Pharmacological properties

Pharmacodynamics. enalozid is an inhibitor combination apf (enalapril a maleate) and diuretic (hydrochlorothiazide).

APF — the peptidilovy dipeptidase catalyzing transformation of angiotensin I into pressor substance angiotensin II. After absorption, enalapril is hydrolyzed to enalaprilat which oppresses APF. Oppression of APF leads to decrease in level in angiotensin II blood plasma that leads to increase in activity of renin of blood plasma (through oppression of negative feedback at renin release) and to reduction of secretion of Aldosteronum.

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APF it is identical to a kininaza of II. Enalapril can also block disintegration of bradykinin which is powerful vasodepressor peptide. However the role of this fact in therapeutic effects of enalapril remains to the unknown. While the mechanism on which enalapril lowers the arterial blood pressure is connected first of all with oppression of activity by the system renin-angiotensin-aldosteronovoy (SRAA) which plays the main role in regulation of the ABP, enalapril can show antihypertensive effect even at patients with lowrenine hypertensia.

Hydrochlorothiazide is the diuretic and antihypertensive medicament increasing activity of renin in blood plasma. Antihypertensive influence of two components is additive and, as a rule, lasts 24 h. Though one enalapril shows hypotensive action even at patients with lowrenine hypertensia, the combined use with a hydrochlorothiazide for these patients leads to bigger decrease in the ABP. The enalapril component in drug, as a rule, weakens the potassium reduction caused by reception of a hydrochlorothiazide.

Pharmacokinetics

Enalapril maleate. After oral administration, enalapril is quickly absorbed, reaching _{C max} in blood plasma during 1 h. Based on a removal indicator with urine, the volume of absorption of enalapril at oral administration is about 60-70%.

enalapril is quickly and extensively hydrolyzed by

After absorption to enalaprilat — the APF powerful inhibitor. The C _max enalaprilat in blood plasma are reached in 3–4 h after oral administration of enalapril of a maleate. Enalapril mainly is emitted with kidneys. The main components in urine are the enalaprilat making about 40% of a dose and enalapril in not changed look. Except for transformation to enalaprilat of signs of significant metabolism there is no enalapril. The profile of concentration of enalaprilat in blood plasma is characterized by the prolonged terminal phase that is probably caused by binding of APF. At persons with normal function of kidneys the equilibrium condition of concentration of enalaprilat in blood plasma is reached for the 4th day of oral administration of enalapril. Effective the T _½ enalaprilat after repeated oral administration of enalapril makes 11 h. Meal does not influence absorption of enalapril in a GIT. The volume of absorption and hydrolysis of enalapril are similar at reception of different doses within the recommended therapeutic range.

Hydrochlorothiazide. Pri monitoring of level in blood plasma during at least 24 h T _½ made 5.6-14.8 h of blood plasma. The hydrochlorothiazide is not metabolized, but quickly allocated with kidneys. Pri oral administration of at least 61% of a dose is removed in not changed look during 24 h. The hydrochlorothiazide gets through a placental barrier and does not get through GEB.

Enalapril/hydrochlorothiazide. Simultaneous repeated use of enalapril and a hydrochlorothiazide slightly or at all does not affect bioavailability of these drugs. The combined tablet is bioequivalent to its separate components applied at the same time.

Indication

Treatment at ag at patients to whom combination therapy is shown.

Use

Pri ag. an initial dose of medicament — 1 tablet enalozid 12.5 or enalozid 25 1 times a day. if the desired effect is not reached, then the daily dose should be raised to 2 tablets of 1 times a day. the maximum dose — 2 tablets a day.

In a renal failure. For patients with impaired renal function, in the moderate or profound renal failure (at the level of clearance of creatinine of ≤30 ml/min.) tiazida can be insufficiently effective.

If creatinine level in the range from 30 to 80 ml/min., Enalozid it is necessary to apply only after preliminary selection of a dose of each of components.

