk of effects on the cardiovascular system and kidneys due to the lack of sufficient clinical experience with the use. In a later period, the use of Enap by nursing mothers may be considered in cases where treatment is necessary for the mother, and the child is observed for any side effects.
Impact on ability to drivecar andwork with machinery
In some patients, the drug can cause severe hypotension and dizziness, especially at the initial stage of treatment, thus exerting an indirect and temporary effect on the ability to drive a car and work with mechanisms.
Release form and packaging
20 tablets of 10 mg (blister of 10 tablets, 2 blisters per pack).
20 tablets of 20 mg (blister of 10 tablets, 2 blisters per pack).
30 tablets of 10 mg (blister of 10 tablets, 3 blisters per pack).
30 tablets of 20 mg (blister of 10 tablets, 3 blisters per pack).
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging to protect against moisture.
Keep out of the reach of children.
Best before date
Terms of dispensing from pharmacies
On prescription.
Manufacturer
Krka, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia.
Pills round, biconvex, with a beveled edge, white.
Excipients:
Pills round, flat, with a beveled edge and a notch on one side, white.
Excipients: sodium bicarbonate, lactose monohydrate, corn starch, hyprolose (hydroxypropyl cellulose), talc (hydrogen silicate), magnesium stearate.
10 pieces. - blisters (2) - packs of cardboard.
Pills round, flat, with a beveled edge and a notch on one side, red-brown in color with white patches on the surface and in the mass of the tablet.
Excipients: sodium bicarbonate, lactose monohydrate, corn starch, talc (magnesium hydrosilicate), magnesium stearate, iron oxide red (dye Sikofarm red 30, E172).
10 pieces. - blisters (2) - packs of cardboard.
Pills round, flat, with a beveled edge and a notch on one side, light orange in color with white patches on the surface and in the mass of the tablet.
Excipients: sodium bicarbonate, lactose monohydrate, corn starch, talc (magnesium hydrosilicate), magnesium stearate, iron oxide yellow (dye Sikofarm yellow 10, E172).
10 pieces. - blisters (2) - packs of cardboard.
Clinical and pharmacological group
ACE inhibitorpharmachologic effect
Antihypertensive drug, ACE inhibitor. Enalapril is a "prodrug": as a result of its hydrolysis, enalaprilat is formed. The mechanism of action is associated with inhibition of ACE activity under the influence of enalaprilat. This leads to a decrease in the formation of angiotensin II, which causes a direct decrease in aldosterone secretion. As a result, there is a decrease in peripheral vascular resistance, a decrease in systolic and diastolic blood pressure, post- and preload on the myocardium.
It dilates the arteries to a greater extent than the veins, while there is no reflex increase in heart rate.
The hypotensive effect is more pronounced with a high level of plasma renin than with normal or reduced levels. A decrease in blood pressure within therapeutic limits does not affect cerebral circulation, blood flow in the vessels of the brain is maintained at a sufficient level even against the background of reduced blood pressure. Enhances coronary and renal blood flow.
With prolonged use, the hypertrophy of the left ventricle of the myocardium and myocytes of the walls of the arteries of the resistive type decreases, prevents the progression of heart failure and slows down the development of left ventricular dilatation. Improves blood supply to ischemic myocardium.
Inhibits platelet aggregation.
Has some diuretic effect.
When taking the drug orally, the hypotensive effect develops after 1 hour, reaches a maximum after 4-6 hours and lasts up to 24 hours. In some patients, therapy for several weeks is necessary to achieve the optimal level of blood pressure. In heart failure, a noticeable clinical effect is observed with prolonged use - 6 months or more.
Pharmacokinetics
Suction
After taking the drug, about 60% of enalapril is absorbed orally. C max enalapril in plasma is reached after 1 hour. Food intake does not affect absorption.
Distribution and metabolism
Enalapril is metabolized in the liver to form the active metabolite enalaprilat, which is a more potent ACE inhibitor than enalapril. C max enalaprilat in serum observed after 3-4 hours, C ss - after 4 days.
The binding of enalaprilat to plasma proteins is 50-60%.
Enalaprilat easily penetrates through histohematogenous barriers, with the exception of the BBB. A small amount crosses the placental barrier and is excreted in breast milk.
breeding
T 1/2 enalaprilat - 11 hours. Excreted mainly by the kidneys - 60% (20% - in the form of enalapril and 40% - in the form of enalaprilat), through the intestines - 33% (6% - in the form of enalapril and 27% - in the form of enalaprilat ).
