Berlipril 10 mg (30 tablets)
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The instruction for medical use
of Берлиприл® 10 medicine
the Trade name
Берлиприл® 10
International unlicensed
name Enalapril Dosage Form
of the Tablet of 10 mg
Structure
One tablet contains
active agent - enalapril a maleate of 10 mg,
excipients: lactoses monohydrate, magnesium carbonate of the main easy, sodium salt of the glikolyat of starch (type A), gelatin, silicon dioxide colloidal anhydrous, magnesium stearate, gland oxide brown (E 172).
The description
the Pale brown tablets slightly biconvex with slanted edges and a notch for division on one party
Pharmacotherapeutic group
the Drugs influencing a system renin-angiotensin. Angiotenzinkonvertiruyushchy enzyme (AKF) inhibitors.
AKF inhibitors. Enalapril
the ATX C09AA02 Code
the Pharmacological
Pharmacokinetics Absorption Later properties of oral administration of enalapril a maleate 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®, existence of food in digestive tract, does not influence extent of its absorption.
Enalapril the maleate accepted orally after the absorption is exposed to fast and full-scale hydrolysis to enalaprilat, powerful 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. At constant 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 kilogram of weight.
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), the level of content of enalapril was not defined.
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 effect of Berliprila®, at least, is summarized. 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 slows 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.
Enalapril reduces risk of death and hospitalization in connection with aggravation of symptoms of patients with symptoms of heart failure. At patients with asymptomatic dysfunction of a left ventricle, treatment by enalapril reduces a likelihood of developing heart failure and mortality. Smaller frequency of development of a myocardial infarction and hospitalization concerning unstable stenocardia is observed at the patients from symptomatic or asymptomatic dysfunction of a left ventricle receiving enalapril.
Indications
- treatment of an arterial hypertension
- treatment simptomny (with existence of symptoms) warm insufficiency
- prevention of simptomny warm insufficiency at patients with asymptomatic dysfunction of a left ventricle (ejection fraction from a left ventricle ≤ 35%)
the Route of administration and doses
Meal does not influence maleate enalapril absorption.
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.
In need of reception of higher or low doses there are tablets with the corresponding content in them active ingredient.
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® belong to various dosages: 5 mg of enalapril of a maleate (Берлиприл® 5), 10 mg of enalapril of a maleate (Берлиприл® 10) and 20 mg of enalapril of a maleate (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
(Kr-Cl) of ml/min.
the Initial dose
of mg/day
30 & lt, Kr-Cl & lt, 80
ml/min. 5 - 10 mg
10 & lt, Kr-Cl ≤ 30
ml/min. 2.5 mg
of Kr-Cl ≤ 10
ml/min. 2.5 mg in day of carrying out dialysis *
* see 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.
Side effects
Very often (³ 1/10)
- a disorder of vision, in the form of illegibility of sight
- dizziness
- cough
- nausea
- an asthenia
Often (from ³ 1/100 to & lt, 1/10)
- a headache, a depression
- hypotonia (including orthostatic hypotonia), a faint, thorax pain, disturbances of a warm rhythm, stenocardia, tachycardia
- short wind
- diarrhea, an abdominal pain, change of flavoring perception
- rash, hypersensitivity / a Quincke's disease (it was reported about a Quincke's disease with involvement of the face, extremities, lips, language, voice folds and/or throats)
- fatigue
- a hyperpotassemia, increase in level of serumal creatinine
Sometimes (from ³ 1/1000 to & lt, 1/100)
- anemia (including aplastic and hemolytic anemia)
- a hypoglycemia, increase in level of urea of serum, a hyponatremia
- confusion of consciousness, drowsiness, insomnia, nervousness, paresthesias, dizziness
- 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
- a rhinorrhea, a sore throat and an osiplost, bronchospasm/asthma
- intestinal impassability, pancreatitis, vomiting, dyspepsia, a constipation, lack of appetite, the phenomenon of irritation of a stomach, dryness in a mouth, a round ulcer
- perspiration, an itching, a small tortoiseshell, an alopecia
- disorders of renal function, a renal failure, a proteinuria
- impotence
- muscular spasms, inflows, sonitus, discomfort, fever
- increase in level of urea of serum, a hyponatremia
Seldom (from ³ 1/10000 to & lt, 1/1000)
- a neutropenia, decrease in hemoglobin and a hematocrit, thrombocytopenia, an agranulocytosis, increase in level of liver enzymes, increase in indicators of bilirubin of serum, 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 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.
It is unknown: on the available data does not give in to assessment.
