The instruction for medical use
of Eneas® medicine
the Trade name
of Eneas®
the International unlicensed name
Is not present
the Dosage form
of the Tablet of 10 mg / 20 mg
Structure
One tablet contains
active agents: enalapril maleate of 10 mg
nitrendipin 20 mg,
excipients: Natrii hydrocarbonas, cellulose microcrystalline, starch corn, sodium lauryl sulfate, K-25 povidone, magnesium stearate, lactoses monohydrate.
The description
Oblong, biconvex tablets of yellow color with an engraving of E/N on one party
the AKF Pharmacotherapeutic group inhibitors in a combination with blockers of slow calcium channels.
The code of automatic telephone exchange C09BB
the Pharmacological
Pharmacokinetics Enalapril properties after oral administration is quickly soaked up, the maximum concentration in blood serum is reached within 1 hour. 60% of the accepted dose get to a blood stream, and this size does not depend on meal. Linking with proteins of blood plasma makes 50-60%.
After absorption, enalapril is quickly and substantially hydrolyzed to enalaprilat which is active inhibitor of angiotensin-converting enzyme. The maximum concentration of enalaprilat in blood serum is reached in 3-4 hours after oral administration of enalapril. Enalaprilat is removed generally through kidneys. In urine generally intact enalapril and enalaprilat (40% of the accepted dose) are found. Considering the volume of transformation of enalapril into enalaprilat, it is possible to draw a conclusion on lack of other ways of metabolism of enalapril.
At patients with normal function of kidneys the equilibrium concentration of enalaprilat in blood serum is reached for the 4th day of intake of enalapril. Effective time of semi-life of enalaprilat after multiple dose of enalapril is 11 hours. Extent of absorption and hydrolysis of enalapril are identical at all recommended therapeutic doses.
Nitrendipin is soaked up quickly and almost completely (88%). The maximum concentration in blood plasma is reached in 1-3 hours after reception.
The bioavailability of drug is 20-30% because of the significant metabolism at the first passing through a liver. Nitrendipin contacts proteins of blood plasma (albumine) for 96-98% therefore it is not dialyzed. Distribution volume in an equilibrium state equals 5-9 l/kg therefore the hemodialysis and a plasma exchange are inefficient.
Nitrendipin is almost completely metabolized in a liver, generally by oxidation. Metabolites are inactive. Nitrendipin is brought generally through kidneys in the form of metabolites (about 77% of the accepted dose), and the rest is removed with bile and a stake. In the form of not changed nitrendipin with urine less than 0.1% of the accepted dose are removed.
Time of semi-removal of a nitrendipin after oral administration is 8-12 hours. Accumulation of active agent or its metabolites is not revealed. As nitrendipin it eliminirutsya generally by metabolism, at patients with chronic diseases of a liver the concentration of substance in blood plasma is increased. However with disturbance of functions of kidneys of titration of a dose it is not required from patients.
Researches of interaction of enalapril and a nitrendipin at healthy volunteers did not reveal change of pharmacokinetics of a nitrendipin. As for enalapril, its bioavailability was a little increased at reception of this combination, but it, apparently, has no clinical value. The bioavailability of a nitrendipin at use of the combined drug was higher, than at use of two drugs separately.
A pharmacodynamics
Two Eneasa® active components have complementary hypotensive effect.
After absorption, enalapril is hydrolyzed to enalaprilat which, actually, and is inhibitor of angiotensin-converting enzyme (APF). APF is a dipeptidilpeptidaza which catalyzes transformation of angiotensin I into vasoconstrictive substance – angiotensin II. Braking of activity of APF leads to decrease in concentration of angiotensin II in blood plasma that is followed by increase in activity of renin of blood plasma (owing to weakening of control of secretion of renin on a negative feedback mechanism) and oppression of secretion of Aldosteronum.
Though it is supposed that enalapril reduces the arterial blood pressure (ABP) mainly due to braking of activity renin-angiotensin-aldosteronovoy of a system which plays the main role in regulation of pressure of blood, but enalapril has hypotensive effect even at patients with arterial hypertension with the low level of renin.
Prolonged use of enalapril at patients with the essential hypertension which is followed by a renal failure can lead to improvement of function of kidneys in the form of increase in glomerular filtration rate.
Nitrendipin is a blocker of calcium channels of group digidropiridina1-4 which works as antihypertensive. The mechanism of action of a nitrendipin consists in blockade of an entrance of calcium ions to smooth muscle cells of vessels. This action has the following pharmacological consequences: prevention of an excess input of calcium in cells, easing calcium - dependent reduction of muscles of vessels, decrease in peripheric resistance of vessels, decrease patholologically supertension of blood and weak natriuretic effect, especially in an initiation of treatment.
In researches within the III phase of clinical trials the use of Eneasa® for the patients with arterial hypertension insensitive to monotherapy with enalapril of 10 mg or nitrendipiny 20 mg, reduced both the diastolic, and systolic pressure of blood more effectively, and provided higher frequency of effect.
Indications
- arterial hypertension
the Route of administration and doses
Is recommended to select doses of components by titration individually.
In the presence of clinical indications it is possible to consider the possibility of direct transition from monotherapy to the fixed dose combination.
Tablets should be swallowed entirely, without breaking and without chewing, washing down with enough water.
Adult, including elderly patients:
The dosage 1 tablet a day is recommended.
Patients with disturbance of functions of a liver:
Энеас® it is contraindicated to patients with heavy disturbance of functions of a liver. Patients with disturbance of functions of kidneys:
Энеас® it is contraindicated to patients with heavy disturbance of functions of kidneys (clearance of creatinine less than 10 ml/min.) and the patient who is on a hemodialysis.
