Berlipril 5 mg (30 tablets)
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The instruction for medical use
of Берлиприл® 5 medicine
the Trade name
Берлиприл® 5
International unlicensed
name Enalapril Dosage Form
of the Tablet of 5 mg
Structure
One tablet contains
active agent - enalapril a maleate of 5 mg,
excipients: lactoses monohydrate, magnesium a carbonate easy, gelatin, silicon dioxide colloidal anhydrous, sodium of starch glikolit (type A), magnesium stearate.
The description
of the Tablet of almost white color, with slightly biconvex surface, with a facet and risky on one party.
Pharmacotherapeutic group
the Drugs influencing a system renin-angiotensin. Angiotensin of the Converting Enzyme (ACE) inhibitors. AKF inhibitors. Enalapril.
The ATX C09AA02 code
the Pharmacological
Pharmacokinetics Absorption Later properties of oral administration enalapril is quickly soaked up, at the same time in one hour its maximum concentration in plasma is reached. After oral administration of a tablet of enalapril of a maleate the absorption determined by extent of repeated detection in urine is, about, 60%. After oral administration of Berliprila® the existence of food in digestive tract of influence on extent of its absorption does not render.
Enalapril the maleate accepted orally after the absorption is exposed to fast and full-scale hydrolysis to enalaprilat, inhibitor of angiotensin-converting enzyme. After oral administration of a tablet of enalapril of a maleate the peak of concentration of enalaprilat in plasma is found, pribl., in 4 hours. Effective time of semi-accumulation of enalaprilat after multiple oral administration is 11 hours. At probands with normal renal function the concentration of enalaprilat in serum reaches the stationary level approximately in 4 days after an initiation of treatment.
Distribution
At the person in the range therapeutic of significant concentration linking of enalaprilat with proteins of plasma does not exceed 60%.
Biotransformation
Krom of transformation into enalaprilat, given about further significant metabolism of enalapril of a maleate is not available.
Removal
Enalaprilat is allocated in, mainly, renal way. The main components in urine are enalaprilat to which share about 40% of the accepted dose, and the maleate (about 20%) which is not changed enalapril fall.
Restriction of function of kidneys
At patients with a renal failure the exposure of enalapril of a maleate and enalaprilat in an organism is increased.
Patients with renal insufficiency from easy to average degree (clearance of creatinine of 40-60 ml/min.) in the period of stationary level at its use in number of 5 mg/days had an AUC value of enalaprilat, pribl., is twice higher, than at patients with normal renal function. At heavy renal insufficiency (clearance of creatinine ≤ 30 ml/min.) this AUC value was, pribl., eight times higher. At this stage of renal insufficiency the effective period poluvyvedeniya enalaprilat after introduction of repeated doses is extended, achievement of stationary level in a slowed-up way.
Enalaprilat can be removed from the blood circulatory system by means of a hemodialysis. Enalaprilat gives in to dialysis, and degree of its dialization makes 62 ml/minute.
Children and teenagers
the pharmacokinetics research with introduction of various doses of enalapril of a maleate (orally 0.07-0.14 mg/kg/days) at 40 girls and boys having an arterial hypertension aged from 2 months up to 16 years Was conducted. Concerning enalaprilat pharmacokinetics the results of this research, in total, did not give big differences between children and adults. Results indicate increase in AUC (when rationing doses per body weight) with age, however, such increase in AUC was not observed if doses normalized per the area of a body. In a condition of stationary level the average effective period polunakopleniya enalaprilat was 14 hours.
Lactation:
Within 4 - 6 hours after administration of drug in a dose of 20 mg orally by five women in a puerperal period the peak of concentration of enalapril in milk of mother averaged 1.7 mkg/l (range of peaks from 0.54 to 5.9 mkg/l).
The average value of peaks of concentration of enalaprilat was 1.7 mkg/l (from 1.2 to 2.3 mkg/l), the peaks of concentration were observed at different times within 24 hours. According to data on peak concentration in mother's milk, the established single dose for the baby receiving only mother's milk should not exceed 0.16% of a dose of mother who is picked up per weight kg.
At the woman accepting 10 mg of enalapril a day within 11 months, the peak of concentration making 2 mkg/l was observed about 4 hours later after reception of a dose, and the peak of concentration of enalaprilat making 0.75 mkg/l - about 9 hours later after reception of a dose. At the same time the general daily content of enalapril in milk of mother was 1.44 mkg/l, and the general daily content of enalaprilat - 0.63 mkg/l.
4 hours later after reception of a single dose of enalapril of 5 mg by one patient and a single dose of enalapril of 10 mg by two patients the level of content of enalaprilat was in milk below a detection limit (& lt, 0.2 mkg/l), levels of content of enalapril were not established.
The pharmacodynamics
of Berlipril® (enalapril a maleate) is a salt of maleic acid and the enalapril which is to derivatives of two amino acids (L-alanine and L-proline). Angiotensin-converting enzyme (APF) represents itself peptidildipeptidazu which catalyzes transformation of angiotensin I into angiotensin II – the substance possessing vasopressor action. After enalapril absorption the maleate is exposed to hydrolysis before formation of enalaprilat which inhibits APF. Suppression of APF leads to reduction of content of angiotensin II in plasma. It causes increase in activity of renin of plasma (result of loss of negative return communication concerning renin secretion) and reduction of secretion of Aldosteronum.
APF is identical to a kininaza of II. Therefore it is possible that Berlipril® also slows down disintegration of bradykinin, the peptide rendering on vessels expressed the weakening action. What role this mechanism plays in therapeutic effect of enalapril of a maleate, is not clear so far.
Though Berlipril® has hypotensive effect, thanking, first of all, to suppression system renin-angiotensin-aldosteronovoy, nevertheless enalapril reduces arterial blood pressure even at patients with the low level of renin in blood.
At patients with a hypertension of Berlipril® leads to decrease in blood pressure in provisions lying and standing without significant increase in frequency of warm reductions.
Simptomny orthostatic hypotonia happens seldom. At some patients before achievement of optimum level of a lowering of arterial pressure there can pass several weeks. Sharp cancellation of Berliprila® was not followed by excessive increase in arterial blood pressure.
Effective suppression of activity of APF comes, usually, in 2-4 hours after reception of one dose of enalapril of a maleate. The beginning of hypotensive action was observed, most often, in 1 hour, and the maximum action – in 4-6 hours after intake of drug. Duration of action depends on a dose. However, at the recommended doses the hypotensive and hemodynamic effects remain not less than 24 hours.
In hemodynamics researches at the patients having essential arterial hypertension it was shown that the lowering of arterial pressure was followed by reduction of peripheral resistance in arteries and increase in minute volume of blood, but heart rate almost did not undergo changes. After reception of Berliprila® the blood stream in kidneys increased, extent of glomerular filtration was left without changes. Signs of a delay of salts or liquid were not. However, at patients who before treatment of Berliprilom® had a low extent of glomerular filtration it raised.
