Berlipril Plus - instructions for use, dose, side effects, contraindications

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 colloidal - 3.5 mg, magnesium stearate 2.0 mg, iron oxide color yellow (E 172) 0.5 mg.

Description:Round tablets of light yellow color with flat surfaces, facets, with one-sided risk.

Pharmacotherapeutic group:antihypertensive combination drug (diuretic + angiotensin-converting enzyme inhibitor).

ATX: & nbsp

C.09.B.A.02 Enalapril in combination with diuretics

Pharmacodynamics: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 summarized.

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 a decrease in aldosterone secretion, which may lead to an increase in serum potassium content with the simultaneous elimination of sodium and liquid. Elimination of negative reverse effect of angiotensin II on renin secretion leads to activation of renin of blood plasma. The mechanism of lowering enalapril blood pressure (BP) is based on the primary inhibition 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 that has 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 in both the "standing" and "lying" positions, without significantly increasing the heart rate (heart rate).

Hydrochlorothiazide disrupts the reabsorption of sodium, chlorine and water in the renal tubules. Increases the excretion of potassium, magnesium, hydrocarbonates, delays calcium ions in the body. Diuretic effect develops 2 hours after taking hydrochlorothiazide inside, reaches a maximum after 4 hours and lasts up to 12 hours. Reduces elevated blood pressure.

With the simultaneous use of enalapril and hydrochlorothiazide, there is a decrease in potassium losses associated with the action of the diuretic, thereby preventing the development of hypokalemia.

Pharmacokinetics:

The combined use of enalapril and hydrochlorothiazide has virtually no effect on the bioavailability of each of the active substances alone.

Enalapril is a prodrug, its pharmacological activity is its metabolite - enalaprilate.

Suction. After oral administration enalapril quickly and completely absorbed from the gastrointestinal tract (GIT). In organism enalapril is almost completely transformed into enalaprilate, which has a pronounced pharmacological activity. The maximum concentration (C_m_Oh) enalaprilata in the blood serum is achieved 3-4 hours after ingestion. Simultaneous food intake does not affect the full suction.

Distribution. Communication with plasma proteins is less than 50 %.

Metabolism. The main metabolite is enalaprilate.

Excretion. Enalaprilat is excreted mainly through the kidneys. After taking

Inside enalapril the half-life of enalaprilata is about 11h. In patients with

the renal excretion of enalaprilate is slowed down.

Enalaprilat is amenable to dialysis. Hemodialysis reduces the concentration of enalaprilate

in the blood plasma by about 46%. Enalaprilat it is also possible to remove from the plasma

blood with peritoneal dialysis.

Hydrochlorothiazide

Suction. After oral administration hydrochlorothiazide absorbed by 60-80%. Absorption depends on the duration of passage in the intestine (it increases with a slow passage, for example, with simultaneous intake with food). Time to reach the maximum concentration (TC_m_Oh) in the blood plasma after ingestion of hydrochlorothiazide at a dose of 12.5 mg is 1.5-4 hours, in a dose of 25 mg is 2-5 hours. The concentration of hydrochlorothiazide in the blood plasma is characterized by linearity with respect to the accepted dose, but the relationship between the concentration of hydrochlorothiazide in blood plasma and the severity of arterial hypotension is not established.

Distribution. Thiazides are characterized by extensive distribution in body fluids and in large amounts (92%) bind to blood plasma proteins, in particular with albumin. This leads to a lower renal clearance, compared to the original compounds, and, thus, to a longer duration of action. The relative volume of distribution is 0.5-1.1 l / kg. Hydrochlorothiazide passes through the placental barrier, but does not penetrate the blood-brain barrier.

Metabolism and excretion. Hydrochlorothiazide is not metabolized and almost completely (more than 95%) is excreted by the kidneys unchanged.In elderly patients and with renal dysfunction, clearance of hydrochlorothiazide significantly decreases, which leads to a significant increase in its concentration in blood plasma. In patients with cirrhosis of the liver, there is no change in the pharmacokinetics of hydrochlorothiazide. Penetrates through the placenta, but does not penetrate the blood-brain barrier.

Indications:Essential hypertension I-II degree (patients who are shown combined therapy or in case of insufficient effectiveness of monotherapy with enalapril).

