Berlipril Plus, pills 25mg+10mg, 30pcs

Composition

1 tablet contains:

Active ingredients

Enalapril maleate 10 mg.

Hydrochlorothiazide 25 mg.

Auxiliary substances

Lactose monohydrate 139.5 mg,

magnesium carbonate 25.0 mg,

gelatin 6.0 mg,

sodium carboxymethyl starch (Type A) 8.5 mg,

colloidal silicon dioxide 3.5 mg,

magnesium stearate 2.0 mg,

iron oxide yellow dye (E 172) 0.5 mg

Pharmacological action

Berlipril plus is a combination drug consisting of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, and a hydrochlorothiazide-thiazide diuretic, which potentiate the action of each other, and their antihypertensive effect is summed up.

Enalapril

Enalapril inhibits the enzyme that catalyzes the conversion of angiotensin I to angiotensin II-a peptide with vasoconstrictor action, while there is a weakening of vasoconstrictor activity and a decrease in aldosterone secretion, which can lead to an increase in serum potassium content with simultaneous elimination of sodium and fluid.

Elimination of the negative reverse effect of angiotensin II on renin secretion leads to activation of plasma renin. The mechanism of enalapril lowering blood pressure (BP) is based on the primary suppression of the activity of the renin-angiotensin-aldosterone system (RAAS). ACE is identical to kininase II, an enzyme that catalyzes the breakdown of bradykinin, a peptide with a potential vasodilating effect. This plays an additional role in the realization of the antihypertensive effect of enalapril.

The use of enalapril in patients with arterial hypertension leads to a decrease in blood pressure both in the “standing” and “lying” positions, without a significant increase in heart rate (HR).

Hydrochlorothiazide

Hydrochlorothiazide interferes with the reabsorption of sodium, chlorine, and water in the renal tubules. Increases the excretion of potassium, magnesium, bicarbonates, detains calcium ions in the body. The diuretic effect develops 2 hours after oral use of hydrochlorothiazide, reaches a maximum in 4 hours and persists for up to 12 hours. Reduces high blood pressure.

Concomitant use of enapapril and hydrochlorothiazide reduces potassium losses associated with the action of a diuretic, thereby preventing the development of hypokalemia

Indications

Essential hypertension of I-II degree (patients who are indicated for combination therapy or with insufficient effectiveness of enalapril monotherapy).

Use during pregnancy and lactation

The use of Berlipril plus during pregnancy is not recommended. If pregnancy is planned or diagnosed during Berlipril plus therapy, the drug should be discontinued as early as possible.

ACE inhibitors can cause disease or death of the fetus or newborn when used during the second and third trimesters of pregnancy.

The use of ACE inhibitors during this period was accompanied by negative effects on the fetus and newborn, which manifested themselves in the form of arterial hypertension, renal failure, hyperkalemia, and/or hypoplasia of the skull bones. Oligohydramnion may develop, apparently due to impaired fetal kidney function. This can lead to contracture of the extremities, deformity of the skull bones, including its facial part, and hypoplasia of the lungs.

The use of diuretics during pregnancy is not recommended, as they can cause jaundice of the fetus and newborn, thrombocytopenia, and possibly other side effects observed in adults.

If the drug is used during pregnancy, the patient should be warned about the potential risk to the fetus. In those rare cases where the use of the drug during pregnancy is considered necessary, ultrasound examinations should be performed periodically to assess the intraamniotic space. Newborns whose mothers have taken the drug should be carefully monitored for the development of arterial hypertension, oliguria and hyperkalemia. Enalapril, which penetrates the placental barrier, can be removed from the blood of a newborn by peritoneal dialysis with some favorable therapeutic effect, and can theoretically be removed by an exchange blood transfusion.

Enalapril and thiazides are excreted in breast milk, so if their use during lactation is necessary, breastfeeding should be discontinued while taking Berlipril plus. There is also a correlation between the use of thiazides during lactation and a decrease or even suppression of lactation, hypokalemia, as well as the occurrence of hypersensitivity to sulfonamide derivatives.