In short-term clinical trials at the patients having diseases of kidneys in combination with diabetes and without it after intake of enalapril of a maleate the reduction of an albuminuria and also reduction of removal with IgG urine and crude protein was observed.
At combined use of drug with diuretics of a tiazidovy row the hypotensive effects of Berliprila®, at least, develop. Берлиприл® can reduce development of the hypopotassemia caused by tiazida or interfere with its emergence.
At the patients having heart failure and being on treatment by drugs of a foxglove and diuretics as a result of administration of enalapril of a maleate (orally or in / c) the peripheral resistance and blood pressure decreased. The minute volume of blood increased, the heart rate which at patients with heart failure is, usually, increased, on the contrary, decreased. In the same way pressure in capillaries of lungs decreased. The shipping of physical activity and degree of heart failure (by criteria of the New York association of cardiologists) in the same way changed to the best. At long-term treatment these effects remain.
At the patients having heart failure from easy to moderate severity, enalapril a maleate slowed down progressing of dilatation/increase in heart and the heart failure determined by reduction of final diastolic and systolic volumes in a left ventricle and by increase in ejection fraction.
In multicenter, randomized, double blind study with placebo control (the research "SOLVD" devoted to prevention) patients with asymptomatic dysfunction of a left ventricle were observed (ejection fraction from a left ventricle & lt, 35%). 4.228 patients there were randomizirovana and received either placebo (n=2.117), or enalapril a maleate (n=2.111). In placebo group took place of 818 cases of heart failure or a lethal outcome (38.6%), in the group receiving enalapril a maleate for comparison - 630 cases (29.8%) (risk reduction: 29%, 95% of CI: 21-36%, p<, 0.001). 518 patients in placebo group (24.5%) and 434 in the group receiving enalapril a maleate (20.6%) died or were hospitalized owing to emergence or aggravation of already being available heart failure (risk reduction: 20%, 95% of CI: 9-30%, p<, 0.001).
In multicenter, randomized, double blind study with placebo control (the research "SOLVD" devoted to treatment) patients with the simptomny heart failure caused by systolic dysfunction were observed (ejection fraction & lt, 35%). 2.569 patients at whom the standard treatment of simptomny heart failure was carried out there were randomizirovana in placebo group (n=1.284) or in the group receiving enalapril a maleate (n=1.285). In placebo group took place of 510 cases of a lethal outcome (39.7%), in the group receiving enalapril a maleate for comparison - 452 cases of a lethal outcome (35.2%) (risk reduction: 16%, 95% of CI: 5-26%, p=0.0036). In placebo group 461 cases of a lethal outcome because of cardiovascular pathology, and, for comparison, in the group receiving enalapril a maleate – 399 cases took place (risk reduction: 18%, 95% of CI: 6-28%, p<, 0.002), are the reason of it, first of all, decrease in quantity of lethal outcomes because of the progressing heart failure (251 in placebo group in comparison with 209 in the group receiving enalapril a maleate, risk reduction: 22%, 95% of CI: 6-35%). The smaller number of patients died or was hospitalized owing to aggravation of heart failure (736 in placebo group and 613 in the group receiving enalapril a maleate, risk reduction: 26%, 95% of CI: 18-34%, p<, 0.0001). In total in the enalapril research "SOLVD" the maleate reduced at patients with dysfunction of a left ventricle risk of a myocardial infarction by 23% (95% of CI: 11-34%, p<, 0.001), and risk of hospitalization because of unstable stenocardia – for 20% (95%CI: 9-29%, p<, 0.001).
Concerning patients of a pediatric profile 6 years having an arterial hypertension are more senior, data on use of enalapril of a maleate are limited. In one clinical trial in which 110 patients of a pediatric profile at the age of 6-16 years having an arterial hypertension, patients with body weight ≥ 20 kg and extent of glomerular filtration & gt, 30 ml/min. / 1.73 in sq.m and also patients with the body weight & lt participated 50 kg received 0.625 mg, 2.5 mg or 20 mg of enalapril of a maleate a day, patients with body weight ≥ 50 kg received 1.25 mg, 5 mg or 40 mg of enalapril of a maleate a day. At intake of enalapril of a maleate once a day arterial blood pressure decreased depending on a dose. The adequate dependence of a lowering of arterial pressure on a dose of enalapril of a maleate was observed in all subgroups (age, a puberty stage, a floor, ethnic origin). However, the lowest doses (0.625 mg and 1.25 mg) corresponding, on average, 0.02 mg/kg/days have probably no uniform hypotensive effect. The maximum dose put trials made 0.58 mg/kg/days (to 40 mg). The profile of side effects at children did not differ from that at adults.
Indications
- arterial hypertension
- heart failure
- prevention of simptomny warm insufficiency at patients with asymptomatic dysfunction of a left ventricle (ejection fraction of a left ventricle & lt, 35%)
the Route of administration and doses
the Dose should be selected individually - depending on a condition of the patient and from impact of drug on the level of arterial blood pressure.
The arterial hypertension
the Initial dose makes from 5 mg to at most 20 mg of enalapril of a maleate - depending on severity of a hypertension and a condition of the patient (see below). Appoint Берлиприл® 1 once a day. In an arterial hypertension of easy degree the recommended initial dose makes 5-10 mg. At patients with the significant activation system renin-angiotensin-aldosteronovoy (for example in a renal hypertension, at a lack of an organism of salts and/or liquid, a decompensation of warm activity or a heavy arterial hypertension) in an initiation of treatment can have the place excessive falling of blood pressure. At such patients the treatment needs to be begun with 5 mg or with a smaller dose and also under careful medical observation.
1 All data concerning Berliprila® also belong to Берлиприл® 5, Берлиприл® 10 and Берлиприл® 20.
At the previous therapy by diuretics in high doses the hypovolemia at which in an enalapril initiation of treatment the danger of hypotonia is available a maleate can develop. At such patients the treatment needs to be begun with 5 mg or with a smaller dose. At an opportunity, before an initiation of treatment of Berliprilom® diuretics should be cancelled for 2-3 days. Control of renal function and level of potassium in serum is recommended.
The usual supporting daily dose makes 20 mg of enalapril of a maleate. The maximum supporting dose makes 40 mg of enalapril of a maleate a day.
Warm insufficiency / asymptomatic dysfunction of a left ventricle
At treatment of simptomny warm insufficiency of Berlipril®, usually, apply in addition to diuretics and in the presence of indications – to drugs of a foxglove or beta-blockers. For patients with simptomny warm insufficiency or asymptomatic dysfunction of a left ventricle the initial dose of enalapril of a maleate makes 2.5 mg. That in an initiation of treatment to define effect of drug on blood pressure, therapy should be begun under careful medical control. If after an initiation of treatment of warm insufficiency of enalapril the symptomatic hypotonia does not arise a maleate or it is eliminated, the dose of drug should be raised to the standard supporting dose making 20 mg gradually. The supporting dose can be accepted once or – depending on shipping – to divide into two receptions. Such selection of a dose is recommended to carry out within 2-4 weeks. The maximum dose making 40 mg a day is divided into two receptions.