It is removed during hemodialysis (speed 62 ml / min) and peritoneal dialysis.
Indications for the use of the drug
- arterial hypertension;
- chronic heart failure (as part of combination therapy);
- asymptomatic dysfunction of the left ventricle (as part of combination therapy).
Dosing regimen
The drug is taken orally, regardless of food intake, at the same time of day. If a drug is missed, it should be taken as soon as possible. If there are only a few hours left before the next dose, then you need to take only the next dose according to the scheme and do not take the missed dose. The dose should never be doubled. The dose of the drug should be adjusted depending on the patient's condition.
At treatment of arterial hypertension the recommended initial dose is 5 mg 1 time / day. After taking the initial dose, patients require medical supervision for 2 hours and an additional 1 hour until blood pressure stabilizes.
Dose adjustment is carried out depending on the achievement of a therapeutic effect (lowering blood pressure). In the absence of a clinical effect, the dose is increased after 1-2 weeks by 5 mg. Usually the maintenance dose is from 10 mg to 20 mg, if necessary and if well tolerated, the dose can be increased to 40 mg / day. The maximum daily dose is 40 mg. It is advisable to divide the high dose into 2 doses.
For patients who continue to take diuretics the initial dose of the drug is 2.5 mg 1 time / day.
For patients with hyponatremia (serum sodium ion concentration less than 130 mmol / l) or serum creatinine content of more than 140 μmol / l, the initial dose is 2.5 mg 1 time / day.
For patients with kidney disease the dose of Enap is determined depending on renal function and / or CC. At CC more than 30 ml / min the initial dose is 5 mg / day; at QC less than 30 ml / min the initial dose is 2.5 mg / day and is gradually increased until a clinical effect is achieved.
on the day of the procedure, the drug is prescribed at a dose of 2.5 mg, on the remaining days the doctor adjusts the dose in accordance with blood pressure.
At elderly patients more often there is a more pronounced hypotensive effect and a prolongation of 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.
At treatment of chronic heart failure the recommended initial dose is 2.5 mg 1 time / day. The dose of Enap should be increased gradually until the maximum clinical effect is achieved, usually after 2-4 weeks. The usual maintenance dose ranges from 2.5 mg to 10 mg 1 time / day; the maximum maintenance dose is 20 mg 2 times / day.
At treatment of asymptomatic left ventricular dysfunction the recommended initial dose is 2.5 mg 2 times / day. Dose adjustment depends on the tolerability of the drug. The usual maintenance dose is 10 mg twice daily.
Treatment with Enap is long-term, usually throughout life, unless circumstances arise that require its cancellation.
Tablets should be swallowed whole with a small amount of liquid.
Side effect
From the side of the cardiovascular system: excessive decrease in blood pressure, orthostatic collapse, rarely - retrosternal pain, angina pectoris, myocardial infarction (usually associated with a pronounced decrease in blood pressure), arrhythmias (brady or tachycardia, atrial fibrillation), palpitations, thromboembolism of the branches of the pulmonary artery, pain in the heart, fainting, Raynaud's syndrome.
From the side of the central nervous system and peripheral nervous system: dizziness, headache, insomnia, weakness, fatigue, drowsiness (2-3%), very rarely confusion, fatigue, very rarely when used in high doses - irritability, depression, paresthesia.
From the sense organs: violation of the vestibular apparatus, impaired hearing and vision, tinnitus.
From the respiratory system: unproductive dry cough, interstitial pneumonitis, bronchospasm/asthma, shortness of breath, rhinorrhea, pharyngitis, sore throat, hoarseness.
From the digestive system: dry mouth, anorexia, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, pain in the abdomen), intestinal obstruction, pancreatitis, impaired liver function and bile secretion, hepatitis (hepatocellular or cholestatic), jaundice, increased liver transaminase activity, hyperbilirubinemia.
From the urinary system: renal dysfunction, proteinuria, hypercreatininemia.
From the side of metabolism: increased urea content, hyperkalemia, hyponatremia.
From the hematopoietic system: decrease in the concentration of hemoglobin and hematocrit, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia.
Dermatological reactions: photosensitivity, pemphigus, alopecia.
Allergic reactions: skin rash, angioedema of the face, extremities, lips, tongue, glottis and/or larynx, dysphonia, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pruritus, urticaria, photosensitivity, serositis, vasculitis, myositis, arthralgia , arthritis, stomatitis, glossitis, increased sweating.
