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 grade I-II (patients who are indicated for combination therapy or when enalapril monotherapy is not effective enough).

Active ingredient

Composition

1 tablet contains:

Active substances

Enalapril maleate 10 mg.

Hydrochlorothiazide25 mg.

Excipients

Lactose monohydrate 139.5 mg,

magnesium carbonate 25.0 mg,

gelatin 6.0 mg,

Sodium carboxymethyl starch (type A) 8.5 mg,

silicon dioxide colloid 3.5 mg,

magnesium stearate 2.0 mg,

iron oxide yellow dye (E 172) 0.5 mg.

How to take, the dosage

Berlipril plus tablets are taken orally once daily (in the morning), regardless of meals, with plenty of fluid.

In the beginning of therapy with berlipril plus symptomatic arterial hypotension may develop, which occurs more frequently in patients with water-electrolyte imbalances due to previous therapy with diuretics. Diuretics should be discontinued 2 to 3 days before therapy with berlipril plus.

Adults: The recommended dose is 1 tablet of Berlipril plus once daily.

Elderly patients (over 65 years): In elderly patients with normal renal function (CKG greater than 90 ml/min) no dosing adjustment is necessary.

Persons with a CKR greater than 30 mL/min but less than 80 mL/min should use Berlipril plus only after adjusting doses of each component.

In patients with severe renal impairment (CKG less than 30 ml/min) the use of the drug is contraindicated.

Interaction

Enalapril

Combined use is not recommended

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

In concomitant use with ACE inhibitors, development of hyperkalemia is possible. If concomitant use of these drugs is still indicated due to diagnosed hypokalemia, they should be used with caution, with regular monitoring of serum potassium and electrocardiograms.

Simultaneous use with caution

Tiazide or “loop” diuretics.

Pre-treatment with high-dose diuretics may decrease the BOD at the start of therapy with enalapril and contribute to arterial hypotension (see Cautionary Note). The hypotensive effect can be reduced if the diuretic is stopped, if fluid or salt intake is increased, or if therapy is initiated with low doses of enalapril.

The drugs for general anesthesia

When used with ACE inhibitors may lead to worsening Orthostatic Hypotension.

Drugs/tricyclic antidepressants/psychotropic drugs/barbiturates

The development of orthostatic hypotension may occur.

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

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

Cimetidine

An increased risk of collapse.

Cyclosporine

Concomitant use with ACE inhibitors increases the risk of renal dysfunction.

Allopurinol, procainamide, cytostatics or immunosuppressants

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

Hypoglycemic agents

In rare cases ACE inhibitors may increase the hypoglycemic effect of insulin and oral hypoglycemic agents (e.g., sulfonylurea derivatives) in diabetic patients. In these cases, concomitant use of ACE inhibitors may require reducing the dose of hypoglycemic agents.

Sympathomimetics

May weaken the hypotensive effect of ACE inhibitors. These patients should be under close medical supervision to confirm the hypotensive effect.

Antacids

Antacids decrease the bioavailability of ACE inhibitors when used concomitantly.

Sodium aurotimalate

Patients have been observed to have “flushes” of blood to the face, nausea, vomiting, and arterial hypotension when used concomitantly with the gold drug (sodium aurotimalate) in injectable form. Arterial hypotension can be regarded as a strengthening of the effect of ACE inhibitors under the influence of the gold drug.

Hydrochlorthiazide

Simultaneous use with caution:

Colestyramine and colestipol

Concomitant use of anion-exchange drugs decreases the absorption of hydrochlorothiazide. Colestiramine or colestipol when taken alone 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 h before or 4-6 h after taking these drugs.

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

When they are taken simultaneously with hydrochlorothiazide, increased electrolyte loss (in particular, development of hypokalemia) may occur.

Calcium salts

Elevated serum calcium concentrations may increase due to reduced calcium excretion when used concomitantly with thiazide diuretics.

Cardiac glycosides

Hypokalemia or hypomagnesemia caused by thiazides contribute to cardiac glycoside-induced arrhythmias.

The drugs can cause pirouette arrhythmias (“pirouette” is a particular form of polymorphic ventricular tachycardia with wave-, spiral-, or spindle-shaped configurations of ventricular complexes combined with an increase or decrease in amplitude of the QRS teeth, which can end in ventricular fibrillation or asystole)/p>

Because of the risk of hypokalemia, caution is required when using hydrochlorothiazide concomitantly with some antiarrhythmic, antipsychotic (neuroleptic) and other drugs that are known to cause pirouette-type arrhythmias.

Vasoconstrictor amines (epinephrine)

The response to vasoconstrictor amines may be reduced, although not so pronounced as to preclude their combined use with hydrochlorothiazide.

Myorelaxants of the non-depolarizing type (tubocurarine chloride)

Possible increased sensitivity to myorelaxants when combined with hydrochlorothiazide.

Amantadine

Tiazides may increase the risk of amantadine side effects.

Antipodagric agents (probenecid, sulfinpyrazone, allopurinol)

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

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

Other interactions:

Laboratory findings

Because of the effect on calcium metabolism, thiazides may distort the results of parathyroid function studies.

Enalapril/Hydrochlorothiazide in combination

Simultaneous use is not recommended

Lithium

The simultaneous use is not recommended. Concomitant use with thiazide diuretics may increase the already increased risk of lithium intoxication associated with ACE inhibitors, so concomitant use of Berlipril plus with lithium preparations is not recommended. If such a combination is nevertheless necessary, careful monitoring of serum lithium concentrations is also necessary.