The recommended selection of a dose of the drug Berlipril® at treatment of warm insufficiency / asymptomatic dysfunction of a left ventricle:
Week
mg/day Dose
Week 1
Day 1-3:
2.5 mg/days * once
Day 4-7:
5 mg/days for 2 receptions
Week of 2
10 mg/day once or for 2 receptions
of Week of 3 and 4
20 mg/day once or for 2 receptions
* to observe special precautionary measures in case of patients with a renal failure or being on treatment by diuretics.
Till the beginning of therapy it is necessary to carry out by the drug Berlipril® careful control of arterial blood pressure and renal function as it was reported about hypotonia (less often) about the subsequent renal failure. For the patients who are on treatment by diuretics follows – if it is possible – before an enalapril initiation of treatment a maleate to reduce a dose of these drugs. Hypotonic reaction at the beginning of therapy of Berliprilom® does not mean that such reactions will take place and at long-term treatment by drug, and does not exclude the further Berlipril® drug treatment. Also it is necessary to carry out control of level of serumal potassium and renal function.
A dosage at restriction of function of kidneys
in principle, intervals between intake of enalapril of a maleate it is necessary to extend and/or reduce its dose.
Clearance of creatinine
(Clcr) of ml/min.
the Initial dose
of mg/day
30 & lt, Clcr & lt, 80
ml/min. 5 - 10 mg
10 & lt, Clcr ≤ 30
ml/min. 2.5 mg
of Clcr ≤ 10
ml/min. 2.5 mg in day of carrying out dialysis *
* the section "Special Instructions": patients who are on treatment by a hemodialysis method".
Enalapril gives in to dialysis. In the days free from carrying out dialysis, the dose depends on degree of a lowering of arterial pressure.
Use by elderly patients
the Dose should be selected depending on a condition of renal function of the patient.
The route of administration
Meal does not influence maleate enalapril absorption.
Side effects
Very often (≥ 1/10):
- a disorder of vision, in the form of illegibility of sight
- cough
- dizziness
- nausea
- an asthenia
Often (≥ 1/100-& lt, 1/10):
- hypotonia (including orthostatic hypotonia), a faint, thorax pain, disturbances of a warm rhythm, stenocardia, tachycardia
- a headache, a depression
- fatigue
- short wind
- diarrhea, an abdominal pain, change of flavoring perception
- skin rash, a Quincke's disease of the face, extremities, lips, language, a glottis and/or throat
- a hyperpotassemia, increase in level of creatinine
Sometimes (≥ 1/1,000 - & lt, 1/100):
- orthostatic hypotonia, heartbeat, a myocardial infarction or a cerebral stroke, presumably as a result of excessive falling of arterial blood pressure at patients with presence of high risk factors
- confusion of consciousness, drowsiness, insomnia, nervousness, dizziness, paresthesias
- heartbeat
- intestinal impassability, pancreatitis, vomiting, dyspepsia, a constipation, lack of appetite, the phenomenon of irritation of a stomach, dryness in a mouth, a round ulcer
- anemia (including aplastic and hemolytic anemia)
- a rhinorrhea, a sore throat and an osiplost, bronchospasm/asthma
- perspiration, an itching, a small tortoiseshell, an alopecia
- a renal failure, a renal failure, a proteinuria
- impotence
- muscular spasms, inflows, sonitus, an indisposition, fever
- increase in level of urea, a hyponatremia, a hypoglycemia
Seldom (≥ 1/10,000 - & lt, 1/1000):
- a liver failure, hepatitis, a cholestasia, jaundice, increase in activity of "hepatic" transaminases, a hyperbilirubinemia
- a neutropenia, decrease in hemoglobin and a hematocrit, thrombocytopenia, an agranulocytosis, oppression of marrow, a pancytopenia, increase in lymph nodes, autoimmune diseases
- change of nature of dreams, sleep disorders
- Reynaud's syndrome
- pulmonary infiltrates, rhinitis, an allergic alveolitis / eosinophilic pneumonia
- stomatitis / aphthous sores, a glossitis
- a liver failure, hepatitis – hepatocellular or cholestatic, including hepatic necrosis, a cholestasia (including jaundice)
- a multiformny erythema, Stephens-Johnson's syndrome, exfoliative dermatitis, a toxic epidermal necrolysis, a bladderwort, an erythrosis
- an oliguria
- a gynecomastia
- increase in level of liver enzymes, increase in indicators of bilirubin of serum
is Very rare (& lt, 1/10,000):
- a Quincke's disease of intestines
Frequency is unknown:
- Parkhon's syndrome (syndrome of inadequate secretion of antidiuretic hormone)
It was reported about symptom complex which can be followed by some or all from the following side effects: fever, serositis, vasculitis, myalgia/miositis, arthralgia/arthritis, increase in a caption of anti-nuclear antibodies (ANA), increase by SOE, eosinophilia and leukocytosis. Skin rash, a photosensitization or other skin manifestations can take place.
Contraindications
- hypersensitivity to enalapril, other components of drug or other APF inhibitors
- the Quincke's disease in the anamnesis connected with the previous use of APF inhibitors
- a hereditary or idiopathic Quincke's disease
- pregnancy
- a hereditary lactose intolerance, deficiency of Lappa lactose or malabsorption of glucose galactose
- children's and teenage age up to 18 years
Medicinal interactions
Kaliysberegayushchy diuretics or drugs
of IAPF potassium reduce the potassium losses caused by diuretics. Kaliysberegayushchy diuretics (for example, Spironolactonum, eplerenon, Triamterenum or amiloride), can lead drugs of potassium or kaliysoderzhashchy substitutes of salt to significant increase in level of potassium in serum. If because of the revealed hypopotassemia the simultaneous use nevertheless is shown, then it should be done with care and at frequent control of level of serumal potassium.
The Previous treatment by diuretics in high doses can lead diuretics (a tiazidovy row or loopback diuretics) at the beginning of enalapril therapy by a maleate to a hypovolemia and, thus, increase risk of developing hypotension. The hypotensive effect can be reduced if to cancel diuretic, to compensate a lack of liquid or salts of an organism or if to begin enalapril therapy with a maleate with its low doses.
Other antihypertensives
Simultaneous use with other antihypertensives can enhance hypotensive effect of enalapril of a maleate. Simultaneous use with nitroglycerine and other nitrates or other vazodilatator can also lead to a further lowering of arterial pressure.
Lithium
It was reported about passing increase in concentration of lithium in serum and about its toxic effects at simultaneous use with IAPF. At simultaneous treatment by diuretics of a tiazidovy row and IAPF can raise concentration of lithium in serum and by that – risk of intoxication lithium. Therefore combined use of enalapril of a maleate and lithium do not recommend if this combination nevertheless is necessary, then careful control of level of serumal lithium is necessary.
