Main physicochemical properties: round, flat, white tablets with a beveled edge and a notch on one side.
Pharmacotherapeutic group
Agents acting on the renin-angiotensin system. Angiotensin-converting enzyme inhibitors. ATC 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.
Mechanism of action
Angiotensin-converting enzyme (ACE) is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the pressor substance angiotensin II. After absorption, enalapril is hydrolyzed to enalaprilat, which inhibits ACE. Inhibition of ACE results in a decrease in plasma angiotensin II levels, which leads to an increase in plasma renin activity (due to inhibition of the negative feedback between angiotensin II activity and renin release) and a decrease in aldosterone secretion.
ACE is identical to kininase II. Thus, enalapril may also block the cleavage of bradykinin, a potent vasodepressor peptide. However, the significance of this phenomenon for the therapeutic effect of the drug remains unclear.
The mechanism by which enalapril lowers blood pressure is primarily associated with inhibition of the renin-angiotensin-aldosterone system (RAAS). Enalapril may exert an antihypertensive effect even in patients with low-renin hypertension.
The use of Enap® in cases of arterial hypertension causes a decrease in blood pressure in patients in horizontal and vertical positions without a significant increase in heart rate.
Symptomatic postural hypotension occurs infrequently. In some patients, achieving optimal blood pressure reduction may require several weeks of therapy. Abrupt withdrawal of Enap® has not been associated with a rapid increase in blood pressure.
Effective inhibition of ACE activity is usually achieved 2-4 hours after oral administration of a single dose of enalapril. The onset of antihypertensive activity is usually observed after 1 hour, and the peak reduction in blood pressure is achieved 4-6 hours after taking the drug. The duration of the effect is dose-dependent. However, when used in recommended doses, the antihypertensive and hemodynamic effects were maintained for at least 24 hours.
In hemodynamic studies in patients with essential hypertension, a decrease in blood pressure is usually accompanied by a decrease in peripheral arterial resistance with an increase in cardiac output and little or no increase in heart rate. Renal blood flow increases after enalapril administration, but glomerular filtration rate does not change. There is no evidence of sodium or water retention. However, in patients with low initial glomerular filtration rates, these rates are usually increased.
In short-term clinical studies in patients with renal impairment, with or without diabetes, reductions in albuminuria, urinary IgG excretion, and total urinary protein were observed after enalapril administration.
When taken together with thiazide diuretics, the hypotensive effects of Enap® are at least additive. Enalapril may reduce or prevent the development of thiazide-induced hypokalemia.
In patients with heart failure receiving cardiac glycosides and diuretics, oral or injectable Enap® was associated with a decrease in peripheral resistance and blood pressure. Cardiac output increased and heart rate (usually increased in patients with heart failure) decreased. Pulmonary end-capillary pressure also decreased. Exercise tolerance improved and the severity of heart failure, as assessed by NYHA (New York Heart Association) criteria, decreased. These effects were maintained during long-term treatment.
In patients with mild to moderate heart failure, enalapril slowed the progression of myocardial dilation/mass gain and heart failure, as evidenced by reduced left ventricular end-diastolic and systolic volumes and improved ejection fraction.
There is limited experience of the effective and safe use of the drug in children with arterial hypertension aged 6 years and older. A clinical study included 110 children with arterial hypertension aged 6 to 16 years with a body weight ≥ 20 kg and a glomerular filtration rate > 0.5 ml/sec/1.73 m2. Children with a body weight < 50 kg received 0.625 mg or 2.5 mg or 20 mg of enalapril once daily, and children with a body weight ≥ 50 kg received 1.25 mg or 5 mg or 40 mg of enalapril once daily. The reduction in blood pressure was dose-dependent; the effect was the same in all dosage subgroups (by age, Tanner stage, gender, race). The results of the study indicate that the lowest doses of 0.625 mg and 1.25 mg, i.e. an average of 0.02 mg/kg/day, do not predict therapeutic efficacy. The maximum dose was 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 1 hour. The extent of absorption is approximately 60% and is not affected by food. After absorption, enalapril is rapidly and extensively hydrolyzed to enalaprilat, a potent ACE inhibitor. Peak serum concentrations of enalaprilat are achieved 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 patients with normal renal function, steady-state serum concentrations of enalaprilat are reached after four days of treatment.