Contraindications

• Hypersensitivity to enalapril or other ACE inhibitors, hydrochlorothiazide or other sulfonamide derivatives, or other components of the drug.
• Lactase deficiency, hereditary lactose intolerance, glucose-galactose malabsorption syndrome.
• Angioedema in the anamnesis, including those associated with the use of ACE inhibitors.
• Hereditary and / or idiopathic angioedema.
• Patients with myocardial infarction undergoing dialysis treatment (efficacy and safety of the drug have not been studied).
• Severe liver dysfunction (more than 9 points on the Child-Pugh scale).
• Severe renal impairment (creatinine clearance less than 30 ml / min).
• Bilateral renal artery stenosis or stenosis of the artery of a single kidney (risk of kidney failure).
• Condition after a recent kidney transplant (no experience with the drug).
• Pregnancy.
• Lactation period.

Age up to 18 years (efficacy and safety of the drug have not been established).

With caution:

• Impaired water-electrolyte balance, decreased circulating blood volume (BCC), including diarrhea, vomiting.
• Coronary heart disease (CHD).
• Severe cerebrovascular diseases, including cerebrovascular insufficiency.
• Chronic heart failure.
• Severe systemic connective tissue diseases, including: :
• Systemic lupus erythematosus.
• Scleroderma.
• Inhibition of bone marrow hematopoiesis.
• Aortic stenosis with impaired hemodynamic parameters or other obstacles to the outflow of blood from the left ventricle.
• Impaired liver function (less than 9 points on the Child-Pugh scale) due to the risk of developing hepatic coma.
• Chronic renal failure (creatinine clearance greater than 30 ml / min).
• Patients undergoing hemodialysis treatment.
• Primary aldosteronism.
• Diabetes mellitus.
• A diet with limited consumption of table salt.
• Advanced age.
• Hyperkalemia.

Side effects

Possible side effects when using Berlipril plus, as in monotherapy with the active components separately, are listed below in descending frequency of occurrence:

Often – >1/100, >

Infrequently – >1/1000, >

Rarely – >1/10000, >

Very rare –

There is no correlation between the frequency of side effects and the gender or age of patients.

Nervous system disorders

Often include headache, systemic dizziness, and increased fatigue.

Infrequently – drowsiness or insomnia, depression, paresthesia, increased excitability, confusion, tinnitus, accommodation disorders, changes in taste perception, asthenia.

Disorders of the cardiovascular system

Often include a marked decrease in blood pressure, regardless of body position.

Infrequently-arrhythmias, loss of consciousness.

In some cases – tachycardia, palpitation, angina pectoris, chest pain, myocardial infarction, cerebral circulation disorders, stroke.

Disorders of the respiratory system, chest organs

Often – cough (disappears after discontinuation of the drug).

Infrequently – dyspnoea, sinusitis, rhinitis.

In some cases – bronchospasm, stomatitis, glossitis, pulmonary edema, interstitial pneumonia.

Gastrointestinal/liver and biliary tract disorders

Infrequently – nausea, vomiting, abdominal pain, digestive disorders, dry oral mucosa, diarrhea, pancreatitis, constipation, flatulence, anorexia.

In some cases – hepatitis and intestinal obstruction.

Very rare-intestinal angioedema associated with ACE inhibitors, including enalapril, has been reported.

Skin disorders

Infrequently – skin pruritus, rash, dry skin.

Rarely-angioedema of the face, limbs, lips, tongue, glottis and / or larynx, increased sweating, photosensitization.

Very rarely – Stevens-Johnson syndrome.

Musculoskeletal disorders

Infrequently-muscle cramps and pain.

Kidney and urinary tract disorders

Infrequently – impaired renal function, renal failure, proteinuria, interstitial nephritis.

Genital and breast disorders

Infrequently-violation of potency.

Violations of laboratory parameters

Infrequently – hypercholesterolemia, hyperglycemia, hyperlipidemia, hypokalemia, hyperkalemia, hyperuricemia, hyponatremia, hypochloremia, hypercalcemia, hypomagnesemia, increased serum creatinine, blood urea and liver function tests, decreased hemoglobin and hematocrit.

Rarely-increased activity of “hepatic” transaminases and bilirubin concentration.

A symptom complex is described: fever, Myalgia /myositis, arthralgia/arthritis, vasculitis, serositis, eosinophilia, leukocytosis, increased ESR, positive antinuclear antibody test.

Interaction

Enalapril

Simultaneous use is not recommended

Potassium-sparing diuretics (spironolactone, triamterene, amiloride) or potassium-containing salts, potassium supplements.