Children and teenagers:
There are no data on use of Eneasa® for children and teenagers therefore it cannot be applied at this category of patients.
Side effects
Adverse reactions, at use of Eneasa®, are similar to reactions to reception of each of drug components separately.
Often
- rushes of blood, hypostases, a headache
Infrequently
- atrial bradycardia, fibrillation of auricles, hypotension and/or orthostatic hypotension, a stethalgia, stenocardia, a myocardial infarction, passing disturbance of cerebral circulation, a stroke, cardiac arrest, an embolism and a heart attack of lungs, a fluid lungs, short wind
- an oliguria, a proteinuria, in certain cases with the accompanying deterioration in function of kidneys, pain in ileal area
- short wind, sinusitis, rhinitis
- an abdominal pain, an abdominal distension, a digestive disturbance, nausea,
dyspepsia, loss of appetite, vomiting, change or passing loss
of flavoring feelings, loss of sense of smell diarrhea, a constipation, a hyperplasia
of gums
- urticaria, erythematic rash, an itching, a Quincke's disease of lips, persons and/or extremities
- a depression, a sleep disorder, impotence, peripheral neuropathy with paresthesia, disturbance of maintenance of balance, nervousness, confusion of consciousness myalgia, vertigo
- sonitus, a sight zamutneniye, xerophthalmus, dacryagogue, a disorder of vision
- anemia, a trombotsitemiya, a neutropenia, an eosinophilia (in some cases – an agranulocytosis or a pancytopenia), especially at patients with disturbance of functions of kidneys,
- collagenoses at the patients receiving Allopyrinolum, procaineamide or immunodepressants, increase in level of urea, creatinine and potassium in blood serum, decrease in level of sodium in blood serum, strengthening of removal of albumine with urine, especially at patients with disturbance of functions of kidneys, heavy heart failure, an arterial hypertension of renal origin and diabetes (at the last - a hyperpotassemia).
Very seldom
- dizziness, weakness, an asthenia, drowsiness, a hypothermia, a grippopodobny state, a tremor and a muscular spasm
- heart failure, arrhythmia, tachycardia, heartbeat, peripheral hypostasis, rushes of blood, vasodilatation, ischemia of peripheral vessels, heavy hypertensia or hypertensia of renal origin, especially in an initiation of treatment and at patients with deficiency of liquid and/or salts, the syncope is after increase in a dose of enalapril of a maleate and/or use of diuretics
- renal failures, in some cases progressing to an acute renal failure
- dry cough, a sore throat, hoarseness, bronchitis, bronchospasm/asthma, pulmonary infiltrates, stomatitis, a glossitis, dryness in a mouth, pneumonia, the Quincke's disease of a throat, throat and/or language bringing in isolated cases to deadly impassability of airways, frequency it is raised among black patients, pharyngitis, tracheitis
- disturbance of functions of a liver, hepatitis, a liver failure, pancreatitis, impassability of intestines, the syndrome beginning with cholestatic jaundice and progressing to liver necrosis, in certain cases from the death
- allergic skin reactions, for example, a dieback, a bladderwort, a multiformny erythema, exfoliative dermatitis, Stephens-Johnson's syndrome or a toxic necrolysis of epidermis
- the phenomena reminding psoriasis, photosensitivity, sweating strengthening, an alopecia, onikholizis and strengthening of a syndrome of Reynaud. Skin manifestations can be followed by fever, a myalgia/miositis, arthralgia/arthritis, a vasculitis, a serositis, an eosinophilia, a leukocytosis, increase in SOE and/or ANA. At suspicion on heavy skin reaction the treatment is stopped
- a hamaturia, decrease in level of hemoglobin, a hematocrit, the maintenance of leukocytes or thrombocytes, hemolysis / hemolytic anemia (also in combination with deficiency of glyukozo-6-phosphate-dehydrogenase), increase in level of bilirubin and liver enzymes, a hypopotassemia, a leukopenia
- increase in frequency of urination
-
the Contraindication gynecomastia
- hypersensitivity to enalapril, a nitrendipin or any excipient of drug
- existence in the anamnesis of the vascular hypostasis connected with use of inhibitors of angiotensin-converting enzyme, or a hereditary/idiopathic Quincke's disease
- pregnancy and the period of a lactation
- the states which are followed by an unstable hemodynamics, in particular, vascular collapse, cardiogenic shock, an acute heart failure, a sharp coronary syndrome, an acute stroke
- a bilateral stenosis of renal arteries or a unilateral stenosis in the presence of only one kidney
- a stenosis of the aortal or mitral valve, significant for a hemodynamics, and a hypertrophic cardiomyopathy
- heavy renal failures (clearance of creatinine less than 10 ml/min.) or carrying out a hemodialysis
- heavy abnormal liver functions
Medicinal interactions
Hypotensive effect of Eneasa® can amplify other antihypertensives, for example, diuretics, beta-blockers or alpha blockers of type of Prazozinum. Besides, components of a combination can show the following interactions:
Enalapril maleate:
Combinations which should be applied with care:
Kaliysberegayushchy diuretics and drugs of potassium
APF Inhibitors weaken the potassium loss caused by diuretics. The Kaliysberegayushchy diuretics, drugs of potassium and other drugs capable to increase potassium level in blood serum (e.g., heparin) can have additive impact on potassium level in blood serum, especially at patients with a renal failure.
If combined use of such drugs is necessary, for example, for elimination of a hypopotassemia, then at the same time it is necessary to show care and to often control potassium level in blood serum.
Lities
Use of enalapril in a combination with lithium are not recommended because of risk of strong increase in level of lithium in blood serum with the accompanying heavy neurotoxicity. If combined use of these drugs is necessary, then it is necessary to control carefully lithium level in blood serum.