- A syndrome of disturbance of 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, increase by SOE, eosinophilia and leukocytosis. Skin rash, a photosensitization or other skin manifestations can take place.
Contraindications
- the increased sensitivity to enalapril to a maleate, other components of drug, other inhibitors of angiotensin-converting enzyme (IAPF)
- existence in the anamnesis of the angioneurotic hypostasis connected with the previous therapy of IAPF
- a hereditary or idiopathic Quincke's disease
- pregnancy
- hypersensitivity to lactose (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 fill a lack of liquid and salts of an organism or to begin enalapril therapy with a maleate (from 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 concentration of lithium in serum can increase that can cause 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 with Berliprilom®.
Sympathomimetics
Sympathomimetics can weaken hypotensive action of IAPF.
Antidiabetic medicines
indicate Results of epidemiological researches 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 Berlipril® 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, the patient needs to be laid in horizontal position and if it is necessary, to carry out intravenous infusion of normal saline 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 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.
Renal failures
in case of a renal failure (clearance of creatinine & lt, 80 ml/minute) an initial dose of enalapril should be selected depending on an indicator of clearance of creatinine at the patient, and after – from degree of a lowering of arterial pressure. 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 decrease in renal function, 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 selecting 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 full involution of symptoms, for the patient it is necessary to establish careful observation. Even if the Quincke's disease affects only language in the absence of respiratory insufficiency, nevertheless long observation as administrations of antihistamines and corticosteroids it can appear insufficiently is necessary.
It was reported about extremely exceptional cases of lethal outcomes against the background of development of a Quincke's disease of a throat or language. In hypostasis of language, an epiglottis or a throat the risk of obstruction of airways, especially at the patients who underwent an operation on airways is increased. Quincke's diseases with involvement of a throat can end with a lethal outcome. When involving language, voice folds or a throat with the advent of threat of obstruction of airways it is necessary to begin urgently the corresponding treatment (for example hypodermic introduction of 0.3-0.5 ml of solution of epinephrine
) and/or to take measures for ensuring passability of airways.
At black patients in comparison with not black it was reported about higher frequency of cases of Quincke's diseases at therapy of IAPF.
Patients with existence in the anamnesis of the Quincke's disease caused not by IAPF perhaps have an increased risk of its development at reception of IAPF.
Anaphylactic reactions during the desensibilizing therapy directed against poison of insects
Occasionally during the performing the desensibilizing therapy directed against poison of insects, and simultaneous use of IAPF were observed the anaphylactic reactions posing a threat for life. If the specific immunotherapy (desensibiliziya) directed against poison of insects is shown, then IAPF needs to be replaced temporarily with other means for treatment of an arterial hypertension or heart failure.
Anaphylactic reactions during LPNP-afereza (a plasma exchange of lipoproteins of low density)
during LPNP-afereza using dextransulphate at simultaneous use of IAPF, life-threatening anaphylactic reactions occasionally took place. If LPNP-aferez it is shown, then IAPF needs to be replaced temporarily with other means for treatment of an arterial hypertension or heart failure.
The patients who are on treatment by a hemodialysis method
When using membranes of high-flukh (for example, "AN 69") when carrying out dialysis and simultaneous use of IAPF it was reported about anaphylactoid reactions. Concerning such patients it is necessary to resolve an issue of use of other type of membranes for dialysis or prescribing of antihypertensive drug of other class.
Hypoglycemia
the Patients having diabetes and being on treatment by oral antidiabetic drugs or insulin in an initiation of treatment of IAPF should report about need of careful control of indicators of glucose of blood, especially in the first month of a concomitant use of the specified drugs.
Cough
It was reported about the cough connected with use of IAPF. The lack of a phlegm is typical, cough has persistent character and passes after treatment cancellation. At the differential diagnosis of cough it is necessary to consider the cough caused by IAPF-therapy also.
Operational interventions / anesthesia
At patients to whom extensive surgery or anesthesia by means of the drugs reducing blood pressure is carried out of enalapril a maleate slows down (as reaction to compensatory secretion of renin) production of angiotensin II. At development on this soil of hypotonia, it can be adjusted by completion of volume of the circulating blood.