Distribution
Within the entire therapeutic concentration range, 60% of enalaprilat binds to serum proteins.
Metabolism
With the exception of conversion to enalaprilat, there is no evidence of significant metabolism of enalapril.
Breeding
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. After administration of 5 mg once daily in patients with mild to moderate renal impairment (creatinine clearance 0.6–1 mL/sec), the steady-state AUC of enalaprilat was approximately 2-fold higher than in patients with normal renal function. In severe renal impairment (creatinine clearance 0.5 mL/sec), the AUC increased approximately 8-fold. At this level of renal impairment, the effective half-life of enalaprilat is prolonged and the time to reach steady-state is increased.
Enalaprilat can be removed from the general circulation by hemodialysis. The dialysis clearance of enalaprilat is 1.03 ml/s.
Indication
Treatment of arterial hypertension. Treatment of clinically significant heart failure. Prevention of clinically significant heart failure in patients with asymptomatic left ventricular dysfunction (ejection fraction ≤ 35%).
Contraindication
Hypersensitivity to enalapril or to any of the other ingredients of the drug, or to other ACE inhibitors. History of angioedema associated with previous treatment with ACE inhibitors. Hereditary or idiopathic angioedema. Pregnancy or planning to become pregnant (see section "Use during pregnancy and breastfeeding"). Enap® should not be used with drugs containing aliskiren in patients with diabetes mellitus or with impaired renal function (GFR < 60 ml/min/1.73 m2).
Concomitant use in combination with neprilysin inhibitors (e.g. sacubitril) - due to increased risk of angioedema. The drug should not be used within 36 hours of the last administration of sacubitril/valsartan, a drug containing a neprilysin inhibitor, or after switching from it to another drug (see sections "Special instructions for use" and "Interaction with other medicinal products and other types of interactions").
Interaction with other medicinal products and other types of interactions
Potassium-sparing diuretics, potassium supplements or potassium salt substitutes
Although serum potassium levels are usually within normal limits, hyperkalemia may occur in some patients receiving enalapril. The use of potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene or amiloride) and the use of potassium-containing food supplements or salt substitutes may lead to a significant increase in serum potassium. Caution should also be exercised when enalapril is administered concomitantly with other drugs that increase serum potassium levels, such as trimethoprim and co-trimoxazole (trimethoprim/sulfamethoxazole), since trimethoprim is known to act as a potassium-sparing diuretic similar to amiloride. Therefore, the combination of enalapril with the above-mentioned drugs is not recommended. If the above agents are indicated in connection with hypokalemia, they should be used with caution, with regular determination of serum potassium levels (see section "Special warnings and precautions for use").
Previous treatment with high doses of diuretics may lead to volume depletion and an increased risk of hypotension at the start of enalapril therapy (see section 4.4). Hypotensive effects may be reduced by discontinuing the diuretic, increasing salt intake, or initiating therapy with a low dose of enalapril.
Other antihypertensive drugs
The combination of enalapril with other antihypertensive agents may enhance the hypotensive effect of enalapril. Concomitant administration with nitroglycerin, other nitrates, or other vasodilators may further reduce blood pressure.
Antidiabetic drugs
Epidemiological studies have shown that the concomitant use of ACE inhibitors and antidiabetic agents (e.g. insulin, oral hypoglycaemic agents) may lead to a decrease in blood glucose levels with a risk of hypoglycaemia. This phenomenon is most likely during the first weeks of concomitant treatment and in patients with renal impairment (see sections 4.4 and 4.8).
Lithium
Reversible increases in serum lithium levels and toxicity have been reported with concomitant use of ACE inhibitors and lithium. Concomitant use of ACE inhibitors and thiazide diuretics may further increase serum lithium levels and increase the risk of lithium toxicity. The use of enalapril with lithium is not recommended, but if the combination proves necessary for the patient, careful monitoring of serum lithium levels should be performed (see section 4.4).
