Description
Release form
Tablets.
Packing
In a blister pack of 10 tablets. There are 3 blisters in the package.
Pharmacological action
Berlipril plus is a combination drug, consisting of enalapril – an angiotensin converting enzyme (ACE) inhibitor and hydrochlorothiazide – thiazide diuretic, which potentiate each other’s action, and their antihypertensive effect is summarized.
enalapril
enalapril inhibits the enzyme that catalyzes the conversion of angiotensin I to angiotensin II – a peptide with a vasoconstrictor effect, while the vasoconstrictor activity is weakened and aldosterone secretion decreases, which can lead to an increase in serum potassium and simultaneously excretion.
The elimination of the negative inverse effect of angiotensin II on renin secretion leads to the 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 position and in the lying position, without a significant increase in heart rate (HR).
Hydrochlorothiazide
Hydrochlorothiazide disrupts the reabsorption of sodium, chlorine and water in the renal tubules. It increases the excretion of potassium, magnesium, bicarbonates, retains calcium ions in the body. The diuretic effect develops 2 hours after ingestion of hydrochlorothiazide inside, reaches a maximum after 4 hours and lasts up to 12 hours. It reduces high blood pressure.
With the simultaneous use of enapapril and hydrochlorothiazide, potassium losses associated with the action of a diuretic are reduced, thereby preventing the development of hypokalemia.
Indications
Essential hypertension of the I-II degree (to patients who are shown combination therapy or with insufficient effectiveness of enalapril monotherapy).
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 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 impaired liver function (more than 9 points on the Child-Pugh scale).
Severe impairment of renal function (CC less than 30 ml / min).
Bilateral renal artery stenosis or stenosis of a single kidney artery (risk of developing renal failure).
Condition after a recent kidney transplant (no experience with the drug).
Pregnancy.
Lactation.
Age up to 18 years (efficacy and safety of the drug have not been established).
Caution:
Impaired water-electrolyte balance, decreased circulating blood volume (BCC), including diarrhea, vomiting.
Coronary heart disease (CHD).
Severe cerebrovascular disease, including cerebrovascular insufficiency.
Chronic heart failure.
Severe systemic diseases of the connective tissue, including: Systemic lupus erythematosus.
Scleroderma.
Inhibition of bone marrow hematopoiesis.
Stenosis of the aortic orifice with impaired hemodynamics or other obstruction of the outflow of blood from the left ventricle.
Impaired liver function (less than 9 Child-Pugh scores) because of the risk of developing hepatic coma.
Chronic renal failure (CC more than 30 ml / min).
Patients undergoing hemodialysis treatment.
Primary aldosteronism.
Diabetes mellitus.
Salt-limited diet.
Old age.
Hyperkalemia.
Use during pregnancy and lactation
The use of Berlipril plus during pregnancy is not recommended. In the case of planning or diagnosing pregnancy during therapy with Berlipril plus, the drug must be discontinued as soon as possible.
ACE inhibitors can cause illness or death in 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 a negative effect on the fetus and newborn, which manifested itself in the form of arterial hypertension, renal failure, hyperkalemia, and / or hypoplasia of the skull bones. Perhaps the development of oligohydramnios, apparently due to impaired renal function of the fetus. This can lead to limb contracture, deformations of the bones of the skull, including its facial part, and hypoplasia of the lungs.
The use of diuretics during pregnancy is not recommended, as it can cause fetal and newborn jaundice, 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 when 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, penetrating the placental barrier, can be removed from the blood of a newborn using peritoneal dialysis with some beneficial therapeutic effect, and theoretically can be removed by exchange blood transfusion.
Enalapril and thiazides are excreted in breast milk, so if necessary, use during lactation, breastfeeding while taking Berlipril plus should be discontinued. A relationship was also established between the use of thiazides during lactation and the reduction or even suppression of lactation, hypokalemia, as well as the occurrence of hypersensitivity to sulfonamide derivatives.
Specific guidance
Effect on vehicle driving ability and driving mechanisms
Effect of Berlipril plus on vehicle driving ability and operating mechanisms has not been specifically studied, therefore, caution should be exercised when driving vehicles and activities during treatment with Berlipril plus dangerous activities requiring increased concentration of attention and speed of psychomotor reactions.
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,
carboxymethyl starch sodium (type A) 8.5 mg,
silicon dioxide colloidal 3.5 mg,
magnesium 2.0 mg,
dye iron oxide yellow (E 172) 0.5 mg.
Dosage and administration of
Berlipril plus tablets are taken orally once a day (in the morning), regardless of food intake, with plenty of fluids.
Initial therapy with Berlipril plus may develop symptomatic arterial hypotension, which occurs more often in patients with impaired water-electrolyte balance due to prior diuretic therapy. The intake of diuretics should be stopped 2-3 days before the start of therapy with Berlipril plus.
Adults: The recommended dose is 1 tablet of Berlipril plus 1 time per day.
Elderly patients (over 65 years of age): in elderly patients with normal renal function (CC more than 90 ml / min), dosage adjustment is not required.