Recommended initial dose of enalapril of a maleate which is accepted separately in a slight renal failure makes from 5 to 10 mg.

Previous treatment by diuretics. If the patient already receives diuretics, it is recommended to cancel treatment or to lower a diuretic dose at least in 2–3 days prior to therapy by Enalozid in order to avoid sharp decrease in the ABP. Symptomatic arterial hypotension can arise at the beginning of therapy by Enalozid, it is more often observed at patients in whom the previous therapy by diuretics caused disturbance of water and electrolytic balance.

Children. Safety and efficiency of use of medicament for children are not established.

Contraindication

Hypersensitivity to medicament components. the Quincke's disease in the anamnesis connected with the previous treatment by inhibitors apf and also a hereditary or idiopathic Quincke's disease. heavy renal (clearance of creatinine of 30 ml/min.) or liver failure. anury. simptomny hyperuricemia (gout). hypersensitivity to other medicaments which are derivatives of sulfonamides. stenosis of renal arteries. hypopotassemia, resistant to treatment, or hypercalcemia. refractory hyponatremia. when carrying out a hemodialysis.

during pregnancy or to the women planning pregnancy (see Use during pregnancy or feeding by a breast).

should not be applied with the medicaments containing aliskiren, to patients with diabetes or with a renal failure (SKF of 60 ml/min. / 1.73 m ² ).

Side effects

from heart: arterial hypotension, orthostatic hypotension, tachycardia, heartbeat, arrhythmia, stenocardia.

from vessels: Reynaud's phenomenon, inflows, a heart attack a myocardium/stroke (perhaps, owing to excessive arterial hypotension of patients of group of high risk), a vasculitis, a necrotizing angiitis.

from digestive system: anorexia, dryness in a mouth, feeling of thirst, a sialadenitis (inflammation of sialadens) stomatitis / aphthous stomatitis, a glossitis, nausea, vomiting, pancreatitis, diarrhea, dyspepsia, an abdominal pain, a meteorism, a constipation, a Quincke's disease of intestines, Ilheus, irritation of a stomach, round ulcers.

from nervous system / mental disturbances: a headache, a syncope, change of flavoring feelings, insomnia, nervousness, concern, drowsiness, paresthesias, vertigo, dizziness, spasms, confusion of consciousness, sleep disorder, abnormal dreams, paresis (owing to a hypopotassemia), decrease a libido, a depression, a disorientation, changes of mood.

from a musculoskeletal system and connective tissue: myalgia, muscular spasms, arthralgia.

from respiratory organs, a thorax and bodies of mediastinum: a sore throat and hoarseness of a voice, rhinitis, a rhinorrhea, cough, dispnoe, pulmonary infiltrates, an allergic alveolitis / eosinophilic pneumonia, a bronchospasm / OH, a respiratory distress (including a pneumonitis and a fluid lungs).

from a gepatobiliarny system: a liver failure, liver necrosis (can be lethal), hepatitis (hepatocellular or cholestatic), jaundice, cholecystitis (in particular at patients with already existing cholelithiasis).

Endocrine disturbances: syndrome of disturbance of secretion of antidiuretic hormone. Metabolic disturbances: a hypopotassemia, a hyperpotassemia, a hyponatremia, increase in level XC and TG of blood, a hypoglycemia, a hyperuricemia which can provoke gouty attacks at patients with an asimptomny course of the disease, a hypomagnesiemia, a hyperglycemia, decrease in a glyukozotolerantnost which can cause a demonstration of latent diabetes, a hypercalcemia, a gipokhloremichesky alkalosis which can induce hepatic encephalopathy or a hepatic coma, at use of medicament in high doses the increase in level of lipids of blood is possible.

from kidneys and an urinary system: renal dysfunction, renal failure, proteinuria, oliguria, interstitial nephrite, glucosuria.

from an organ of hearing: sonitus.

from an organ of sight: illegibility of sight, tranzitorny disorder of vision, xanthopsia.

from a reproductive system: gynecomastia, impotence, sexual disorders.

from skin and hypodermic fatty tissue: pour (dieback), a purpura, an itching, the increased sweating, an alopecia, a small tortoiseshell, a multiformny erythema (Stephens's syndrome — Johnson), a skin lupus erythematosus, an erythrosis, a toxic epidermal necrolysis, exfoliative dermatitis, a pempigus.