Tricyclic antidepressants / neuroleptics / means for anesthesia / anesthetic
the Simultaneous use of IAPF with certain means for carrying out an anesthesia, tricyclic antidepressants and neuroleptics can strengthen a lowering of arterial pressure.
Non-steroidal anti-inflammatory drugs (NPVLS)
Long-term treatment of NPVLS can weaken hypotensive action of IAPF.
Effects of NPVLS, including, so-called, TsOG-2 inhibitors (selection inhibitors of cyclooxygenase-2) and IAPF concerning increase in level of serumal potassium develop and can lead to deterioration in renal function. This phenomenon is, usually, reversible. Occasionally the acute renal failure – especially, at patients with decrease in renal function, at such, e.g., as elderly patients or patients with decrease in amount of liquid in an organism can take place (for example, in the result of treatment with diuretics). As in an initiation of treatment along with the specified drugs, and periodically after the end of treatment, it is necessary to provide the corresponding intake of liquid in an organism and control of function of kidneys.
Gold drugs.
It was in rare instances reported about nitritoidny reactions (symptoms: face reddening, nausea, vomiting and arterial hypotension) at use of injection drugs of gold (sodium aurotimalat) together with APF inhibitors, including from enalapril a maleate.
Sympathomimetics
Sympathomimetics can weaken hypotensive action of IAPF.
Antidiabetic medicines
indicate Results of researches of epidemiology possible strengthening of hypoglycemic action of antidiabetic means (insulin, oral hypoglycemic means) at simultaneous use of IAPF, at the same time there is a risk of development of a hypoglycemia. Obviously, such cases take place, in particular, in the first weeks of the combined treatment and also at patients with decrease in renal function.
Alcohol
Alcohol enhances hypotensive effect of IAPF.
Acetilsalicylic acid, thrombolytic means and beta-blockers
of Enalapril a maleate it is possible, without being afraid, to appoint along with acetilsalicylic acid (in cardiological doses), thrombolytic means and beta-blockers.
Special instructions
Symptomatic hypotension
In an uncomplicated arterial hypertension the hypotonia is observed seldom.
At a lack of liquid of an organism, for example, owing to therapy by diuretics, the food which is grown poor by salts, dialysis, a diarrhea or vomiting at the patients having an arterial hypertension at treatment of Berliprilom® the simptomny hypotonia develops more often. At patients with heart failure - the followed renal failure or without that - observed simptomny hypotonia. In particular, it can concern patients with heavy heart failure whose severity of a disease is expressed in high doses of loopback diuretics, a hyponatremia or in decrease in renal function. Treatment of such patients – if is necessary selection of a new dose of Berliprila® and/or diuretic – it is necessary to begin and carry out under control of the doctor. In this way arrive also in case of patients with coronary heart disease or cerebrovascular pathology at which excessive falling of blood pressure can lead to a myocardial infarction or a cerebral stroke.
In case of development of hypotonia of the patient it is necessary to lay in horizontal position and – if it is necessary – to carry out intravenous infusion of solution of sodium of chloride. Passing hypotonic reaction is not a contraindication for further treatment which can, usually, be carried out without problems after normalization (by means of completion of volume of the circulating blood) arterial blood pressure.
At some patients with heart failure who have normal or low figures of arterial blood pressure the additional decrease in arterial system blood pressure at drug Berlipril® use can be observed. This effect is expected, and, as a rule there is no reason for the treatment termination. If arterial hypotension becomes symptomatic, there can be necessary a dose decline of Berliprila® and/or diuretic and/or cancellation of Berliprila®.
The aortal or mitral stenosis / a hypertrophic cardiomyopathy
As well as other vazodilatator, APF inhibitors should be applied with extra care at patients with a left ventricular stenosis or a stenosis of an aorta and also to avoid use of drug in cases of cardiogenic shock and hemodynamically caused obstruction
of the Renal failure
in case of a renal failure (clearance of creatinine & lt, 80 ml/minute) the initial dose of enalapril of a maleate should be selected depending on an indicator of clearance of creatinine at the patient, and a lowering of arterial pressure, after from degree. Continuous monitoring of levels of potassium and creatinine at such patients is a part of standard medical practice.
It was reported about a renal failure in interrelation using maleate enalapril at patients with heavy heart failure or with the diseases of kidneys which are the cornerstone of this pathology, including a stenosis of renal arteries. At timely diagnosis and the corresponding treatment the renal failure at enalapril therapy by a maleate has, usually, reversible character.
At some patients having an arterial hypertension who have no diseases of kidneys the maleate enalapril combination with diuretic can lead to increase in level of urea and creatinine in serum. In such cases there can be a need of reduction of a dose of enalapril of a maleate and/or cancellation of diuretic. At the same time the reason of these phenomena should think of a possible stenosis of renal arteries as.
The renovascular hypertension
At patients with a bilateral stenosis of renal arteries or a renal artery stenosis of the only functioning kidney treatment of IAPF constitutes special danger of falling of blood pressure or development of a renal failure. At the same time there can be a loss of renal function which is often shown only easy changes of indicators of creatinine of serum. Treatment of these patients needs to be begun with low doses and under strict medical observation, carefully titrating a dose and controlling renal function.
Transplantation of kidneys
Experience of use of Berliprila® for the patients who recently transferred transplantation of a kidney no. Therefore treatment of such patients this drug is not recommended.
A liver failure
At treatment of IAPF the syndrome beginning with cholestatic jaundice and progressing up to lightning hepatic necrosis was occasionally observed (sometimes with a lethal outcome). The pathogenesis of this syndrome is not clear. In case of patients who at treatment of IAPF have a jaundice or distinct increase in level of liver enzymes the cancellation of IAPF and the corresponding treatment are necessary.
A neutropenia / agranulocytosis
It was reported about a neutropenia/agranulocytosis, thrombocytopenia and anemia at the patients receiving IAPF. At patients with normal renal function and without special risk factors the neutropenia appears seldom. At the patients suffering from collagenoses with involvement in process of vessels and also being on treatment by immunodepressants, Allopyrinolum, procaineamide or at patients with existence of several of the listed risk factors, enalapril the maleate has to be applied extremely carefully, in particular, if depression of function of kidneys takes place. Some of these patients had serious infectious diseases which in certain cases did not give in to intensive antibiotic treatment. If these patients accept enalapril a maleate, then regular control of number of leukocytes is recommended to them and also it is necessary to oblige to report them to the doctor about all symptoms of any infection.
