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Active ingredients
Enalapril
Release form
Pills
Composition
Active ingredient: Enalapril maleate Concentration of active ingredient (mg): 10
Pharmacological effect
Antihypertensive
Pharmacokinetics
AbsorptionAfter enalapril ingestion is rapidly absorbed, the enalapril absorption rate is about 60%. Tmax of enalapril in serum - 1 hour after ingestion. Food intake does not affect absorption. Enalapril is rapidly and actively hydrolyzed to form enalaprilat, a powerful ACE inhibitor. Tmax enalaprilat 3-4 hours after ingestion. T1 / 2 enalapril with repeated use is 11 hours. Patients with normal renal function Css enalaprilat in plasma were achieved on the 4th day of therapy. Distribution Enalaprilat plasma protein in the range of therapeutic doses is 60%. enalaprilat does not undergo significant biotransformation. Enalaprilat is mainly excreted by the kidneys. Enalaprilat (about 40% of the dose) and unchanged enalapril (about 20%) are mainly detected in the urine. Special groups of patients Disruption of renal function. In patients with mild and 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 enalaprilat is about 2 times more than in patients with normal kidney function. In severe renal failure (Cl creatinine ≤ 30 ml / min): the AUC increased by about 8 times. Enalaprilat T1 / 2 after repeated use in severe renal insufficiency is prolonged and the time to reach an equilibrium state is delayed. output speed Ia - 1.03 ml / s (62 ml / min).
Indications
- Arterial hypertension. - Chronic heart failure (as part of combination therapy). - Asymptomatic dysfunction of the left ventricle (as part of combination therapy).
Contraindications
- Increased sensitivity to enalapril or other components of the drug; - Increased sensitivity to other ACE inhibitors; accompanied by suffocation and hoarseness); - Porphyria; - Pregnancy; - Lactation (breastfeeding); - Patients who have ever had angioedema; - Age up to 18 years (efficacy and safety have not been established).With care: - Bilateral renal artery stenosis; - Single kidney stenosis; - Primary hyper aldosteronism; - Hyperkalemia; - Condition after kidney transplantation; - Aortic stenosis; - Mitral stenosis (with impaired hemodynamics); - Idiopathic hypertrophic subaortic stenosis;; connective tissue; - Ischemic heart disease; - Inhibition of bone marrow hematopoiesis; - Cerebrovascular diseases; - Diabetes; - Renal failure (proteinuria - more than 1 g / day); - Hepatic deficiency; - In patients on a salt-restricted diet; - In patients on hemodialysis; - Concurrent use with immunosuppressants and saluretics; - In elderly people (over 65).
Precautionary measures
Keep out of the reach of children.
Use during pregnancy and lactation
The use of ACE inhibitors, incl. drug Enap, in the first trimester of pregnancy is not recommended. The use of ACE inhibitors, incl. Enap, in the second and third trimesters of pregnancy is contraindicated. Epidemiological data on the risk of teratogenic effects of ACE inhibitors during pregnancy do not make it possible to draw definitive conclusions. However, one cannot rule out the risk of their development. If it is necessary to use ACE inhibitors, the patient should be transferred to therapy with another approved antihypertensive drug with a proven safety profile for pregnant women. When pregnancy is confirmed, Enap should be canceled as early as possible. Taking ACE inhibitors during the II and III trimesters can cause fetotoxicity reactions (impaired function kidney, oligohydramnios, delayed ossification of the bones of the fetal skull) and neonatal toxic effects (renal failure, arterial hypotension, hyperkale mission). If the ACE inhibitor was taken in the II and III trimesters of pregnancy, an ultrasound scan of the kidneys and fetal bones is recommended. In those rare cases where the use of an ACE inhibitor during pregnancy is considered necessary, periodic ultrasound scans should be performed to estimate the amniotic fluid index. If an oligohydramnion is detected during an ultrasound scan, it is necessary to stop taking the drug.Patients and the physician should be aware that oligohydramnios develops with irreversible damage to the fetus. If ACE inhibitors are used during pregnancy and oligohydramnios develop, then, depending on the week of pregnancy, a stress test, a non-stress test, or determination biophysical profile of the fetus. Newborns whose mothers took ACE inhibitors during pregnancy should be monitored, given the risk of developing arteries Flax hypotension. Enalapril, which crosses the placenta, can be partially removed from the blood circulation of a newborn using peritoneal dialysis, it can theoretically be removed by exchange transfusion. should stop.
