Enalozid Forte of the tab. No. 20

Pharmacological properties

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

APF is a peptidildipeptidaza which catalyzes 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 in blood plasma (through oppression of negative feedback at renin release) and to reduction of secretion of Aldosteronum. A hydrochlorothiazide — diuretic and antihypertensive drug, increasing activity of renin of blood plasma. The mechanism of antihypertensive action of tiazid is unknown. Usually the hydrochlorothiazide does not influence normal the ABP.

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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 effects of two components are additive and, as a rule, last 24 h. Though one enalapril shows hypotensive action even at patients with lowrenine hypertensia, simultaneous use with a hydrochlorothiazide for such patients leads to bigger decrease in the ABP. The enalapril component in drug, as a rule, weakens the decrease in level of potassium caused by use of a hydrochlorothiazide.

Pharmacokinetics

Absorption. After oral administration, enalapril is quickly absorbed, reaching the C _max in blood plasma during 1 h. Taking into account a removal indicator with urine the volume of absorption of enalapril at oral administration is about 60%.

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 generally is removed by kidneys. The main components in urine are enalaprilat which makes about 40% of a dose, and enalapril in not changed look. Except for transformation to enalaprilat, there are no signs of significant metabolism of enalapril. The profile of concentration of enalaprilat in blood plasma is characterized by the prolonged terminal phase that is probably associated with 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. The effective half-cycle of cumulation of 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 various doses within the recommended therapeutic range.

Distribution. Within all range of therapeutic concentration of 60% of enalaprilat contacts proteins of blood plasma.

Biotransformation. Except for transformation to enalaprilat, there are no signs of significant metabolism of enalapril. The hydrochlorothiazide does not give in to metabolism and is quickly removed by kidneys.

Removal. Enalaprilat is removed mainly by kidneys. The main components of medicament in urine is enalaprilat that makes about 40% of a dose, and not changed enalapril (about 20%). The hydrochlorothiazide does not give in to metabolism and is quickly removed by kidneys. At oral administration of at least 61% of a dose it is removed in not changed look during 24 h.

Renal failure. At patients with a renal failure the exposure to enalapril and enalaprilat increases. At patients with a slight and average renal failure (clearance of creatinine of 40-60 ml/min.) of AUC enalaprilat in a stable state was approximately twice more, than patients with normal function of kidneys, have later introductions of 5 mg of 1 times a day. At a severe form of a renal failure (clearance of creatinine of ≤30 ml/min.) AUC increased approximately by 8 times. At this level of a renal failure effective T _½ enalaprilat increases, and time to a stable state is late (see USE).

Enalaprilat can be brought out of general circulation by means of a hemodialysis. The clearance of enalaprilat at dialysis is 62 ml/min.

Indication

Lecheniye ag at patients to whom combination therapy is shown.

Use

Ag. a usual dose — ½ tablets, if necessary it is possible to raise to 1 tablet of 1 times a day. the maximum dose makes 2 tablets a day.

Preliminary treatment by diuretics. Symptomatic arterial hypotension can arise in an initiation of treatment the medicament Enalozid Forte; more often arterial hypotension is noted at patients with disturbance of water or salt balance as a result of the previous use of diuretics. Therapy by diuretics should be stopped in 2–3 days prior to use of the medicament Enalozid Forte (see. Special INSTRUCTIONS).

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

to Patients with clearance of creatinine in the range of 30-80 ml/min. can use the medicament Enalozid Forte only after preliminary selection of doses of each of components.

Recommended initial dose of enalapril of the maleate applied separately in a slight renal failure makes 5–10 mg therefore Enalozid Forte is not recommended as initial therapy for such patients (see. Special INSTRUCTIONS).

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

Contraindication

Hypersensitivity to active agent or any other component of drug. renal failure of heavy degree (clearance of creatinine of ≤30 ml/min.) hypopotassemia, .rezistentny to treatment. simptomny hyperuricemia (gout) .anuriya. the Quincke's disease connected with appointment before inhibitors apf in the anamnesis. hereditary or idiopathic Quincke's disease. hypersensitivity to medicaments which are sulfonamide derivatives. the pregnant women or women planning pregnancy (see use during pregnancy and feeding by a breast) .narusheny functions of a liver of heavy degree. simultaneous use with the medicaments containing aliskiren, to patients with diabetes or with a renal failure (glomerular filtration rate of 60 ml/min. / 1.73м2) (see interactions).

Side effects

Enalozid forte is usually well had by

. side effects were lungs, had passing character and did not demand the therapy termination.

Most widespread side effects revealed during clinical trials of a combination of enalapril of a maleate and hydrochlorothiazide.

from a cardiovascular system: dizziness, hypotension, orthostatic hypotension, disturbance of a rhythm, stenocardia, tachycardia, inflows, heartbeat, a myocardial infarction or a stroke, perhaps, owing to excessive hypotension at patients of group of high risk, Reynaud's syndrome.

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

from nervous system / mental disturbances: a headache, a syncope, change of flavoring feelings, insomnia, nervousness, concern, drowsiness, paresthesias, vertigo, confusion of consciousness, a sleep disorder, pathological dreams, paresis (owing to a hypopotassemia), weakening of a libido, a depression.