Others: decreased libido, hot flashes, decreased potency, increased ESR.
A complex symptom complex may develop, which may include all or some of the following symptoms: fever, serositis, vasculitis, myalgia / myositis, arthralgia / arthritis, positive antinuclear antibody test, increased ESR, eosinophilia, leukocytosis.
Side effects observed with the use of Enap, as a rule, are mild, transient in nature and do not require discontinuation of the drug.
Contraindications to the use of the drug
- angioedema in history (including associated with the use of ACE inhibitors);
- porphyria;
- pregnancy;
- lactation (breastfeeding);
- hypersensitivity to enalapril and other components of the drug;
- Hypersensitivity to other ACE inhibitors.
Do not use the drug in patients with a history of angioedema associated with previous use of ACE inhibitors (allergic reaction with a sharp swelling of the lips, face, neck and possibly hands and feet, accompanied by choking and hoarseness) or with other causes, in children and adolescents under the age of 18 years (efficacy and safety have not been established).
WITH caution the drug should be used 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, mitral stenosis (with hemodynamic disorders), idiopathic hypertrophic subaortic stenosis, with systemic connective tissue diseases, coronary artery disease, cerebrovascular diseases, diabetes mellitus, with renal failure (proteinuria - more than 1 g /day), liver failure, in patients on a salt-restricted diet or on hemodialysis; simultaneously with immunosuppressants and saluretics; in elderly patients (over 65 years of age).
The use of the drug during pregnancy and lactation
The drug is contraindicated for use during pregnancy and lactation (breastfeeding). If pregnancy occurs during treatment with Enap, the drug should be discontinued immediately.
Application for violations of kidney function
The dosage regimen is set depending on the severity of renal dysfunction or on the values of CC. At CC more than 30 ml / min the initial dose is 5 mg / day, with QC less than 30 ml / min- 2.5 mg / day, the dose of the drug should be gradually increased until a satisfactory clinical effect is achieved.
Patients on hemodialysis on the day of dialysis, the drug is prescribed at a dose of 2.5 mg, on other days the dose is adjusted depending on the level of blood pressure.
Avoid prescribing the drug to patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney.
special instructions
In the course of treatment with Enap, regular medical examinations are required, especially at the beginning of treatment and / or when selecting the optimal dose of the drug. The frequency of medical examinations is determined by the attending physician.
It should be borne in mind the possibility of developing arterial hypotension (even a few hours after taking the first dose) in patients with severe heart failure, severe renal dysfunction, as well as in patients with impaired water and electrolyte balance due to treatment with diuretics, salt-free diet, diarrhea, vomiting, as well as in patients on hemodialysis.
A pronounced decrease in blood pressure is usually manifested by nausea, an increase in heart rate, and fainting. In the event of arterial hypotension, the patient should be transferred to a horizontal position with a low headboard, and medical supervision is necessary.
Arterial hypotension and its severe consequences are rare and transient. Transient arterial hypotension is not a contraindication to further treatment with the drug. As soon as blood pressure stabilizes, you can continue therapy with the drug at the average recommended doses. Arterial hypotension can be avoided by interrupting treatment with diuretics and giving up a salt-free diet before starting treatment with Enap, if possible. The patient should be warned that if there are relapses of arterial hypotension, accompanied by nausea, increased heart rate and fainting, then a doctor's consultation is necessary.
Before starting treatment and during therapy, renal function should be monitored.
During the period of treatment with Enap, an increase in the content of potassium in the blood serum is possible, especially in patients with chronic renal failure, diabetes mellitus, while prescribing potassium-sparing diuretics (such as spironolactone, amiloride and triamterene) or potassium preparations. Such patients should be informed about the need to consult a doctor if muscle weakness and arrhythmias appear.
Patients receiving Enap ® should not drink alcohol because of the risk of arterial hypotension.
In the event of the development of side effects or angioedema (sharp swelling of the lips, face, neck, arms and legs, accompanied by choking and hoarseness), Enap ® should be canceled and appropriate treatment prescribed.
The drug should be discontinued before the study of the function of the parathyroid glands.
Before carrying out the planned surgical intervention, the anesthesiologist should be informed that the patient is receiving Enap ®, since there is a risk of arterial hypotension during general anesthesia.
