Berlipril Plus, tablets 25 mg+10 mg 30 pcs

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

Enalapril

. Enalapril inhibits the enzyme that catalyzes the conversion of angiotensin I into angiotensin II, a peptide with vasoconstrictor action, with a decrease in vasoconstrictor activity and reduction of aldosterone secretion, which may lead to an increase in serum potassium with simultaneous excretion of sodium and fluid.

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

The use of enalapril in patients with arterial hypertension leads to a decrease in BP in both standing and lying position, without a significant increase in heart rate (HR).

Hydrochlorothiazide

Hydrochlorothiazide impairs sodium, chlorine, and water reabsorption in the renal tubules. It increases the excretion of potassium , magnesium , hydrocarbonates , delays calcium ions in the body. Diuretic effect develops 2 hours after ingestion of hydrochlorothiazide, reaches a maximum after 4 hours and lasts up to 12 hours. It reduces the high blood pressure.

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

Indications

Essential hypertension of I-II degree (patients who are indicated for combination therapy or when monotherapy with enalapril is insufficiently effective).

Pharmacological effect

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

Enalapril

Enalapril inhibits the enzyme that catalyzes the conversion of angiotensin I to angiotensin II, a peptide with a vasoconstrictor effect, thereby weakening vasoconstrictor activity and reducing aldosterone secretion, which can lead to an increase in potassium in the blood serum with simultaneous excretion of sodium and fluid.

Elimination of the negative feedback effect of angiotensin II on renin secretion leads to activation of plasma renin. The mechanism of enalapril’s reduction in 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 implementation 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, and retains calcium ions in the body. The diuretic effect develops 2 hours after taking hydrochlorothiazide orally, reaches a maximum after 4 hours and lasts up to 12 hours. Reduces high blood pressure.

With the simultaneous use of enapapril and hydrochlorothiazide, potassium losses associated with the action of the diuretic are reduced, thereby preventing the development of hypokalemia

Special instructions

Impact on the ability to drive vehicles and operate machinery

The effect of Berlipril Plus on the ability to drive vehicles and operate machinery has not been specifically studied, therefore, during treatment with Berlipril Plus, care should be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Hydrochlorothiazide, Enalapril

Composition

1 tablet contains:

Active ingredients

Enalapril maleate 10 mg.

Hydrochlorothiazide 25 mg.

Excipients

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 dye yellow oxide (E 172) 0.5 mg.

Pregnancy

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

ACE inhibitors may cause illness 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 itself in the form of arterial hypertension, renal failure, hyperkalemia, and/or hypoplasia of the skull bones. The development of oligohydramnios is possible, apparently due to impaired fetal renal function. This can lead to contracture of the limbs, deformation of the bones of the skull, including its facial part, and hypoplasia of the lungs.

The use of diuretics during pregnancy is not recommended because they may cause fetal and neonatal jaundice, thrombocytopenia, and possibly other side effects observed in adults.

If the drug is used during pregnancy, the patient should be warned of the potential risk to the fetus. In those rare cases where the use of the drug during pregnancy is considered necessary, periodic ultrasound examinations should be performed to assess the intra-amniotic space. Newborns whose mothers took the drug should be carefully monitored for the development of hypertension, oliguria and hyperkalemia. Enalapril, which crosses the placental barrier, can be removed from the neonatal blood by peritoneal dialysis with some beneficial therapeutic effect, and theoretically could be removed by exchange 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. A relationship has also been established 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.
History of angioedema, including that associated with the use of ACE inhibitors.
Hereditary and/or idiopathic angioedema.
Patients with myocardial infarction undergoing dialysis treatment (the effectiveness and safety of the drug have not been studied).
Severe liver dysfunction (more than 9 points on the Child-Pugh scale).
Severe renal dysfunction (creatinine clearance less than 30 ml/min).
Bilateral renal artery stenosis or stenosis of the artery of a single kidney (risk of developing renal failure).
Condition after a recent kidney transplant (no experience with the drug).
Pregnancy.
Lactation period.

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

With caution:

Violation of water and electrolyte balance, decrease in circulating blood volume (CBV), 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.
Stenosis of the aortic mouth with impaired hemodynamic parameters or other obstructions 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 more than 30 ml/min).
Patients undergoing hemodialysis treatment.
Primary aldosteronism.
Diabetes mellitus.
Diet with limited salt intake.
Old age.
Hyperkalemia.

Side Effects

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

Often – >1/100,

Uncommon – >1/1000,

Rarely – >1/10000,

Very rarely –

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

Nervous system disorders

Often – headache, systemic dizziness, increased fatigue.

Uncommon: drowsiness or insomnia, depression, paresthesia, increased excitability, confusion, tinnitus, impaired accommodation, changes in taste perception, asthenia.

Cardiovascular disorders

Often – a pronounced decrease in blood pressure, regardless of body position.

Uncommon – arrhythmias, loss of consciousness.

In some cases – tachycardia, palpitations, angina pectoris, chest pain, myocardial infarction, cerebrovascular accident, stroke.

Disorders of the respiratory system, chest organs

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

Uncommon: dyspnea, sinusitis, rhinitis.