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It was reported about symptom complex which can include several or all following symptoms: fever, serositis, vasculitis, myalgia/miositis and arthralgia/arthritis, positive test for antinuclear antibodies (ANA), increase SOE, eosinophilia, leukocytosis. There can be rash, photosensitivity or other dermatological reactions.

from blood and lymphatic system: decrease in level of hemoglobin and a hematocrit, thrombocytopenia, a neutropenia, a leukopenia, a pancytopenia, an agranulocytosis, anemia (including aplastic and hemolytic anemia), a lymphadenopathy, oppression of function of marrow, autoimmune diseases.

from the immune system: hypersensitivity, anaphylactic reaction, a Quincke's disease, including a Quincke's disease of the face, extremities, lips, language, a glottis and/or throat, an acute anaphylaxis.

Datas of laboratory: increase in level of urea of blood, increase in level of urea nitrogen of blood, increase in creatinine in blood plasma, increase in level of liver enzymes and/or bilirubin in blood serum.

Disorder of the general state and from the injection site: asthenia, stethalgia, fever, increased fatigue, indisposition, exhaustion.

Special instructions

Enalapril maleate and hydrochlorothiazide

Arterial hypotension and electrolytic/water imbalance. Symptomatic hypotension seldom arises at patients from uncomplicated AG. Symptomatic hypotension is more often noted at the patients with disturbances of water balance accepting Enalozid, for example as a result of therapy by diuretics, diets with the limited use of table salt, diarrhea and vomiting. For these patients it is required regularly, to determine through certain periods levels of electrolytes in blood plasma. Special attention should be paid to treatment of patients with an ischemic heart disease or cerebrovascular diseases as considerable decrease in the ABP can lead to a myocardial infarction or a stroke.

Symptomatic hypotension was noted by

at patients with heart failure which was followed or was not followed by a renal failure. More often symptomatic hypotension developed at persons with more severe forms of heart failure to which used medicament in the highest doses of loopback diuretics, with a hyponatremia or renal failures. These patients should begin treatment under observation of the doctor and also to watch carefully a condition of their health at change of a dose of medicament and/or diuretic. It also concerns treatment of patients with an ischemic heart disease and cerebrovascular diseases as considerable decrease in the ABP can lead to a myocardial infarction or a stroke.

At development of arterial hypotension is required to be put the patient on a back and if necessary to enter in into infusionally physiological solution of sodium of chloride. Temporary hypotension is not a contraindication to further use of drug. If after normalization of OCK there is an increase in the ABP, therapy can be restored in usual doses.

At some patients with heart failure and with the normal or lowered pressure the ABP level can decrease in addition. Such effect predicted is also not the basis for the treatment termination. In cases when hypotension becomes symptomatic, it is necessary to lower a dose and/or to stop treatment by diuretic and/or drug.

Renal failure. It was reported about development of the renal failure connected with enalapril use that was observed mainly at persons with heavy heart failure or a basic disease of kidneys, including a renal artery stenosis. At timely diagnostics and the corresponding treatment the renal failure connected with enalapril use, as a rule, is reversible. Enalozid patients should not appoint with a renal failure (clearance of creatinine of 80 ml/min. 30 ml/min.) until the enalapril dose at a titration reaches dosing in this drug.

At therapy by enalapril in combination with diuretic some patients with AG without any symptoms of a disease of kidneys prior to treatment had an increase in content of urea and creatinine in blood. In such cases the treatment by Enalozid needs to be stopped and also to consider a question of a possible renal artery stenosis.

Hyperpotassemia. The combination of enalapril and diuretic in low doses can cause emergence of a hyperpotassemia.

