Instructions for use Enalapril-Teva tablets 5 mg blister No. 30
Composition
active ingredient: enalapril maleate;
1 tablet contains enalapril maleate 2.5 mg or 5 mg, or 10 mg, or 20 mg;
excipients:
2.5 mg and 5 mg tablets: lactose monohydrate, corn starch, talc, sodium bicarbonate, hydroxypropyl cellulose, magnesium stearate;
10 mg and 20 mg tablets: lactose monohydrate, corn starch, talc, sodium bicarbonate, magnesium stearate, red iron oxide, yellow iron oxide (for 20 mg tablets).
Dosage form
Pills.
Main physicochemical properties:
2.5 mg tablets: white, round, biconvex tablets;
5 mg tablets: white, round, biconvex snap tab tablets with a score on one side;
10 mg tablets: red-brown with specks, round, biconvex snap tab tablets with a score on one side;
20 mg tablets: pale orange with specks, round, biconvex snap tab tablets with a score on one side.
Pharmacotherapeutic group
Angiotensin-converting enzyme inhibitors, monocomponent. ATC code C09A A02.
Pharmacological properties
Pharmacodynamics.
Enalapril maleate is the maleic acid salt of 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 angiotensin II in plasma, 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 renin-angiotensin-aldosterone system (RAAS). Enalapril may have 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 in patients in horizontal and vertical positions without a significant increase in heart rate.
Symptomatic postural hypotension is uncommon. In some patients, achieving optimal blood pressure control may require several weeks of therapy. 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 after 1 hour, with peak blood pressure reduction achieved 4-6 hours after administration. The duration of the effect is dose-dependent. However, at recommended doses, it has been demonstrated that the antihypertensive and hemodynamic effects are 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, with or without a slight increase in heart rate. After enalapril administration, there was an increase in renal blood flow; glomerular filtration rate (GFR) remained unchanged. There was no evidence of sodium or water retention. However, in patients with low baseline glomerular filtration rate, this rate was usually increased.
In short-term clinical studies in patients with and without diabetes mellitus and renal disease, reductions in albuminuria, urinary IgG excretion, and total urinary protein were observed after enalapril administration.
A multicenter, randomized, double-blind, placebo-controlled trial (SOLVD Warning) was conducted in a population with asymptomatic left ventricular dysfunction (left ventricular ejection fraction <35%). 4228 patients were randomized to receive placebo (n=2117) or enalapril (n=2111). In the placebo group, 818 patients developed heart failure or death (38.6%) compared with 630 patients in the enalapril group (29.8%) (risk reduction 29%, 95% CI, 21-36%, p<0.001). 518 patients in the placebo group (24.5%) and 434 in the enalapril group (20.6%) died or were hospitalized for new or worsening heart failure (20% risk reduction, 95% CI; 9-30%, p<0.001). The multicenter, randomized, double-blind, placebo-controlled trial (SOLVD Treatment) studied a population with symptomatic congestive heart failure due to systolic dysfunction (ejection fraction <35%). 2569 patients receiving conventional heart failure treatment were randomized to placebo (n=1284) or enalapril (n=1285). There were 510 deaths in the placebo group (39.7%) compared with 452 in the enalapril group (35.2%) (risk reduction 16%, 95% CI, 5-26%, p=0.0036). There were 461 cardiovascular deaths in the placebo group compared with 399 in the enalapril group (risk reduction 18%, 95% CI, 6-28%, p<0.002), mainly due to a reduction in mortality from progressive heart failure (251 in the placebo group and 209 in the enalapril group, risk reduction 22%, 95% CI, 6-35%). Fewer patients died or were hospitalized for worsening heart failure (736 in the placebo group and 613 in the enalapril group, a 26% risk reduction, 95% CI 18-34%, p<0.0001). Overall, in the SOLVD trial, in patients with left ventricular dysfunction, enalapril reduced the risk of myocardial infarction by 23% (95% CI 11-34%, p<0.001) and reduced the risk of hospitalization for unstable angina by 20% (95% CI, 9-29%, p<0.001).