Hypersensitivity / a Quincke's disease
It was reported about Quincke's diseases with involvement of the face, extremities, lips, language, voice folds and/or throats at the patients treated by IAPF including Berlipril®. During treatment they can appear at any time. In these cases of Berlipril® it is necessary to cancel immediately. That to discharge from hospital to be convinced of the full return ra
to Develop
of Берлиприл® 5 medicine
the Trade name
Берлиприл® 5
International unlicensed
name Enalapril Dosage Form
of the Tablet of 5 mg
Structure
One tablet contains
active agent - enalapril a maleate of 5 mg,
excipients: lactoses monohydrate, magnesium a carbonate easy, gelatin, silicon dioxide colloidal anhydrous, sodium of starch glikolit (type A), magnesium stearate.
The description
of the Tablet of almost white color, with slightly biconvex surface, with a facet and risky on one party.
Pharmacotherapeutic group
the Drugs influencing a system renin-angiotensin. Angiotensin of the Converting Enzyme (ACE) inhibitors. AKF inhibitors. Enalapril.
The ATX C09AA02 code
the Pharmacological
Pharmacokinetics Absorption Later properties of oral administration enalapril is quickly soaked up, at the same time in one hour its maximum concentration in plasma is reached. After oral administration of a tablet of enalapril of a maleate the absorption determined by extent of repeated detection in urine is, about, 60%. After oral administration of Berliprila® the existence of food in digestive tract of influence on extent of its absorption does not render.
Enalapril the maleate accepted orally after the absorption is exposed to fast and full-scale hydrolysis to enalaprilat, inhibitor of angiotensin-converting enzyme. After oral administration of a tablet of enalapril of a maleate the peak of concentration of enalaprilat in plasma is found, pribl., in 4 hours. Effective time of semi-accumulation of enalaprilat after multiple oral administration is 11 hours. At probands with normal renal function the concentration of enalaprilat in serum reaches the stationary level approximately in 4 days after an initiation of treatment.
Distribution
At the person in the range therapeutic of significant concentration linking of enalaprilat with proteins of plasma does not exceed 60%.
Biotransformation
Krom of transformation into enalaprilat, given about further significant metabolism of enalapril of a maleate is not available.
Removal
Enalaprilat is allocated in, mainly, renal way. The main components in urine are enalaprilat to which share about 40% of the accepted dose, and the maleate (about 20%) which is not changed enalapril fall.
Restriction of function of kidneys
At patients with a renal failure the exposure of enalapril of a maleate and enalaprilat in an organism is increased.
Patients with renal insufficiency from easy to average degree (clearance of creatinine of 40-60 ml/min.) in the period of stationary level at its use in number of 5 mg/days had an AUC value of enalaprilat, pribl., is twice higher, than at patients with normal renal function. At heavy renal insufficiency (clearance of creatinine ≤ 30 ml/min.) this AUC value was, pribl., eight times higher. At this stage of renal insufficiency the effective period poluvyvedeniya enalaprilat after introduction of repeated doses is extended, achievement of stationary level in a slowed-up way.
Enalaprilat can be removed from the blood circulatory system by means of a hemodialysis. Enalaprilat gives in to dialysis, and degree of its dialization makes 62 ml/minute.
Children and teenagers
the pharmacokinetics research with introduction of various doses of enalapril of a maleate (orally 0.07-0.14 mg/kg/days) at 40 girls and boys having an arterial hypertension aged from 2 months up to 16 years Was conducted. Concerning enalaprilat pharmacokinetics the results of this research, in total, did not give big differences between children and adults. Results indicate increase in AUC (when rationing doses per body weight) with age, however, such increase in AUC was not observed if doses normalized per the area of a body. In a condition of stationary level the average effective period polunakopleniya enalaprilat was 14 hours.
Lactation:
Within 4 - 6 hours after administration of drug in a dose of 20 mg orally by five women in a puerperal period the peak of concentration of enalapril in milk of mother averaged 1.7 mkg/l (range of peaks from 0.54 to 5.9 mkg/l).
The average value of peaks of concentration of enalaprilat was 1.7 mkg/l (from 1.2 to 2.3 mkg/l), the peaks of concentration were observed at different times within 24 hours. According to data on peak concentration in mother's milk, the established single dose for the baby receiving only mother's milk should not exceed 0.16% of a dose of mother who is picked up per weight kg.
At the woman accepting 10 mg of enalapril a day within 11 months, the peak of concentration making 2 mkg/l was observed about 4 hours later after reception of a dose, and the peak of concentration of enalaprilat making 0.75 mkg/l - about 9 hours later after reception of a dose. At the same time the general daily content of enalapril in milk of mother was 1.44 mkg/l, and the general daily content of enalaprilat - 0.63 mkg/l.
4 hours later after reception of a single dose of enalapril of 5 mg by one patient and a single dose of enalapril of 10 mg by two patients the level of content of enalaprilat was in milk below a detection limit (& lt, 0.2 mkg/l), levels of content of enalapril were not established.
The pharmacodynamics
of Berlipril® (enalapril a maleate) is a salt of maleic acid and the enalapril which is to derivatives of two amino acids (L-alanine and L-proline). Angiotensin-converting enzyme (APF) represents itself peptidildipeptidazu which catalyzes transformation of angiotensin I into angiotensin II – the substance possessing vasopressor action. After enalapril absorption the maleate is exposed to hydrolysis before formation of enalaprilat which inhibits APF. Suppression of APF leads to reduction of content of angiotensin II in plasma. It causes increase in activity of renin of plasma (result of loss of negative return communication concerning renin secretion) and reduction of secretion of Aldosteronum.
APF is identical to a kininaza of II. Therefore it is possible that Berlipril® also slows down disintegration of bradykinin, the peptide rendering on vessels expressed the weakening action. What role this mechanism plays in therapeutic effect of enalapril of a maleate, is not clear so far.
Though Berlipril® has hypotensive effect, thanking, first of all, to suppression system renin-angiotensin-aldosteronovoy, nevertheless enalapril reduces arterial blood pressure even at patients with the low level of renin in blood.
At patients with a hypertension of Berlipril® leads to decrease in blood pressure in provisions lying and standing without significant increase in frequency of warm reductions.
Simptomny orthostatic hypotonia happens seldom. At some patients before achievement of optimum level of a lowering of arterial pressure there can pass several weeks. Sharp cancellation of Berliprila® was not followed by excessive increase in arterial blood pressure.
Effective suppression of activity of APF comes, usually, in 2-4 hours after reception of one dose of enalapril of a maleate. The beginning of hypotensive action was observed, most often, in 1 hour, and the maximum action – in 4-6 hours after intake of drug. Duration of action depends on a dose. However, at the recommended doses the hypotensive and hemodynamic effects remain not less than 24 hours.
In hemodynamics researches at the patients having essential arterial hypertension it was shown that the lowering of arterial pressure was followed by reduction of peripheral resistance in arteries and increase in minute volume of blood, but heart rate almost did not undergo changes. After reception of Berliprila® the blood stream in kidneys increased, extent of glomerular filtration was left without changes. Signs of a delay of salts or liquid were not. However, at patients who before treatment of Berliprilom® had a low extent of glomerular filtration it raised.