Lities. The combined use of enalapril and lithium usually is not recommended.

Enalapril maleate

Aortal stenosis / hypertrophic cardiomyopathy. APF inhibitors (as well as all other vazodilatator) should be applied with care at patients with obstruction of the valve and outflow tracts from a left ventricle. Use of APF inhibitors needs to be avoided in case of cardiogenic shock and in case of hemodynamically significant obstruction.

Renovascular hypertensia. At treatment the increased risk of developing of hypotension and renal failure exists APF inhibitors of patients with a bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney. The renal failure can arise even at minor changes of level of creatinine in blood plasma. At these patients the treatment should be begun with low doses and under observation of the doctor, with care to raise a dose and to control function of kidneys.

Patients to whom carry out a hemodialysis. Use of enalapril is contraindicated to patients who need carrying out dialysis in a renal failure. Anaphylactoid reactions were observed at the persons which were on dialysis with use of membranes with a high capacity (such as AN 69) and received at the same time treatment by APF inhibitors. At these patients it is necessary to use dialysis membranes of other type or hypotensive medicaments of other classes.

Transplantation of a kidney. There is no experience of use of medicament for the patients who recently underwent an operation on transplantation of a kidney. Therefore medicament treatment is not recommended to such patients.

Liver failure. Seldom use of APF inhibitors was followed by a syndrome which begins with cholestatic jaundice or hepatitis and progresses to fulminantny necrotic hepatitis, sometimes with a lethal outcome. The mechanism of this syndrome is unknown. Patients who are treated by APF inhibitors and who had a jaundice or substantial increase of levels of enzymes of a liver should cancel APF inhibitor and to establish the corresponding medical observation.

Neutropenia/agranulocytosis. Among the patients accepting APF inhibitors it was reported about appearance of a neutropenia/agranulocytosis, thrombocytopenia and anemia. At persons with normal function of kidneys and in the absence of other complicating factors the neutropenia appeared seldom. Patients should appoint enalapril very carefully with collagenoses of the vessels undergoing immunosupressantny therapy, treatment by Allopyrinolum or procaineamide or at a combination of these complicating factors, especially in the presence of a renal failure. At some patients serious infections which in some cases did not respond to intensive care with antibiotics developed. When prescribing enalapril the periodic monitoring of quantity of leukocytes is recommended to such patients, patients have to report about any manifestations of an infection.

Hyperpotassemia. At some patients applying APF inhibitors, including enalapril, noted increase in level of potassium in blood plasma.

renal failure, diabetes, patients at the age of 70 years, intercurrent conditions, in particular dehydration, a sharp warm decompensation, a metabolic acidosis and simultaneous use of kaliysberegayushchy diuretics (for example Spironolactonum, Triamterenum or amiloride), the nutritional supplements or salt substitutes containing potassium and also use of other medicaments associated with increase in level of potassium in blood plasma belong To factors of development of a hyperpotassemia (for example heparin).

Use of additives of potassium, the kaliysberegayushchy diuretics and substitutes of salt containing potassium, in particular at persons with renal failures can lead

to substantial increase of level of potassium in blood plasma. The hyperpotassemia can become the cause of serious and even lethal arrhythmia.

If co-administration of the medicament Enalozid and the means stated above is considered necessary, they should be applied with care and under frequent control of level of potassium in blood plasma.

Hypoglycemia. Patients with the diabetes taking the oral anti-diabetic medicaments or insulin and beginning to apply APF inhibitor should recommend to control carefully glucose level in blood, especially within the first several months of combination therapy (see INTERACTIONS).

Hypersensitivity / Quincke's disease. At treatment by APF inhibitors, including enalapril a maleate, separate cases of a Quincke's disease of the face, extremities, lips, language, a glottis and/or throat are described. In such cases it is necessary to stop immediately medicament treatment and to establish careful health surveillance of the patient for the purpose of control of clinical symptoms. Only after their disappearance the medical observation can be stopped. When hypostasis extends to area of the face and lips, therapy by antihistamines provides favorable effect. Even when only the paraglossa without respiratory distress is observed, long health surveillance of the patient as treatment by antihistaminic medicaments and GKS can be insufficient is necessary.