Contraindications:

- Hypersensitivity to enalapril or other ACE inhibitors, hydrochlorothiazide or other derivatives of sulfonamides or other components of the drug (see Composition);

- Lactase deficiency, hereditary intolerance, lactose, 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 who are on dialysis treatment (efficacy and safety of the drug have not been studied);

- pronounced violations of the liver (more than 9 points on the scale Child-Pugh);

- severe renal dysfunction (CC less than 30 ml / min);

- bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney (risk of developing renal failure);

- a condition after a recent kidney transplantation (no experience with the drug);

- Pregnancy;

- lactation period;

- age to 18 years (efficacy and safety of the drug are not established).

Carefully:

- Violation of the water-electrolyte balance, decrease in the volume of circulating blood (BCC) (including diarrhea, vomiting);

- Ischemic heart disease (CHD);

- expressed cerebrovascular diseases (including cerebral circulatory insufficiency);

- Chronic heart failure;

- severe systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma);

- oppression of bone marrow hematopoiesis;

- Stenosis of the aortic aorta with a violation of the parameters of hemodynamics or other obstacles to outflow of blood from the left ventricle;

- impaired liver function (less than 9 on the Child-Pugh scale) (risk of hepatic coma);

- chronic renal failure (QC more than 30 ml / min); patients undergoing hemodialysis treatment; primary aldosteronism;

- diabetes;

- diet with restriction of consumption of table salt;

- elderly age;

hyperkalemia.

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 should be discontinued as soon as possible. ACE inhibitors can cause disease or death of the fetus or newborn when applied 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 the newborn, which manifested itself in the form of arterial hypertension, renal failure, hyperkalemia, and / or hypoplasia of the skull bones. Perhaps the development of oligohydramnion, apparently due to impaired fetal kidney function. This can lead to limb contracture, deformation of the skull bones, including its facial part, and lung hypoplasia.

The use of diuretics during pregnancy is not recommended because they can cause jaundice 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 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 through the placental barrier, can be removed from the blood of the newborn with peritoneal dialysis with some favorable therapeutic effect, and can theoretically be removed by exchange blood transfusion.

Enalapril and thiazides are excreted in breast milk, so if they are needed during lactation, breastfeeding should be discontinued at the time of taking Berlipril® Plus.Also, the relationship between the use of thiazides during lactation and the reduction or even suppression of lactation, hypokalemia, as well as the emergence of hypersensitivity to sulfonamide derivatives.

Dosing and Administration:

Berlipril ® Plus tablets are taken orally once a day (in the morning) regardless of the meal, with plenty of liquid.

Adults RThe recommended dose is 1 tablet of Berlipril® plus once a day.

At the beginning of therapy with Berlipril® Plus, symptomatic arterial hypotension may occur, which is more likely to occur in patients with impaired water-electrolyte balance due to previous diuretic therapy. Reception of diuretics should be stopped 2-3 days before the beginning of therapy with Berlipril® Plus.

Elderly patients (over 65 years of age)

In elderly patients with normal renal function (KK more than 90 ml / min), correction of the dosing regimen is not required.

In patients with QC greater than 30 ml / min, but less than 80 ml / min, Berlipril ® Plus should only be used after pre-adjusting the doses of each component.With severe renal dysfunction (KK less than 30 ml / min), the use of the drug is contraindicated (see section Contraindications).

Side effects:

Possible side effects with the use of Berlipril® plus, as in monotherapy with the active components alone, are shown below in the descending incidence frequency: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000, <1/1000), very rarely (<1/10000), including individual messages. Correlations of the incidence of side effects with the sex or age of patients are not observed.

Disturbances from the nervous system

Often: headache, systemic dizziness, increased fatigue.

Infrequently: drowsiness or insomnia, depression, paresthesia, increased

excitability, confusion, noise in the ears, disruption of accommodation,

change in taste perception, asthenia.

Disorders from the cardiovascular system

Often: marked 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.

Disturbances from the respiratory system, chest and mediastinal organs

Often: cough (disappears after drug discontinuation). Infrequently: dyspnea, sinusitis, rhinitis.