It should be borne in mind that during treatment with Enap, allergic reactions may develop due to the use of certain types of filter membranes used in hemodialysis or other types of blood filtration.
During the period of allergy treatment (desensitization) to wasp or bee venom in patients receiving Enap ®, hypersensitivity reactions may develop.
Pediatric use
You should not prescribe the drug to children, because. efficacy and safety of its use in pediatrics have not been established.
Influence on the ability to drive vehicles and control mechanisms
In some cases, the drug can cause severe arterial hypotension and dizziness, especially at the beginning of treatment, thus providing an indirect and transient effect on the ability to drive vehicles and work with mechanisms.
Overdose
Symptoms: excessive decrease in blood pressure up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications, convulsions, stupor.
Treatment: the patient should be placed in a horizontal position with a low headboard. In mild cases, gastric lavage and saline ingestion are indicated; in more serious cases - measures aimed at stabilizing blood pressure, intravenous administration of physiological saline, plasma substitutes, if necessary - intravenous administration of angiotensin II, hemodialysis (enalaprilat excretion rate - 62 ml / min).
drug interaction
The simultaneous use of enalapril and diuretics or other antihypertensive drugs increases the effectiveness of these drugs.
Interaction with drugs used to treat heart failure (cardiac glycosides) has no clinical significance.
With the simultaneous use of enalapril and NSAIDs, incl. acetylsalicylic acid, it is possible to reduce the effectiveness of enalapril and increase the risk of impaired renal function.
With the simultaneous use of certain diuretics (spironolactone, amiloride or triamterene) and / or additional administration of potassium preparations, an increase in the level of potassium in the blood serum (hyperkalemia) is possible.
Enalapril weakens the effect of drugs containing theophylline. The simultaneous use of lithium preparations may increase the side effects of lithium.
Preparations containing cimetidine increase the duration of action of enalapril.
In patients receiving enalapril, there is a risk of arterial hypotension during general anesthesia.
Ethanol enhances the hypotensive effect of enalapril.
Terms of dispensing from pharmacies
The drug is dispensed by prescription.
Terms and conditions of storage
The drug should be stored out of the reach of children, in a dry place at a temperature not exceeding 25°C. Shelf life - 3 years.
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Owner/Registrar
International Classification of Diseases (ICD-10)
I10 Essential [primary] hypertension I50.0 Congestive heart failurePharmacological group
ACE inhibitor
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 reduce the incidence of myocardial infarction and reduce the frequency of hospitalizations for unstable angina.
Angioedema in history associated with the use of ACE inhibitors;
Hereditary angioedema or idiopathic angioedema;
Simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (CC<60 мл/мин);
Porfiria;
Pregnancy;
lactation period (breastfeeding);
Age up to 18 years (efficacy and safety not established);
Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
Hypersensitivity to enalapril and other components of the drug;
Hypersensitivity to other ACE inhibitors.
WITH caution the drug should be used in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney; with primary hyperaldosteronism; hyperkalemia; after kidney transplant; 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; 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 of age).
Classification of the incidence of side effects (WHO): very often (≥1/10), often (≥1/100 and<1/10), нечасто (≥1/1000 и <1/100), редко (≥1/10 000 и <1/1000), очень редко (<1/10 000), частота неизвестна (не может быть оценена на основании имеющихся данных). В каждой группе нежелательные эффекты представлены в порядке уменьшения их тяжести.
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.
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 sense organs: often - a change in taste perception; infrequently - tinnitus; very rarely - blurred vision.
From the side of the cardiovascular system: often - a pronounced 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 - 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 test for antinuclear antibodies. Skin rash, 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 - a decrease in potency; rarely - gynecomastia.
From the musculoskeletal system: infrequently - muscle cramps.
From the side of laboratory indicators: often - hyperkalemia, increased serum creatinine concentration; infrequently - hyponatremia, an increase in the concentration of urea in the blood serum; 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 - itching, urticaria.
Others: frequency unknown - syndrome of inappropriate ADH secretion.
Adverse events identified during the post-marketing use of the drug Enap ®, however, a causal relationship with taking the drug has not been established: urinary tract infections, upper respiratory tract infections, bronchitis, cardiac arrest, atrial fibrillation, herpes zoster, melena, ataxia, pulmonary embolism and pulmonary infarction, hemolytic anemia, including cases of hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.
The drug is taken orally, regardless of food intake, preferably at the same time of day. 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 arterial hypertension. With mild hypertension, the recommended initial dose is 5-10 mg / day.