Clinical pharmacology in children. There is limited experience in the study of efficacy and safety in children with hypertension aged 6 years and older. A clinical study enrolled 110 children with hypertension aged 6 to 16 years with a body weight ≥20 kg and a GFR >0.5 ml/s/1.73 m2. Children weighing <50 kg received 0.625 mg or 2.5 mg or 20 mg of enalapril once daily, and children weighing ≥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 similar across dose subgroups (age, Tanner stage, gender, race). The results of the study indicate that the lowest doses of 0.625 mg and 1.25 mg, which are equivalent to a mean dose of 0.02 mg/kg/day, did not provide a sustained antihypertensive effect. The maximum dose studied was 0.58 mg/kg (40 mg) once daily. The adverse reaction 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 food intake does not affect absorption. 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 elimination half-life of enalaprilat after multiple doses of enalapril is 11 hours.
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 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%).
Renal impairment. Exposure to enalapril and enalaprilat is increased in patients with renal impairment. 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. After multiple administration of enalapril maleate, the effective half-life of enalaprilat is prolonged and the time to steady state is increased (see section 4.2).
Enalaprilat can be removed from the general circulation by hemodialysis. The dialysis clearance of enalaprilat is 62 ml/min.
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, to any of the excipients 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 or breastfeeding").
Concomitant use with sacubitril/valsartan. Enalapril should not be used in combination with sacubitril/valsartan as this combination increases the risk of angioedema. Enalapril should not be used within 36 hours of switching from/to sacubitril/valsartan, a drug containing a neprilysin inhibitor (see sections 4.5 and 4.4).
Interaction with other medicinal products and other types of interactions
Medicinal products that increase the risk of angioedema. Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated due to an increased risk of angioedema (see sections 4.3 and 4.4). Concomitant use of ACE inhibitors with racecadotril (an antidiarrhoeal agent), mammalian target of rapamycin (mTOR) inhibitors (e.g. sirolimus, everolimus, temsirolimus) or vildagliptin may lead to an increased risk of angioedema (see section 4.4).
Potassium-sparing diuretics, potassium supplements, or other drugs that may increase serum potassium. ACE inhibitors increase the potassium loss caused by diuretics. Although serum potassium usually remains within normal limits, hyperkalemia may occur in some patients taking this drug. Potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Caution should also be exercised when enalapril is used concomitantly with other drugs that increase serum potassium levels, such as trimethoprim and co-trimoxazole (trimethoprim/sulfamethoxazole), as trimethoprim is known to act as a potassium-sparing diuretic in the same way as amiloride. Therefore, the combination of enalapril with the above-mentioned drugs is not recommended. If concomitant use of such drugs is indicated, treatment should be carried out with caution and serum potassium should be monitored frequently (see section 4.4).
Cyclosporine: Concomitant use of ACE inhibitors with cyclosporine may cause hyperkalemia. Monitoring of serum potassium is recommended.
Heparin: Concomitant use of ACE inhibitors with heparin may lead to hyperkalemia. Monitoring of serum potassium is recommended.
Other antihypertensive drugs. Concomitant use of antihypertensive drugs may enhance the hypotensive effect of enalapril. Concomitant use with nitroglycerin, other nitrates, or other vasodilators may further reduce blood pressure.
Diuretics (thiazide or loop diuretics). Previous treatment with high doses of diuretics may result in volume depletion and excessive hypotension at the start of enalapril therapy. The hypotensive effect may be reduced by discontinuing the diuretic, increasing salt and fluid intake, or initiating therapy with a low dose of enalapril.
Lithium. Concomitant use of ACE inhibitors and lithium may result in reversible 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 administration 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), including selective cyclooxygenase-2 inhibitors. 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 or ACE inhibitors may be attenuated by NSAIDs, including selective COX-2 inhibitors.
Concomitant use of NSAIDs, including COX-2 inhibitors, and angiotensin II receptor antagonists 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 administered with caution to patients with impaired renal function. Patients should be adequately hydrated and renal function should be closely monitored at the beginning of concomitant therapy and periodically during such treatment.
Sympathomimetics: Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.
Antidiabetic agents: Epidemiological studies have shown that concomitant use of ACE inhibitors and antidiabetic agents (insulin, oral hypoglycaemic agents) may lead to a decrease in blood glucose levels with a risk of hypoglycaemia. This phenomenon is more likely to occur during the first weeks of combined treatment and in cases of impaired renal function.
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.
Dual blockade of the RAAS. Dual blockade (e.g., by 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, in patients with established atherosclerotic vascular disease, heart failure, or diabetes with end-organ damage, dual blockade of the RAAS 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 a single RAAS-acting agent. Enalapril should not be used with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m2) (see sections 4.3 and 4.4).