In short-term clinical trials at the patients having diseases of kidneys in combination with diabetes and without it after intake of enalapril of a maleate the reduction of an albuminuria and also reduction of removal with IgG urine and crude protein was observed.
At combined use of drug with diuretics of a tiazidovy row the hypotensive effects of Berliprila®, at least, develop. Берлиприл® can reduce development of the hypopotassemia caused by tiazida or interfere with its emergence.
At the patients having heart failure and being on treatment by drugs of a foxglove and diuretics as a result of administration of enalapril of a maleate (orally or in / c) the peripheral resistance and blood pressure decreased. The minute volume of blood increased, the heart rate which at patients with heart failure is, usually, increased, on the contrary, decreased. In the same way pressure in capillaries of lungs decreased. The shipping of physical activity and degree of heart failure (by criteria of the New York association of cardiologists) in the same way changed to the best. At long-term treatment these effects remain.
At the patients having heart failure from easy to moderate severity, enalapril a maleate slowed down progressing of dilatation/increase in heart and the heart failure determined by reduction of final diastolic and systolic volumes in a left ventricle and by increase in ejection fraction.
In multicenter, randomized, double blind study with placebo control (the research "SOLVD" devoted to prevention) patients with asymptomatic dysfunction of a left ventricle were observed (ejection fraction from a left ventricle & lt, 35%). 4.228 patients there were randomizirovana and received either placebo (n=2.117), or enalapril a maleate (n=2.111). In placebo group took place of 818 cases of heart failure or a lethal outcome (38.6%), in the group receiving enalapril a maleate for comparison - 630 cases (29.8%) (risk reduction: 29%, 95% of CI: 21-36%, p<, 0.001). 518 patients in placebo group (24.5%) and 434 in the group receiving enalapril a maleate (20.6%) died or were hospitalized owing to emergence or aggravation of already being available heart failure (risk reduction: 20%, 95% of CI: 9-30%, p<, 0.001).
In multicenter, randomized, double blind study with placebo control (the research "SOLVD" devoted to treatment) patients with the simptomny heart failure caused by systolic dysfunction were observed (ejection fraction & lt, 35%). 2.569 patients at whom the standard treatment of simptomny heart failure was carried out there were randomizirovana in placebo group (n=1.284) or in the group receiving enalapril a maleate (n=1.285). In placebo group took place of 510 cases of a lethal outcome (39.7%), in the group receiving enalapril a maleate for comparison - 452 cases of a lethal outcome (35.2%) (risk reduction: 16%, 95% of CI: 5-26%, p=0.0036). In placebo group 461 cases of a lethal outcome because of cardiovascular pathology, and, for comparison, in the group receiving enalapril a maleate – 399 cases took place (risk reduction: 18%, 95% of CI: 6-28%, p<, 0.002), are the reason of it, first of all, decrease in quantity of lethal outcomes because of the progressing heart failure (251 in placebo group in comparison with 209 in the group receiving enalapril a maleate, risk reduction: 22%, 95% of CI: 6-35%). The smaller number of patients died or was hospitalized owing to aggravation of heart failure (736 in placebo group and 613 in the group receiving enalapril a maleate, risk reduction: 26%, 95% of CI: 18-34%, p<, 0.0001). In total in the enalapril research "SOLVD" the maleate reduced at patients with dysfunction of a left ventricle risk of a myocardial infarction by 23% (95% of CI: 11-34%, p<, 0.001), and risk of hospitalization because of unstable stenocardia – for 20% (95%CI: 9-29%, p<, 0.001).
Concerning patients of a pediatric profile 6 years having an arterial hypertension are more senior, data on use of enalapril of a maleate are limited. In one clinical trial in which 110 patients of a pediatric profile at the age of 6-16 years having an arterial hypertension, patients with body weight ≥ 20 kg and extent of glomerular filtration & gt, 30 ml/min. / 1.73 in sq.m and also patients with the body weight & lt participated 50 kg received 0.625 mg, 2.5 mg or 20 mg of enalapril of a maleate a day, patients with body weight ≥ 50 kg received 1.25 mg, 5 mg or 40 mg of enalapril of a maleate a day. At intake of enalapril of a maleate once a day arterial blood pressure decreased depending on a dose. The adequate dependence of a lowering of arterial pressure on a dose of enalapril of a maleate was observed in all subgroups (age, a puberty stage, a floor, ethnic origin). However, the lowest doses (0.625 mg and 1.25 mg) corresponding, on average, 0.02 mg/kg/days have probably no uniform hypotensive effect. The maximum dose put trials made 0.58 mg/kg/days (to 40 mg). The profile of side effects at children did not differ from that at adults.
Indications
- arterial hypertension
- heart failure
- prevention of simptomny warm insufficiency at patients with asymptomatic dysfunction of a left ventricle (ejection fraction of a left ventricle & lt, 35%)
the Route of administration and doses
the Dose should be selected individually - depending on a condition of the patient and from impact of drug on the level of arterial blood pressure.
The arterial hypertension
the Initial dose makes from 5 mg to at most 20 mg of enalapril of a maleate - depending on severity of a hypertension and a condition of the patient (see below). Appoint Берлиприл® 1 once a day. In an arterial hypertension of easy degree the recommended initial dose makes 5-10 mg. At patients with the significant activation system renin-angiotensin-aldosteronovoy (for example in a renal hypertension, at a lack of an organism of salts and/or liquid, a decompensation of warm activity or a heavy arterial hypertension) in an initiation of treatment can have the place excessive falling of blood pressure. At such patients the treatment needs to be begun with 5 mg or with a smaller dose and also under careful medical observation.
1 All data concerning Berliprila® also belong to Берлиприл® 5, Берлиприл® 10 and Берлиприл® 20.
At the previous therapy by diuretics in high doses the hypovolemia at which in an enalapril initiation of treatment the danger of hypotonia is available a maleate can develop. At such patients the treatment needs to be begun with 5 mg or with a smaller dose. At an opportunity, before an initiation of treatment of Berliprilom® diuretics should be cancelled for 2-3 days. Control of renal function and level of potassium in serum is recommended.
The usual supporting daily dose makes 20 mg of enalapril of a maleate. The maximum supporting dose makes 40 mg of enalapril of a maleate a day.
Warm insufficiency / asymptomatic dysfunction of a left ventricle
At treatment of simptomny warm insufficiency of Berlipril®, usually, apply in addition to diuretics and in the presence of indications – to drugs of a foxglove or beta-blockers. For patients with simptomny warm insufficiency or asymptomatic dysfunction of a left ventricle the initial dose of enalapril of a maleate makes 2.5 mg. That in an initiation of treatment to define effect of drug on blood pressure, therapy should be begun under careful medical control. If after an initiation of treatment of warm insufficiency of enalapril the symptomatic hypotonia does not arise a maleate or it is eliminated, the dose of drug should be raised to the standard supporting dose making 20 mg gradually. The supporting dose can be accepted once or – depending on shipping – to divide into two receptions. Such selection of a dose is recommended to carry out within 2-4 weeks. The maximum dose making 40 mg a day is divided into two receptions.