Dosage and administration
Tablets should be taken orally with a small amount of liquid. Tablets can be taken before, during or after a meal. You should get used to taking the drug regularly and at the same time. If the patient misses taking the drug, it should be taken as soon as possible, but not if there are several hours left before taking the next dose. In this case, you should take only the next dose according to the scheme and not take the missed dose. Doses should never be doubled. Enapom treatment requires regular medical examinations, especially at the beginning of treatment and / or when determining the most appropriate dose of the drug. The frequency of medical examinations is determined by the attending physician. The dose of the drug is always adjusted depending on the condition of the patient. Treatment of hypertension: the recommended initial dose is 5 mg once a day. After taking the initial dose, patients should be under medical supervision for 2 hours and an additional 1 hour until blood pressure stabilizes. Dose adjustment depends on achieving a therapeutic effect (lowering blood pressure) and, in the absence of a clinical effect, increases in 1–2 weeks by 5 mg.The maintenance dose is usually from 10 to 20 mg, if necessary, and with sufficiently good tolerance, the dose can be increased to 40 mg per day. The maximum daily dose is 40 mg. At higher doses, it is advisable division into 2 doses. Treatment of arterial hypertension in special clinical situations: the initial dose for patients who could not interrupt diuretic administration before the start of treatment with Enap is 2.5 mg as a single dose. Patients with hyponatremia (the concentration of sodium ions in the serum is less than 130 mmol / l) or the concentration of creatinine in the serum more than 0.14 mmol / l, the initial dose is 2.5 mg 1 time per day. Older patients are more likely to have a more pronounced hypotensive effect and lengthening the time of action of the drug, which is associated with a decrease in the rate of enalapril elimination, therefore the recommended initial dose to the elderly is 1.25 mg Treatment of congestive heart failure: the recommended initial dose is 2.5 mg once a day. The dose of Enap should be increased gradually until the maximum clinical effect is achieved, usually in 2 to 4 weeks. The usual maintenance dose ranges from 2.5 mg to 10 mg as a single dose; the maximum maintenance dose is 20 mg twice a day. Treatment of asymptomatic dysfunction of the left ventricle: the recommended initial dose is 2.5 mg twice a day; some dose adjustment depends on the tolerance of the drug to patients. Usually the maintenance dose is 10 mg twice a day. Treatment of hypertension in renal disease: the dose of Enap is determined depending on the renal function and / or creatinine clearance parameters. For patients with creatinine clearance of more than 0.5 ml / sec (30 ml / min), the initial dose is 5 mg per day. For patients with creatinine clearance less than 0.5 ml / sec (30 ml / min), the initial dose is 2.5 mg per day and gradually increases until a clinical effect is achieved. Treatment of patients on hemodialysis: for patients on the day of hemodialysis, 2.5 mg; on other days, the doctor adjusts the dose according to blood pressure. Treatment by Enap is long, usually during the whole life, unless circumstances arise that require its cancellation.
Side effects
Classification of the incidence of side effects (WHO): very often {> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely (> 1/10 000 and <1/1000), very rarely (<1/10 000), including individual messages. From the hematopoietic system: rarely - neutropenia, decreased hemoglobin and hematocrit, thrombocytopenia, agranulocytosis, bone marrow suppression, pancytopenia, lymphadenopathy, autoimmune diseases ; very rarely - anemia (including aplastic and hemolytic). On the side of metabolism: infrequently - exacerbation of the course of gout, hypoglycemia. On the side of the nervous system: very often - dizziness, weakness; often - headache, asthenia, depression; infrequently - insomnia, drowsiness, paresthesia, irritability; rarely, unusual dreams, sleep disturbances; very rarely - confusion, insomnia. From the sense organs: often - changes in taste; infrequently - tinnitus, blurred vision. From the cardiovascular system: often - marked reduction in blood pressure, orthostatic hypotension, fainting, chest pain, heart rhythm disturbances (atrial brady- or tachycardia, atrial fibrillation), tachycardia, angina; infrequently - a feeling of heartbeat, myocardial infarction or stroke (due to a pronounced decrease in blood pressure); rarely - thromboembolism branches of the pulmonary artery, Raynaud's syndrome. On the part of the respiratory system: very often - cough; often - shortness of breath; infrequently - rhinorrhea, sore throat and hoarseness, bronchospasm; rarely - infiltrates in the lungs, rhinitis, allergic alveolitis / eosinophilic pneumonia. On 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, liver dysfunction and biliary excretion, hepatitis (hepatocellular or cholestatic), cholestatic jaundice, fulminant necrosis of the liver, stomatitis / aphthous ulcers, glossitis; very rarely - intestinal angioedema. From the skin: often - skin rash; infrequently - erythema multiforme exudative, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma, profuse sweating, pruritus, urticaria,alopecia, photosensitivity. From the urinary system: rarely - impaired renal function, acute renal failure; seldom - oliguria. From the reproductive system: infrequently - decrease in potency, decrease in libido; rarely - gynecomastia. From the musculoskeletal system: often - muscle spasms; infrequently - arthralgia. From the laboratory parameters: often - hyperkalemia, increased serum creatinine concentration; infrequently - hyperglycemia, hyperuricemia, hypokalemia, hyponagriemia, increased serum urea concentration; rarely, increased liver transaminase activity and bilirubin concentration. Allergic reactions: infrequently, Stevens-Johnson syndrome; rarely - angioneurotic edema of the face, lips, tongue, pharynx, larynx, konechnostey.Prochie: describes a symptom that can include fever, myalgia and arthralgia, serositis, vasculitis, increased erythrocyte sedimentation rate, leukocytosis and eosinophilia, skin rash, a positive test for antinuclear antibodies. Also, a symptom complex has been described, which includes facial flushing, nausea, vomiting and arterial hypotension and may develop with simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) IV.