Application features
Symptomatic hypotension. Symptomatic hypotension is rarely observed in patients with uncomplicated hypertension. In hypertensive patients receiving enalapril, symptomatic hypotension is more likely to occur in patients with hypovolemia, for example, due to diuretic therapy, salt restriction, in patients undergoing hemodialysis, and in patients with diarrhea or vomiting. Symptomatic hypotension has also been observed in patients with heart failure, with or without renal insufficiency. Symptomatic hypotension has been more common in patients with more severe heart failure, who have been treated with higher doses of loop diuretics, with hyponatremia, or with impaired renal function. In such patients, treatment with enalapril should be initiated under medical supervision. When changing the dose of enalapril and/or diuretic, monitoring should be particularly careful. This also applies to patients with coronary heart disease or cerebrovascular disease, in whom excessive reduction in blood pressure could lead to myocardial infarction or stroke.
If hypotension develops, the patient should be placed on his back 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, additional reduction in blood pressure may occur when enalapril is used. This effect is expected and is not usually a reason for discontinuation of treatment. If hypotension becomes symptomatic, it may be necessary to reduce the dose and/or discontinue the diuretic and/or enalapril.
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 outflow tract obstruction, and should be avoided in cardiogenic shock and hemodynamically significant obstruction.
Renal impairment: Patients with renal impairment (creatinine clearance <80 ml/min) require dosage adjustment based on creatinine clearance and then on response to treatment. Serum creatinine and potassium levels should be monitored regularly.
Renal impairment has been reported in association with enalapril, predominantly in patients with severe heart failure or renal disease, including renal artery stenosis. Renal impairment associated with enalapril therapy is usually reversible with prompt recognition and appropriate treatment.
Renovascular hypertension. Patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney who are taking ACE inhibitors are at increased risk of hypotension and renal failure. Loss of renal function with minor changes in serum creatinine may occur. 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. Rarely, a syndrome that begins with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis, sometimes fatal, may occur 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, the ACE inhibitor should be discontinued, 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 disease, concomitant immunosuppressants, allopurinol or procainamide, or a combination of these factors, especially if there is pre-existing renal impairment. 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 promptly.
Hypersensitivity/angioedema. Cases of angioedema of the face, extremities, lips, tongue, glottis and/or larynx have been reported with ACE inhibitors, including enalapril, occurring at different times during treatment. In such cases, enalapril should be discontinued immediately and the patient should be closely monitored to ensure complete resolution of symptoms. Only then should monitoring be discontinued. Even if only tongue swelling is present without respiratory compromise, patients may require prolonged observation, as treatment with antihistamines and corticosteroids may be inadequate.
Fatal cases of angioedema of the larynx and tongue have been reported very rarely. In the event of angioedema of the tongue, glottis or larynx, which may cause airway obstruction, especially in patients with a history of surgery, appropriate therapy should be initiated immediately, which may include the administration of adrenaline (0.3-0.5 ml of epinephrine solution for subcutaneous injection in a ratio of 1:1000) and/or measures to ensure a patent airway.
Angioedema has been reported more frequently in black patients receiving ACE inhibitors than in non-black patients. Patients with a history of angioedema unrelated to ACE inhibitor therapy are at increased risk of developing angioedema while receiving ACE inhibitors.
Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated due to an increased risk of angioedema. Sacubitril/valsartan treatment should not be started until 36 hours after the last dose of enalapril. Enalapril treatment should not be started until 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.5).
Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) or 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 desensitization with hymenoptera venom. Rarely, patients receiving ACE inhibitors during desensitization with hymenoptera venom have developed anaphylactoid reactions, which may be life-threatening. Such reactions can be avoided by temporarily stopping the ACE inhibitor before desensitization begins.
Patients on hemodialysis: Anaphylactoid reactions have occasionally been reported in patients on dialysis using high-flux membranes (e.g. AN69®) and concomitantly treated with an ACE inhibitor. Therefore, it is recommended that a different type of dialysis membrane or a different class of antihypertensive agent be considered in such patients.
Hypoglycemia: Diabetic patients receiving 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 Interactions with other medicinal products and other forms of interaction).
Cough: Cough has been reported with ACE inhibitors. The cough is usually non-productive, persistent, and resolves after discontinuation of the drug. Cough due to ACE inhibitor therapy should be considered in the differential diagnosis of cough.
Surgery/Anesthesia: During major surgery or during 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 this mechanism of interaction, it is corrected by increasing the volume of fluid.
