Berlipril 5, pills 5mg, 30pcs

Composition

Active ingredient:

enalapril maleate – 5 mg.

Auxiliary substances:

lactose monohydrate – 171 mg,

magnesium hydroxycarbonate-25 mg,

gelatin-6 mg,

colloidal silicon dioxide-3 mg,

sodium carboxymethyl starch-8 mg,

magnesium stearate-2 mg

Pharmacological action

Enalapril maleate is a hypotensive agent from the group of ACE inhibitors. Enalapril maleate is a salt of maleic acid and enalapril, a derivative of L-alanine and L-proline. Enalapril is a prodrug: as a result of its hydrolysis, enalaprilate is formed, which directly inhibits ACE.

The mechanism of its action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in the content of which leads to a direct decrease in the release of aldosterone. At the same time, OPSS, systolic and diastolic blood pressure, post – and preload on the myocardium are reduced.

Enalapril dilates the arteries to a greater extent than the veins, while there is no reflex increase in heart rate. Reduces the degradation of bradykinin, increases the synthesis of prostaglandins.

The hypotensive effect of enalapril is more pronounced at high plasma renin concentrations than at normal or reduced levels. Lowering blood pressure within therapeutic limits does not affect cerebral circulation, blood flow in the brain vessels is maintained at a sufficient level and against the background of reduced blood pressure. Enalapril improves coronary and renal blood flow.

Long-term use of enalapril reduces hypertrophy of the left ventricular myocardium and myocyte walls of resistive arteries, prevents the progression of heart failure and slows down the development of left ventricular dilation. Improves blood supply to the ischemic myocardium. It has a weak diuretic effect.

The time of onset of antihypertensive action when taken orally is 1 hour, reaches a maximum in 4-6 hours and persists for up to 24 hours. In some patients, enalapril therapy is necessary for several weeks to achieve optimal blood pressure levels. In chronic heart failure, a significant clinical effect is observed with long-term treatment with enalapril-6 months or more.

Indications

• Arterial hypertension (including renovascular).
• Chronic heart failure.
• Prevention of clinically significant heart failure in patients with asymptomatic left ventricular dysfunction.

Use during pregnancy and lactation

The use of Berlipril® during pregnancy is contraindicated.

Patients planning pregnancy should be transferred to alternative treatment with a proven safety profile for use in pregnant women. If pregnancy is confirmed, Berlipril should be discontinued immediately and alternative therapy initiated if necessary.

The use of ACE inhibitors in the second and third trimesters of pregnancy was accompanied by negative effects on the fetus, including the development of arterial hypotension, renal failure, hyperkalemia and / or hypoplasia of the skull bones in the newborn. Oligohydramnion may develop, apparently due to a decrease in fetal kidney function.

This complication can lead to contracture of the extremities, deformity of the skull bones, including its facial part, and hypoplasia of the lungs. When using Berlipril®, the patient should be informed about the potential risk to the fetus.

If it is not possible to discontinue Berlipril® during pregnancy, it is necessary to carefully monitor newborns whose mothers took Berlipril® to detect possible blood pressure reduction, oliguria and hyperkalemia, monitor the state of renal function, as well as the skull bones of the newborn using ultrasound.

Enalapril and enalaprilat are excreted in breast milk in trace amounts, but their safety has not been studied. If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Enalapril can be removed from the newborn’s circulation by peritoneal dialysis; theoretically, by an exchange blood transfusion.

Contraindications

• The presence in the anamnesis of angioedema, while taking ACE inhibitors.
• Hereditary or idiopathic angioedema.
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
• Pregnancy.
• Breast-feeding period.
• Age up to 18 years (efficacy and safety have not been established).
• Hypersensitivity to enalapril and other ACE inhibitors or components of the drug.

With caution:  primary hyperaldosteronism, bilateral renal artery stenosis, single kidney artery stenosis, condition after kidney transplantation, hyperkalemia, aortic stenosis, mitral stenosis (with impaired hemodynamic parameters), idiopathic hypertrophic subaortic stenosis, systemic connective tissue diseases, CHD, cerebrovascular diseases, diabetes mellitus, renal failure (CC

Side effects

Possible side effects associated with the use of Berlipril® are listed below in descending frequency of occurrence:

• Very often (≥1/10).
• Often (≥1/100,
• Infrequently (≥1/1000,
• Rare (≥1/10 000,
• Very rare (

From the hematopoietic system: infrequently-anemia (including aplastic and hemolytic); rarely-neutropenia, decreased hemoglobin and hematocrit in the blood serum, eosinophilia, thrombocytopenia, enlarged lymph nodes, pancytopenia, agranulocytosis, inhibition of bone marrow hematopoiesis, autoimmune diseases.