Overdose
Symptoms: about 6 hours after ingestion - marked reduction in blood pressure, up to the development of collapse, impaired water and electrolyte balance, renal failure, hyperventilation, tachycardia, feeling of heartbeat, bradycardia, dizziness, anxiety, cough, cramps, stupor. After ingestion of 300 and 440 mg of enalapril, serum plasma plasma concentrations of enalaprilat were 100 and 200 times higher than usual therapeutic concentrations, respectively. Treatment: The patient should be placed in a horizontal position with a low head. In mild cases, gastric lavage and ingestion of activated carbon are shown, in more severe cases, intravenous infusion of 0.9% sodium chloride solution, plasma substitutes, and, if necessary, intravenous catecholamines. Perhaps the elimination of enalaprilat by hemodialysis, the elimination rate is 62 ml / min. Patients with bradycardia resistant to therapy are shown to set a pacemaker. The serum electrolyte and serum creatinine levels should be carefully monitored.
Interaction with other drugs
Double blockade of RAASRisk of development of arterial hypotension, hyperkalemia and renal dysfunction (includingacute renal failure) is higher in the case of a double blockade of the RAAS, i.e. with the simultaneous use of antagonists of angiotensin II receptors, ACE inhibitors or aliskiren, in comparison with the use of the drug of one of these groups. If necessary, the simultaneous use of drugs is recommended to control blood pressure, kidney function and water and electrolyte balance. Simultaneous use of enalapril with aliskiren in patients with diabetes mellitus or renal dysfunction (Cl creatinine less than 60 ml / min) is contraindicated. KaliSaving diuretics and potassium preparationsInhibitors decrease the loss potassium under the action of diuretics. Simultaneous use of enalapril and potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), drugs ka ia or potassium-containing substitutes, as well as the use of other drugs that increase the plasma potassium content (for example, heparin) can lead to hyperkalemia. If necessary, use caution and regularly monitor the serum potassium content. Diuretics (thiazide or loop) Prior therapy is high doses of diuretics can lead to a decrease in BCC and an increase in the 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, as well as provided that treatment with enalapril is started at a low dose. Other nitrates can additionally reduce blood pressure. In case of simultaneous use of ACE inhibitors with lithium preparations, a transient increase in serum concentration was observed. entratsii lithium and development of lithium intoxication. The use of thiazide diuretics can lead to an additional increase in the serum concentration of lithium and the risk of lithium intoxication, while the use of ACE inhibitors. The simultaneous use of enalapril with lithium is not recommended. If necessary, the use of such a combination should be carefully monitored serum concentrations of lithium. Tricyclic antidepressants / antipsychotics (neuroleptics) / anesthetics / narcotic drugs Simultaneous use of some anesthetics,tricyclic antidepressants and antipsychotics (neuroleptics) with ACE inhibitors can lead to an additional decrease in blood pressure. additive effect on the increase in the content of potassium in the blood serum, which can lead to a deterioration in 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 during the use of diuretics). Before beginning therapy, it is necessary to replenish the BCC. It is recommended to monitor kidney function during treatment. Hypoglycemic agents for oral administration and insulin Epidemiological studies suggest that the simultaneous use of ACE inhibitors and hypoglycemic agents (insulin and hypoglycemic agents for oral administration) may lead to increased hypoglycemic effect with the risk of hypoglycemia. More often, hypoglycemia develops during the first weeks of therapy in patients with impaired renal function. Ethanol Ethanol enhances the antihypertensive effect of APF inhibitors. Sympathomimetics can reduce the antihypertensive effect of APA inhibitors. thrombolytic and beta-blockers. Reduces the effect of drugs containing theophylline. Allopurino , Cytotoxic agents and immunosuppressive agents (including methotrexate, cyclophosphamide) The simultaneous use of ACE inhibitors may increase the risk of leukopenia. With simultaneous use with allopurinol increases the risk of an allergic reaction, especially in patients with impaired kidney function. Cyclosporine Simultaneous use with ACE inhibitors may increase the risk of developing hyperkalemia. Antacids Antacids may reduce the bioavailability of ACE inhibitors. Gold preparations When using inhibitors of ACE, incl.enalapril, to patients receiving IV gold medication (sodium aurothiomalate), a symptom complex was described, including facial skin flushing, nausea, vomiting, arterial hypotension. There was no clinically significant pharmacokinetic interaction of enalapril with hydrochlorothiazide, furosemide syndrome, and furosemide syndrome. , indomethacin, sulindac and cimetidine. With simultaneous use with propranolol, the concentration of enalaprilat in serum decreases, but this effect is clinically insignificant.