When used concomitantly with ACE inhibitors, hyperkalemia may develop. If, due to the diagnosed hypokalemia, the simultaneous use of these drugs is still indicated, then they should be used with caution, with regular monitoring of the content of potassium in the blood serum and electrocardiogram.

Concomitant use with caution

Thiazide or loop diuretics.

Previous treatment with high-dose diuretics may lead to a decrease in BCC at the beginning of enalapril therapy and contribute to the development of arterial hypotension (see section Special Instructions). The antihypertensive effect can be reduced by discontinuing the diuretic, increasing the absorption of fluids or salts into the body, or starting therapy with low doses of enalapril.

Preparations for general anesthesia

When used with ACE inhibitors, orthostatic hypotension may worsen.

Narcotic drugs / Tricyclic antidepressants / Psychotropic drugs / Barbiturates

Orthostatic hypotension may occur.

Other antihypertensive drugs (alpha-and beta-blockers, slow calcium channel blockers)

The hypotensive effect can be summed up or potentiated. Caution is required when treating with nitroglycerin in various dosage forms and other nitrates or other vasodilators.

Cimetidine

Increased risk of collapse.

Cyclosporine

Concomitant use with ACE inhibitors increases the risk of developing impaired renal function.

Allopurinol, procainamide, cytostatics or immunosuppressants

Concomitant use with ACE inhibitors increases the risk of hypersensitivity reactions and leukopenia.

Hypoglycemic agents

In rare cases, ACE inhibitors may enhance the hypoglycemic effect of insulin and hypoglycemic agents for oral use (for example, sulfonylureas) in patients with diabetes mellitus. In these cases, when ACE inhibitors are used simultaneously, it may be necessary to reduce the dose of the hypoglycemic agent.

Sympathomimetics

May weaken the antihypertensive effect of ACE inhibitors. To confirm the hypotensive effect, such patients should be under close medical supervision.

Antacids

Reduce the bioavailability of ACE inhibitors with simultaneous use.

Sodium Aurotimalate

When used concomitantly with the drug gold (sodium aurotimalate) in injectable form, patients were observed: “hot flashes” of blood to the skin of the face, nausea, vomiting, and arterial hypotension. Arterial hypotension can be regarded as an increase in the effect of ACE inhibitors under the influence of the drug gold.

Hydrochlorothiazide

Concomitant use with caution:

Colestyramine and colestipol

Simultaneous use of anion-exchange drugs reduces the absorption of hydrochlorothiazide. Colestyramine or colestipol in a single dose bind hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by 85 and 43%, respectively.

Diuretics that are derivatives of sulfonamides should be taken at least 1 hour before or 4-6 hours after taking these drugs.

Glucocorticosteroids, corticotropin (ACTH), amphotericin B (intravenous), carbenocloxone, stimulating type laxanthines

When they are taken simultaneously with hydrochlorothiazide, there may be an increase in electrolyte losses (in particular, the development of hypokalemia).

Calcium Salts

It is possible to increase the concentration of calcium in the blood serum due to a decrease in its excretion when used simultaneously with thiazide diuretics.

Cardiac Glycosides

Hypokalemia or hypomagnesemia caused by thiazides contributes to the occurrence of arrhythmias caused by cardiac glycosides.

Drugs that can cause arrhythmia of the “pirouette” type (“pirouette” is a special form of polymorphic ventricular tachycardia with a wave -, screw-or spindle-shaped configuration of ventricular complexes in combination with an increase or decrease in the amplitude of the QRS complex waves, which can result in ventricular fibrillation or asystole)

Due to the risk of hypokalemia, caution is required when using hydrochlorothiazide concomitantly with certain antiarrhythmic, antipsychotic (neuroleptics) and other medications that are known to cause pirouette-type arrhythmia.

Vasoconstrictor amines (epinephrine)

It is possible to reduce the reaction to vasoconstrictor amines, although not so pronounced as to exclude their combined use with hydrochlorothiazide.

Non-depolarizing muscle relaxants (tubocurarine chloride)

It is possible to increase sensitivity to muscle relaxants when used together with hydrochlorothiazide.

Amantadine

Thiazides may increase the risk of side effects of amantadine.

Gout medications (probenecid, sulfinpyrazone, allopurinol)

It may be necessary to adjust the dose of the hypouricemic drug (increasing the dose of probenecid or sulfinpyrazone), since hydrochlorothiazide can increase the concentration of uric acid in the blood serum.