From the side of metabolism and nutrition:  infrequently – hypoglycemia.

Nervous system disorders:  often – headache, depression; infrequently-confusion, insomnia, increased excitability, paresthesia, vertigo, tinnitus; rarely-changes in the nature of dreams, sleep disorders.

From the side of the visual organ:  rarely – blurred vision.

From the cardiovascular system:  very often – dizziness; often-hypotension (including orthostatic hypotension), syncope, chest pain, cardiac arrhythmias, angina pectoris; infrequently-orthostatic hypotension, palpitation, myocardial infarction or cerebral stroke, possibly due to a sharp drop in blood pressure in high-risk patients; rarely-Raynaud’s syndrome.

Respiratory system disorders:  very often-unproductive dry cough; infrequently-rhinorrhea, sore throat and hoarseness of voice, bronchospasm/bronchial asthma; rarely-shortness of breath, rhinitis, pulmonary infiltrates, allergic alveolitis/eosinophilic pneumonia.

From the digestive system:  very often – nausea; often-diarrhea, abdominal pain, changes in taste perception; infrequently-intestinal obstruction, pancreatitis, lack of appetite, dryness of the oral mucosa, changes in taste perception, peptic ulcer; rarely – stomatitis/aphthous ulcers, glossitis; very rarely – angioedema of the intestine.

Liver and biliary tract disorders:  rarely – hepatic insufficiency, hepatitis (hepatocellular or cholestatic), hepatic necrosis, cholestasis (including jaundice).

Skin and subcutaneous tissue disorders:  often – skin rash, urticaria, hypersensitivity reactions/angioedema of the face, extremities, lips, tongue, vocal folds and / or larynx; infrequently – increased sweating, pruritus, urticaria, alopecia; rarely – erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma.

A symptom complex has been reported, which may be accompanied by some and/or all of the following side effects:  fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, increased antinuclear antibody titer, increased erythrocyte sedimentation rate, eosinophilia and leukocytosis. Skin rash, photosensitization, or other skin manifestations may occur.

From the side of the kidneys and urinary tract:  infrequently-impaired renal function, proteinuria, renal failure; rarely-oliguria.

From the genitals and mammary glands:  infrequently-erectile dysfunction; rarely-gynecomastia.

General violations:  very often – asthenia; often-fatigue; infrequently-muscle cramps, flushes of blood to the face, tinnitus, fever.

Laboratory parameters:  often-hyperkalemia, increased serum creatinine concentration; infrequently-increased serum urea concentration, hyponatremia; rarely-increased activity of liver enzymes, hyperbilirubinemia.

In rare cases, with the simultaneous use of ACE inhibitors (including enalapril) and intravenous administration of gold preparations (sodium aurothiomalate), a symptom complex has been described, including redness of the facial skin, nausea, vomiting and hypotension.

Interaction

Concomitant use with NSAIDs, including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors), may reduce the hypotensive effect of ACE inhibitors, including enalapril.In some patients with impaired renal function, concomitant use of NSAIDs and ACE inhibitors may lead to further deterioration of renal function. These changes are usually reversible.

The use of potassium-containing dietary supplements, potassium-containing salt substitutes and/or the use of potassium-sparing diuretics, as well as heparin, can lead to a significant increase in the concentration of potassium ions in the blood serum, especially in patients with impaired renal function and / or diabetes mellitus. If it is necessary to use the above drugs simultaneously with enalapril, regular monitoring of the concentration of potassium ions in the blood serum should be carried out.

When Berlipril is co-administered with thiazide diuretics, hypokalemia caused by taking the latter usually decreases under the influence of enalapril.

Previous therapy with high doses of diuretics may lead to hypovolemia and the risk of hypotension at the beginning of enalapril therapy. The excessive hypotensive effect of enalapril can be reduced either by discontinuing the diuretic, or by increasing the BCC or using table salt, as well as by starting treatment with enalapril at a low dose. Concomitant use of thiazide-type diuretics and ACE inhibitors may lead to hypovolemia and thus increase the risk of hypotension.

Concomitant use of Berlipril and lithium preparations is not recommended due to the risk of lithium intoxication. If this combination is necessary, careful monitoring of the lithium concentration in the blood serum is necessary.

Concomitant use with antipyretics and painkillers may reduce the effectiveness of the drug.