special instructions
Arterial hypotension Symptomatic arterial hypotension rarely develops in patients with uncomplicated arterial hypertension. 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 diets, 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 begin under the supervision of a physician, up to the optimal dose adjustment of Enap and / or a diuretic. A similar tactic can be applied to patients with coronary artery disease or cerebrovascular diseases in whom a sharp excessive decrease in blood pressure can lead to the development of myocardial infarction or cerebral circulation. In the case of severe arterial hypotension, the patient should be given a horizontal position, legs raised and, if necessary, in / in enter a 0.9% solution of sodium chloride. Transient arterial hypotension is not a contraindication to further treatment with Enap after stabilization of blood pressure and BCC. toryh patients with heart failure and normal or low blood pressure may further decrease its Enap when taking the drug. This effect is predictable and usually not a reason for discontinuing therapy. If arterial hypotension is accompanied by clinical symptoms, reduce the dose and / or cancel the diuretic and / or drug Enap. Aortic or mitral stenosis, GOKMPKak and all vasodilators, ACE inhibitors should be used carefully in patients with valvular obstruction and hypertrophy of the outflow tract of the left ventricle.Patients with cardiogenic shock and hemodynamically significant left ventricular obstruction should not be prescribed. Renal dysfunction In patients with renal insufficiency (Cl creatinine <80 ml / min (1.33 ml / s), the initial dose of Enap should be selected primarily taking into account Cl creatinine and then the clinical response to treatment. In such patients, potassium levels and serum creatinine levels should be regularly monitored. In patients with severe heart failure and kidney disease, including renal stenosis arteries, when treatment with Enap is possible, renal failure may develop.The changes were usually reversible after discontinuation of the drug Enap. In some patients with arterial hypertension who did not have kidney disease prior to treatment, there was a slight and transient increase in serum urea and creatinine during use of 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 diuretic. This situation indicates the possibility of latent renal artery stenosis. Renovascular hypertension In patients with bilateral renal artery stenosis or arterial stenosis of the only functioning kidney, treatment with ACF inhibitors increases the risk of developing arterial hypotension and renal failure. Only slight changes in serum creatinine levels may indicate a decrease in kidney function. In these patients, treatment should begin with small doses under the close supervision of a physician. It is necessary to carefully titrate the dose and monitor renal function. Renal transplantationExperience in using Enap in patients who have recently undergone renal transplantation is absent. Therefore, the treatment of such patients with Enap is not recommended. Impairment of liver function In rare cases, therapy with ACE inhibitors has been accompanied by the development of a syndrome that starts with cholestatic jaundice and hepatitis until the development of fulminant hepatic necrosis. The mechanism of development of this syndrome is unknown. When jaundice appears or a significant increase in liver enzyme activity, it is necessary to immediately discontinue treatment with an ACE inhibitor, carefully monitor the patient and, if necessary, treat.In patients with normal renal function in the absence of other complications, neutropenia rarely develops. Enap must be used with great caution in patients with connective tissue diseases (including systemic lupus erythematosus, scleroderma) who are also receiving immunosuppressive therapy, allopurinol or procainamide, as well as with a combination of these factors, especially for existing disorders of renal function. Such patients may develop severe infections that are not susceptible to intensive antibiotic therapy. If patients still take the drug Enap, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that if any signs of infection appear, you should immediately consult a doctor. Hypersensitivity / angioedema Patients who received ACE inhibitors, including enalapril, reported the development of angioedema of the face, extremities, lips, voice folds and / or larynx at any time after starting treatment. It is necessary to immediately