Concomitant administration of certain anesthetics, tricyclic antidepressants and neuroleptics with ACE inhibitors may lead to an additional decrease in blood pressure (see section "Special warnings and precautions for use").
Nonsteroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors
Non-steroidal anti-inflammatory drugs (NSAIDs), 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 (ARBs) or ACE inhibitors may be attenuated by NSAIDs, including selective COX-2 inhibitors.
Concomitant use of NSAIDs, including COX-2 inhibitors, and ARA II or ACE inhibitors has an additive effect on serum potassium and may lead to deterioration of renal function. These effects are usually reversible.
Acute renal failure may occur rarely, especially in some patients with impaired renal function (e.g. elderly patients or patients with reduced circulating blood volume, including those taking diuretics). Therefore, this combination should be used with caution in patients with impaired renal function. Patients should be adequately hydrated; renal function should be closely monitored at the beginning of concomitant therapy and periodically during treatment.
Dual blockade of the renin-angiotensin-aldosterone system.
Dual blockade (e.g., adding an ACE inhibitor to an ARB) should be limited to isolated cases with close monitoring of blood pressure, renal function, and electrolytes. Several studies have reported that in patients with established atherosclerotic vascular disease, heart failure, or diabetes with end-organ damage, dual RAAS blockade is associated with a higher incidence of hypotension, syncope, hyperkalemia, and worsening renal function (including acute renal failure) compared with the use of a single RAAS-acting agent. ACE inhibitors and ARBs should not be used concomitantly in patients with diabetic nephropathy.
Enap® with aliskiren should not be used in patients with diabetes mellitus or with impaired renal function (GFR < 60 ml/min/1.73 m2) (see sections “Contraindications” or “Special warnings and precautions for use”).
Gold preparations
Nitritoid reactions (symptoms including facial swelling, nausea, vomiting and hypotension) have been reported rarely in patients treated with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitors, including enalapril.
Drugs that increase the risk of angioedema
Concomitant use with neprilysin inhibitors (e.g. sacubitril) is contraindicated due to an increased risk of angioedema (see sections "Contraindications" and "Special warnings and precautions for use").
mTOR inhibitors
Concomitant use with racecadotril, mTOR inhibitors (such as temsirolimus, sirolimus, everolimus) and vildagliptin may lead to an increased risk of angioedema (see section 4.4).
Sympathomimetics
Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.
Alcohol
Alcohol enhances the hypotensive effect of ACE inhibitors.
Acetylsalicylic acid, thrombolytics and β-blockers
Enalapril can be safely used concomitantly with acetylsalicylic acid (in cardiological doses), thrombolytics, and β-blockers.
Patients receiving concomitant co-trimoxazole (trimethoprim/sulfamethoxazole) are at increased risk of hyperkalemia (see section 4.4).
Cyclosporine
Hyperkalemia may occur with concomitant use of ACE inhibitors with cyclosporine. Monitoring of serum potassium is recommended.
Heparin
Hyperkalemia may occur during concomitant use of ACE inhibitors with heparin. Monitoring of serum potassium levels is recommended.
Application features
Symptomatic hypotension
Symptomatic hypotension is rarely observed in patients with uncomplicated hypertension. In patients with hypertension receiving enalapril, symptomatic hypotension develops more often in case of hypovolemia, which occurs, for example, as a result of diuretic therapy, salt restriction, in patients undergoing hemodialysis, as well as in patients with diarrhea or vomiting (see sections "Interaction with other medicinal products and other forms of interaction" and "Adverse reactions"). Symptomatic hypotension has also been observed in patients with heart failure, which was accompanied or not accompanied by renal failure. Symptomatic hypotension developed more often in patients with more severe forms of heart failure, who were treated with higher doses of loop diuretics, with hyponatremia or impaired renal function. Such patients should start therapy with Enap® under medical supervision. When changing the dose of the drug and/or diuretic, special care should be taken. Similarly, patients with ischemic heart disease and cerebrovascular disease should be monitored, in whom an excessive decrease in blood pressure could lead to myocardial infarction or stroke.