Enalapril weakens the effect of drugs containing theophylline.

The antihypertensive effect of enalapril is enhanced by diuretics, as well as antihypertensive drugs of other groups, including beta-blockers, methyldopa, nitroglycerin and other nitrates, slow calcium channel blockers, hydralazine, prazosin, as well as some drugs for anesthesia, ethanol, tricyclic antidepressants, antipsychotics.

ACE inhibitors may increase the hematotoxicity of immunosuppressants, allopurinol, and cytostatics.

Drugs that cause inhibition of bone marrow hematopoiesis increase the risk of neutropenia and agranulocytosis.

ACE inhibitors increase the bioavailability of digoxin, increasing its concentration in the blood. In this regard, when ACE inhibitors and cardiac glycosides are co-administered, the dose of the latter should be slightly reduced in order to avoid the development of undesirable effects or the effect of relative overdose.

Antipsychotics may increase the antihypertensive effect of enalapril.

Sympathomimetics may weaken the hypotensive effect of enalapril.

Concomitant use of antacids and adsorbents can lead to a decrease in the bioavailability of ACE inhibitors by almost 50%, as well as to a slowdown and weakening of their antihypertensive effect, so you should observe an interval between drug doses of at least 2 hours.

Enalapril can be used simultaneously with acetylsalicylic acid (in cardiological doses of less than 300 mg / day), thrombolytics and beta-blockers.

Epidemiological studies have shown that the simultaneous use of ACE inhibitors and hypoglycemic agents (insulin, hypoglycemic agents for oral use) can additionally contribute to a decrease in blood glucose concentration, leading to the development of hypoglycemia. This phenomenon is most often observed during the first weeks of concomitant use of the above drugs, as well as in patients with renal insufficiency. In patients with diabetes mellitus receiving oral hypoglycemic agents and/or insulin, regular monitoring of blood glucose concentration is necessary, especially careful – during the first month of simultaneous use with ACE inhibitors.

How to take, course of use and dosage

Inside. Tablets are taken regardless of the meal time, without chewing, with a sufficient amount of liquid.

To select the appropriate dosage regimen, it is advisable to use the most appropriate dosage of the drug-5 mg,10 mg or 20 mg (Berlipril® 5, Berlipril® 10 or Berlipril® 20, respectively). The drug is used both as monotherapy and in combination with other antihypertensive agents.

Arterial hypertension

The initial dose is from 5 mg to 20 mg of enalapril maleate 1 time / day, depending on the severity of arterial hypertension.

With mild arterial hypertension: the recommended maintenance dose is 5-10 mg enalapril maleate 1 time/day, with moderate arterial hypertension-10-20 mg enalapril maleate 1 time/day.

With more pronounced arterial hypertension: The recommended daily maintenance dose of enalapril maleate is 20 mg once daily. The dose is selected individually for each patient, but should not exceed 40 mg / day. The maximum daily dose of the drug is 40 mg (in 1 or 2 doses).

Renovascular hypertension

The initial dose is 5 mg of enalapril maleate 1 time/day. After taking the first dose of the drug, careful monitoring of blood pressure is necessary. Then the dose is selected according to the therapeutic effect. The maximum daily dose is 20 mg 1 time/day with daily use. In the future, careful monitoring of the patient is necessary, including mandatory monitoring of the state of renal function.

Patients taking diuretics at the same time should temporarily discontinue diuretic therapy 2-3 days before prescribing the drug. If this is not possible, the initial dose of enalapril maleate should not exceed 5 mg / day. The drug is recommended to be prescribed with caution, since such patients may experience fluid deficiency and / or hyponatremia; in the future, the dosage is selected individually.

Chronic heart failure and asymptomatic left ventricular dysfunction

In patients with chronic heart failure and asymptomatic left ventricular dysfunction, Berlipril® is used in combination therapy simultaneously with diuretics, and, if necessary, cardiac glycosides or beta-blockers. The initial minimum dose of the drug is 2.5 mg 1 time/day, treatment should be started under the careful supervision of a doctor. Increasing the dose of enalapril maleate should be carried out gradually, usually by 2.5-5 mg every 3-4 days in accordance with the individual patient response to the maximum tolerated doses, but not higher than 40 mg/day for chronic heart failure and 20 mg/day for asymptomatic left ventricular dysfunction, in 1 or 2 doses. The maintenance dose is selected within 2-4 weeks.