discontinue the drug Enap and monitor the patient until the symptoms disappear. Even in the presence of edema of the tongue only, when there is only difficulty in swallowing without respiratory distress syndrome, patients may need long-term observation, since use of antihistamines and corticosteroids may be insufficient. Angioedema of the larynx or tongue can be very rarely fatal. Swelling of the tongue, vocal cords or larynx can lead to airway obstruction, especially after a history of airway surgery. In the presence of edema of the tongue, vocal folds or larynx, appropriate therapy is indicated, which may include: s / c administration of a 0.1% solution of epinephrine (adrenaline) (0.3–0.5 ml) and / or measures aimed at restoring airway patency (intubation or tracheostomy). Among the patients of the Negroid race, receiving therapy with an ACE inhibitor, the incidence of angioedema is higher than among patients of a different race. Patients with angioedema, not associated with ACE inhibitors,have an increased risk of developing angioedema when taking any ACE inhibitor. Anaphylactoid reactions during desensitization with hymenoptera (hymenoptera) In patients who took ACE inhibitors during desensitization with hymenoptera, life-threatening anaphylactoid reactions developed in rare cases. To prevent such reactions, it is necessary to temporarily stop taking the ACE inhibitor during desensitization procedures. Anaphylactoid reactions during apheresis of LDLU patients who took ACE inhibitors during apheresis of LDL using dextran sulfate rarely developed life-threatening anaphylactoid reactions. Another group of drugs should be temporarily replaced. Hemodialysis Due to the increased risk of anaphylactoid reactions, the drug should not be used in patients on hemodialysis using high-current polyacrylonitrile membranes (AN69) undergoing LDL apheresis with dextran sulfate. If hemodialysis is needed, it is advisable to use dialysis membranes of another type or antihypertensive drugs of another group. Hypoglycemia In patients with diabetes who receive hypoglycemic agents for oral administration or insulin, during the first month of treatment with an ACE inhibitor, blood glucose concentration should be carefully monitored. dry, non-productive, long-lasting cough may occur, which disappears after discontinuation of the use of ACE inhibitors, which is necessary Ito consider the differential diagnosis of cough while using an ACE inhibitor. Surgical intervention / general anesthesia Before surgery (including dental procedures), the surgeon / anesthesiologist should be warned about the use of Enap. With extensive surgery or general anesthesia using agents that cause arterial hypotension, ACE inhibitors can block the formation of angiotensin II in response to compensatory renin release. If this develops a pronounced decrease in blood pressure, explained by a similar mechanism, it can be corrected by the introduction of plasma substitutes. Hyperkalemia Can develop during treatment with ACE inhibitors, including and the drug Enap.Risk factors for the development of hyperkalemia are renal failure, advanced age (older than 70 years), diabetes mellitus, some concomitant states (decreased BCC, acute heart failure in the decompensation stage, metabolic acidosis), simultaneous use of potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride) , as well as preparations of potassium or potassium-containing substitutes and the use of other drugs that increase the content of potassium in the blood plasma (for example, heparin). The use of potassium preparations, potassium-sparing diuretics, and potassium-containing food salt substitutes may lead to a significant increase in the serum potassium content, especially in patients with impaired renal function. Hyperkalemia can lead to serious heart rhythm disturbances, sometimes fatal. Simultaneous use of the above preparations should be carried out with caution under the control of potassium in the blood serum. Lithium Simultaneous use of lithium salts and Enap is not recommended. Ethnic features Enap, like other ACE inhibitors, has a less pronounced antihypertensive effect in patients of the negroid race compared to representatives of Other rass.Spetsialnaya information on excipientsPreparation Enap contains lactose, so the drug is contraindicated in the patient m with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome. The effect on the ability to perform potentially hazardous activities that require special attention and speed of reaction (for example, driving, working with mechanisms). When using the drug Enap, care must be taken when driving and engaging in other potentially dangerous activities that require increased concentration and psychomotor speed (dizziness may develop as a result of a sharp decrease in blood pressure, especially after taking the initial dose of Enap in patients taking diuretics).