In patients with severe activation of the RAAS (for example, with renovascular hypertension, loss of electrolytes and / or dehydration, decompensated heart failure or severe arterial hypertension), excessive reduction in blood pressure at the beginning of treatment is possible. In such situations, it is recommended to start therapy with a low initial dose - 5 mg / day or less, under the supervision of a physician.
Prior therapy with diuretics in high doses can 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. Treatment with diuretics should be discontinued 2-3 days before the start of the use of the drug Enap ® . Caution should be exercised when using the drug Enap ®, monitor kidney function and serum potassium levels.
The usual maintenance dose is 20 mg once daily.
The dose 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 is 2.5 mg 1 time / day, treatment should be started under close medical supervision.
The drug 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 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 drug tolerance. Dose selection is carried out within 2-4 weeks. The maximum daily dose is 40 mg in 2 divided doses.
*Special precautions should be observed in patients with impaired renal function taking diuretics.
Given the risk of developing arterial hypotension and renal failure (observed much less frequently), blood pressure and kidney function should be carefully monitored before and after starting the use of the drug Enap ®. In patients taking diuretics, the doses of the latter, if possible, should be reduced before taking the drug 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 kidney function
In patients with impaired renal function, the intervals between doses should be increased and / or the dose of Enap should be reduced.
* Enalaprilat is excreted by hemodialysis. In the interval between sessions of hemodialysis, 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 time of action of the drug are more often observed, 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.
The composition of the drug Enap includes an active component enalapril maleate (may contain 2.5 mg / 5 mg / 10 mg / 20 mg).
The preparation also contains additional components: sodium bicarbonate, corn starch, magnesium stearate, lactose monohydrate, hyprolose, dye, talc.
Release form
Enap tablets are produced containing different amounts of the active ingredient.
- Means Enap 2.5 mg- These are white or almost white tablets, biconvex, round, with a chamfer. Packed in blisters of 10 pcs.
- Means Enap 5 mg- These are white or almost white tablets, flat-cylindrical, with a chamfer and risk. Packed in blisters of 10 pcs.
- Means Enap 10 mg- These are red-brown tablets, flat-cylindrical, with a chamfer and a risk. There may be white and burgundy blotches inside and on the surface of the tablet. Packed in blisters of 10 pcs.
- Means Enap 20 mg- These are light orange tablets, flat-cylindrical, with a chamfer and a risk. There may be blotches of white and brown-burgundy color inside and on the surface of the tablet. Packed in blisters of 10 pcs.
In cardboard packs - 2, 3, 6 blisters.
pharmachologic effect
Enap is an antihypertensive drug. The mechanism of action of enalapril is based on the inhibition of ACE activity, resulting in a decrease in the production of angiotensin II.
The substance Enalapril is a derivative of amino acids: L-alanine And L-proline . After the substance has been taken orally, it is hydrolyzed to enalaprilat, which inhibits ACE. Under its influence, the production of angiotensin II from angiotensin I decreases, due to a decrease in its level in plasma, an increase in plasma renin activity and a decrease in aldosterone secretion are noted. Since ACE is identical to kininase II, there is the ability of enalapril to block the destruction of bradykinin (this is a peptide that produces a vasopressor effect). At the moment, it is not completely known what is the significance of this effect in the mechanism of action of the substance enalapril.
The antihypertensive effect of the active substance is primarily associated with the inhibition of RAAS activity, which plays an important role in the regulation process. But even in people with high blood pressure and low renin concentrations, the antihypertensive effect of enalapril is noted.
After the use of this drug, blood pressure decreases, regardless of the position in which the human body is, while the heart rate does not increase significantly.
Development symptomatic orthostatic hypotension occurs only in rare cases. Sometimes it takes several weeks of medication to achieve a pronounced decrease in blood pressure. With a sharp withdrawal of the drug, there was no rise in blood pressure.
Pronounced inhibition of ACE activity, as a rule, is observed 2-4 hours after ingestion of the tablet. The antihypertensive effect is usually felt 1 hour after ingestion of drugs inside, the maximum effect occurs after 4-6 hours. The duration of action depends on the dose of the drug. If the patient takes those doses of Enap that the doctor recommended to him, then the hemodynamic and antihypertensive effect is maintained for at least 24 hours.