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

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

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 inadequate secretion of antidiuretic hormone (SIADH).

Metabolic disturbances: hypopotassemia, disturbances of water and electrolytic balance (including hyponatremia), increase in level XC and TG of blood, hypoglycemia, hyperuricemia, gout, hypomagnesiemia, hyperglycemia, hypercalcemia.

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

Dysfunction of hearing and balance: sonitus.

from an organ of sight: loss of visual acuity, passing loss of visual acuity, xanthopsia.

from a reproductive system and mammary glands: gynecomastia, impotence.

from skin and hypodermic cellulose: pour (dieback), hypersensitivity, a Quincke's disease: it was reported about a Quincke's disease of the face, extremities, lips, language, a glottis and/or throat, diaforez, an itching, urticaria, an alopecia, photosensitivity, a multiformny erythema, Stephens's syndrome — Johnson, exfoliative dermatitis, a toxic epidermal necrolysis, a purpura, a skin lupus erythematosus, a bladderwort, an erythrosis.

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It was reported about symptom complex which can include several or all following symptoms, such as: fever, a serositis, a vasculitis, a myalgia/miositis and arthralgia/arthritis, positive take of the analysis on an antinuclear factor, increase SOE, an eosinophilia, a leukocytosis. There can be rash, photosensitivity or other dermatological manifestations.

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: anaphylactic reactions.

Datas of laboratory: a hyperpotassemia, increase in level of creatinine in blood plasma, increase in level of urea nitrogen of blood, a hyponatremia, increase in level of liver enzymes, increase in level of bilirubin in blood plasma.

Infection and invasion: sialadenitis.

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

Special instructions

Enalapril maleate and hydrochlorothiazide

Hypotension and disturbance of water and electrolytic balance. Symptomatic hypotension is seldom noted at patients from uncomplicated AG. Among the patients accepting Enalozid Forte, symptomatic hypotension arises at patients with disturbance of water balance, for example as a result of therapy by diuretics, diets with limited consumption of salt, diarrhea or vomiting more often. At such patients follows regularly, through the established time intervals, to determine levels of electrolytes in blood plasma. Approach to treatment of patients with an ischemic heart disease or cerebrovascular diseases as excessive decrease in the ABP can lead to a myocardial infarction or a stroke has to be especially attentive. Symptomatic hypotension was noted at patients with AG and heart failure with renal failures and without them.

At development of hypotension should be put the patient in a bed and to use in case of need in/in administration of physiological solution. Passing hypotension when prescribing medicament is not a contraindication to its further use. If after normalization of OCK there is an increase in the ABP, therapy can be restored in usual doses.

Renal failure. Enalozid Forte patients should not appoint with a renal failure (clearance of creatinine of 80 ml/min. and 30 ml/min.) until titration of separate components of medicament reaches medicament doses in this dosage form (see USE).

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 Enalozid Forte medicament treatment should be stopped. Such situation can indicate a possibility of existence of a stenosis of renal arteries.

Double blockade of RAAS. There are data that at patients at simultaneous use of APF inhibitors, antagonists of receptors of angiotensin II or an aliskiren risk of developing arterial hypotension, a hyperpotassemia and renal failures increases (including OPN). In this regard double blockade of RAAS (simultaneous use of APF inhibitors, antagonists of receptors of angiotensin II or an aliskiren) is not recommended (see INTERACTIONS). If double blockade is considered necessary absolutely, it should be seen off under observation of the doctor with careful regular monitoring of function of kidneys, water and electrolytic balance, the ABP. It is not necessary to apply at the same time APF inhibitors and antagonists of receptors of angiotensin II to patients with a diabetic nephropathy.

Hyperpotassemia. At the combined use of enalapril and low-dose diuretic it is impossible to exclude a possibility of development of a hyperpotassemia.

Lities. As a rule, it is not recommended to apply lithium in a combination with enalapril and diuretics (see INTERACTIONS).

Lactose. To patients with such rare hereditary diseases as intolerance of a galactose, deficiency of Lappa lactase or disturbance of malabsorption of glucose galactose, it is not necessary to take this drug.

Combined therapy by APF inhibitor and antagonist of receptors of angiotensin. Combination of APF inhibitor with the antagonist of receptors of angiotensin II should be limited to individually certain cases which are followed by careful monitoring of function of kidneys, level of potassium and the ABP (see INTERACTIONS).

Enalapril maleate

Aortal stenosis / hypertrophic cardiomyopathy. As well as all other vazodilatator, APF inhibitors should be applied with care to patients with obstruction of outflow tracts from a left ventricle. Use of such medicaments it is necessary to avoid in case of cardiogenic shock and hemodynamically significant obstruction.

Renal failure. It was reported about development of the renal failure connected with enalapril use that was noted mainly at patients 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 (see USE).

Renovascular hypertensia. There is an increased risk of developing of hypotension and renal failures if the patient with a bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney receives treatment by APF inhibitors. Depression of function of kidneys can arise even at easy changes of level of serumal creatinine. For such 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.