Non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NPVP) and APF inhibitors it is additive increase potassium level in blood serum that can lead to deterioration in function of kidneys. With dehydration such combination can cause an acute renal failure due to direct impact on glomerular filtration in elderly patients and patients. Moreover, NPVP can weaken hypotensive effect of APF inhibitors.
Hypoglycemic effect of these drugs therefore it is necessary to control carefully glucose level in blood can strengthen the oral anti-diabetic drugs Enalapril.
Baclofenum
Can enhance hypotensive effect. In need of the combined use it is necessary to control arterial blood pressure and to titrate a dose.
Neuroleptics
Use together with these drugs can cause postural hypotension.
Antidepressants
Use together with tricyclic antidepressants can cause postural hypotension.
Allopyrinolum, cytostatics, immunodepressants, system corticosteroids, procaineamide
of the Combination can cause a leukopenia.
Combinations which should be considered
Amifostin
Kombination strengthens hypotensive action.
Nitrendipin
Tsimetidin and
Tsimetidin's ranitidine and, to a lesser extent, ranitidine, can increase concentration of a nitrendipin in blood plasma, but the clinical value of these data is unknown.
Digoxin
Enalapril was applied together with digoxin without any signs of clinically significant adverse interaction. Simultaneous use of a nitrendipin and digoxin can lead to increase in concentration of digoxin in blood plasma. Therefore it is necessary to control emergence of symptoms of overdose of digoxin or if it is necessary, to control concentration of digoxin in blood plasma.
Muscle relaxants
Use of a nitrendipin can increase duration and intensity of effect of muscle relaxants, for example, a pankuroniya.
Grapefruit juice suppresses oxidizing metabolism of a nitrendipin. Reception of the last with grapefruit juice increases concentration of a nitrendipin in blood plasma that can strengthen its hypotensive action.
Nitrendipin is metabolized by an isoenzyme 3A4 of P450 cytochrome in a mucous membrane of intestines and in a liver. The substances stimulating activity of this enzyme, for example, anticonvulsant drugs (Phenytoinum, phenobarbital, carbamazepine) and rifampicin can reduce bioavailability of a nitrendipin considerably. The substances braking activity of this enzyme, for example, antifungal imidazoles (itrakonazol, etc.) can increase concentration of a nitrendipin in blood plasma.
Beta-blockers
Nitrendipin and beta-blockers work synergy. It can be of particular importance for patients at whom additional beta blockade does not allow to compensate sympathetic vascular reactions, and concerning such patients it is recommended to show care.
The special
instructions Quincke's Edema At use of APF inhibitors, especially in the first weeks, vascular hypostasis of extremities, persons, lips, mucous membranes, language, a throat or a throat can develop. However in rare instances heavy vascular hypostasis can develop also after prolonged use of APF inhibitors. In such cases the treatment is cancelled at once.
The vascular paraglossa, throats or drinks can be deadly, in these cases it is necessary to carry out the emergency therapy with hospitalization of the patient. It is necessary to watch the patient at least 12-24 hours, and he can be discharged from hospital only after total disappearance of symptoms.
A neutropenia/agranulocytosis
At use of APF inhibitors cases of a neutropenia / agranulocytosis, thrombocytopenia and anemia are registered. At patients with normal function of the kidneys which do not have other risk factors, the neutropenia happens seldom. Enalapril should be applied extremely carefully at patients with collagenoses, the patients receiving immunodepressants, Allopyrinolum or procaineamide, or their combination, especially in renal failures. At Eneas's use for such patients it is recommended to control fractions of leukocytes. During treatment it is necessary to instruct about need to report to the doctor about any symptoms of an infection. Энеас® it is necessary to cancel at identification of a neutropenia or suspicion on it (the maintenance of neutrophils less than 1000/mm3).
A renal failure
At use of inhibitors of angiotensin-converting enzyme for patients with disturbance of functions of kidneys it is necessary to control these functions, especially on the first weeks of treatment. It is necessary to show care concerning patients from activated renin-angiotenzinovoy a system.
For patients with a moderate renal failure (the clearance of creatinine more than 30 ml/min., blood serum creatinine
At some patients with APF inhibitors can lead pressure drop in an initiation of treatment to small further deterioration in function of kidneys. In such cases the acute renal failure which usually was reversible was observed.
Experience of use of Eneasa® for the patients who were recently exposed to renal transplantation no.
The proteinuria
At patients with a renal failure in rare instances developed a proteinuria. At patients with clinically significant proteinuria (more than 1 g/days) of Eneas® it is possible to apply only after careful assessment of a ratio advantage - risk and with regular control of clinical and biochemical indicators of blood.
Patients with an abnormal liver function
Sick with a weak or moderate abnormal liver function enalapril monotherapy with a maleate or nitrendipiny are not contraindicated, but as there is no experience of use of Eneasa® for such patients, drug should be used with care if for this purpose there are indications. In a liver failure the removal of a nitrendipin can be slowed down, especially at elderly patients, and it can lead to sharp falling of arterial blood pressure.
As separate cases of the syndrome beginning with cholestatic jaundice and progressing to liver necrosis from the death are described, at appearance of jaundice or the significant increase in level of liver enzymes it is necessary to stop treatment and to watch patients.
Hypertensia of renal origin / renal artery stenosis
At use of APF inhibitors for patients with arterial hypertension of renal origin, a bilateral stenosis of renal arteries or a unilateral renal artery stenosis in the presence of only one functioning kidney the risk of serious pressure drop of blood and a renal failure is increased. The renal failure can be followed only by little change of level of creatinine in blood serum even at patients with a unilateral renal artery stenosis.
