Instructions for use Enalapril-Darnitsa tablets 10 mg No. 90
Composition
active ingredient: enalapril;
1 tablet contains enalapril maleate 10 mg;
excipients: microcrystalline cellulose, potato starch, lactose monohydrate, calcium stearate.
Dosage form
Pills.
Main physicochemical properties: white tablets, flat-cylindrical in shape, with a bevel and a score.
Pharmacotherapeutic group
Angiotensin-converting enzyme inhibitors.
ATX code C09A A02.
Pharmacological properties
Pharmacodynamics
Enalapril maleate is a salt of maleic acid and enalapril, a derivative of two amino acids: L-alanine and L-proline. Angiotensin-converting enzyme (ACE) is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasopressor substance angiotensin II. After absorption, enalapril is hydrolyzed to enalaprilat, which inhibits ACE. Inhibition of ACE leads to a decrease in plasma angiotensin II, resulting in increased plasma renin activity (due to the elimination of negative feedback on renin release) and decreased aldosterone secretion.
ACE is identical to kininase II. Thus, enalapril can also block the cleavage of bradykinin, a potent vasodepressor peptide. However, the significance of this phenomenon for the therapeutic effect of enalapril remains unclear.
The mechanism by which enalapril lowers blood pressure is primarily associated with inhibition of the activity of the renin-angiotensin-aldosterone system; enalapril may exert an antihypertensive effect even in patients with low-renin hypertension.
The use of enalapril in patients with arterial hypertension leads to a decrease in blood pressure both in the supine and standing positions, without an increase in heart rate.
Symptomatic postural hypotension is uncommon. In some patients, it may take several weeks of therapy to achieve optimal blood pressure control. Abrupt withdrawal of enalapril has not been associated with a rapid increase in blood pressure.
Effective inhibition of ACE activity usually occurs 2–4 hours after oral administration of a single dose of enalapril. The onset of antihypertensive activity is usually observed within 1 hour, with peak blood pressure reduction occurring 4–6 hours after administration. The duration of the effect is dose-dependent. However, at recommended doses, antihypertensive and hemodynamic effects have been demonstrated to be maintained for at least 24 hours.
In hemodynamic studies of enalapril in hypertensive patients, the reduction in blood pressure was accompanied by a decrease in peripheral arterial resistance with an increase in cardiac output and sometimes with a slight change in heart rate. After enalapril administration, there was an increase in renal blood flow; the glomerular filtration rate remained unchanged. There was no evidence of sodium or water retention. However, in patients with a low glomerular filtration rate before treatment, the rate usually increases.
In short-term clinical studies in patients with or without diabetes mellitus and with renal disease, a decrease in proteinuria and urinary immunoglobulin G excretion and total urinary protein was observed after administration of enalapril.
When given with thiazide-like diuretics, the blood pressure-lowering effects of enalapril were at least additive to those of the diuretics. Enalapril may reduce or prevent thiazide-induced hypokalemia. In patients with heart failure receiving cardiac glycosides and diuretics, enalapril reduces peripheral resistance and blood pressure. Cardiac output increases and heart rate (which is usually increased in patients with heart failure) decreases. Pulmonary end-capillary pressure decreases. Treatment with enalapril improves exercise tolerance and the severity of heart failure according to the New York Heart Association criteria. These effects persist throughout long-term enalapril therapy. In patients with mild to moderate heart failure, enalapril slows the progression of cardiac dilatation/enlargement and failure (reduction in left ventricular end-diastolic and systolic pressures and improvement in ejection fraction).
There is limited experience with efficacy and safety in children with hypertension aged 6 years and older. A clinical study included 110 children with hypertension aged 6 to 16 years with a body weight ≥ 20 kg and a glomerular filtration rate > 0.5 ml/s/1.73 m2. Children weighing 50 kg received 0.625 mg and 2.5 mg or 20 mg of enalapril once daily, and children weighing ≥ 50 kg received 1.25 mg and 5 mg or 40 mg of enalapril once daily. The reduction in blood pressure was dose-dependent; the effect was similar in all dosing subgroups (age, Tanner stage, gender, race). The results of the study indicate that the lowest doses of 0.625 mg and 1.25 mg, corresponding to a mean dose of 0.02 mg/kg/day, do not predict therapeutic efficacy. The maximum dose is 0.58 mg/kg (40 mg) once daily. The adverse event profile in children did not differ from that in adult patients.