If hypotension develops, the patient should be placed in a horizontal position and, if necessary, intravenous saline should be administered. Transient hypotension while taking enalapril is not a contraindication for further administration, which can usually be continued without complications after normalization of blood pressure by restoring fluid volume.
In some patients with heart failure with normal or low blood pressure, enalapril may further reduce blood pressure. This reaction to the drug is expected and is usually not a reason to stop treatment. If hypotension becomes resistant to treatment, the dose should be reduced and/or the diuretic and/or enalapril should be discontinued.
Aortic or mitral stenosis/hypertrophic cardiomyopathy
As with all vasodilators, ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction and outflow tract obstruction and should be avoided in cardiogenic shock and hemodynamically significant obstruction.
Kidney dysfunction
In patients with impaired renal function (creatinine clearance < 1.33 ml/h), the initial dose of enalapril should be adjusted according to creatinine clearance (see section 4.2) and then according to response to treatment. Regular monitoring of potassium and creatinine levels is standard medical practice in such patients.
Renal impairment has been reported in association with enalapril, primarily in patients with severe heart failure or renal disease, including renal artery stenosis. With timely recognition and appropriate treatment, renal impairment associated with enalapril therapy is usually reversible.
In some hypertensive patients with no known pre-existing renal disease, enalapril in combination with diuretics has caused, usually minor and transient increases in blood urea and serum creatinine. In such cases, dose reduction and/or discontinuation of the diuretic may be necessary. This situation increases the likelihood of underlying renal artery stenosis (see section 4.4: Renovascular hypertension).
Renovascular hypertension
There is an increased risk of hypotension and renal failure when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with ACE inhibitors. Loss of renal function may occur with minimal changes in serum creatinine. In such patients, treatment should be initiated at low doses under close medical supervision with careful titration and monitoring of renal function.
Kidney transplantation
There is no experience with the use of Enap® in patients who have recently undergone kidney transplantation. Therefore, treatment with Enap® is not recommended for these patients.
Liver failure
Rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and (sometimes) fatal outcome. The mechanism of this syndrome remains unclear. Patients taking ACE inhibitors who develop jaundice or marked elevations of liver enzymes should discontinue the ACE inhibitor and receive appropriate medical attention.
Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving ACE inhibitors. Neutropenia has been reported rarely in patients with normal renal function and in the absence of other complicating factors. Enalapril should be used with great caution in patients with collagen vascular disease who are receiving immunosuppressive therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing renal impairment. Some of these patients have developed serious infections, sometimes unresponsive to intensive antibiotic therapy. Periodic monitoring of white blood cell counts is recommended when enalapril is prescribed to such patients. Patients should report any signs of infection.
Hypersensitivity/angioedema
With the use of ACE inhibitors, including enalapril, isolated cases of angioedema of the face, extremities, lips, tongue, glottis and/or larynx have been described, occurring at different times during treatment. In these cases, treatment with enalapril should be discontinued immediately and the patient should be closely monitored to ensure complete resolution of symptoms. Only after this monitoring should be discontinued. Even in the case of swelling of the tongue alone without respiratory distress, patients may require prolonged observation, since treatment with antihistamines and corticosteroids may not be sufficient.
Very rarely, fatal cases of angioedema of the larynx or tongue have been reported. If the swelling is localized to the tongue, glottis or larynx, especially in patients with a history of airway surgery, airway obstruction may occur. When there is involvement of the tongue, pharynx or larynx and this may cause airway obstruction, appropriate therapy should be initiated immediately, which may include subcutaneous administration of epinephrine 1:1000 (0.3-0.5 ml) and/or measures to maintain a patent airway.
Black patients taking ACE inhibitors had a higher incidence of angioedema compared to non-black patients.
Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of developing angioedema while receiving an ACE inhibitor (see section 4.3).
Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated due to an increased risk of angioedema. Sacubitril/valsartan should not be initiated within 36 hours of the last dose of enalapril. Enalapril should not be initiated within 36 hours of the last dose of sacubitril/valsartan (see sections 4.3 and 4.4).
Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin may lead to an increased risk of angioedema, e.g. swelling of the airways or tongue, with or without respiratory distress (see section 4.5).