A hyperpotassemia
APF Inhibitors can increase potassium level in blood serum, especially at patients with a renal failure and/or heart failure. Therefore it is not recommended to use at the same time kaliysberegayushchy diuretics or drugs of potassium. Ate these drugs are necessary, it is necessary to control potassium level in blood serum.
Hypotension
In certain cases of Eneas® can cause orthostatic hypotension which risk is increased at patients with the system activated renin-angiotensin-aldosteronovoy, for example, at the reduced volume of blood or reduced content of salts because of use of diuretics, the use of a saltless diet, carrying out a hemodialysis, presence of diarrhea or vomiting and also when weakening function of a left ventricle and in arterial hypertension of renal origin. At such patients at first it is necessary to correct the volume of blood or concentration of salts. At patients with heart failure (with the accompanying renal failure or without it) symptomatic hypotension can develop. The risk of pressure drop of blood at such patients is increased in the profound heart failure, at use of high doses of loopback diuretics and in the presence of a hyponatremia or a renal failure. In an initiation of treatment for such patients the careful observation is required. It also to treat patients with coronary heart disease or disturbance of cerebral circulation at which the considerable lowering of arterial pressure can lead to a myocardial infarction or a stroke.
At pressure drop of blood of the patient it is necessary to put horizontally and, if necessary, it is necessary to enter intravenously isotonic saline solution. Passing hypotensive reaction is not a contraindication for continuation of use of Eneasa® which usually does not represent difficulties after restoration of volume of the circulating blood and pressure of blood.
The stenosis of the aortal valve
At patients with difficulty of an exit of blood from a left ventricle APF inhibitors should be applied with care. If this difficulty is significant for a hemodynamics, then enalapril the maleate is contraindicated.
Cough
At use of APF inhibitors the appearance of cough is described. It is unproductive, constant cough which disappears at treatment cancellation.
Primary hyper aldosteronism
As a rule, patients with primary aldosteronism are not sensitive to the hypotensive drugs operating by braking of activity system renin-angiotenzinovoy. Maleate enalapril use in such cases is not recommended.
The patients who are on a hemodialysis
Use of Eneasa® when carrying out dialysis through high-speed membranes (from a poliakrilnitril, methylallyl-sodium sulphonate, e.g., AN69) can lead to anaphylactic reactions, including a face edema, rushes of blood, falling of arterial blood pressure and an asthma within several minutes after the beginning of dialysis. Therefore such combinations should be avoided.
Anaphylactic reactions in the course of an aferez of LDL and a desensitization to poison of insects
the Use of APF inhibitors when carrying out an aferez of lipoproteins of the low density (LDL) by means of sulfate of a dextran can be followed by life-threatening anaphylactic reactions. Use of APF inhibitors when carrying out a specific immunotherapy (desensitization) to poisons of insects (bees, wasps) can be followed by anaphylactoid reactions (e.g., falling of arterial blood pressure, short wind, vomiting, a skin allergy) which in certain cases can threaten life. In need of an aferez of LDL or a specific immunotherapy (desensitization) to poisons nasekomykhingibitor APF should be replaced temporarily with other means for treatment aretialny hypertensia or heart failure.
Surgery/anesthesia
At the patients who are exposed to large surgeries or anesthesia using the drugs reducing arterial blood pressure, enalapril blocks angiotensin II synthesis stimulated by compensatory emission of renin. At pressure drop of blood in these cases (if it is supposed that it happens on this mechanism) it should be adjusted increase in volume of blood plasma.
Influence on reproductive function
Use for men of blockers of calcium channels, for example, of a nitrendipin, in some cases was followed by reversible disturbances of a spermatogenesis, in communication with what it is recommended not to use drug by preparation of carrying out in vitro fertilization.
A warning of excipients
Patients with rare hereditary intolerance of a galactose, deficiency of Lapp lactase or disturbance of absorption of a glucose/galactose should not take this drug.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms.
Use of Eneasa® can be followed by the certain adverse reactions reducing the level of attention and complicating ability to driving of the vehicle and control of mechanisms. It is especially important in an initiation of treatment, when changing treatment and/or at a concomitant use of alcohol. Therefore it is recommended to show care, the satisfactory effect of treatment will not be reached yet.
Overdose
Symptoms: still cases of overdose of this combination are not registered.
Falling of arterial blood pressure will be the most probable manifestation of overdose of Eneasa®.
Treatment: primary detoxication by gastric lavage, administration of absorbents and/or sodium sulfate (whenever possible, the first 30 minutes). It is necessary to control vital signs.
At sharp falling of arterial blood pressure the patient of a leg needs to lift and to begin infusional therapy for increase in volume of the circulating blood. At inefficiency of these measures it is possible to begin infusion of vasoconstrictors, under control of arterial blood pressure. Seldom or never intravenous administration of catecholamines is necessary.
It is necessary to control constantly the level of electrolytes and creatinine in blood serum.
Enalapril is dialyzed with a speed of 62 ml/min., but it is necessary to avoid use of high-speed polyacrylonitrile membranes.
A form of release and packing
On 10 tablets in blister strip packaging. On the 3rd blister strip packagings together with the instruction for medical use in the state and Russian languages in a cardboard box.
At a temperature not above 30 °C
to Store storage conditions out of children's reach!