In people who are sick essential hypertension , with a decrease in blood pressure, there is a decrease in peripheral vascular resistance and an increase in cardiac output. However, there was no significant change in heart rate. Renal blood flow increases, no change in glomerular filtration rate is observed. But there is an increase in this indicator in people with a low glomerular filtration rate.
In people suffering diabetic nephropathy And non-diabetic , when taking enalapril, albuminuria/ and excretion of IgG by the kidneys decreased.
In patients suffering from CHF in the treatment of diuretics and cardiac glycosides and the use of enalapril, there is a decrease in blood pressure, OPSS, an increase in cardiac output, a decrease in heart rate (as a rule, this figure is increased in people with chronic heart failure).
There is a decrease in the jamming of the pulmonary capillaries. With prolonged use of tablets, enalapril increases tolerance to physical loads, reduces the severity of manifestations heart failure . In people with mild to moderate CHF, the drug slows down the progression of the disease, and also reduces the rate of development of left ventricular dilatation.
In people suffering from left ventricular dysfunction, Enap reduces the likelihood of major ischemic outcomes (the frequency of manifestations decreases, the number of hospitalizations due to decreases).
Pharmacokinetics and pharmacodynamics
After taking enalapril rapid absorption is noted - the degree of absorption is about 60%. The highest concentration of enalapril in the blood is observed 1 hour after application, while eating does not affect absorption. The substance is actively hydrolyzed, during which enalaprilat, an ACE inhibitor, is formed. The highest concentration of enalaprilat is fixed 3-4 hours after oral administration. With repeated use of enalapril, the half-life is 11 hours.
Enalapril does not undergo significant biotransformation in the body, with the exception of the transformation of the substance into enalaprilat.
It is mainly excreted from the body by the kidneys. Enalaprilat at a dose of 40% and unchanged enalapril at a dose of 20% are determined in the urine.
Indications for use Enap
The following indications for the use of Enap are determined:
- essential hypertension ;
- CHF (in combination treatment);
- in order to prevent the manifestation of severe heart failure in those patients who are diagnosed with asymptomatic left ventricular dysfunction (in combination treatment);
- to reduce the frequency of manifestation myocardial infarction ;
- to reduce the rate of hospital admissions for people with unstable angina .
From what tablets Enap, and whether they should be used in each case, the patient should consult a doctor.
Contraindications
There are such contraindications to the use of Enap:
- increased sensitivity to a substance enalapril , as well as to other components of the drug;
- angioedema in history, which developed during the period of treatment with ACE inhibitors;
- idiopathic , and angioedema hereditary type;
- porphyria ;
- application at the same time aliskiren in patients with kidney disease or with;
- syndrome of glucose-galactose malabsorption, lactose intolerance, lack of lactase (the composition of Enap drugs contains lactose);
- pregnancy and the period of natural feeding;
- the patient's age is under 18 years.
Enap pressure tablets are carefully prescribed:
- people from stenosis of the renal arteries ;
- patients with hyperkalemia ;
- people after kidneys;
- with primary hyperaldosteronism ;
- with reduced BCC;
- hypertrophic obstructive cardiomyopathy ;
- mitral stenosis , aortic ;
- systemic ailments of the connective tissue;
- diabetes ;
- oppression of hematopoiesis;
- cerebrovascular diseases;
- kidney failure .
Caution, pressure medicine should be taken by people who comply with a reduced salt content, those who stay on and those who take diuretics and immunosuppressants.
Before taking Enap, people who are over 65 years old should consult a doctor.
Side effects
The following side effects may occur during treatment (negative effects in each group are given in order from more frequent to rarer):
- hematopoiesis: anemia , neutropenia , decrease in hematocrit concentration and , , thrombocytopenia , oppression of hematopoiesis, pancytopenia, autoimmune diseases, ;
- metabolism: hypoglycemia ;
- nervous system: , headache, impaired consciousness, paresthesia, high excitability, vertigo, sleep disturbances;
- heart and blood vessels: marked decrease in blood pressure, chest pain, angina pectoris, cardiac arrhythmias, palpitations, or myocardial infarction, Raynaud's syndrome;
- sense organs: taste changes, tinnitus, blurred vision;
- digestion: , nausea , abdominal pain, intestinal obstruction, vomit , dyspepsia , anorexia , dryness of the oral mucosa, peptic ulcer, impaired bile secretion and liver function, hepatitis, hepatic necrosis, cholestasis, aphthous ulcers;
- respiratory system: cough, sore throat, rhinorrhea, hoarseness, bronchospasm, eosinophilic pneumonia, rhinitis;
- skin covers: rash, manifestations of hypersensitivity, angioedema, severe sweating, itching, , erythema multiforme, erythroderma, exfoliative dermatitis, epidermal toxic necrolysis, pemphigus;
- genitourinary system: impaired renal function, proteinuria, renal failure, gynecomastia , oliguria;
- musculoskeletal system: muscle cramps;
- indicators of laboratory tests: hyperkalemia, an increase in the level of creatinine in the blood serum; hyponatremia; an increase in the concentration of urea in the blood, the activity of liver enzymes, the level of bilirubin in the blood;
- other manifestations: syndrome of inappropriate ADH secretion, myalgia, myositis, arthritis, vasculitis, serositis, leukocytosis, photosensitivity reactions.