Pharmacokinetics
Absorption.
Enalapril is rapidly absorbed from the gastrointestinal tract with peak serum concentrations occurring within one hour. The extent of absorption is approximately 60% and is not affected by food. Following absorption, enalapril is rapidly and extensively hydrolyzed to enalaprilat, a potent ACE inhibitor. Peak serum concentrations of enalaprilat occur 4 hours after an oral dose of enalapril. The effective half-life for accumulation of enalaprilat after multiple doses of enalapril is 11 hours. In subjects with normal renal function, steady-state serum concentrations of enalaprilat are achieved within 4 days of treatment.
Distribution.
Within the entire therapeutic concentration range, 60% of enalaprilat binds to serum proteins.
Metabolism.
With the exception of hydrolysis to enalaprilat, there is no further evidence of significant metabolism of enalapril.
Excretion.
Enalaprilat is excreted primarily by the kidneys. The major components in the urine are enalaprilat, which accounts for approximately 40% of the dose, and unchanged enalapril (approximately 20%).
Kidney dysfunction.
In patients with renal impairment, exposure to enalapril and enalaprilat is increased. In patients with mild to moderate renal impairment (creatinine clearance 40-60 mL/min), steady-state AUC of enalaprilat was approximately 2-fold higher than in patients with normal renal function after administration of 5 mg once daily. In severe renal impairment (creatinine clearance ≤ 30 mL/min), AUC increased approximately 8-fold. At this level of renal impairment, the effective half-life of enalaprilat is prolonged and the achievement of steady-state is delayed.
Enalaprilat can be removed from the general circulation by hemodialysis. The dialysis clearance of enalaprilat is 62 ml/min.
Children and adolescents.
A multiple-dose pharmacokinetic study was conducted in 40 hypertensive boys and girls aged 2 months to 16 years who received daily oral doses of 0.07 to 0.14 mg/kg of enalapril maleate. There were no differences in the pharmacokinetic parameters of enalaprilat in children compared with adults. The data indicated an increase in AUC (normalized to dose per body weight) with increasing age; however, no increase in AUC was observed when the data were normalized for body surface area. At steady state, the mean effective half-life for accumulation of enalaprilat is 14 hours.
Lactation period.
Following a single oral dose of 20 mg to five postpartum women, the mean peak enalapril level in breast milk was 1.7 μg/L (range 0.54–5.9 μg/L) at 4–6 hours. The mean peak enalaprilat level was 1.7 μg/L (range 1.2–2.3 μg/L); peaks occurred at various times during the 24-hour period. Using data on peak breast milk levels, the maximum intake by exclusively breastfed infants was estimated to be approximately 0.16% of the maternal weight-adjusted dose. Women who took oral enalapril 10 mg daily for 11 months had peak milk levels of enalapril of 2 mcg/L 4 hours after dosing and peak enalaprilat levels of 0.75 mcg/L approximately 9 hours after dosing. The total amounts of enalapril and enalaprilat measured in breast milk over a 24-hour period were 1.44 mcg/L and 0.63 mcg/L of milk, respectively. Enalaprilat levels in milk were undetectable (
Indication
· Treatment of arterial hypertension.
· Treatment of clinically pronounced heart failure.
· Prevention of clinically significant heart failure in patients with asymptomatic left ventricular dysfunction (ejection fraction ≤ 35%).
Contraindication
· Hypersensitivity to enalapril, to any of the excipients or to any other ACE inhibitor.
· History of angioedema associated with the use of ACE inhibitors.
Hereditary or idiopathic angioedema.
· Contraindicated in pregnant women and women planning to become pregnant (see "Use during pregnancy or breastfeeding").
· Enalapril should not be used with aliskiren-containing medicines in patients with diabetes mellitus or with impaired renal function (glomerular filtration rate (GFR) <2).
Interaction with other medicinal products and other types of interactions
Potassium-sparing diuretics, potassium supplements. ACE inhibitors reduce potassium loss caused by diuretics. Potassium-sparing diuretics (e.g., spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to hyperkalemia. If co-administered in the presence of pre-existing hypokalemia, they should be used with great caution and serum potassium levels should be monitored frequently.
Diuretics (thiazide or loop). Previous treatment with high doses of diuretics may result in volume depletion and an increased risk of excessive hypotension. The hypotensive effect may be reduced by discontinuing the diuretic, increasing salt and fluid intake, or initiating therapy with a low dose of enalapril.