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

Disturbances from the gastrointestinal tract / liver and bile ducts

Infrequently: nausea, abdominal pain, digestive disorders, dry mucous membranes

membranes of the oral cavity, diarrhea, vomiting, pancreatitis, constipation, flatulence, anorexia.

In some cases - hepatitis and intestinal obstruction.

Very rarely reported on the development of angioedema edema of the intestine,

associated with the administration of ACE inhibitors, including enalapril.

Disturbances from the skin

Infrequently: skin itching, rash, dry skin.

Rarely: angioedema, edema of the face, limbs, lips, tongue, glottis

and / or larynx, increased sweating, photosensitivity.

Rarely: Stevens-Johnson syndrome.

Disorders from the musculoskeletal system

Infrequently: muscle cramps and pain.

Disorders from the kidneys and urinary tract

Infrequently: renal dysfunction; insufficiency, proteinuria, interstitial nephritis.

Violations of the genitals and mammary gland Infrequently: violation of potency.

Laboratory indicators

Infrequently: hypercholesterolemia, hyperglycemia, hyperlipidemia, hypokalemia, hyperkalemia, hyperuricemia, hyponatremia, hypochloremia, hypercalcemia, hypomagnesemia, increased serum creatinine, blood urea and functional hepatic samples, decreased hemoglobin and hematocrit.

Rarely: increased activity of "hepatic" transaminases and bilirubin concentrations.

A symptom complex is described: fever, myalgia / myositis, arthralgia / arthritis, vasculitis, serositis, eosinophilia, leukocytosis, increased erythrocyte sedimentation rate (ESR), positive antinuclear antibody test.

Other: decreased libido, gout, arthralgia.

Overdose:Symptoms: marked decrease in blood pressure, shock, stupor, bradycardia, violation of water-electrolyte balance and renal failure. The most common symptoms of an overdose of hydrochlorothiazide are nausea and drowsiness. Overdosage of hydrochlorothiazide is associated with loss of electrolytes (hypokalemia, hypochloraemia) and dehydration (due to an increase in diuresis).Hypokalemia can lead to muscle cramps and / or simultaneous administration of cardiac glycosides or antiarrhythmic drugs to aggravation of arrhythmia flow due to hypokalemia (see Interactions with Other Drugs).

Treatment: is symptomatic and supportive. Strict medical supervision is required, preferably in a separation / intensive care unit. 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, you can take measures 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; to decide on the use of drugs that increase bcc (intravenous infusion of 0.9% sodium chloride solution). Effectively the introduction of angiotensin II. Bradycardia or severe vagal reactions should be eliminated with atropine; it is possible to use an artificial pacemaker. Enalaprilat can be removed from the systemic circulation by hemodialysis. ACE inhibitors are amenable to dialysis, but the use of high-density polyacrylonitrile membranes should be avoided (see Special instructions).

Interaction:

ENALAPRIL

SIMULTANEOUS APPLICATION NOT RECOMMENDED Potassium-sparing diuretics (spironolactone, triamterene, amiloride) or potassium-containing salts, potassium supplements: when used simultaneously with ACE inhibitors, hyperkalemia may develop. If, as a result of diagnosed hypokalemia, simultaneous application of these drugs is indicated, they should be used with caution, with regular monitoring of serum potassium and electrocardiogram (see section Special instructions).

SIMULTANEOUS APPLICATION WITH CARE

Thiazide or "loop" diuretics: previous treatment with diuretics in

high doses may lead to a decrease in bcc at the beginning of enalapril therapy

promote the development of arterial hypotension (see section Special instructions).

The hypotensive effect can be reduced if the diuretic is canceled, increased

the flow of fluid or salts into the body or start therapy with low doses

enalapril.

Preparations for general anesthesia: when used with ACE inhibitors may lead to aggravation of orthostatic hypotension.

Drugs / tricyclic antidepressants / psychotropic drugs / barbiturates: there may be a development of orthostatic hypotension.

Other antihypertensive drugs (alpha and beta-adrenoblockers, blockers of "slow" calcium channels): the hypotensive effect can be summed up or potentiated. Care is required when treating with nitroglycerin various dosage forms and other nitrates or other vasodilators.

Cimetidine: increased risk of collapse.

Cyclosporine: while concomitant use with ACE inhibitors increases the risk of developing a violation of kidney function.