Enap tablets, instructions for use (Method and dosage)
The official instructions for the use of Enap provide that patients take the drug orally, regardless of food intake. It is recommended to drink the medicine at the same time of day with a small amount of liquid.
At arterial hypertension initially, the drug is prescribed at a dose of 5 to 20 mg once a day, the dosage depends on the severity of hypertension. In the case of mild hypertension, a daily intake of 5 mg or 10 mg of the drug is recommended.
In people with severe RAAS activation, BP may drop too much. In this case, it is recommended to use low doses of the drug - 5 mg per day, under the supervision of a specialist.
Before taking the medicine, it must be taken into account that previous treatment with large doses of diuretic drugs can lead to dehydration and an increased risk of arterial hypotension at the very beginning of treatment. In this case, it is recommended to use a dose of not more than 5 mg per day. It is necessary to stop taking diuretics 2-34 days before starting Enap. During treatment, it is important to monitor the condition of the kidneys, to determine the content of potassium in the blood.
The maintenance dose is 20 mg once a day. If there is such a need, then the daily dose is increased to 40 mg, the dosage is determined individually.
With CHF, as well as with left ventricular dysfunction, the initial dose is 2.5 mg of the drug per day. Sometimes, for the treatment of heart failure, diuretics, beta-blockers, and cardiac glycosides are simultaneously prescribed.
After correction arterial hypertension the dose can be gradually increased by 2.5–5 mg every 3–4 days, bringing it up to a maintenance dose of 20 mg per day. The highest allowable dose is 40 mg per day.
Since in the course of treatment there is a possibility of developing renal failure and arterial hypotension, it is necessary to carefully monitor blood pressure and kidney function during treatment. There is no need to discontinue the drug if hypotension develops after the first dose.
People with kidney disease need to increase the intervals between the use of tablets or reduce the dose of the drug.
Overdose
If an overdose occurs, then after about 6 hours there is a pronounced decrease in blood pressure. Collapse may develop, the water and electrolyte balance may be disturbed, hyperventilation, renal failure, bradycardia are also manifested due to an overdose, convulsions , strong heartbeat .
In case of an overdose, you need to transfer the person to a horizontal position, while the head should be at the level of the body. If the overdose is mild, you need to rinse the stomach, give. It is practiced in severe cases of an overdose of Enap in / in the introduction of a 0.9% solution, intravenous plasma substitutes, catecholamines can also be practiced.
Enalaprilat can be removed from the body using hemodialysis, the excretion rate is 62 ml per minute.
People with bradycardia are given a pacemaker. In case of overdose, careful monitoring of serum electrolytes and concentrations should be carried out. creatinine .
Interaction
With a double blockade of the RAAS, that is, in the case of simultaneous administration of ACE inhibitors, angiotensin II receptor antagonists or aliskiren, the risk of arterial hypotension . If such a combination is necessary, it is necessary to carefully monitor the functioning of the kidneys, water and electrolyte balance, and blood pressure.
It is contraindicated to combine enalapril and aliskiren people with diabetes and kidney disease.
ACE inhibitors reduce the loss of potassium under the influence of diuretics. When using enalapril and potassium-sparing diuretics, potassium-containing products, as well as potassium-containing substitutes, hyperkalemia may develop. With this combination, it is important to ensure the control of serum potassium levels.
With previous diuretic therapy, BCC may decrease and the likelihood of arterial hypotension may increase while taking enalapril. Such exposure can be reduced by canceling diuretics, increasing the daily intake of water and salt, and reducing the dosage of enalapril.