Quincke's disease which is followed by edema of laryngeal or language can lead

to a lethal outcome. In cases when hypostasis is localized in the field of language, a glottis or a throat that can lead to obstruction of airways, it is necessary to enter immediately subcutaneously adrenaline 1:1000 solution (0.3-0.5 ml) and to perform other corresponding treatment.

Patients who had a Quincke's disease which is not connected with use of APF inhibitors earlier can be prone more to developing of a Quincke's disease against the background of therapy by APF inhibitors.

representatives of negroid race applying APF, a thicket had a Quincke's disease in comparison with patients of other races.

Anaphylactoid reactions during performing desensitization by poison of Hymenoptera. Occasionally at the patients receiving APF inhibitors heavy anaphylactoid reactions developed during desensitization allergen from poison of Hymenoptera. Similar reactions can be avoided if prior to carrying out desensitization it is temporary to stop intake of APF inhibitor.

Anaphylactoid reactions during an aferez of LDL. The patients accepting APF inhibitors during an aferez of LDL from a dextran sulfate seldom had life-threatening anaphylactoid reactions. Similar reactions can be avoided, having temporarily stopped use of APF inhibitor before holding each session of an aferez.

Cough. Noted cough cases against the background of therapy by APF inhibitors. Usually cough has unproductive, constant character and stops after medicament withdrawal. The cough resulting from use of APF inhibitors should be considered at the differential diagnosis of cough.

Surgery/anesthesia. During big surgical interventions or at anesthesia using the means causing arterial hypotension, enalaprilat blocks formation of angiotensin II again to compensatory release of renin. If at the same time the arterial hypotension explained with the similar mechanism it develops it is possible to korrigirovat increase in volume of liquid.

Ethnic distinctions. As well as at use of other APF inhibitors, enalapril is less effective in decrease in the ABP at persons of negroid race in comparison with patients of other races. Perhaps, it is explained by higher rate of a prevalence of a low-active reninovy system among patients of negroid race, patients with a hypertension.

Hydrochlorothiazide

Arterial hypotension and disturbances of water-salt balance. As well as at use of other antihypertensive medicines, some patients can have a simptomny arterial hypotension. Patients demand observation for early detection of clinical signs of disturbance of water-salt balance (for example hypovolemia, hyponatremias, a gipokhloremichesky alkalosis, a hypomagnesiemia or a hypopotassemia) which can develop in case of simultaneous diarrhea or vomiting. At these patients it is necessary to control periodically the level of electrolytes in blood plasma.

Renal failure. Tiazida can be insufficiently effective diuretics for treatment of patients with a renal failure and also at clearance of creatinine of ≤30 ml/min. and below (that is in the moderate or profound renal failure).

Enalozid patients should appoint

with a renal failure (clearance of creatinine of 80 ml/min.) until titration of separate components of medicament reaches doses of this drug.

Abnormal liver function. Tiazida it is necessary to apply with care at patients with abnormal liver functions or the progressing liver disease as even at insignificant deviations of water and electrolytic balance there can be a hepatic coma.

Metabolic and endocrine effects. Therapy of a tiazidama can change tolerance to glucose. Correction of doses of anti-diabetic drugs, including insulin can be required. Against the background of therapy of a tiazidama can demonstrate latent diabetes.

Tiazida's

can reduce the level of sodium, magnesium and potassium in blood plasma.

Increase in levels XC and TG can be associated with therapy by thiazide diuretics, however throughout use in low doses (12.5 mg) was reported about the minimum effect or its absence. At use of 6 mg of a hydrochlorothiazide clinically significant influence on glucose levels, XC, by TG, sodium, magnesium and potassium was not observed.

Tiazida's

can reduce calcium discharge with urine and cause periodic slight increase of calcium in blood plasma.