Treatment with enalapril is long-term, with chronic heart failure and asymptomatic left ventricular dysfunction, it is possible to fully assess the effect no earlier than 6 months after the start of therapy. In cases of too pronounced decrease in blood pressure, the maintenance dose of the drug is gradually reduced.

Elderly patients often have a more pronounced hypotensive effect and prolongation of the drug’s action time, which is associated with a decrease in the rate of elimination of enalapril, so the recommended initial dose of enalapril maleate for elderly patients is no more than 2.5 mg. The maintenance daily dose should be selected depending on the concentration of serum creatinine.

Overdose

Symptoms: approximately 6 hours after ingestion – a marked decrease in blood pressure, up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications, impaired water and electrolyte balance, renal failure, rapid breathing, tachycardia, palpitation, bradycardia, dizziness, anxiety, fear, muscle cramps, cough, stupor.

Plasma concentrations of enalaprilate were 100-200 times higher than after therapeutic doses and were observed after oral use of 300 mg and 440 mg of enalapril maleate, respectively.

Treatment: the use of the drug should be stopped immediately; treatment measures should be aimed at eliminating enalapril and enalaprilat and correcting arterial hypotension.

The patient is placed in a horizontal position with a low headboard. In mild cases, gastric lavage and use of activated charcoal are indicated, in more severe cases – intravenous infusion of saline solution, plasma substitutes, if necessary-use of angiotensin II or catecholamines; hemodialysis (enalaprilate excretion rate-62 ml / min). Patients with bradycardia who are resistant to therapy should have a pacemaker installed.

Special instructions

Caution should be exercised in patients with reduced BCC (including when used concomitantly with diuretics, in conditions of limited salt intake, with hemodialysis, diarrhea, vomiting), in whom a sudden and pronounced decrease in blood pressure may develop in response to the use of an ACE inhibitor.

In patients with mild chronic heart failure, with or without chronic renal failure, symptomatic hypotension is usually not observed. Hypotension is most likely to occur in patients with more severe chronic heart failure due to high-dose diuretics, hyponatremia, or functional renal failure.

In these patients, treatment should be initiated under the supervision of a physician until optimal dose adjustment of Berlipril and/or a diuretic is made. Similar tactics can be applied to patients with CHD and cerebrovascular diseases, in which an excessive drop in blood pressure can lead to a myocardial infarction or brain stroke.In case of severe hypotension, the patient should be placed in a horizontal position and, if necessary, an intravenous infusion of saline solution should be initiated.

Transient arterial hypotension is not a contraindication for continuing enalapril treatment after BP stabilization. In case of repeated pronounced decrease in blood pressure, the dose should be reduced or the drug should be discontinued. Before and during treatment with ACE inhibitors, dynamic monitoring of blood pressure, certain biochemical and electrolyte parameters of the blood (concentrations of hemoglobin, potassium ions, sodium ions, creatinine, urea, liver enzymes in the blood serum), as well as urine for the presence of protein is necessary.

As with all vasodilators, ACE inhibitors should be used with caution in patients with left ventricular hypertrophy and valvular obstruction and should be avoided in cases of cardiogenic shock and hemodynamically significant obstruction.

In cases of impaired renal function (CC In patients with renal insufficiency, it may be necessary to reduce the dose and / or frequency of taking the drug.

Some patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney experienced an increase in serum urea and creatinine concentrations. The changes were usually reversible and returned to normal after discontinuation of treatment.

Some patients who did not develop kidney disease prior to treatment experienced a slight and transient increase in serum urea and creatinine concentrations when enalapril was administered concomitantly with diuretics. In such cases, it may be necessary to reduce the dose and/or discontinue enalapril and / or the diuretic.

There is an increased risk of hypotension and renal failure in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney who are on therapy with ACE inhibitors. Only moderate changes in serum creatinine concentration can indicate a decrease in renal function. In these patients, treatment should begin with small doses under close medical supervision, accurate gradual selection of individual dose and monitoring of serum creatinine concentration.

There is no experience of using Berlipril® in patients who have recently undergone a kidney transplant. Therefore, treatment of such patients with this drug is not recommended.

The use of Berlipril in patients with hepatic insufficiency usually does not require dose adjustment. Rarely, the use of ACE inhibitors is associated with a syndrome that begins with the development of cholestatic jaundice up to the development of fulminant liver necrosis. If symptoms of jaundice or increased liver enzyme activity occur in patients taking ACE inhibitors, discontinue therapy with the drug and conduct an appropriate examination.