Hyperkalemia/Serum potassium: During treatment with ACE inhibitors, including enalapril, increases in serum potassium have been observed in some patients. The risk of hyperkalemia is increased in patients with renal insufficiency, with impaired renal function, age >70 years, with diabetes mellitus, hypoaldosteronism, transient conditions, including dehydration, acute cardiac decompensation, metabolic acidosis. ACE inhibitors may cause hyperkalemia because they inhibit the release of aldosterone. This effect is usually insignificant in patients with normal renal function. However, hyperkalaemia may occur in patients with impaired renal function and/or in patients taking potassium supplements (including salt substitutes), potassium-sparing diuretics (spironolactone, eplerenone, triamterene or amiloride), other drugs that increase serum potassium (e.g. heparin, trimethoprim or co-trimoxazole, also known as trimethoprim/sulfamethoxazole), especially aldosterone antagonists or angiotensin receptor antagonists. Caution should be exercised when potassium-sparing diuretics and angiotensin receptor antagonists are used in patients taking ACE inhibitors. Serum potassium and renal function should be monitored in such patients (see section 4.5). Hyperkalaemia may cause serious, sometimes fatal, arrhythmias. If concomitant use of enalapril and any of the above-mentioned drugs is considered necessary, they should be used with caution, with regular monitoring of serum potassium (see section "Interaction with other medicinal products and other types of interactions").
Lithium: The combination of lithium and enalapril is generally not recommended (see section 4.5).
Concomitant therapy with an ACE inhibitor and an angiotensin receptor antagonist. There is evidence that the simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of arterial hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see sections "Pharmacological properties" and "Interaction with other medicinal products and other types of interactions"). If dual blockade is necessary, therapy should be carried out under specialist supervision and with constant monitoring of renal function, electrolytes and blood pressure. ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy (see section “Interaction with other medicinal products and other types of interactions”).
Children. There is limited experience of effective and safe use in children with hypertension aged 6 years and older, but no experience in other indications. There are also limited pharmacokinetic data in children aged 2 months and older (see sections 5.1 and 5.2). Enalapril is not recommended for use in children with conditions other than hypertension. Enalapril is not recommended for use in neonates and children with a glomerular filtration rate <30 ml/min/1.73 m2 due to the lack of data (see section 5.2).
Lactose. Enalapril-Teva contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Sodium. Enalapril-Teva contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially sodium-free.
Use during pregnancy or breastfeeding
Pregnancy: ACE inhibitors are contraindicated in pregnant women or in women planning pregnancy (see section 4.3). 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 exposure to ACE inhibitors during the second and third trimesters of pregnancy may induce fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia). Oligohydramnios is likely to indicate decreased fetal renal function and may result in limb contractures, craniofacial deformities, and pulmonary hypoplasia.
If ACE inhibitors have been used from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken ACE inhibitors should be closely monitored for hypotension.
Breastfeeding. Limited pharmacokinetic data indicate very low concentrations in breast milk. Although these concentrations are not considered clinically relevant, the use of Enalapril is not recommended during breast-feeding of premature and first-week-old infants because of the hypothetical risk of cardiovascular and renal effects and because of insufficient experience. For older infants, the use of Enalapril in breastfeeding women may be considered if treatment is necessary for the mother and the infant is observed for any adverse reactions.
Ability to influence reaction speed when driving vehicles or other mechanisms
When driving or operating other machinery, the possible development of dizziness or fatigue should be taken into account.
Method of administration and doses
The drug Enalapril-Teva is administered orally. Food intake does not affect the absorption of Enalapril-Teva tablets.
The dosage should be selected individually, according to the condition of each patient (see section "Special instructions for use") and blood pressure response.
If it becomes necessary to split a tablet, it is best to do so as follows.
Place the tablet on a hard, flat surface with the break line facing up (on a table or plate), press with your index fingers on both sides of the fold line and press sharply and firmly at the same time (as shown in the figure below):
Children
There is limited experience in clinical trials of enalapril in the treatment of hypertension in children (see sections “Pharmacological properties” and “Special instructions for use”).
Arterial hypertension
The dose of enalapril ranges from an initial 5 mg to a maximum of 20 mg depending on the degree of arterial hypertension and the patient's condition (see below). The drug Enalapril-Teva is taken once a day. In mild arterial hypertension, a starting dose of