Laboratory measures

The thiazides may decrease protein-bound iodine levels without causing symptoms of thyroid dysfunction.

Simultaneous 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 impair the hypotensive effects of ACE inhibitors and diuretics. In addition, there are reports that the effects of NSAIDs and ACE inhibitors that increase serum potassium levels may add up, while renal function may decrease. The corresponding effects are reversible and develop in patients with existing renal dysfunction. Rarely, acute renal failure may develop, especially in patients with impaired renal function (elderly or dehydrated patients).

Ethanol

Ethanol enhances the hypotensive effect of ACE inhibitors and hydrochlorothiazide.

Trimethoprim

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

Special Instructions

Impact on driving and operating machinery

The effect of the drug Berlipril plus on driving and operating machinery has not been specifically studied, so during the treatment with Berlipril plus caution should be exercised while driving vehicles and engaging in potentially dangerous activities that require increased concentration and quick psychomotor reactions.

Contraindications

Age under 18 years (effectiveness and safety of drug have not been established).

Cautions:

Side effects

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

Frequent – >1/100,

Infrequent – >1/1000,

Rare – >1/10000,

Very rare –

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

Nervous system disorders

Often – headache, systemic dizziness , increased fatigue.

Infrequent – somnolence or insomnia, depression, paresthesia, increased excitability, confusion, tinnitus, accommodation disorder, change in taste perception, asthenia.

Cardiovascular system disorders

Often – pronounced BP decrease regardless of body position.

Infrequent – arrhythmias, loss of consciousness.

In rare cases – tachycardia, palpitations, angina pectoris, chest pain, myocardial infarction, cerebral circulatory disorders, stroke.

Respiratory system, chest organ disorders

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

Infrequent – dyspnea, sinusitis, rhinitis.

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

Gastrointestinal tract/liver and biliary tract disorders

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

In isolated 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

Infrequent – skin itching, rash, dry skin.

Rarely – angioedema of the face, extremities, lips, tongue, vocal cleft and/or larynx, excessive sweating, photosensitization.

Very rarely – Stevens-Johnson syndrome.

Motor system disorders

Infrequent – muscle cramps and pain.

Repnal and urinary tract disorders

Infrequent – renal function disorders, renal failure, proteinuria, interstitial nephritis.

Disorders of reproductive organs and mammary gland

Infrequent – potency disorders.

Disorders of laboratory parameters

. In rare cases – hypercholesterolemia, hyperglycemia, hyperlipidemia, hypokalemia, hyperkalemia, hyperuricemia, hyponatremia, hypochloremia, hypercalcemia, hypomagnesaemia, increase of serum creatinine, blood urea and liver function tests, decrease of hemoglobin and hematocrit.

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

The symptom complex is described as fever, Myalgia/myositis, arthralgia/arthritis, vasculitis, serositis, eosinophilia, leukocytosis, increased sed rate , positive antinuclear antibody test.

Overdose

Symptoms: marked BP decrease, shock, stupor, bradycardia, electrolyte-water 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 may lead to muscle cramps and/or in concomitant administration of cardiac glycosides or antiarrhythmic drugs to aggravation of the course of arrhythmia due to hypokalemia.

Treatment: is symptomatic and supportive in nature. Strict medical control is necessary, preferably in an intensive care unit. Regular monitoring of serum electrolytes and creatinine is necessary.

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

In case of significant decrease of blood pressure the patient should be placed in a horizontal position with elevated legs, and the use of agents that increase the blood circulation (intravenous infusion of 0.9% sodium chloride solution) should be considered. Angiotensin II administration is effective.

Bradycardia or marked vagus reactions should be eliminated with atropine; an artificial pacemaker may be used.

Enalaprilat may be removed from the systemic circulation by hemodialysis.

The ACE inhibitors are amenable to dialysis, but high-flow polyacrylonitrile membranes should be avoided (see section Dangerous Instructions).

Pregnancy use

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 soon as possible.

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

The use of ACE inhibitors during this period has been accompanied by adverse effects on the fetus and the newborn in the form of arterial hypertension, renal failure, hyperkalemia, and/or skull bone hypoplasia. Oligohydramnios may develop, apparently due to impaired fetal renal function. This can lead to limb contractures, cranial bone deformities, including the facial portion, and pulmonary hypoplasia.

The use of diuretics during pregnancy is not recommended because they can cause fetal and neonatal jaundice, thrombocytopenia, and possibly other side effects seen 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 use of the drug during pregnancy is deemed necessary, periodic ultrasound examinations should be performed to evaluate the intra-amniotic space. Newborns whose mothers have taken the drug should be closely monitored with respect to the development of arterial hypertension, oliguria, and hyperkalemia. Enalapril, which penetrates the placental barrier, can be removed from the blood of the newborn by peritoneal dialysis with some favorable therapeutic effect, and can theoretically be removed by exchange blood transfusion.

Enalapril and thiazides are excreted with the breast milk, so breastfeeding should be discontinued during lactation while taking Berlipril plus. There was also found a correlation between thiazides use during lactation and decrease or even suppression of lactation, hypokalemia, and also occurrence of hypersensitivity to sulphonamide derivatives.

Similarities