Expressed hypercalcemia can be manifestation of the hidden hyper parathyroidism. Use of tiazid should be stopped before carrying out tests on function of epithelial bodies.

Therapy by thiazide diuretics can cause a hyperuricemia and/or exacerbation of gout in some patients. However enalapril can increase the level of uric acid in urine and thus can weaken giperurikemichesky effect of a hydrochlorothiazide.

should be measured by

For the patients receiving therapy by diuretics regularly levels of electrolytes in blood plasma through the corresponding intervals of time.

imbalance of liquid and electrolytes (hypopotassemia, a hyponatremia and a gipokhloremichesky alkalosis) can cause Tiazida's

(including a hydrochlorothiazide). Dangerous signs of disturbance of water and electrolytic balance is xerostomia, thirst, weakness, a lethargical sleep, drowsiness, fatigue, muscular pain or spasms, muscle weakness, arterial hypotension, an oliguria, tachycardia, disturbances from a GIT (nausea, vomiting).

Though during use of thiazide diuretics the hypopotassemia can arise, the combined therapy with enalapril can reduce the hypopotassemia caused by diuretic use. The risk of a hypopotassemia can increase at patients with cirrhosis, at persons with the raised diuresis, with the insufficient oral use of electrolytes and at the patients who are at the same time receiving therapy of GKS or adrenocorticotropic hormone (AKTG).

In hot weather the persons inclined to hypostases, can have a hyponatremia due to blood fluidifying. Deficiency of chlorides usually moderate also does not demand treatment.

Tiazida's

increase removal of magnesium with urine that can lead to a hypomagnesiemia.

Anti-doping test. Drug contains a hydrochlorothiazide that can yield positive result in the anti-doping test.

Hypersensitivity. The patients inclined to an allergy, or at patients OH in the anamnesis can have hypersensitivity reactions to a hydrochlorothiazide and also if patients did not have these diseases earlier.

At use of thiazide diuretics noted aggravation or activation of a system lupus erythematosus.

Drug can affect results of the following laboratory analyses:

• medicament can reduce the level of the iodine connected with proteins in blood plasma;
• medicament treatment should be stopped before carrying out laboratory inspection for the purpose of assessment of function of epithelial bodies;
• medicament is capable to increase concentration of free bilirubin in blood plasma.

Special cautions of rather inactive components of drug. Patients with rare inherited disorders of galaktozny insufficiency, a lactose intolerance of Lapp or a syndrome of glyukozo-galaktozny malabsorption should not use this drug.

Patients of advanced age. The efficiency and tolerance of enalapril of a maleate and hydrochlorothiazide at simultaneous use are similar at patients of advanced and young age.

should not take alcohol during treatment by Enalozid.

Use during pregnancy or feeding by a breast. Drug should not be used pregnant women or women, planning pregnancy. If during therapy the pregnancy is confirmed by this medicine, its use needs to be stopped and replaced immediately with other medicament allowed for use for pregnant women.

APF Inhibitors

Knows that use of APF inhibitors in II and III trimester of pregnancy can cause development of a fetotoksichnost (depression of function of kidneys, oligogidramnion, a retardation of ossification of a skull) and neonatal toxicity (renal failure, hypotension, a hyperpotassemia).

If in ІІ a trimester of pregnancy were applied by APF inhibitors, it is recommended to carry out ultrasonography for check of function of kidneys and a condition of bones of a skull. Babies, mother whom applied APF inhibitor should perform often examination concerning developing of arterial hypotension.

Hydrochlorothiazide

Exists limited experience of use of a hydrochlorothiazide during pregnancy, especially in І a trimester. Researches on animals are not enough.

Hydrochlorothiazide gets through a placental barrier. Considering the pharmacological mechanism of action of a hydrochlorothiazide, its use in II and III trimester of pregnancy can damage to blood supply between a placenta and a fruit and to cause jaundice, disorder of electrolytic balance and thrombocytopenia in a fruit and the newborn.