Application in special clinical cases
In patients with CC more than 30 ml / min, but less than 80 ml / min, Berlipril plus should be used only after preliminary selection of doses of each component.
In severe renal impairment (CC less than 30 ml / min), the use of the drug is contraindicated.
Side effects of
Possible side effects when using Berlipril plus, as monotherapy with the active ingredients alone, are listed below in descending incidence rate:
Often -> 1/100, srdl 1/1000,
Rarely -> 1/10000,
Very rare –
There is no correlation between the incidence of side effects and the gender or age of patients.
Disturbances from the nervous system
Often – headache, systemic dizziness, increased fatigue.
Infrequently – drowsiness or insomnia, depression, paresthesia, irritability, confusion, tinnitus, disturbance of accommodation, change in taste perception, asthenia.
Disorders from the cardiovascular system
Often – a pronounced decrease in blood pressure regardless of body position.
Infrequently – 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).
Infrequently – dyspnea, sinusitis, rhinitis.
In some cases – bronchospasm, stomatitis, glossitis, pulmonary edema, interstitial pneumonia.
Disorders of the gastrointestinal tract / liver and biliary tract
Uncommon – nausea, vomiting, abdominal pain, indigestion, dry mouth, diarrhea, pancreatitis, constipation, flatulence, anorexia.
In some cases, hepatitis and intestinal obstruction.
Very rare – reported the development of angioedema of the intestine associated with the use of ACE inhibitors, including enalapril.
Disorders of the skin
Infrequently – itching, rash, dry skin.
Rarely – angioedema of the face, limbs, lips, tongue, glottis and / or larynx, increased sweating, photosensitivity.
Very rarely – Stevens-Johnson syndrome.
Disorders of the musculoskeletal system
Infrequently – muscle cramps and pain.
Disorders of the kidneys and urinary tract
Infrequently – impaired renal function, renal failure, proteinuria, interstitial nephritis.
Violations of the genitals and mammary gland
Infrequently – a violation of potency.
Abnormalities in laboratory parameters
Infrequently – hypercholesterolemia, hyperglycemia, hyperlipidemia, hypokalemia, hyperkalemia, hyperuricemia, hyponatremia, hypochloremia, hypercalcemia, hypomagnesemia, increased serum creatinine, hematogen, and urea.
Rarely – increased activity of hepatic transaminases and bilirubin concentration.
The symptom complex is described – fever, myalgia / myositis, arthralgia / arthritis, vasculitis, serositis, eosinophilia, leukocytosis, an increase in ESR, a positive test for antinuclear antibodies.
Drug Interactions
Enalapril
Concomitant use is not recommended
Potassium-sparing diuretics (spironolactone, triamteren, amiloride) or potassium-containing salts, potassium supplements.
With simultaneous use with ACE inhibitors, the development of hyperkalemia is possible. 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 serum potassium and electrocardiograms.
Concomitant use with caution
Thiazide or loop diuretics.
Prior treatment with high-dose diuretics can, at the beginning of enalapril therapy, lead to a decrease in BCC and contribute to the development of arterial hypotension (see Special instructions). The antihypertensive effect can be reduced if you stop the diuretic, increase the intake of fluids or salts in the body, or start 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 antihypertensive effect can be summed up or potentiated. Caution is required when treating with nitroglycerin in various dosage forms and with other nitrates or other vasodilators.
cimetidine
Increased risk of collapse.
Cyclosporine
When used concurrently with ACE inhibitors, the risk of developing renal dysfunction increases.
Allopurinol, procainamide, cytostatics or immunosuppressants
slow calcium channel blockers)
The antihypertensive effect can be summed up or potentiated. Caution is required when treating with nitroglycerin in various dosage forms and with other nitrates or other vasodilators.
cimetidine
Increased risk of collapse.
Cyclosporine
When used concurrently with ACE inhibitors, the risk of developing renal dysfunction increases.
Allopurinol, procainamide, cytostatics or immunosuppressants
slow calcium channel blockers)
The antihypertensive effect can be summed up or potentiated. Caution is required when treating with nitroglycerin in various dosage forms and with other nitrates or other vasodilators.
cimetidine
Increased risk of collapse.
Cyclosporine
When used concurrently with ACE inhibitors, the risk of developing renal dysfunction increases.
Allopurinol, procainamide, cytostatics or immunosuppressants
Cyclosporine
When used concurrently with ACE inhibitors, the risk of developing renal dysfunction increases.
Allopurinol, procainamide, cytostatics or immunosuppressants
Cyclosporine
When used concurrently with ACE inhibitors, the risk of developing renal dysfunction increases.
Allopurinol, procainamide, cytostatics or immunosuppressants
When used 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 hypoglycemic agents for oral administration (for example, sulfonylurea derivatives) in patients with diabetes mellitus. In these cases, with the simultaneous use of ACE inhibitors, a dose reduction of a hypoglycemic agent may be required.
Sympathomimetics
May weaken the hypotensive effect of ACE inhibitors. To confirm the hypotensive effect of such patients should be under close medical supervision.