Caution should be exercised when initiating racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin in patients already taking an ACE inhibitor.
Anaphylactoid reactions during hyposensitization with a hymenoptera venom allergen
Rarely, patients receiving ACE inhibitors during hymenoptera venom desensitization have developed anaphylactoid reactions, which may be life-threatening. Such reactions can be avoided by temporarily stopping the ACE inhibitor before the desensitization begins.
Anaphylactoid reactions during low-density lipoprotein apheresis
Rarely, patients receiving ACE inhibitors during low-density lipoprotein apheresis with dextran sulfate have experienced life-threatening anaphylactoid reactions. These reactions can be avoided by temporarily stopping ACE inhibitors before each apheresis.
Patients on hemodialysis
Anaphylactoid reactions have occasionally been reported in patients dialysed with high-flux membranes (e.g. AN 69®) and concomitantly treated with an ACE inhibitor. Therefore, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent in such patients.
Hypoglycemia
Diabetic patients taking oral antidiabetic agents or insulin and initiating therapy with an ACE inhibitor should be advised to monitor their blood sugar levels closely, especially during the first few months of concomitant use (see section 4.5).
Cough
Cough has been reported with ACE inhibitors. The cough is usually non-productive and persistent and resolves after discontinuation of the drug. Cough due to ACE inhibitor therapy should be considered in the differential diagnosis of cough.
During major surgery or anesthesia with drugs that cause hypotension, enalapril blocks the formation of angiotensin II secondary to compensatory renin release. If hypotension develops, which can be explained by these mechanisms of interaction, it is corrected by increasing the volume of fluid.
Hyperkalemia
Some patients treated with ACE inhibitors, including enalapril, have experienced increases in serum potassium. The risk of hyperkalemia is increased in patients with renal insufficiency, hypoaldosteronism, impaired renal function, in patients > 70 years of age, in patients with diabetes mellitus, in transient conditions, in particular dehydration, acute cardiac decompensation, metabolic acidosis and in patients receiving concomitant potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene or amiloride); in patients using dietary supplements or salt substitutes containing potassium; and also in case of taking other drugs that may cause an increase in blood potassium (e.g. heparin, trimethoprim or co-trimoxazole, also known as trimethoprim/sulfamethoxazole, and especially aldosterone antagonists or angiotensin receptor blockers). In particular, the use of potassium-sparing diuretics, food supplements or salt substitutes containing potassium in patients with impaired renal function may lead to a significant increase in blood potassium levels. Hyperkalemia may cause serious, sometimes fatal arrhythmias. Potassium-sparing diuretics and angiotensin receptor blockers should be used with caution in patients receiving ACE inhibitors and serum potassium should be monitored regularly (see section "Interaction with other medicinal products and other forms of interaction").
Lithium
The combination of lithium and enalapril is generally not recommended (see section “Interaction with other medicinal products and other types of interactions”).
Concomitant therapy with an ACE inhibitor and angiotensin receptor antagonist
The combination of an ACE inhibitor with an ARB should be limited to individually defined cases, accompanied by careful monitoring of renal function, potassium levels and blood pressure (see section “Interaction with other medicinal products and other types of interactions”).
Use in children
There is limited experience of efficacy and safety in hypertensive children over 6 years of age, but no experience in other indications. Limited pharmacokinetic data are available in children over 2 months of age (see sections 4.2, 4.3 and 4.4).
Enalapril is not recommended for children for indications other than arterial hypertension.
Due to the lack of safety data, enalapril is not recommended for neonates and pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m2.
Pregnancy/breastfeeding
ACE inhibitors should not be initiated during pregnancy. Patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.8).
Racial affiliation
Enalapril, like other ACE inhibitors, is less effective in lowering blood pressure in patients with arterial hypertension of the Negroid race than in people of other races, which is probably due to the low level of renin in the blood plasma of such patients.
Special warnings regarding inactive ingredients
Enap® contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Ability to influence reaction speed when driving vehicles or other mechanisms
When driving or operating other machinery, the possible development of dizziness or increased fatigue should be taken into account.