The recommended selection of a dose of the drug Berlipril® at treatment of warm insufficiency / asymptomatic dysfunction of a left ventricle:
Week
mg/day Dose
Week 1
Day 1-3:
2.5 mg/days * once
Day 4-7:
5 mg/days for 2 receptions
Week of 2
10 mg/day once or for 2 receptions
of Week of 3 and 4
20 mg/day once or for 2 receptions
* to observe special precautionary measures in case of patients with a renal failure or being on treatment by diuretics.
Till the beginning of therapy it is necessary to carry out by the drug Berlipril® careful control of arterial blood pressure and renal function as it was reported about hypotonia (less often) about the subsequent renal failure. For the patients who are on treatment by diuretics follows – if it is possible – before an enalapril initiation of treatment a maleate to reduce a dose of these drugs. Hypotonic reaction at the beginning of therapy of Berliprilom® does not mean that such reactions will take place and at long-term treatment by drug, and does not exclude the further Berlipril® drug treatment. Also it is necessary to carry out control of level of serumal potassium and renal function.
A dosage at restriction of function of kidneys
in principle, intervals between intake of enalapril of a maleate it is necessary to extend and/or reduce its dose.
Clearance of creatinine
(Clcr) of ml/min.
the Initial dose
of mg/day
30 & lt, Clcr & lt, 80
ml/min. 5 - 10 mg
10 & lt, Clcr ≤ 30
ml/min. 2.5 mg
of Clcr ≤ 10
ml/min. 2.5 mg in day of carrying out dialysis *
* the section "Special Instructions": patients who are on treatment by a hemodialysis method".
Enalapril gives in to dialysis. In the days free from carrying out dialysis, the dose depends on degree of a lowering of arterial pressure.
Use by elderly patients
the Dose should be selected depending on a condition of renal function of the patient.
The route of administration
Meal does not influence maleate enalapril absorption.
Side effects
Very often (≥ 1/10):
- a disorder of vision, in the form of illegibility of sight
- cough
- dizziness
- nausea
- an asthenia
Often (≥ 1/100-& lt, 1/10):
- hypotonia (including orthostatic hypotonia), a faint, thorax pain, disturbances of a warm rhythm, stenocardia, tachycardia
- a headache, a depression
- fatigue
- short wind
- diarrhea, an abdominal pain, change of flavoring perception
- skin rash, a Quincke's disease of the face, extremities, lips, language, a glottis and/or throat
- a hyperpotassemia, increase in level of creatinine
Sometimes (≥ 1/1,000 - & lt, 1/100):
- orthostatic hypotonia, heartbeat, a myocardial infarction or a cerebral stroke, presumably as a result of excessive falling of arterial blood pressure at patients with presence of high risk factors
- confusion of consciousness, drowsiness, insomnia, nervousness, dizziness, paresthesias
- heartbeat
- intestinal impassability, pancreatitis, vomiting, dyspepsia, a constipation, lack of appetite, the phenomenon of irritation of a stomach, dryness in a mouth, a round ulcer
- anemia (including aplastic and hemolytic anemia)
- a rhinorrhea, a sore throat and an osiplost, bronchospasm/asthma
- perspiration, an itching, a small tortoiseshell, an alopecia
- a renal failure, a renal failure, a proteinuria
- impotence
- muscular spasms, inflows, sonitus, an indisposition, fever
- increase in level of urea, a hyponatremia, a hypoglycemia
Seldom (≥ 1/10,000 - & lt, 1/1000):
- a liver failure, hepatitis, a cholestasia, jaundice, increase in activity of "hepatic" transaminases, a hyperbilirubinemia
- a neutropenia, decrease in hemoglobin and a hematocrit, thrombocytopenia, an agranulocytosis, oppression of marrow, a pancytopenia, increase in lymph nodes, autoimmune diseases
- change of nature of dreams, sleep disorders
- Reynaud's syndrome
- pulmonary infiltrates, rhinitis, an allergic alveolitis / eosinophilic pneumonia
- stomatitis / aphthous sores, a glossitis
- a liver failure, hepatitis – hepatocellular or cholestatic, including hepatic necrosis, a cholestasia (including jaundice)
- a multiformny erythema, Stephens-Johnson's syndrome, exfoliative dermatitis, a toxic epidermal necrolysis, a bladderwort, an erythrosis
- an oliguria
- a gynecomastia
- increase in level of liver enzymes, increase in indicators of bilirubin of serum
is Very rare (& lt, 1/10,000):
- a Quincke's disease of intestines
Frequency is unknown:
- Parkhon's syndrome (syndrome of inadequate secretion of antidiuretic hormone)
It was reported about symptom complex which can be followed by some or all from the following side effects: fever, serositis, vasculitis, myalgia/miositis, arthralgia/arthritis, increase in a caption of anti-nuclear antibodies (ANA), increase by SOE, eosinophilia and leukocytosis. Skin rash, a photosensitization or other skin manifestations can take place.
Contraindications
- hypersensitivity to enalapril, other components of drug or other APF inhibitors
- the Quincke's disease in the anamnesis connected with the previous use of APF inhibitors
- a hereditary or idiopathic Quincke's disease
- pregnancy
- a hereditary lactose intolerance, deficiency of Lappa lactose or malabsorption of glucose galactose
- children's and teenage age up to 18 years
Medicinal interactions
Kaliysberegayushchy diuretics or drugs
of IAPF potassium reduce the potassium losses caused by diuretics. Kaliysberegayushchy diuretics (for example, Spironolactonum, eplerenon, Triamterenum or amiloride), can lead drugs of potassium or kaliysoderzhashchy substitutes of salt to significant increase in level of potassium in serum. If because of the revealed hypopotassemia the simultaneous use nevertheless is shown, then it should be done with care and at frequent control of level of serumal potassium.
The Previous treatment by diuretics in high doses can lead diuretics (a tiazidovy row or loopback diuretics) at the beginning of enalapril therapy by a maleate to a hypovolemia and, thus, increase risk of developing hypotension. The hypotensive effect can be reduced if to cancel diuretic, to compensate a lack of liquid or salts of an organism or if to begin enalapril therapy with a maleate with its low doses.
Other antihypertensives
Simultaneous use with other antihypertensives can enhance hypotensive effect of enalapril of a maleate. Simultaneous use with nitroglycerine and other nitrates or other vazodilatator can also lead to a further lowering of arterial pressure.
Lithium
It was reported about passing increase in concentration of lithium in serum and about its toxic effects at simultaneous use with IAPF. At simultaneous treatment by diuretics of a tiazidovy row and IAPF can raise concentration of lithium in serum and by that – risk of intoxication lithium. Therefore combined use of enalapril of a maleate and lithium do not recommend if this combination nevertheless is necessary, then careful control of level of serumal lithium is necessary.