A period of storage
3 years
not to apply after expiry date
Prescription status
According to the prescription
of Proizvoditel Ferrer Internasyonal S.A., Spain
it Is provided Nikomed Austria, GmbH, Austria
the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods)
of Nikomed Ostevropa Marketing Service GmbH
Almaty, Begalin St. 136 and
Phone number (727) 2444004
Fax number (727) 2444005
To Develop the e-mail address of aknu@nycomed.com
of Eneas® medicine
the Trade name
of Eneas®
the International unlicensed name
Is not present
the Dosage form
of the Tablet of 10 mg / 20 mg
Structure
One tablet contains
active agents: enalapril maleate of 10 mg
nitrendipin 20 mg,
excipients: Natrii hydrocarbonas, cellulose microcrystalline, starch corn, sodium lauryl sulfate, K-25 povidone, magnesium stearate, lactoses monohydrate.
The description
Oblong, biconvex tablets of yellow color with an engraving of E/N on one party
the AKF Pharmacotherapeutic group inhibitors in a combination with blockers of slow calcium channels.
The code of automatic telephone exchange C09BB
the Pharmacological
Pharmacokinetics Enalapril properties after oral administration is quickly soaked up, the maximum concentration in blood serum is reached within 1 hour. 60% of the accepted dose get to a blood stream, and this size does not depend on meal. Linking with proteins of blood plasma makes 50-60%.
After absorption, enalapril is quickly and substantially hydrolyzed to enalaprilat which is active inhibitor of angiotensin-converting enzyme. The maximum concentration of enalaprilat in blood serum is reached in 3-4 hours after oral administration of enalapril. Enalaprilat is removed generally through kidneys. In urine generally intact enalapril and enalaprilat (40% of the accepted dose) are found. Considering the volume of transformation of enalapril into enalaprilat, it is possible to draw a conclusion on lack of other ways of metabolism of enalapril.
At patients with normal function of kidneys the equilibrium concentration of enalaprilat in blood serum is reached for the 4th day of intake of enalapril. Effective time of semi-life of enalaprilat after multiple dose of enalapril is 11 hours. Extent of absorption and hydrolysis of enalapril are identical at all recommended therapeutic doses.
Nitrendipin is soaked up quickly and almost completely (88%). The maximum concentration in blood plasma is reached in 1-3 hours after reception.
The bioavailability of drug is 20-30% because of the significant metabolism at the first passing through a liver. Nitrendipin contacts proteins of blood plasma (albumine) for 96-98% therefore it is not dialyzed. Distribution volume in an equilibrium state equals 5-9 l/kg therefore the hemodialysis and a plasma exchange are inefficient.
Nitrendipin is almost completely metabolized in a liver, generally by oxidation. Metabolites are inactive. Nitrendipin is brought generally through kidneys in the form of metabolites (about 77% of the accepted dose), and the rest is removed with bile and a stake. In the form of not changed nitrendipin with urine less than 0.1% of the accepted dose are removed.
Time of semi-removal of a nitrendipin after oral administration is 8-12 hours. Accumulation of active agent or its metabolites is not revealed. As nitrendipin it eliminirutsya generally by metabolism, at patients with chronic diseases of a liver the concentration of substance in blood plasma is increased. However with disturbance of functions of kidneys of titration of a dose it is not required from patients.
Researches of interaction of enalapril and a nitrendipin at healthy volunteers did not reveal change of pharmacokinetics of a nitrendipin. As for enalapril, its bioavailability was a little increased at reception of this combination, but it, apparently, has no clinical value. The bioavailability of a nitrendipin at use of the combined drug was higher, than at use of two drugs separately.
A pharmacodynamics
Two Eneasa® active components have complementary hypotensive effect.
After absorption, enalapril is hydrolyzed to enalaprilat which, actually, and is inhibitor of angiotensin-converting enzyme (APF). APF is a dipeptidilpeptidaza which catalyzes transformation of angiotensin I into vasoconstrictive substance – angiotensin II. Braking of activity of APF leads to decrease in concentration of angiotensin II in blood plasma that is followed by increase in activity of renin of blood plasma (owing to weakening of control of secretion of renin on a negative feedback mechanism) and oppression of secretion of Aldosteronum.
Though it is supposed that enalapril reduces the arterial blood pressure (ABP) mainly due to braking of activity renin-angiotensin-aldosteronovoy of a system which plays the main role in regulation of pressure of blood, but enalapril has hypotensive effect even at patients with arterial hypertension with the low level of renin.
Prolonged use of enalapril at patients with the essential hypertension which is followed by a renal failure can lead to improvement of function of kidneys in the form of increase in glomerular filtration rate.
Nitrendipin is a blocker of calcium channels of group digidropiridina1-4 which works as antihypertensive. The mechanism of action of a nitrendipin consists in blockade of an entrance of calcium ions to smooth muscle cells of vessels. This action has the following pharmacological consequences: prevention of an excess input of calcium in cells, easing calcium - dependent reduction of muscles of vessels, decrease in peripheric resistance of vessels, decrease patholologically supertension of blood and weak natriuretic effect, especially in an initiation of treatment.
In researches within the III phase of clinical trials the use of Eneasa® for the patients with arterial hypertension insensitive to monotherapy with enalapril of 10 mg or nitrendipiny 20 mg, reduced both the diastolic, and systolic pressure of blood more effectively, and provided higher frequency of effect.
Indications
- arterial hypertension
the Route of administration and doses
Is recommended to select doses of components by titration individually.
In the presence of clinical indications it is possible to consider the possibility of direct transition from monotherapy to the fixed dose combination.
Tablets should be swallowed entirely, without breaking and without chewing, washing down with enough water.
Adult, including elderly patients:
The dosage 1 tablet a day is recommended.
Patients with disturbance of functions of a liver:
Энеас® it is contraindicated to patients with heavy disturbance of functions of a liver. Patients with disturbance of functions of kidneys:
Энеас® it is contraindicated to patients with heavy disturbance of functions of kidneys (clearance of creatinine less than 10 ml/min.) and the patient who is on a hemodialysis.