Other antihypertensive drugs. Concomitant use of enalapril and other antihypertensive drugs may increase the antihypertensive effect of enalapril. Enalapril can be used with any other drugs for the treatment of hypertension. Concomitant use with nitroglycerin, other nitrates or other vasodilator drugs may further reduce blood pressure.
Lithium. Concomitant use of ACE inhibitors and lithium may result in transient increases in serum lithium levels and lithium toxicity. Concomitant use of ACE inhibitors and thiazide diuretics may further increase serum lithium levels and increase the risk of lithium toxicity. Enalapril is not recommended with lithium. If this combination proves necessary for the patient, careful monitoring of serum lithium levels should be performed.
Tricyclic antidepressants/neuroleptics/anesthetics/narcotics: Concomitant use of certain anesthetics, tricyclic antidepressants, and neuroleptics with ACE inhibitors may result in an additional decrease in blood pressure.
Non-steroidal anti-inflammatory drugs (NSAIDs). Non-steroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors), may reduce the effect of diuretics and other antihypertensive drugs. Therefore, the hypotensive effect of angiotensin II receptor antagonists or ACE inhibitors may be attenuated by non-steroidal anti-inflammatory drugs, including selective COX-2 inhibitors. Continuous use of non-steroidal anti-inflammatory drugs may reduce the antihypertensive effect of ACE inhibitors. ACE inhibitors and non-steroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, have an additive effect on increasing serum potassium levels, which may lead to impaired renal function and/or heart failure. This effect is usually reversible. Acute renal failure may occur rarely, especially in patients with impaired renal function (elderly patients or patients with reduced circulating blood volume, including those taking diuretics). Patients should be adequately hydrated and renal function should be monitored after initiation of combination therapy and periodically during treatment.
Gold: Nitrite-like reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients receiving gold injections (sodium aurothiomalate) and concomitant use of ACE inhibitors, including enalapril.
Antidiabetic medicinal products: Epidemiological studies have shown that concomitant use of ACE inhibitors and antidiabetic medicinal products (insulin or oral antidiabetic medicinal products) may lead to hypoglycaemia. This symptom is more likely to occur during the first weeks of combined treatment and in patients with impaired renal function.
Ethanol. Ethanol enhances the hypotensive effect of ACE inhibitors.
Sympathomimetics: Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.
Acetylsalicylic acid, thrombolytics and β-blockers. Enalapril can be safely used concomitantly with acetylsalicylic acid (at doses for cardiac indications), thrombolytics and β-blockers.
An increased risk of angioedema has been reported in patients receiving concomitant ACE inhibitors with alteplase.
Dual blockade of the renin-angiotensin-aldosterone system. Dual blockade (e.g., adding an ACE inhibitor to an angiotensin II receptor antagonist) should be limited to isolated cases with close monitoring of blood pressure, renal function, and electrolytes. In several studies, dual blockade of the renin-angiotensin-aldosterone system has been reported to be associated with a higher incidence of hypotension, syncope, hyperkalemia, and worsening renal function (including acute renal failure) in patients with established atherosclerotic vascular disease, heart failure, or diabetes with end-organ damage compared with the use of a single agent acting on the renin-angiotensin-aldosterone system. Enalapril with aliskiren should not be used in patients with diabetes mellitus or with impaired renal function (GFR 2).
Concomitant therapy with an ACE inhibitor and an angiotensin receptor antagonist. In patients with established atherosclerotic disease, heart failure, or diabetes mellitus with end-organ damage, concomitant therapy with an ACE inhibitor and an angiotensin receptor antagonist has been reported to be associated with a higher incidence of hypotension, syncope, hyperkalemia, and worsening renal function (including acute renal failure) compared with the use of medicinal products that affect the renin-angiotensin-aldosterone system alone. Dual blockade (e.g., by combining an ACE inhibitor with an angiotensin II receptor antagonist) should be limited to individually defined cases and accompanied by close monitoring of renal function, potassium levels, and blood pressure.
mTOR inhibitors: Concomitant use with mTOR inhibitors (such as temsirolimus, sirolimus, everolimus) increases the risk of angioedema.
Trimethoprim/sulfamethoxazole combination: Patients receiving the combination drugs trimethoprim/sulfamethoxazole are at increased risk of developing hyperkalemia.