Concomitant use with thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.

Other types of interaction:

Laboratory parameters

Because of the effect on calcium metabolism, thiazides can distort the result of a study of parathyroid function.

Enalapril / Hydrochlorothiazide in combination

Simultaneous use is not recommended

Lithium

Concomitant use with thiazide diuretics may increase the already increased risk of lithium intoxication due to ACE inhibitors, so the combined use of Berlipril plus and lithium preparations is not recommended. If such a combination is still necessary, then careful monitoring of the concentration of lithium in the blood serum is also necessary.

Laboratory parameters

Thiazides can reduce the level of protein-bound iodine without causing symptoms of thyroid dysfunction.

Concomitant use with caution:

Nonsteroidal anti-inflammatory drugs (NSAIDs) (including acetylsalicylic acid at a dose of 3 g / day, including cyclooxygenase-2 (COX-2) inhibitors)

The use of NSAIDs may weaken the antihypertensive effect of ACE inhibitors and diuretics. In addition, there are reports that the effects of NSAIDs and ACE inhibitors that increase serum potassium may add up, while renal function may decrease. The corresponding effects are reversible and develop in patients with existing renal impairment. In rare cases, acute renal failure may occur, especially in patients with impaired renal function (elderly or dehydrated patients).

Ethanol

Increases the hypotensive effect of ACE inhibitors and hydrochlorothiazide.

Trimethoprim

Concomitant use with ACE inhibitors and thiazides increases the risk of hypercalcemia.

How to take, course of use and dosage

Berlipril plus tablets are taken orally once a day (in the morning), regardless of food intake, with a sufficient amount of liquid.

At the beginning of therapy with Berlipril plus, symptomatic hypotension may develop, which more often occurs in patients with impaired water-electrolyte balance due to previous diuretic therapy. Diuretics should be discontinued 2-3 days before starting Berlipril plus therapy.

Adults: the recommended dose is 1 tablet of Berlipril plus once a day.

Elderly patients (over 65 years of age): no dosage adjustment is required in elderly patients with normal renal function ( creatinine clearance greater than 90 ml/min).

Use in special clinical cases

In patients with creatinine clearance greater than 30 ml/min, but less than 80 ml/min, Berlipril plus should be used only after preliminary selection of doses of each of the components.

In severe renal impairment (creatinine clearance less than 30 ml / min), the drug is contraindicated.

Overdose

Symptoms: marked decrease in blood pressure, shock, stupor, bradycardia, impaired water-electrolyte balance and renal failure.

The most common symptoms of a hydrochlorothiazide overdose are nausea and drowsiness. Overdose of hydrochlorothiazide is associated with loss of electrolytes (hypokalemia, hypochloremia) and dehydration (due to increased diuresis). Hypokalemia can lead to muscle cramps and/or, when taking cardiac glycosides or antiarrhythmic drugs at the same time, to an aggravation of the course of arrhythmia due to hypokalemia.

Treatment: it is symptomatic and supportive. Strict medical supervision is required, preferably in an intensive care unit/ward setting. Regular monitoring of serum electrolytes and creatinine is necessary.

Therapeutic measures depend on the nature and severity of the symptoms. Within 30 minutes after taking the drug, measures can be taken to prevent its absorption from the gastrointestinal tract (gastric lavage, the use of adsorbents and sodium sulfate).

With a marked decrease in blood pressure, the patient should be given a horizontal position with raised legs; decide on the use of drugs that increase BCC (intravenous infusion of 0.9% sodium chloride solution). use of angiotensin II is effective.

Bradycardia or severe vagal reactions should be eliminated with atropine ; an artificial pacemaker may be used.

Enalaprilate can be removed from the systemic circulation by hemodialysis.

ACE inhibitors are dialyzable, but the use of high-flow polyacrylonitrile membranes should be avoided (see section Special Instructions).

Special instructions

Influence on the ability to drive vehicles and manage mechanisms

The effect of Berlipril plus on the ability to drive vehicles and control mechanisms has not been specifically studied, so during treatment with Berlipril plus, caution should be exercised when driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

Store at a temperature not exceeding 30°C.

Shelf

life is 3 years.

Active ingredient

Hydrochlorothiazide, Enalapril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults, For adults as prescribed by a doctor

Indications

Heart Failure, Hypertension