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

Gastrointestinal/liver and biliary tract disorders

Uncommon: nausea, vomiting, abdominal pain, indigestion, dry oral mucosa, diarrhea, pancreatitis, constipation, flatulence, anorexia.

In some cases – hepatitis and intestinal obstruction.

Very rarely, the development of angioedema of the intestine associated with the use of ACE inhibitors, including enalapril, has been reported.

Skin disorders

Uncommon: itching, rash, dry skin.

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

Very rarely – Stevens-Johnson syndrome.

Musculoskeletal disorders

Uncommon: muscle cramps and pain.

Renal and urinary tract disorders

Uncommon: renal dysfunction, renal failure, proteinuria, interstitial nephritis.

Disorders of the genital organs and breast

Infrequently – impaired potency.

Laboratory abnormalities

Uncommon – 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 “liver” transaminases and bilirubin concentration.

A symptom complex is described – fever, myalgia/myositis, arthralgia/arthritis, vasculitis, serositis, eosinophilia, leukocytosis, increased ESR, positive test for antinuclear antibodies.

Interaction

Enalapril

Concomitant use is not recommended

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

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

Concomitant use with caution

Thiazide or loop diuretics.

Previous treatment with diuretics in high doses may, at the beginning of enalapril therapy, lead to a decrease in blood volume and contribute to the development of arterial hypotension (see section Special instructions). The hypotensive effect can be reduced by discontinuing the diuretic, increasing the intake 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 develop.

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

The hypotensive effect can be additive 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

When used simultaneously with ACE inhibitors, the risk of developing renal dysfunction increases.

Allopurinol, procainamide, cytostatics or immunosuppressants

When used simultaneously with ACE inhibitors, the risk of developing hypersensitivity reactions and leukopenia increases.

Hypoglycemic agents

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

Sympathomimetics

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

Antacids

Reduce the bioavailability of ACE inhibitors when used simultaneously.

Sodium aurothymalate

When used simultaneously with the drug gold (sodium aurothymalate) in injection form, patients experienced: “flushes” of blood to the facial skin, nausea, vomiting, as well as arterial hypotension. Arterial hypotension can be regarded as an increase in the effect of ACE inhibitors under the influence of the gold drug.

Hydrochlorothiazide

Concomitant use with caution:

Cholestyramine and colestipol

Concomitant use of anion exchange drugs reduces the absorption of hydrochlorothiazide. Cholestyramine or colestipol, when taken once, binds hydrochlorothiazide and reduces its absorption from the gastrointestinal tract by 85 and 43%, respectively.

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

Glucocorticosteroids, corticotropin (ACTH), amphotericin B (intravenous), carbenocloxone, stimulant type laxanthins

When 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 contribute to the appearance 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 the 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 antiarrhythmics, antipsychotics (neuroleptics) and other drugs known to cause torsades de pointes.

Amines that have a vasoconstrictor effect (epinephrine)

A decrease in the response to vasoconstrictor amines is possible, although not so pronounced as to preclude their combined use with hydrochlorothiazide.

Non-depolarizing muscle relaxants (tubocurarine chloride)

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

Amantadine

Thiazides may increase the risk of side effects from amantadine.

Antigout drugs (probenecid, sulfinpyrazone, allopurinol)

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

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

Other types of interaction:

Laboratory indicators

Due to their effect on calcium metabolism, thiazides may distort the results of studies 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 caused by ACE inhibitors, therefore the combined use of Berlipril Plus and lithium preparations is not recommended. If such a combination is still necessary, then careful monitoring of serum lithium concentrations is also necessary.

Laboratory indicators

Thiazides can reduce protein-bound iodine levels 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 hypotensive effect of ACE inhibitors and diuretics. In addition, there are reports that the effects of NSAIDs and ACE inhibitors, which increase serum potassium levels, may be additive, while renal function may be reduced. The corresponding effects are reversible and they develop in patients with existing renal impairment. In rare cases, acute renal failure may develop, especially in patients with impaired renal function (elderly or dehydrated patients).

Ethanol

Strengthens the hypotensive effect of ACE inhibitors and hydrochlorothiazide.

Trimethoprim

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

Overdose

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

The most common symptoms of 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, with concomitant use of cardiac glycosides or antiarrhythmic drugs, aggravation of arrhythmia due to hypokalemia.

Treatment: is symptomatic and supportive. Strict medical supervision is necessary, 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 symptoms. Within 30 minutes after taking the drug, measures can be taken to prevent its absorption from the gastrointestinal tract (gastric lavage, use of adsorbents and sodium sulfate).

If there is a pronounced decrease in blood pressure, the patient should be placed in a horizontal position with legs elevated; resolve the issue of using drugs that increase blood volume (intravenous infusion of 0.9% sodium chloride solution). The administration of angiotensin II is effective.

Bradycardia or severe vagal reactions should be treated with atropine; It is possible to use an artificial pacemaker.

Enalaprilat can be removed from the systemic circulation by hemodialysis.

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

Storage conditions

Store at a temperature not exceeding 30°C.

Shelf life

3 years.

Manufacturer

Berlin-Chemie AG, Germany