Feeding by a breast. Use of the medicament Enalozid during feeding by a breast is not recommended. Enalapril and thiazide diuretics get into breast milk. If use of medicament is considered necessary, feeding by a breast should be stopped.

Ability to influence speed of response at control of vehicles or other mechanisms. At control of vehicles and mechanisms it is necessary to remember possibility of dizziness or fatigue.

Interaction

Enalapril maleate and hydrochlorothiazide

Other antihypertensive drugs. Simultaneous use of these medicaments can enhance hypotensive effect of enalapril and a hydrochlorothiazide. Simultaneous use with nitroglycerine, other nitrates or other vazodilatator can lower the arterial blood pressure in addition.

Lities. It was reported about reversible increase in concentration of lithium in blood plasma and toxicity at simultaneous use of lithium with APF inhibitors. The combined use of thiazide diuretics can increase in addition the level of lithium and increase risk of toxic effect of lithium at APF inhibitor use.

Use of the medicament Enalozid along with medicaments of lithium is not recommended to

, but if such combination is necessary, it is necessary to control carefully lithium level in blood plasma.

, including selection TsOG-2 inhibitors, antihypertensive effects of APF inhibitors, effects of diuretics and/or other antihypertensive medicaments can weaken

NPVP. For this reason the antihypertensive effect of antagonists of receptors of angiotensin II, APF inhibitors or diuretics can be weakened at use of NPVP, including selection TsOG-2 inhibitors.

Simultaneous use of NPVP (including TsOG-2 inhibitors) and antagonists of receptors of angiotensin II or APF inhibitors shows to

additional effect concerning increase in level of potassium in blood plasma and can lead to a renal failure. These effects, as a rule, are reversible.

renal failure, in particular, at patients with the weakened function of kidneys Seldom can develop (for example at elderly people or patients with dehydration, including receiving treatment by diuretics). Therefore such combination of medicaments should be applied with care at patients with the weakened function of kidneys.

Double blockade of RAAS. Double blockade of RAAS at use of blockers of angiotenzinovy receptors, APF inhibitors or direct inhibitors of renin (for example aliskiren) is associated with the increased risk of developing of arterial hypotension, faint, a hyperpotassemia and change of function of kidneys (including OPN) at patients with the established atherosclerotic defeat of vessels, heart failure or with damage of target organs in diabetes in comparison with monotherapy. It is necessary to control carefully the ABP, function of kidneys and levels of electrolytes at the patients receiving Enalozid and other medicaments influencing RAAS. Patients with diabetes cannot appoint along with aliskireny the medicament Enalozid. It is necessary to avoid use of an aliskiren along with Enalozid to persons with a renal failure (SKF of 60 ml/min. / 1.73 m ² ).

Enalapril maleate

Kaliysberegayushchy diuretics or potassium additives. APF inhibitors reduce the potassium losses induced by use of diuretics. Kaliysberegayushchy diuretics (such as Spironolactonum, eplerenon, Triamterenum or amiloride), can lead the additives of potassium or substitutes of salt containing potassium to substantial increase of level of potassium in blood plasma. If simultaneous use of such medicaments because of a hypopotassemia is shown, treatment needs to be carried out with care and to often control potassium level in blood plasma.

Diuretics (thiazide or loopback diuretics). Preliminary treatment by diuretics in high doses can lead to dehydration and risk of developing hypotension in an initiation of treatment enalapril. The hypotensive effect can be weakened by diuretic cancellation, increase in volume of liquid in an organism or increase in consumption of table salt.

Tricyclic antidepressants / neuroleptics / anesthetics/hypnotic drugs. Simultaneous use of certain anesthetics, tricyclic antidepressants and neuroleptics with APF inhibitors can lead to additional decrease in the ABP.

gold Drugs. It was reported about emergence of nitroidny reactions (face reddening, nausea, vomiting and arterial hypotension) at the patients treated by injection medicaments of gold (sodium aurotiomalat) along with APF inhibitor, in that h