Children and teenagers:
There are no data on use of Eneasa® for children and teenagers therefore it cannot be applied at this category of patients.
Side effects
Adverse reactions, at use of Eneasa®, are similar to reactions to reception of each of drug components separately.
Often
- rushes of blood, hypostases, a headache
Infrequently
- atrial bradycardia, fibrillation of auricles, hypotension and/or orthostatic hypotension, a stethalgia, stenocardia, a myocardial infarction, passing disturbance of cerebral circulation, a stroke, cardiac arrest, an embolism and a heart attack of lungs, a fluid lungs, short wind
- an oliguria, a proteinuria, in certain cases with the accompanying deterioration in function of kidneys, pain in ileal area
- short wind, sinusitis, rhinitis
- an abdominal pain, an abdominal distension, a digestive disturbance, nausea,
dyspepsia, loss of appetite, vomiting, change or passing loss
of flavoring feelings, loss of sense of smell diarrhea, a constipation, a hyperplasia
of gums
- urticaria, erythematic rash, an itching, a Quincke's disease of lips, persons and/or extremities
- a depression, a sleep disorder, impotence, peripheral neuropathy with paresthesia, disturbance of maintenance of balance, nervousness, confusion of consciousness myalgia, vertigo
- sonitus, a sight zamutneniye, xerophthalmus, dacryagogue, a disorder of vision
- anemia, a trombotsitemiya, a neutropenia, an eosinophilia (in some cases – an agranulocytosis or a pancytopenia), especially at patients with disturbance of functions of kidneys,
- collagenoses at the patients receiving Allopyrinolum, procaineamide or immunodepressants, increase in level of urea, creatinine and potassium in blood serum, decrease in level of sodium in blood serum, strengthening of removal of albumine with urine, especially at patients with disturbance of functions of kidneys, heavy heart failure, an arterial hypertension of renal origin and diabetes (at the last - a hyperpotassemia).
Very seldom
- dizziness, weakness, an asthenia, drowsiness, a hypothermia, a grippopodobny state, a tremor and a muscular spasm
- heart failure, arrhythmia, tachycardia, heartbeat, peripheral hypostasis, rushes of blood, vasodilatation, ischemia of peripheral vessels, heavy hypertensia or hypertensia of renal origin, especially in an initiation of treatment and at patients with deficiency of liquid and/or salts, the syncope is after increase in a dose of enalapril of a maleate and/or use of diuretics
- renal failures, in some cases progressing to an acute renal failure
- dry cough, a sore throat, hoarseness, bronchitis, bronchospasm/asthma, pulmonary infiltrates, stomatitis, a glossitis, dryness in a mouth, pneumonia, the Quincke's disease of a throat, throat and/or language bringing in isolated cases to deadly impassability of airways, frequency it is raised among black patients, pharyngitis, tracheitis
- disturbance of functions of a liver, hepatitis, a liver failure, pancreatitis, impassability of intestines, the syndrome beginning with cholestatic jaundice and progressing to liver necrosis, in certain cases from the death
- allergic skin reactions, for example, a dieback, a bladderwort, a multiformny erythema, exfoliative dermatitis, Stephens-Johnson's syndrome or a toxic necrolysis of epidermis
- the phenomena reminding psoriasis, photosensitivity, sweating strengthening, an alopecia, onikholizis and strengthening of a syndrome of Reynaud. Skin manifestations can be followed by fever, a myalgia/miositis, arthralgia/arthritis, a vasculitis, a serositis, an eosinophilia, a leukocytosis, increase in SOE and/or ANA. At suspicion on heavy skin reaction the treatment is stopped
- a hamaturia, decrease in level of hemoglobin, a hematocrit, the maintenance of leukocytes or thrombocytes, hemolysis / hemolytic anemia (also in combination with deficiency of glyukozo-6-phosphate-dehydrogenase), increase in level of bilirubin and liver enzymes, a hypopotassemia, a leukopenia
- increase in frequency of urination
-
the Contraindication gynecomastia
- hypersensitivity to enalapril, a nitrendipin or any excipient of drug
- existence in the anamnesis of the vascular hypostasis connected with use of inhibitors of angiotensin-converting enzyme, or a hereditary/idiopathic Quincke's disease
- pregnancy and the period of a lactation
- the states which are followed by an unstable hemodynamics, in particular, vascular collapse, cardiogenic shock, an acute heart failure, a sharp coronary syndrome, an acute stroke
- a bilateral stenosis of renal arteries or a unilateral stenosis in the presence of only one kidney
- a stenosis of the aortal or mitral valve, significant for a hemodynamics, and a hypertrophic cardiomyopathy
- heavy renal failures (clearance of creatinine less than 10 ml/min.) or carrying out a hemodialysis
- heavy abnormal liver functions
Medicinal interactions
Hypotensive effect of Eneasa® can amplify other antihypertensives, for example, diuretics, beta-blockers or alpha blockers of type of Prazozinum. Besides, components of a combination can show the following interactions:
Enalapril maleate:
Combinations which should be applied with care:
Kaliysberegayushchy diuretics and drugs of potassium
APF Inhibitors weaken the potassium loss caused by diuretics. The Kaliysberegayushchy diuretics, drugs of potassium and other drugs capable to increase potassium level in blood serum (e.g., heparin) can have additive impact on potassium level in blood serum, especially at patients with a renal failure.
If combined use of such drugs is necessary, for example, for elimination of a hypopotassemia, then at the same time it is necessary to show care and to often control potassium level in blood serum.
Lities
Use of enalapril in a combination with lithium are not recommended because of risk of strong increase in level of lithium in blood serum with the accompanying heavy neurotoxicity. If combined use of these drugs is necessary, then it is necessary to control carefully lithium level in blood serum.