A hyperpotassemia
At some patients at treatment of IAPF, including enalapril, increase in concentration of serumal potassium was observed. Risk factors of development of a hyperpotassemia are: a renal failure, a renal failure, advanced age (70 years are more senior), diabetes, such intercurrent factors as dehydration, a sharp warm decompensation, a metabolic acidosis and simultaneous treatment by kaliysberegayushchy diuretics (e.g., Spironolactonum, eplerenon
to Develop
of Берлиприл® 10 medicine
the Trade name
Берлиприл® 10
International unlicensed
name Enalapril Dosage Form
of the Tablet of 10 mg
Structure
One tablet contains
active agent - enalapril a maleate of 10 mg,
excipients: lactoses monohydrate, magnesium carbonate of the main easy, sodium salt of the glikolyat of starch (type A), gelatin, silicon dioxide colloidal anhydrous, magnesium stearate, gland oxide brown (E 172).
The description
the Pale brown tablets slightly biconvex with slanted edges and a notch for division on one party
Pharmacotherapeutic group
the Drugs influencing a system renin-angiotensin. Angiotenzinkonvertiruyushchy enzyme (AKF) inhibitors.
AKF inhibitors. Enalapril
the ATX C09AA02 Code
the Pharmacological
Pharmacokinetics Absorption Later properties of oral administration of enalapril a maleate 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®, existence of food in digestive tract, does not influence extent of its absorption.
Enalapril the maleate accepted orally after the absorption is exposed to fast and full-scale hydrolysis to enalaprilat, powerful 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. At constant 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 kilogram of weight.
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), the level of content of enalapril was not defined.
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 effect of Berliprila®, at least, is summarized. 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 slows 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.
Enalapril reduces risk of death and hospitalization in connection with aggravation of symptoms of patients with symptoms of heart failure. At patients with asymptomatic dysfunction of a left ventricle, treatment by enalapril reduces a likelihood of developing heart failure and mortality. Smaller frequency of development of a myocardial infarction and hospitalization concerning unstable stenocardia is observed at the patients from symptomatic or asymptomatic dysfunction of a left ventricle receiving enalapril.
Indications
- treatment of an arterial hypertension
- treatment simptomny (with existence of symptoms) warm insufficiency
- prevention of simptomny warm insufficiency at patients with asymptomatic dysfunction of a left ventricle (ejection fraction from a left ventricle ≤ 35%)
the Route of administration and doses
Meal does not influence maleate enalapril absorption.
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.
In need of reception of higher or low doses there are tablets with the corresponding content in them active ingredient.
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® belong to various dosages: 5 mg of enalapril of a maleate (Берлиприл® 5), 10 mg of enalapril of a maleate (Берлиприл® 10) and 20 mg of enalapril of a maleate (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
(Kr-Cl) of ml/min.
the Initial dose
of mg/day
30 & lt, Kr-Cl & lt, 80
ml/min. 5 - 10 mg
10 & lt, Kr-Cl ≤ 30
ml/min. 2.5 mg
of Kr-Cl ≤ 10
ml/min. 2.5 mg in day of carrying out dialysis *
* see 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.
Side effects
Very often (³ 1/10)
- a disorder of vision, in the form of illegibility of sight
- dizziness
- cough
- nausea
- an asthenia
Often (from ³ 1/100 to & lt, 1/10)
- a headache, a depression
- hypotonia (including orthostatic hypotonia), a faint, thorax pain, disturbances of a warm rhythm, stenocardia, tachycardia
- short wind
- diarrhea, an abdominal pain, change of flavoring perception
- rash, hypersensitivity / a Quincke's disease (it was reported about a Quincke's disease with involvement of the face, extremities, lips, language, voice folds and/or throats)
- fatigue
- a hyperpotassemia, increase in level of serumal creatinine
Sometimes (from ³ 1/1000 to & lt, 1/100)
- anemia (including aplastic and hemolytic anemia)
- a hypoglycemia, increase in level of urea of serum, a hyponatremia
- confusion of consciousness, drowsiness, insomnia, nervousness, paresthesias, dizziness
- 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
- a rhinorrhea, a sore throat and an osiplost, bronchospasm/asthma
- intestinal impassability, pancreatitis, vomiting, dyspepsia, a constipation, lack of appetite, the phenomenon of irritation of a stomach, dryness in a mouth, a round ulcer
- perspiration, an itching, a small tortoiseshell, an alopecia
- disorders of renal function, a renal failure, a proteinuria
- impotence
- muscular spasms, inflows, sonitus, discomfort, fever
- increase in level of urea of serum, a hyponatremia
Seldom (from ³ 1/10000 to & lt, 1/1000)
- a neutropenia, decrease in hemoglobin and a hematocrit, thrombocytopenia, an agranulocytosis, increase in level of liver enzymes, increase in indicators of bilirubin of serum, 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 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.
It is unknown: on the available data does not give in to assessment.