Allopurinol, procainamide, cytostatics or immunosuppressants: while simultaneous use with ACE inhibitors increases the risk of developing hypersensitivity reactions, leukopenia.

Hypoglycemic agents: In rare cases, ACE inhibitors can increase the hypoglycemic action of insulin,and hypoglycemic agents for oral administration (eg, sulfonylureas) in patients with diabetes mellitus. In these cases, simultaneous use of ACE inhibitors may require a reduction in the dose of hypoglycemic agent.

Sympathomimetics can reduce the hypotensive effect of ACE inhibitors. To confirm the hypotensive effect of such patients should be under careful medical supervision.

Antacids reduce the bioavailability of ACE inhibitors when used simultaneously.

With the simultaneous use of gold (sodium arotomalate) in injectable form, patients experienced "hot flashes" of the blood to the skin of the face, nausea, vomiting, and hypotension. Arterial hypotension can be regarded as an increase in the effect of ACE inhibitors under the influence of the gold preparation.

HYDROCHLOROTHYASIDE

SIMULTANEOUS APPLICATION WITH CARE

Kolestyramine and colestipol: simultaneous intake of anion-exchange drugs reduces the absorption of hydrochlorothiazide. Kolestyramine or colestipol in their single admission are associated hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by 85 and 43%, respectively.

Diuretics, which 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 (intravenously), carbenoxolone, laxanthins of stimulating type: when they are taken together with hydrochlorothiazide, there may be an increase in electrolyte loss (in particular, hypokalemia).

Salts of calcium: 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 occurrence of arrhythmias caused by cardiac glycosides. Medications that can cause piruet-type arrhythmia (pirouette is a special form of polymorphic ventricular tachycardia with a wave, screw or spindle configuration of ventricular complexes in combination with an increase or decrease in the amplitude of the teeth of the complex QRS, which can result in ventricular fibrillation or asystole): caution is necessary because of the risk of developing hypokalemia with the simultaneous use of hydrochlorothiazide with certain antiarrhythmic, antipsychotic (neuroleptics) and other medications known to cause piruet-type arrhythmia.

Amines with vasoconstrictive action (epinephrine): a decrease in the response to vasoconstrictor amines, although not as pronounced, is possible to exclude their use with hydrochlorothiazide. Nondepolarizing muscle relaxants (tubocurarine chloride): it is possible to increase the sensitivity to muscle relaxants when combined with hydrochlorothiazide application.

Amantadine: Thiazides may increase the risk of side effects of amantadine.

Anti-gouty drugs (probenecid, sulfinpirazone, allopurinol): it may be necessary to correct the dose of the hypo-uricemic drug (increasing the dose of probenecid or sulfinpyrazone), since hydrochlorothiazide can increase the concentration of uric acid in the serum. Simultaneous use with thiazide diuretics can increase the frequency of development of hypersensitivity reactions to allopurinol.

OTHER KINDS OF INTERACTION

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

ENALAPRIL / HYDROCHLOROTHYASIDE IN THE COMBINATION SIMULTANEOUS APPLICATION IS NOT RECOMMENDED

Lithium: concomitant use with thiazide diuretics can increase the already high risk of lithium intoxication caused by ACE inhibitors, so the combined use of Berlipril plus and lithium preparations is not recommended. If such a combination is still necessary, careful monitoring of the concentration of lithium in serum is also necessary.

Laboratory indicators: Thiazides can reduce the level of iodine associated with protein without causing symptoms of thyroid dysfunction.

SIMULTANEOUS APPLICATION WITH CARE

Non-steroidal anti-inflammatory drugs (NSAIDs) (including acetylsalicylic acid in a dose > 3 g / day, including cyclooxygenase-2 inhibitors (COX-2)): The use of NSAIDs may reduce the hypotensive effect of ACE inhibitors and diuretics. In addition, there are reports that the effects of NSAIDs and ACE inhibitors that increase potassium levels in the blood serum can be summarized, while kidney function may be reduced.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: simultaneous use with ACE inhibitors and thiazides increases the risk of hypercalcemia.