Application features
Symptomatic hypotension. Symptomatic hypotension is very rarely observed in patients with uncomplicated hypertension. It is more likely to occur in hypertensive patients who have been volume-depleted, for example by diuretic therapy, salt restriction, dialysis, diarrhoea or vomiting. Symptomatic hypotension may occur in patients with heart failure, with or without concomitant renal insufficiency. It is more likely to occur in patients with more severe heart failure due to high doses of loop diuretics, hyponatraemia or impaired renal function. Such patients should be started under medical supervision and should be closely monitored, even if the dose of enalapril and/or diuretic is adjusted. This also applies to patients with ischaemic heart disease or cerebrovascular disease, in whom an excessive decrease in blood pressure could lead to myocardial infarction or stroke.
If hypotension develops, the patient should be placed in the supine position and, if necessary, volume expansion should be achieved with 0.9% sodium chloride infusion. Transient hypotension is not a contraindication to enalapril treatment. Once blood pressure and plasma volume have normalized, subsequent doses are usually well tolerated.
Some heart failure patients with normal or low blood pressure may experience an additional decrease in blood pressure when taking enalapril. This effect is expected and is not usually a reason for discontinuation of treatment. If hypotension becomes refractory to treatment, the dose should be reduced and/or the diuretic and/or enalapril should be discontinued.
Aortic or mitral valve stenosis/hypertrophic cardiomyopathy. As with all vasodilators, ACE inhibitors should be used with great caution in patients with left ventricular outflow tract obstruction and should be avoided in cases of cardiogenic shock and hemodynamically significant left ventricular outflow tract obstruction with generalized atherosclerosis. In such patients, excessive reduction in blood pressure may lead to hypoperfusion and ischemia of the heart, brain, or kidneys.
Renal impairment: Patients with renal impairment (creatinine clearance, and then according to response to treatment. Serum creatinine and potassium levels should be monitored regularly.
In patients with severe heart failure or renal disease, including renal artery stenosis, renal failure may occur during treatment with enalapril. With timely detection and appropriate treatment, it is usually reversible.
Renovascular hypertension. Transient hypotension or renal failure may occur in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney who are receiving ACE inhibitors. Loss of renal function may occur with very minor changes in serum creatinine. In such patients, treatment should be initiated under medical supervision at low doses; careful titration and monitoring of renal function are necessary during treatment.
Kidney transplantation: There is no experience with the use of enalapril in patients with a recent kidney transplantation, therefore enalapril is not recommended in such patients.
Hepatic failure. A syndrome that begins with cholestatic jaundice, progresses to sudden necrotizing hepatitis and (sometimes) is fatal may occur rarely during treatment with ACE inhibitors. The mechanism of this syndrome is not understood. If jaundice or a marked increase in liver enzymes occurs during treatment with ACE inhibitors, treatment should be discontinued immediately, the patient should be closely monitored and treatment should be initiated if necessary.
Neutropenia/agranulocytosis. Neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. Neutropenia is rare in patients with normal renal function and in the absence of other complications. Enalapril should be used with great caution in patients with collagen vascular diseases (e.g. systemic lupus erythematosus, scleroderma) receiving concomitant antidepressant therapy, treatment with allopurinol or procainamide, or a combination of these factors, especially if renal function is already impaired. Some of these patients may develop serious infections, which sometimes do not respond to intensive antibiotic therapy. If enalapril is used in such patients, periodic monitoring of white blood cell counts is recommended. Patients should report any signs of infection immediately to their physician.
Hypersensitivity/angioedema. Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported rarely during treatment with ACE inhibitors, including enalapril. This may occur at any time during treatment with the drug. In such cases, treatment should be discontinued permanently and appropriate monitoring should be instituted to ensure that all symptoms have resolved.
Even if only tongue swelling is noted without respiratory compromise, patients may require prolonged observation, as treatment with antihistamines and corticosteroids may be insufficient. Fatalities due to laryngeal and tongue angioedema have been reported very rarely.
In case of angioedema of the tongue, glottis or larynx, which may cause airway obstruction, especially in patients with a history of surgery, adrenaline (0.3–0.5 ml of adrenaline solution for subcutaneous injection in a ratio of 1:1000) should be administered immediately and the patient should be provided with air access.
Patients with a history of angioedema unrelated to ACE inhibitor therapy are at increased risk of developing angioedema while taking ACE inhibitors.
Angioedema has been reported more frequently in black patients treated with ACE inhibitors than in patients of other races.