- A syndrome of disturbance of 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, increase by SOE, eosinophilia and leukocytosis. Skin rash, a photosensitization or other skin manifestations can take place.
Contraindications
- the increased sensitivity to enalapril to a maleate, other components of drug, other inhibitors of angiotensin-converting enzyme (IAPF)
- existence in the anamnesis of the angioneurotic hypostasis connected with the previous therapy of IAPF
- a hereditary or idiopathic Quincke's disease
- pregnancy
- hypersensitivity to lactose (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 fill a lack of liquid and salts of an organism or to begin enalapril therapy with a maleate (from 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 concentration of lithium in serum can increase that can cause 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 with Berliprilom®.
Sympathomimetics
Sympathomimetics can weaken hypotensive action of IAPF.
Antidiabetic medicines
indicate Results of epidemiological researches 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 Berlipril® 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, the patient needs to be laid in horizontal position and if it is necessary, to carry out intravenous infusion of normal saline 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 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.
Renal failures
in case of a renal failure (clearance of creatinine & lt, 80 ml/minute) an initial dose of enalapril should be selected depending on an indicator of clearance of creatinine at the patient, and after – from degree of a lowering of arterial pressure. 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 decrease in renal function, 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 selecting 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 full involution of symptoms, for the patient it is necessary to establish careful observation. Even if the Quincke's disease affects only language in the absence of respiratory insufficiency, nevertheless long observation as administrations of antihistamines and corticosteroids it can appear insufficiently is necessary.
It was reported about extremely exceptional cases of lethal outcomes against the background of development of a Quincke's disease of a throat or language. In hypostasis of language, an epiglottis or a throat the risk of obstruction of airways, especially at the patients who underwent an operation on airways is increased. Quincke's diseases with involvement of a throat can end with a lethal outcome. When involving language, voice folds or a throat with the advent of threat of obstruction of airways it is necessary to begin urgently the corresponding treatment (for example hypodermic introduction of 0.3-0.5 ml of solution of epinephrine
) and/or to take measures for ensuring passability of airways.
At black patients in comparison with not black it was reported about higher frequency of cases of Quincke's diseases at therapy of IAPF.
Patients with existence in the anamnesis of the Quincke's disease caused not by IAPF perhaps have an increased risk of its development at reception of IAPF.
Anaphylactic reactions during the desensibilizing therapy directed against poison of insects
Occasionally during the performing the desensibilizing therapy directed against poison of insects, and simultaneous use of IAPF were observed the anaphylactic reactions posing a threat for life. If the specific immunotherapy (desensibiliziya) directed against poison of insects is shown, then IAPF needs to be replaced temporarily with other means for treatment of an arterial hypertension or heart failure.
Anaphylactic reactions during LPNP-afereza (a plasma exchange of lipoproteins of low density)
during LPNP-afereza using dextransulphate at simultaneous use of IAPF, life-threatening anaphylactic reactions occasionally took place. If LPNP-aferez it is shown, then IAPF needs to be replaced temporarily with other means for treatment of an arterial hypertension or heart failure.
The patients who are on treatment by a hemodialysis method
When using membranes of high-flukh (for example, "AN 69") when carrying out dialysis and simultaneous use of IAPF it was reported about anaphylactoid reactions. Concerning such patients it is necessary to resolve an issue of use of other type of membranes for dialysis or prescribing of antihypertensive drug of other class.
Hypoglycemia
the Patients having diabetes and being on treatment by oral antidiabetic drugs or insulin in an initiation of treatment of IAPF should report about need of careful control of indicators of glucose of blood, especially in the first month of a concomitant use of the specified drugs.
Cough
It was reported about the cough connected with use of IAPF. The lack of a phlegm is typical, cough has persistent character and passes after treatment cancellation. At the differential diagnosis of cough it is necessary to consider the cough caused by IAPF-therapy also.
Operational interventions / anesthesia
At patients to whom extensive surgery or anesthesia by means of the drugs reducing blood pressure is carried out of enalapril a maleate slows down (as reaction to compensatory secretion of renin) production of angiotensin II. At development on this soil of hypotonia, it can be adjusted by completion of volume of the circulating blood.
A hyperpotassemia
At some patients at treatment of IAPF, including enalapril, increase in concentration of serumal potassium was observed. Risk factors of development of a hyperpotassemia are: a renal failure, a renal failure, advanced age (70 years are more senior), diabetes, such intercurrent factors as dehydration, a sharp warm decompensation, a metabolic acidosis and simultaneous treatment by kaliysberegayushchy diuretics (e.g., Spironolactonum, eplerenon
to Develop
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