Special instructions:

ENALAPRIL

During the treatment with Berlipril® Plus, the patient's condition should be monitored regularly, especially at the beginning of treatment. As with other ACE inhibitors, one should keep in mind the possibility of developing symptomatic arterial hypotension (even a few hours after the first dose) in patients with severe chronic heart failure, expressed renal impairment, as well as in patients with water disturbance Electrolyte balance, conditioned by previous therapy with diuretics, diet with restriction of consumption of table salt, diarrhea, vomiting, or on hemodialysis.In patients with ischemic heart disease, severe cerebrovascular disease, stenosis of the aortic aorta with hemodynamic disturbances or other obstructions to outflow of blood from the left ventricle, a significant reduction in blood pressure can lead to myocardial infarction and / or stroke.

Arterial hypotension with severe consequences is rare and transient. Transient arterial hypotension is not a contraindication to further therapy with the drug.

Rarely with the treatment with ACE inhibitors, there is a syndrome that begins with cholestatic jaundice, which progresses to sudden hepatic necrosis, sometimes with a fatal outcome. The mechanism of this syndrome is unclear. Patients who have jaundice or marked increase in the activity of "hepatic" transaminases in treatment with ACE inhibitors should abolish ACE inhibitors and conduct medical surveillance. If a patient with hypertension is treated with diuretics, then, if possible, they should be canceled 2-3 days before starting treatment with Berlipril® plus (because of the risk of developing arterial hypotension).Before the beginning of treatment and during therapy, it is necessary to monitor the kidney function (determine the protein content in the urine with the help of test strips in the first dose of morning urine), tk. proteinuria can occur both in patients with already existing renal dysfunction and in those taking relatively high doses of ACE inhibitors.

In patients with diabetes mellitus receiving treatment with hypoglycemic agents for ingestion or insulin, the first month of treatment with ACE inhibitors should regularly monitor the concentration of glucose in the blood (see section Interactions with Other Drugs). During the treatment with Berlipril® Plus, potassium may be increased in the blood serum, especially in patients with CRF, diabetes mellitus, while using potassium-sparing diuretics, potassium or potassium-containing salt substitutes, as well as in patients taking other drugs that lead to an increase in content potassium in the blood serum (heparin); this effect is usually weakened by thiazide diuretics because of increased excretion of potassium. If the simultaneous use of the above mentioned means is necessary, it is recommended that regular monitoring of potassium in the blood serum (cm.section Interaction with other medicinal products).

There are reports of the development of neutropenia / agranulocytosis, thrombocytopenia and anemia in patients receiving treatment with ACE inhibitors. The risk of neutropenia is likely to depend on the dose and clinical state of the patient. Neutropenia may occur more frequently in patients with impaired renal function, especially if there is concomitant connective tissue disease (systemic, lupus erythematosus, scleroderma) or in the treatment of immunosuppressants, allopurinol or procainamide, and a combination of these risk factors. Some of these patients developed severe infectious diseases, in which in some cases there was no response to intensive antibiotic therapy.

When enalapril is used in such patients, it is desirable before the treatment, every 2 weeks in the first three months of treatment and then regularly monitor blood leukocytes and a detailed blood test. It should be strongly recommended that the patient be informed of any symptom of an infectious disease (sore throat, fever); In this case, the leukocyte blood count should be monitored.If suspected or detected neutropenia (less than 1 000 / mm³), which is reversible, it is necessary to cancel the drug Berlipril® Plus and other concomitant drugs (see section Interactions with Other Drugs).

Before the planned surgical procedure, the anesthetist should be informed that the patient is receiving Berlipril® plus, since there is a risk of developing arterial hypotension during surgical intervention under general anesthesia. If the ACE inhibitors can not be withdrawn, BCC should be carefully monitored. It should be borne in mind that in the treatment with Berlipril® plus in patients who are shown hemodialysis or other blood filtration, anaphylactoid reactions may develop (facial edema, hyperemia, marked decrease in blood pressure, dyspnea) due to the use of filter membranes with high throughput the ability, consisting of polyacrylonitrile (high-flow membrane). It is recommended to use other types of filter membranes for dialysis or alternative antihypertensive therapy with a drug from another pharmacotherapeutic group.

During the period of desensitizing therapy to aspen or bee venom in patients receiving the drug Berlipril® Plus, it is possible to develop hypersensitivity reactions that are life threatening. To avoid the corresponding reactions, prior to each session of desensitizing therapy, the therapy with ACE inhibitors should be temporarily discontinued.