Non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NPVP) and APF inhibitors it is additive increase potassium level in blood serum that can lead to deterioration in function of kidneys. With dehydration such combination can cause an acute renal failure due to direct impact on glomerular filtration in elderly patients and patients. Moreover, NPVP can weaken hypotensive effect of APF inhibitors.
Hypoglycemic effect of these drugs therefore it is necessary to control carefully glucose level in blood can strengthen the oral anti-diabetic drugs Enalapril.
Baclofenum
Can enhance hypotensive effect. In need of the combined use it is necessary to control arterial blood pressure and to titrate a dose.
Neuroleptics
Use together with these drugs can cause postural hypotension.
Antidepressants
Use together with tricyclic antidepressants can cause postural hypotension.
Allopyrinolum, cytostatics, immunodepressants, system corticosteroids, procaineamide
of the Combination can cause a leukopenia.
Combinations which should be considered
Amifostin
Kombination strengthens hypotensive action.
Nitrendipin
Tsimetidin and
Tsimetidin's ranitidine and, to a lesser extent, ranitidine, can increase concentration of a nitrendipin in blood plasma, but the clinical value of these data is unknown.
Digoxin
Enalapril was applied together with digoxin without any signs of clinically significant adverse interaction. Simultaneous use of a nitrendipin and digoxin can lead to increase in concentration of digoxin in blood plasma. Therefore it is necessary to control emergence of symptoms of overdose of digoxin or if it is necessary, to control concentration of digoxin in blood plasma.
Muscle relaxants
Use of a nitrendipin can increase duration and intensity of effect of muscle relaxants, for example, a pankuroniya.
Grapefruit juice suppresses oxidizing metabolism of a nitrendipin. Reception of the last with grapefruit juice increases concentration of a nitrendipin in blood plasma that can strengthen its hypotensive action.
Nitrendipin is metabolized by an isoenzyme 3A4 of P450 cytochrome in a mucous membrane of intestines and in a liver. The substances stimulating activity of this enzyme, for example, anticonvulsant drugs (Phenytoinum, phenobarbital, carbamazepine) and rifampicin can reduce bioavailability of a nitrendipin considerably. The substances braking activity of this enzyme, for example, antifungal imidazoles (itrakonazol, etc.) can increase concentration of a nitrendipin in blood plasma.
Beta-blockers
Nitrendipin and beta-blockers work synergy. It can be of particular importance for patients at whom additional beta blockade does not allow to compensate sympathetic vascular reactions, and concerning such patients it is recommended to show care.
The special
instructions Quincke's Edema At use of APF inhibitors, especially in the first weeks, vascular hypostasis of extremities, persons, lips, mucous membranes, language, a throat or a throat can develop. However in rare instances heavy vascular hypostasis can develop also after prolonged use of APF inhibitors. In such cases the treatment is cancelled at once.
The vascular paraglossa, throats or drinks can be deadly, in these cases it is necessary to carry out the emergency therapy with hospitalization of the patient. It is necessary to watch the patient at least 12-24 hours, and he can be discharged from hospital only after total disappearance of symptoms.
A neutropenia/agranulocytosis
At use of APF inhibitors cases of a neutropenia / agranulocytosis, thrombocytopenia and anemia are registered. At patients with normal function of the kidneys which do not have other risk factors, the neutropenia happens seldom. Enalapril should be applied extremely carefully at patients with collagenoses, the patients receiving immunodepressants, Allopyrinolum or procaineamide, or their combination, especially in renal failures. At Eneas's use for such patients it is recommended to control fractions of leukocytes. During treatment it is necessary to instruct about need to report to the doctor about any symptoms of an infection. Энеас® it is necessary to cancel at identification of a neutropenia or suspicion on it (the maintenance of neutrophils less than 1000/mm3).
A renal failure
At use of inhibitors of angiotensin-converting enzyme for patients with disturbance of functions of kidneys it is necessary to control these functions, especially on the first weeks of treatment. It is necessary to show care concerning patients from activated renin-angiotenzinovoy a system.
For patients with a moderate renal failure (the clearance of creatinine more than 30 ml/min., blood serum creatinine
At some patients with APF inhibitors can lead pressure drop in an initiation of treatment to small further deterioration in function of kidneys. In such cases the acute renal failure which usually was reversible was observed.
Experience of use of Eneasa® for the patients who were recently exposed to renal transplantation no.
The proteinuria
At patients with a renal failure in rare instances developed a proteinuria. At patients with clinically significant proteinuria (more than 1 g/days) of Eneas® it is possible to apply only after careful assessment of a ratio advantage - risk and with regular control of clinical and biochemical indicators of blood.
Patients with an abnormal liver function
Sick with a weak or moderate abnormal liver function enalapril monotherapy with a maleate or nitrendipiny are not contraindicated, but as there is no experience of use of Eneasa® for such patients, drug should be used with care if for this purpose there are indications. In a liver failure the removal of a nitrendipin can be slowed down, especially at elderly patients, and it can lead to sharp falling of arterial blood pressure.
As separate cases of the syndrome beginning with cholestatic jaundice and progressing to liver necrosis from the death are described, at appearance of jaundice or the significant increase in level of liver enzymes it is necessary to stop treatment and to watch patients.
Hypertensia of renal origin / renal artery stenosis
At use of APF inhibitors for patients with arterial hypertension of renal origin, a bilateral stenosis of renal arteries or a unilateral renal artery stenosis in the presence of only one functioning kidney the risk of serious pressure drop of blood and a renal failure is increased. The renal failure can be followed only by little change of level of creatinine in blood serum even at patients with a unilateral renal artery stenosis.