Antacids
Reduce the bioavailability of ACE inhibitors with simultaneous use.
Sodium aurotimalate
When used simultaneously with a gold preparation (sodium aurotimalate) in an injectable form, the following were observed: flushing 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 a gold preparation.
Hydrochlorothiazide
Concomitant use with caution:
Colestyramine and colestipol
Concomitant use of anion exchange drugs reduces the absorption of hydrochlorothiazide. When taken once, colestyramine or colestipol binds hydrochlorothiazide and reduces its absorption from the gastrointestinal tract by 85 and 43%, respectively.
Diuretics derived from sulfonamides should be taken at least 1 hour before or 4-6 hours after taking these drugs.
glucocorticosteroids, corticotropin (ACTH), amphotericin B (intravenously), carbenocloxone, stimulant-type laxanthines
While taking them 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 while using thiazide diuretics.
Cardiac glycosides
Hypokalemia or hypomagnesemia caused by thiazides contributes to arrhythmias due to cardiac glycosides.
Drugs that can cause pirouette type arrhythmia (pirouette is a special form of polymorphic ventricular tachycardia with a wave, screw, or vein configuration of the ventricular complexes in combination with an increase or decrease in the amplitude of the teeth of the QRS complex, which can result in ventricular fibrillation or asystole)
Because of the risk of hypokalemia, caution is required when using hydrochlorothiazide with some antiarrhythmic, antipsychotic (antipsychotics) and other drugs that are known to cause pirouette arrhythmias.
Amines with vasoconstrictor action (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)
May increase sensitivity to muscle relaxants when used together with hydrochlorothiazide.
Amantadine
Thiazides may increase the risk of side effects of amantadine.
Anti-gout medications (probenecid, sulfinpyrazone, allopurinol)
It may be necessary to adjust the dose of a hypouricemic drug (increasing the dose of probenecid or sulfinpyrazone), since hydrochlorothiazide can increase the concentration of uric acid in blood serum.
Concomitant use with thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.
Other interactions:
Laboratory readings
Due to the effect on calcium metabolism, thiazides can distort the result of a study of parathyroid function.
Enalapril / hydrochlorothiazide in combination
Concomitant use is not recommended
Lithium
Concomitant use with thiazide diuretics may increase the already increased risk of lithium intoxication due to ACE inhibitors, therefore, the combined use of Berlipril plus and lithium preparations is not recommended. If such a combination is nevertheless necessary, careful monitoring of the serum lithium concentration is also necessary.
Laboratory findings
Thiazides can reduce 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 inhibitors (COX-2))
NSAIDs may weaken the hypotensive effect of ACE inhibitors and diuretics. In addition, there are reports that the effects of NSAIDs and ACE inhibitors that increase serum potassium can be summarized, while kidney function may decrease. The corresponding effects are reversible and they develop in patients with existing impaired renal function. In rare cases, acute renal failure may develop – primarily in patients with impaired renal function (elderly or dehydrated patients).
Ethanol
Enhances the hypotensive effect of ACE inhibitors and hydrochlorothiazide.
Trimethoprim
Concomitant use with ACE inhibitors and thiazides increases the risk of hypercalcemia.
Overdose
Symptoms: marked BP, shock, stupor, bradycardia, impaired electro-electrolyte balance and renal failure.
The most common symptoms of a hydrochlorothiazide overdose are nausea and drowsiness. Hydrochlorothiazide overdose is associated with loss of electrolytes (hypokalemia, hypochloremia) and dehydration (due to increased diuresis). Hypokalemia can lead to muscle cramps and / or concomitant cardiac glycosides or antiarrhythmic drugs to aggravate the course of arrhythmia due to hypokalemia.
Treatment: It is symptomatic and supportive. Strict medical monitoring is required, preferably in an intensive care unit / ward. Regular monitoring of serum electrolytes and creatinine is required.
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, use of adsorbents and sodium sulfate).
With a marked decrease in blood pressure, the patient should be given a horizontal position with his legs elevated to decide on the use of drugs that increase BCC (intravenous infusion 0, 9% sodium chloride solution). Effective administration of angiotensin II.
Bradycardia or pronounced vagal reactions should be eliminated with atropine, possibly using an artificial rhythm driver.
Enalaprilat can be removed from the systemic circulation by hemodialysis.
ACE inhibitors are dialysable, however, high-permeability polyacrylonitrile membranes should be avoided (see Special Instructions).
Storage conditions
Do not store above 30 ° C.
Shelf life
3 years.
Deystvuyushtee substance
Gidrohlorotiazid, nalapril
Dosage form
tablets
Possible product names
BERLIPRIL PLUS 0.025 + 0.01 N30 TABLE
BERLIPRIL PLUS 25G. + 10G. No. 30 TAB. / BERLIN-HEMI /
Berlipril plus 25mg + 10mg Tab. X30
Berlipril plus tab 10mg + 25mg N30
Berlipril plus tab 25mg + 10mg x 30