Use during pregnancy or breastfeeding
Pregnancy
ACE inhibitors are contraindicated in pregnant women and women planning pregnancy (see section "Contraindications").
Patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if possible, alternative therapy should be started.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy is inconclusive, but a small increase in risk cannot be excluded. It is known that the use of ACE inhibitors during the second and third trimesters of pregnancy may cause fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia).
Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension, oliguria and hyperkalemia (see sections 4.3 and 4.4).
Breastfeeding period
Limited pharmacokinetic data indicate very low concentrations in breast milk. Although these concentrations are considered to be clinically insignificant, the use of Enap® 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 Enap® during breastfeeding may be considered if treatment is necessary for the mother and the infant is observed for any adverse effects.
Method of administration and doses
The tablets should be taken whole with a little water, regardless of the meal. The drug should be taken at the same time every day. Two doses should not be taken at the same time.
The dosage should be selected individually, according to the condition of each patient (see section "Special instructions") and blood pressure response.
Arterial hypertension
The dose of the drug ranges from an initial 2.5 mg to a maximum of 20 mg once daily, depending on the degree of arterial hypertension and the patient's condition. In mild arterial hypertension, the recommended initial dose is 5-10 mg.
In patients with a highly activated RAAS (e.g. renovascular hypertension, salt and/or fluid imbalance, cardiac decompensation or severe hypertension), an excessive decrease in blood pressure after the initial dose may occur. In such patients, a starting dose of 5 mg or less is recommended, and the patient should be under medical supervision at the beginning of treatment.
Previous therapy with high doses of diuretics may lead to fluid depletion and the risk of hypotension at the beginning of therapy with enalapril. For such patients, an initial dose of 5 mg or lower is recommended. If possible, diuretic therapy should be discontinued 2-3 days before starting treatment with Enap®. For patients who cannot discontinue diuretics before starting therapy with Enap®, the initial dose is 2.5 mg of the drug as a single dose. Renal function and serum potassium should be monitored.
The usual maintenance dose is 20 mg once daily. The maximum maintenance dose is 40 mg daily given as a single dose or in 2 divided doses.
Heart failure/asymptomatic left ventricular dysfunction
For the treatment of clinically significant heart failure, enalapril should be used together with diuretics, and if necessary, with digitalis or beta-blockers. The initial dose of Enap® for patients with clinically significant heart failure or asymptomatic left ventricular dysfunction is 2.5 mg, and the drug should be used under close medical supervision in order to establish the initial effect of the drug on blood pressure. In the absence of effect or after appropriate correction of symptomatic hypotension that occurred at the beginning of treatment with enalapril for heart failure, the dose should be gradually increased to the usual maintenance dose of 20 mg, which is taken once or divided into 2 doses, depending on what is better tolerated by the patient. Dose selection is recommended to be carried out within 2-4 weeks. Such a therapeutic regimen effectively reduces mortality rates in patients with clinically significant heart failure. The maximum dose is 40 mg per day in 2 doses.
Table 1. Suggested enalapril dose titration for patients with heart failure/asymptomatic left ventricular dysfunction
Week
Dose, mg/day
Week 1
from 1 to 3 days: 2.5 mg/day* in 1 dose
from day 4 to 7: 5 mg/day in 2 divided doses
T
Specifications
Characteristics
Active ingredient
Enalapril maleate
Adults
Can
ATC code
C MEDICINES AFFECTING THE CARDIOVASCULAR SYSTEM; C09 MEDICINES AFFECTING THE RENIN-ANGIOTENSIN SYSTEM; C09A ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS; C09A A ACE inhibitors, monocomponent; C09A A02 Enalapril
Country of manufacture
Slovenia
Diabetics
With caution
Dosage
5 мг
Drivers
With caution, dizziness and fatigue may occur.
For allergies
With caution
For children
From the age of 6
Form
Tablets
Method of application
Inside, solid
Nursing
It is impossible.
Pregnant
It is impossible.
Primary packaging
blister
Producer
KRKA
Quantity per package
20 pcs
Trade name
Enap
Vacation conditions
By prescription
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