A hyperpotassemia
APF Inhibitors can increase potassium level in blood serum, especially at patients with a renal failure and/or heart failure. Therefore it is not recommended to use at the same time kaliysberegayushchy diuretics or drugs of potassium. Ate these drugs are necessary, it is necessary to control potassium level in blood serum.
Hypotension
In certain cases of Eneas® can cause orthostatic hypotension which risk is increased at patients with the system activated renin-angiotensin-aldosteronovoy, for example, at the reduced volume of blood or reduced content of salts because of use of diuretics, the use of a saltless diet, carrying out a hemodialysis, presence of diarrhea or vomiting and also when weakening function of a left ventricle and in arterial hypertension of renal origin. At such patients at first it is necessary to correct the volume of blood or concentration of salts. At patients with heart failure (with the accompanying renal failure or without it) symptomatic hypotension can develop. The risk of pressure drop of blood at such patients is increased in the profound heart failure, at use of high doses of loopback diuretics and in the presence of a hyponatremia or a renal failure. In an initiation of treatment for such patients the careful observation is required. It also to treat patients with coronary heart disease or disturbance of cerebral circulation at which the considerable lowering of arterial pressure can lead to a myocardial infarction or a stroke.
At pressure drop of blood of the patient it is necessary to put horizontally and, if necessary, it is necessary to enter intravenously isotonic saline solution. Passing hypotensive reaction is not a contraindication for continuation of use of Eneasa® which usually does not represent difficulties after restoration of volume of the circulating blood and pressure of blood.
The stenosis of the aortal valve
At patients with difficulty of an exit of blood from a left ventricle APF inhibitors should be applied with care. If this difficulty is significant for a hemodynamics, then enalapril the maleate is contraindicated.
Cough
At use of APF inhibitors the appearance of cough is described. It is unproductive, constant cough which disappears at treatment cancellation.
Primary hyper aldosteronism
As a rule, patients with primary aldosteronism are not sensitive to the hypotensive drugs operating by braking of activity system renin-angiotenzinovoy. Maleate enalapril use in such cases is not recommended.
The patients who are on a hemodialysis
Use of Eneasa® when carrying out dialysis through high-speed membranes (from a poliakrilnitril, methylallyl-sodium sulphonate, e.g., AN69) can lead to anaphylactic reactions, including a face edema, rushes of blood, falling of arterial blood pressure and an asthma within several minutes after the beginning of dialysis. Therefore such combinations should be avoided.
Anaphylactic reactions in the course of an aferez of LDL and a desensitization to poison of insects
the Use of APF inhibitors when carrying out an aferez of lipoproteins of the low density (LDL) by means of sulfate of a dextran can be followed by life-threatening anaphylactic reactions. Use of APF inhibitors when carrying out a specific immunotherapy (desensitization) to poisons of insects (bees, wasps) can be followed by anaphylactoid reactions (e.g., falling of arterial blood pressure, short wind, vomiting, a skin allergy) which in certain cases can threaten life. In need of an aferez of LDL or a specific immunotherapy (desensitization) to poisons nasekomykhingibitor APF should be replaced temporarily with other means for treatment aretialny hypertensia or heart failure.
Surgery/anesthesia
At the patients who are exposed to large surgeries or anesthesia using the drugs reducing arterial blood pressure, enalapril blocks angiotensin II synthesis stimulated by compensatory emission of renin. At pressure drop of blood in these cases (if it is supposed that it happens on this mechanism) it should be adjusted increase in volume of blood plasma.
Influence on reproductive function
Use for men of blockers of calcium channels, for example, of a nitrendipin, in some cases was followed by reversible disturbances of a spermatogenesis, in communication with what it is recommended not to use drug by preparation of carrying out in vitro fertilization.
A warning of excipients
Patients with rare hereditary intolerance of a galactose, deficiency of Lapp lactase or disturbance of absorption of a glucose/galactose should not take this drug.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms.
Use of Eneasa® can be followed by the certain adverse reactions reducing the level of attention and complicating ability to driving of the vehicle and control of mechanisms. It is especially important in an initiation of treatment, when changing treatment and/or at a concomitant use of alcohol. Therefore it is recommended to show care, the satisfactory effect of treatment will not be reached yet.
Overdose
Symptoms: still cases of overdose of this combination are not registered.
Falling of arterial blood pressure will be the most probable manifestation of overdose of Eneasa®.
Treatment: primary detoxication by gastric lavage, administration of absorbents and/or sodium sulfate (whenever possible, the first 30 minutes). It is necessary to control vital signs.
At sharp falling of arterial blood pressure the patient of a leg needs to lift and to begin infusional therapy for increase in volume of the circulating blood. At inefficiency of these measures it is possible to begin infusion of vasoconstrictors, under control of arterial blood pressure. Seldom or never intravenous administration of catecholamines is necessary.
It is necessary to control constantly the level of electrolytes and creatinine in blood serum.
Enalapril is dialyzed with a speed of 62 ml/min., but it is necessary to avoid use of high-speed polyacrylonitrile membranes.
A form of release and packing
On 10 tablets in blister strip packaging. On the 3rd blister strip packagings together with the instruction for medical use in the state and Russian languages in a cardboard box.
At a temperature not above 30 °C
to Store storage conditions out of children's reach!
A period of storage
3 years
not to apply after expiry date
Prescription status
According to the prescription
of Proizvoditel Ferrer Internasyonal S.A., Spain
it Is provided Nikomed Austria, GmbH, Austria
the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods)
of Nikomed Ostevropa Marketing Service GmbH
Almaty, Begalin St. 136 and
Phone number (727) 2444004
Fax number (727) 2444005
To Develop the e-mail address of aknu@nycomed.com
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