Tricyclic antidepressants / neuroleptics / means for anesthesia / anesthetic
the Simultaneous use of IAPF with certain means for carrying out an anesthesia, tricyclic antidepressants and neuroleptics can strengthen a lowering of arterial pressure.
Non-steroidal anti-inflammatory drugs (NPVLS)
Long-term treatment of NPVLS can weaken hypotensive action of IAPF.
Effects of NPVLS, including, so-called, TsOG-2 inhibitors (selection inhibitors of cyclooxygenase-2) and IAPF concerning increase in level of serumal potassium develop and can lead to deterioration in renal function. This phenomenon is, usually, reversible. Occasionally the acute renal failure – especially, at patients with decrease in renal function, at such, e.g., as elderly patients or patients with decrease in amount of liquid in an organism can take place (for example, in the result of treatment with diuretics). As in an initiation of treatment along with the specified drugs, and periodically after the end of treatment, it is necessary to provide the corresponding intake of liquid in an organism and control of function of kidneys.
Gold drugs.
It was in rare instances reported about nitritoidny reactions (symptoms: face reddening, nausea, vomiting and arterial hypotension) at use of injection drugs of gold (sodium aurotimalat) together with APF inhibitors, including from enalapril a maleate.
Sympathomimetics
Sympathomimetics can weaken hypotensive action of IAPF.
Antidiabetic medicines
indicate Results of researches of epidemiology possible strengthening of hypoglycemic action of antidiabetic means (insulin, oral hypoglycemic means) at simultaneous use of IAPF, at the same time there is a risk of development of a hypoglycemia. Obviously, such cases take place, in particular, in the first weeks of the combined treatment and also at patients with decrease in renal function.
Alcohol
Alcohol enhances hypotensive effect of IAPF.
Acetilsalicylic acid, thrombolytic means and beta-blockers
of Enalapril a maleate it is possible, without being afraid, to appoint along with acetilsalicylic acid (in cardiological doses), thrombolytic means and beta-blockers.
Special instructions
Symptomatic hypotension
In an uncomplicated arterial hypertension the hypotonia is observed seldom.
At a lack of liquid of an organism, for example, owing to therapy by diuretics, the food which is grown poor by salts, dialysis, a diarrhea or vomiting at the patients having an arterial hypertension at treatment of Berliprilom® the simptomny hypotonia develops more often. At patients with heart failure - the followed renal failure or without that - observed simptomny hypotonia. In particular, it can concern patients with heavy heart failure whose severity of a disease is expressed in high doses of loopback diuretics, a hyponatremia or in decrease in renal function. Treatment of such patients – if is necessary selection of a new dose of Berliprila® and/or diuretic – it is necessary to begin and carry out under control of the doctor. In this way arrive also in case of patients with coronary heart disease or cerebrovascular pathology at which excessive falling of blood pressure can lead to a myocardial infarction or a cerebral stroke.
In case of development of hypotonia of the patient it is necessary to lay in horizontal position and – if it is necessary – to carry out intravenous infusion of solution of sodium of chloride. Passing hypotonic reaction is not a contraindication for further treatment which can, usually, be carried out without problems after normalization (by means of completion of volume of the circulating blood) arterial blood pressure.
At some patients with heart failure who have normal or low figures of arterial blood pressure the additional decrease in arterial system blood pressure at drug Berlipril® use can be observed. This effect is expected, and, as a rule there is no reason for the treatment termination. If arterial hypotension becomes symptomatic, there can be necessary a dose decline of Berliprila® and/or diuretic and/or cancellation of Berliprila®.
The aortal or mitral stenosis / a hypertrophic cardiomyopathy
As well as other vazodilatator, APF inhibitors should be applied with extra care at patients with a left ventricular stenosis or a stenosis of an aorta and also to avoid use of drug in cases of cardiogenic shock and hemodynamically caused obstruction
of the Renal failure
in case of a renal failure (clearance of creatinine & lt, 80 ml/minute) the initial dose of enalapril of a maleate should be selected depending on an indicator of clearance of creatinine at the patient, and a lowering of arterial pressure, after from degree. Continuous monitoring of levels of potassium and creatinine at such patients is a part of standard medical practice.
It was reported about a renal failure in interrelation using maleate enalapril at patients with heavy heart failure or with the diseases of kidneys which are the cornerstone of this pathology, including a stenosis of renal arteries. At timely diagnosis and the corresponding treatment the renal failure at enalapril therapy by a maleate has, usually, reversible character.
At some patients having an arterial hypertension who have no diseases of kidneys the maleate enalapril combination with diuretic can lead to increase in level of urea and creatinine in serum. In such cases there can be a need of reduction of a dose of enalapril of a maleate and/or cancellation of diuretic. At the same time the reason of these phenomena should think of a possible stenosis of renal arteries as.
The renovascular hypertension
At patients with a bilateral stenosis of renal arteries or a renal artery stenosis of the only functioning kidney treatment of IAPF constitutes special danger of falling of blood pressure or development of a renal failure. At the same time there can be a loss of renal function which is often shown only easy changes of indicators of creatinine of serum. Treatment of these patients needs to be begun with low doses and under strict medical observation, carefully titrating a dose and controlling renal function.
Transplantation of kidneys
Experience of use of Berliprila® for the patients who recently transferred transplantation of a kidney no. Therefore treatment of such patients this drug is not recommended.
A liver failure
At treatment of IAPF the syndrome beginning with cholestatic jaundice and progressing up to lightning hepatic necrosis was occasionally observed (sometimes with a lethal outcome). The pathogenesis of this syndrome is not clear. In case of patients who at treatment of IAPF have a jaundice or distinct increase in level of liver enzymes the cancellation of IAPF and the corresponding treatment are necessary.
A neutropenia / agranulocytosis
It was reported about a neutropenia/agranulocytosis, thrombocytopenia and anemia at the patients receiving IAPF. At patients with normal renal function and without special risk factors the neutropenia appears seldom. At the patients suffering from collagenoses with involvement in process of vessels and also being on treatment by immunodepressants, Allopyrinolum, procaineamide or at patients with existence of several of the listed risk factors, enalapril the maleate has to be applied extremely carefully, in particular, if depression of function of kidneys takes place. Some of these patients had serious infectious diseases which in certain cases did not give in to intensive antibiotic treatment. If these patients accept enalapril a maleate, then regular control of number of leukocytes is recommended to them and also it is necessary to oblige to report them to the doctor about all symptoms of any infection.
Hypersensitivity / a Quincke's disease
It was reported about Quincke's diseases with involvement of the face, extremities, lips, language, voice folds and/or throats at the patients treated by IAPF including Berlipril®. During treatment they can appear at any time. In these cases of Berlipril® it is necessary to cancel immediately. That to discharge from hospital to be convinced of the full return ra
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