Anaphylactoid reactions during desensitization with allergens to wasp or bee venom.
In patients taking ACE inhibitors during desensitization to wasp or bee venom, allergic-like reactions (pseudoanaphylactic reactions) that are life-threatening may rarely occur. Such reactions can be avoided by temporarily stopping ACE inhibitor therapy before each desensitization.
Anaphylactoid reactions during low-density lipoprotein apheresis. Rarely, life-threatening allergic-like (pseudoanaphylactic) reactions may occur in patients receiving ACE inhibitors during low-density lipoprotein apheresis with dextrin sulfate. Such reactions can be avoided by temporarily withholding ACE inhibitor therapy before each apheresis.
Patients undergoing hemodialysis. There have been reports of allergic-like hypersensitivity reactions (pseudoanaphylactic reactions) in patients undergoing dialysis using polyacrylonitrile membranes (e.g. AN 69) and receiving concomitant ACE inhibitors. In such patients, consideration should be given to using other types of dialysis membranes or a different class of antihypertensive agent.
Hypoglycemia: Diabetic patients taking oral antidiabetic agents or insulin require close glycemic control, especially during the first few months of concomitant treatment with ACE inhibitors.
Surgery/Anesthesia: In patients undergoing major surgery or anesthesia with drugs that produce hypotension, enalapril may block the formation of angiotensin II due to compensatory renin release. If hypotension occurs and is thought to be due to this mechanism, correction should be made by expanding blood volume.
Hyperkalemia. During treatment with ACE inhibitors, including enalapril, some patients may develop increases in serum potassium. Risk factors for the development of hyperkalemia include renal insufficiency or decreased renal function, age over 70 years, diabetes mellitus, hypoaldosteronism, intercurrent conditions such as dehydration, acute heart failure, metabolic acidosis, and concomitant use of potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes, or other medicinal products that may increase serum potassium (e.g. heparin). The use of potassium supplements, potassium-sparing diuretics or potassium-containing salt substitutes, especially in patients with impaired renal function, may lead to significant increases in serum potassium. Hyperkalemia may cause serious, sometimes fatal arrhythmias. If concomitant use of the above-mentioned medicinal products is considered necessary, regular monitoring of serum potassium is recommended.
Lithium: The combination of lithium and enalapril is generally not recommended.
Concomitant therapy with an ACE inhibitor and an angiotensin receptor antagonist.
The combination of an ACE inhibitor with an angiotensin II receptor antagonist should be limited to individually defined cases, with careful monitoring of renal function, potassium levels and blood pressure (see section “Interaction with other medicinal products and other types of interactions”).
Ethnic/Racial Features: As with all ACE inhibitors, enalapril is less effective in lowering blood pressure in black patients than in Caucasian patients, possibly because of a higher prevalence of low-renin states in black patients with hypertension.
Special precautions for inactive ingredients: Enalapril-Darnitsa contains lactose, therefore patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use during pregnancy or breastfeeding
Pregnancy.
The drug should not be used by pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment with this drug, its use should be immediately discontinued and replaced with another drug approved for use in pregnant women.
Women of childbearing age who are prescribed ACE inhibitors should be informed about the negative effects of these drugs on the fetus and the need for urgent medical consultation immediately after confirmation of pregnancy.
Breast-feeding.
Some pharmacokinetic data indicate very low concentrations in breast milk (see section 5.2). Although these concentrations are considered clinically insignificant, the use of the drug is not recommended during breastfeeding in premature infants and infants in the first few weeks after birth due to the hypothetical risk of cardiovascular and renal effects, and due to insufficient experience with such use. For older infants, the use of enalapril during breastfeeding may be considered if treatment is necessary for the mother and the infant is observed for any adverse effects.
Ability to influence reaction speed when driving vehicles or other mechanisms
It should be taken into account that dizziness or hypotension may occasionally occur, which may affect the reaction rate when driving or operating other mechanisms.
Method of administration and doses
The tablets should be taken whole with a small amount of water, regardless of meals. Enalapril-Darnitsa should be taken at the same time each day and not exceed the prescribed dose.
A 10 mg tablet can be divided; if a 5 mg dose is prescribed, use ½ tablet.
In patients with a strongly activated renin-angiotensin-aldosterone system (e.g. renovascular hypertension, salt and/or fluid imbalance, cardiac decompensation or severe hypertension), an excessive fall in blood pressure may occur after the initial dose. In such patients, a starting dose of 5 mg or lower is recommended and initiation of treatment should be under medical supervision.