There are reports of life-threatening anaphylactic reactions in patients receiving ACE inhibitors during the hymenopteran venom desensitization procedure (heminoptera). Such reactions can be avoided if you temporarily stop taking an ACE inhibitor before desensitization begins. ACE inhibitors should be avoided in patients receiving bee venom immunotherapy.

Neutropenia, agranulocytosis, thrombocytopenia, and anemia may develop during ACE inhibitor therapy. Neutropenia is rare in patients with normal renal function and no other complications.

ACE inhibitors are prescribed only in emergency cases if the patient has systemic connective tissue diseases, during immunosuppressive therapy, in cases of simultaneous use of allopurinol or procainamide, as well as with a combination of all these factors, especially against the background of existing renal failure.

Some of these patients developed severe infections, which in some cases did not respond to intensive antibiotic therapy. If enalapril is still used in such patients, periodic monitoring of the white blood cell count in the blood formula is recommended, and patients should be instructed accordingly to immediately inform the doctor of any signs of infection.

Cough has been reported during treatment with ACE inhibitors. Usually, the cough is unproductive and permanent and stops after discontinuation of the drug. Cough due to treatment with ACE inhibitors should be considered in the differential diagnosis of cough.

Angioedema (Quincke’s edema) of the face, extremities, lips, tongue, glottis, and/or larynx has been reported in patients treated with ACE inhibitors, including Berlipril, during different periods of treatment. In such cases, treatment with Berlipril® should be stopped immediately, and appropriate medical supervision should be carried out until the relevant symptoms completely disappear. Even in cases where there is only difficulty in swallowing without difficulty in breathing, patients should be kept under medical supervision for a long time, as antihistamines and corticosteroids may not be sufficient. Angioedema of the larynx or tongue can be fatal. Edema of the tongue, vocal folds or larynx can lead to airway obstruction, and appropriate therapy, including subcutaneous use of 0.1% epinephrine solution (0.3-0.5 ml) and / or measures to ensure airway conduction, should be carried out as soon as possible.

In patients of the black race, the incidence of angioedema with ACE inhibitors is higher than in representatives of other races. Like other ACE inhibitors, enalapril appears to be less effective in lowering blood pressure in black patients than in others, possibly due to the high prevalence of low renin levels in this population of hypertensive patients.

During the treatment period, it is not recommended to consume alcoholic beverages, because alcohol increases the hypotensive effect of the drug.

In patients undergoing surgery or general anesthesia with blood pressure-lowering drugs, enalapril may block the formation of angiotensin II under the influence of compensatory renin release. If it is assumed that arterial hypotension develops by this mechanism, it can be corrected by increasing the BCC. Before surgical procedures (including dental procedures), the surgeon/anesthesiologist should be warned about the use of Berlipril®.

In rare cases, patients taking ACE inhibitors during LDL apheresis with dextran sulfate have experienced life-threatening anaphylactoid reactions. If LDL apheresis is used, ACE inhibitors should be temporarily replaced with drugs for the treatment of hypertension or heart failure from other groups.

Anaphylactoid reactions have been observed in patients undergoing dialysis using high-throughput membranes (for example, AN69®) with ACE inhibitors. Therefore, for such patients, it is recommended to either use dialysis membranes of a different type, or use antihypertensive drugs of a different group.

In diabetic patients taking oral hypoglycemic agents or insulin, blood glucose levels should be carefully monitored during the first month of enalapril treatment.

In some patients taking ACE inhibitors, including enalapril, there is an increase in the concentration of potassium ions in the blood serum. The risk group for hyperkalemia includes patients suffering from renal insufficiency or diabetes mellitus, taking potassium-sparing diuretics or potassium-containing salt substitutes, and other medications that increase the concentration of potassium ions in the blood serum (for example, heparin). If the use of the above medications during treatment with Berlipril® is necessary, regular monitoring of the concentration of potassium ions in the blood serum is recommended. Similar to other ACE inhibitors, enalapril may be less effective in lowering blood pressure in black people compared to people of other races, possibly due to low renin levels in hypertensive patients in this population.

Sudden discontinuation of enalapril treatment does not lead to the development of “withdrawal” syndrome (a sharp rise in blood pressure).

Influence on the ability to drive motor vehicles and manage mechanisms

Caution should be exercised when driving vehicles and engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions (dizziness may occur due to a sharp decrease in blood pressure, especially after taking the initial dose of enalapril in patients taking diuretics).

Form of production

Tablets

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Enalapril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as prescribed by a doctor, For adults

Indications

Heart Failure, Hypertension