With simultaneous use with enalapril of alpha-blockers, beta-blockers, methyldopa, CCB, ganglionic blocking agents, or other nitrates, an additional decrease in blood pressure is likely.
When taken in parallel with lithium preparations, a transient increase in the concentration of lithium is noted, as well as lithium intoxication. When taking thiazide diuretics, an increase in the serum concentration of lithium is possible. Such combinations are not recommended, and if necessary, careful monitoring of serum lithium concentrations is important.
When taken simultaneously with enalapril, a number of anesthetic drugs, antipsychotics, tricyclic antidepressants, blood pressure may further decrease.
When taken simultaneously with Enap NSAIDs, the antihypertensive effect may decrease. There may also be a deterioration in kidney function, especially in those patients who suffer from kidney disease. The effect is reversible.
When taken simultaneously with Enap hypoglycemic agents And insulin the hypoglycemic effect may be activated and the risk of hypoglycemia increases.
The antihypertensive effect of the drug enhances ethanol.
Sympathomimetics reduce the antihypertensive effect of ACE inhibitors.
Enalapril reduces the effect of drugs that contain .
When taken simultaneously with Enap immunosuppressants, cytostatics , increases the likelihood of leukopenia. In people with impaired renal function when taking allopurinol and ACE inhibitors increases the risk.
Taking enalapril and cyclosporine at the same time leads to an increase in the likelihood of hyperkalemia.
When taking antacids, the bioavailability of ACE inhibitors is reduced.
Terms of sale
Enap (Enap) is sold by prescription.
Storage conditions
Enap should be protected from children, stored at temperatures up to 25 ° C.
Best before date
Enap can be stored for 3 years.
special instructions
After the first intake of drugs Enap, arterial hypotension may develop. With severe hypotension, the patient should be placed horizontally, if necessary, inject him with a 0.9% solution.
After the patient's condition stabilizes, treatment can be continued.
Very rarely, during treatment, a syndrome may develop, starting with cholestatic jaundice And hepatitis A , later it develops into liver necrosis . If the patient develops jaundice, stop treatment immediately and consult a specialist.
There is a case report of neutropenia or agranulocytosis in people using ACE inhibitors.
This medicine should be used very carefully in people with connective tissue diseases, provided that they are undergoing immunosuppressive treatment, take procainamide , allopurinol . In this case, the development of severe infections that are not treatable is possible. When Enap is taken by such patients, periodic monitoring of the level of leukocytes in the blood is necessary.
There is a possibility of angioedema in people receiving Enap. At the first signs of such a condition, you need to immediately stop the drug and consult a doctor. An increased risk of developing this condition was noted in patients with a history of angioedema.
In the process of taking the drug, in rare cases, the development of anaphylactoid reactions in people who have undergone desensitization with Hymenoptera venom has been noted.
In the process of taking the medication, patients may develop unproductive, disappearing after the withdrawal of enalapril.
Specialists should be warned that the patient is taking Enap before performing general surgery.
It is important to carefully drive vehicles and practice other activities that require concentration of attention during treatment with Enap.
Enap's analogs
Coincidence in the ATX code of the 4th level:Analogues of Enap are being implemented - drugs Enap R , Bagopril , Vasolapril , , Invoril , Ednit , and etc.
Enalapril or Enap - which is better?
Users who are prescribed drugs with the active ingredient enalapril are often interested in whether Enalapril and Enap tablets are the same thing, and what is the difference between them? In fact, the active ingredient in both drugs is similar. Accordingly, they produce the same effect on the body. The only difference is the country of origin.
Enam and Enap - differences
As part of the LS and Enap contains enalapril maleate as an active ingredient. Only the country-manufacturers of medicines differ. But they act in the same way.
Enap and Enap N - differences
The composition includes hydrochlorothiazide and enalapril, that is, in addition to hypotensive, this agent also produces a diuretic effect.
children
The drug is not prescribed for children under 18 years of age.
With alcohol
During pregnancy and lactation
Pregnant women should not drink Enap both in the first trimester and in the subsequent months of pregnancy. To date, the risk of developing teratogenic effects has not been excluded. If pregnancy has been confirmed, in this case, the remedy should be canceled immediately.
If a woman took ACE inhibitors during pregnancy, it is necessary to periodically conduct an ultrasound to assess the level of amniotic fluid, to conduct an ultrasound of the bones of the skull and kidneys of the fetus. The active substance is determined in breast milk, therefore, lactation should be stopped for the duration of treatment.