The initial dose of the drug for adults is 5 mg, 10 mg or 20 mg 1 time per day, depending on the degree of hypertension. In mild hypertension, the recommended initial dose is 5-10 mg per day. In moderate and severe hypertension, the initial dose is 20 mg 1 time per day. The maintenance dose is 10 mg 2 times a day. The dosage should be selected individually for each patient, but the dose should not exceed 40 mg per day.
Renovascular hypertension.
In adult patients in this group, therapy should be initiated with a low initial dose, for example, 5 mg, using ½ tablet under medical supervision. If a dose of less than 5 mg is prescribed, an appropriate dosage form of enalapril with the possibility of such a dosage should be used. The dosage should then be selected individually for each patient. It can be expected that for most patients Enalapril-Darnitsa will be effective when taken daily at a dose of 20 mg per day. Caution should be exercised when treating patients with enalapril who have recently taken diuretics.
Concomitant treatment of hypertension with diuretics.
After the first dose of the drug, arterial hypotension may occur. This effect is most likely in patients receiving diuretic therapy. In this case, Enalapril-Darnitsa is recommended to be prescribed with caution, since such patients may be fluid or sodium depleted.
The usual maintenance dose is 20 mg once daily. The maximum maintenance dose is 40 mg daily. Diuretic therapy should be discontinued 2–3 days before initiating enalapril therapy. If this is not possible, the initial dose should be reduced to 5 mg or less, using an appropriate formulation of enalapril with the possibility of such a dosage, to determine the initial effect of the drug on blood pressure. Renal function and serum potassium should be monitored. The dosage should then be individualized for each patient.
Kidney failure.
In general, it is necessary to increase the interval between enalapril doses and/or reduce the dose of the drug.
| Kidney condition | Creatinine clearance (ml/min) | Starting dose (mg/day) |
| Minor functional impairments | 80 > 30 ml/min | 5-10 mg |
| Moderate dysfunction | £ 30 > 10 ml/min | 2.5 mg |
| Severe impairment. Typically, such patients are on hemodialysis* | £ 10 ml/min | 2.5 mg on dialysis days** |
*See section "Special warnings and precautions for use. Patients undergoing hemodialysis."
**Enalapril is removed by hemodialysis. Dosage adjustment on days when hemodialysis is not performed should be based on blood pressure.
Heart failure/asymptomatic left ventricular dysfunction.
The initial dose of enalapril for adult patients with heart failure is 2.5 mg (use an appropriate dosage form of enalapril with the possibility of such a dosage), while the use of the drug should be carried out under careful medical supervision to establish its initial effect on blood pressure. Enalapril-Darnitsa can be used for the treatment of symptomatic heart failure, together with diuretics and, if necessary, digitalis preparations, beta-blockers. In the absence of effect or after appropriate correction of symptomatic hypotension resulting from treatment with enalapril, the dose should be gradually increased to the target dose of 20 mg, which should be prescribed either once or divided into 2 doses, depending on what is better tolerated by the patient. Dose selection can be carried out over 2-4 weeks or in shorter periods. Such a therapeutic regimen effectively reduces mortality rates in patients with clinically pronounced heart failure.
The maximum daily dose of enalapril is 40 mg, which must be divided into 2 doses.
Enalapril Dose Titration for Patients with Heart Failure/Asymptomatic Left Ventricular Dysfunction
| Weekly | Dose, mg/day |
| Week 1 | From the 1st to the 3rd day: 2.5 mg/day* in 1 dose From the 4th to the 7th day: 5 mg/day in 2 divided doses |
| Week 2 | 10 mg/day in 1 or 2 divided doses |
| Weeks 3 and 4 | 20 mg/day in 1 or 2 divided doses |
*If enalapril is prescribed in a dose of less than 5 mg, use an appropriate dosage form of enalapril with the possibility of such a dosage. Enalapril-Darnitsa should be used with caution in patients with impaired renal function or those taking diuretics.
Both before and after the start of treatment with the drug in patients with heart failure, blood pressure and renal function should be carefully monitored (see section "Special instructions"). The development of arterial hypotension after the initial dose does not mean that hypotension will persist with prolonged treatment, and does not indicate the need to stop taking the drug. During treatment with enalapril, serum potassium should also be monitored (see section "Interaction with other medicinal products and other types of interactions")