If angioedema develops in the lips, face, neck (usually in the first weeks of treatment with ACE inhibitors), Berlipril® Plus should be immediately withdrawn and continued with an antihypertensive drug from another pharmacotherapeutic group. However, in rare cases, severe angioedema with involvement of the tongue, glottis or larynx can also develop after long-term use of ACE inhibitors and lead to death. In this case, emergency measures should be taken, including at least (but not necessarily this limited): immediate subcutaneous injection of 0.3-0.5 ml of epinephrine (adrenaline) 1: 1000 solution or slow intravenous injection of epinephrine 1 mg / ml ( dilute according to the instructions!) under close supervision of the ECG and blood pressure.The patient should be hospitalized and observed for at least 12-24 hours (until the symptoms disappear completely).

HYDROCHLOROTHYASIDE

In patients with kidney disease, thiazides can aggravate azotemia. In patients with impaired renal function hydrochlorothiazide can emulate. With the progression of renal failure, characterized by an increase in the total blood in the blood of nitrogen without increasing the protein nitrogen, should consider the question of the cancellation of the drug Berlipril® plus. Each patient receiving a diuretic requires systematic monitoring of the concentration of electrolytes in the blood plasma.

Thiazides can cause a violation of the water-electrolyte balance (hypokalemia, hyponatremia and hypochloraemic alkalosis). Symptoms-precursors are: dryness of the oral mucosa, thirst, weakness, stupor, drowsiness, anxiety, muscle pain or cramps, muscle weakness, arterial hypotension, oliguria, tachycardia, nausea, or vomiting.

With the use of thiazide diuretics, it is possible to detect signs of a deficiency in potassium, but simultaneous use of enalapril helps to reduce hypokalemia caused by diuretics.The highest risk of hypokalemia exists in patients with cirrhosis of the liver, increased diuresis, as well as insufficient intake of table salt inward, simultaneous use of glucocorticosteroids or corticotropin (ACTH) (see section Interactions with Other Drugs). In hot weather, diluted hyponatremia may occur in patients with edema. Chloride deficiency usually is not expressed and does not require treatment.

Thiazides can reduce the excretion of calcium by the kidneys and cause a transient increase in serum calcium without visible disturbances in its metabolism. Expressed hypercalcemia may be a sign of latent hyperparathyroidism. Thiazides should be discontinued before the parathyroid gland function (see section Interactions with Other Drugs).

Thiazides increase the excretion of magnesium by the kidneys (risk of hypomagnesemia).

In the treatment of thiazides, the development of a violation of glucose tolerance is possible. You may need to adjust the dose of insulin or hypoglycemic agents for oral administration (see section Interactions with Other Drugs). In the treatment of thiazides, latent diabetes mellitus can manifest.

The relationship between increased cholesterol and triglyceride concentrations and the use of thiazide diuretics has been established. Treatment with thiazides can cause hyperuricemia and / or exacerbation of gout.

Hydrochlorothiazide can cause a positive result in doping control.

ENALAPRIL / HYDROCHLOROTHYASIDE IN THE COMBINATION

The combination of ACE inhibitors with thiazide diuretics does not exclude the risk of hypokalemia, therefore, the content of potassium in the blood should be monitored regularly.

Effect on the ability to drive transp. cf. and fur:The effect of the drug Berlipril® plus on the ability to drive vehicles and control mechanisms has not been specifically studied, therefore, during the treatment with Berlipril® Plus, caution should be exercised when driving vehicles and engaging in potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 25 mg + 10 mg.

Packaging:For 10 tablets in a contour squeeze box (blister) made of laminated film (polyamide / aluminum / PVC) and aluminum foil. By 2, 3, 5 or 10 blisters together with instructions for use in a cardboard pack.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep the medicine out of the reach of children!

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000310

Date of registration:18.02.2011

Date of cancellation:2016-02-18

The owner of the registration certificate:BERLIN-PHARMA, CJSC BERLIN-PHARMA, CJSC Russia

Manufacturer: & nbsp

BERLIN-CHEMIE, AG Germany

Information update date: & nbsp30.12.2015

Illustrated instructions

Instructions

Berlipril® plus (Berlipril® plus)