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

Patients on a hemodialysis. Use of enalapril is contraindicated to patients who need carrying out dialysis in a renal failure. Anaphylactoid reactions were noted at the patients who are on dialysis with use of membranes with a high capacity (AN 69 ^® ) and receiving at the same time treatment by APF inhibitors. For such patients it is necessary to use dialysis membranes of other type or hypotensive medicaments of other classes.

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 significant increase in level 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 patients with normal function of kidneys and in the absence of other complicating factors the neutropenia arose seldom. Enalapril patients should appoint very carefully with collagenoses of vessels which undergo immunosupressantny therapy, treatment by Allopyrinolum or procaineamide, or at a combination of these complicating factors, especially if there is already a renal failure. At some patients serious infections which in certain 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, and patients have to report about any manifestations of an infection.

Hyperpotassemia. At some patients receiving treatment by APF inhibitors including enalapril, increase in level of potassium in blood plasma was observed. The 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 (such as Spironolactonum, eplerenon, 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 patients with renal failures can lead to substantial increase of level of potassium in blood plasma.

Hyperpotassemia can become the cause of serious and even lethal arrhythmia. If co-administration of the medicament Enalozid Forte and any of above-mentioned medicaments is necessary, these medicaments should be used with care and to often control potassium level in blood plasma (see INTERACTIONS).

Hypoglycemia. Patients with the diabetes taking the oral antidiabetic medicaments or insulin and beginning to accept APF inhibitor should recommend to check carefully glucose level in blood, especially within the first month of combination therapy (see. INTERACTIONS).

Hypersensitivity / Quincke's disease. At treatment by APF inhibitors, including enalapril a maleate, cases of a Quincke's disease of the face, extremities, lips, language, a glottis and/or throat are described. These reactions can arise during treatment at any time. In such cases it is necessary to stop immediately the Enalozid Forte medicament treatment and to establish careful observation of a condition of the patient for the purpose of control of clinical symptoms. Even in cases when only the paraglossa without respiratory distress is observed, long observation of a condition of the patient as treatment by antihistaminic medicaments and GKS can be insufficient is necessary.

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it was Very seldom reported about lethal cases as a result of a Quincke's disease which was followed by edema of laryngeal or language. At patients with hypostasis of language, a glottis or throat the emergence of obstruction of airways, especially at patients with surgical treatment of airways in the anamnesis is possible. 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 p / to epinephrine 1:1000 solution (0.3-0.5 ml) and/or to perform other corresponding treatment.

representatives of negroid race who applied APF to a thicket had a Quincke's disease in comparison with patients of Caucasian race. However in general it is considered that representatives of negroid race have an increased risk of developing of a Quincke's disease.

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

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. Cough cases against the background of therapy were observed 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 during anesthesia using the means causing hypotension, enalapril blocks formation of angiotensin II again to compensatory release of renin. If at the same time the hypotension explained with the similar mechanism it develops it is possible to adjust increase in volume of liquid (see INTERACTIONS).

Pregnancy. It is not necessary to begin intake of APF inhibitors during pregnancy. If therapy continuation by APF inhibitors is not important, the patients planning pregnancy should be transferred to alternative antihypertensive treatment which has the approved profile of safety of use during pregnancy. If pregnancy is established, treatment by APF inhibitors should be stopped immediately and if it is possible, it is necessary to begin alternative therapy.

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

Hydrochlorothiazide

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

Disease of a liver. Patients with disturbance or the progressing abnormal liver function of a tiazida should appoint with care as even at insignificant disturbances of water and electrolytic balance there can be a hepatic coma.

Metabolic and endocrine effects. Therapy of a tiazidama can change tolerance to glucose. In certain cases correction of doses of antidiabetic drugs, including insulin can be required.

Increase in levels XC and TG can be associated with therapy by thiazide diuretics; however at use of a hydrochlorothiazide in a dose of 12.5 mg it was reported about the minimum effects or their absence.

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

disturbances of water and electrolytic balance (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, increased fatigue, muscular pain or spasms, muscle weakness, arterial hypotension, an oliguria, tachycardia, disturbances from digestive system (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 patients with the raised diuresis, with the insufficient oral use of electrolytes and at patients who at the same time receive therapy of GKS or AKTG (see INTERACTIONS).

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

Tiazida's

can reduce removal of calcium with urine and also be the cause of periodic and slight increase of level of calcium in blood plasma in the absence of calcium metabolism disturbances. The expressed hypercalcemia can be manifestation of the hidden hyper parathyroidism. Use of tiazid should be stopped before carrying out tests concerning function of epithelial bodies.

Tiazida's

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

Hypersensitivity. During reception of tiazid of hypersensitivity reaction can arise at patients with an allergy or OH in the anamnesis or without those. It was reported about cases of aggravation or reactivation of a system lupus erythematosus.

Use during pregnancy and feeding by a breast. The medicament Enalozid Forte should not be used to the pregnant women or women who are going to become pregnant. If during treatment the pregnancy is confirmed by medicine, its use should be stopped and replaced immediately with other medicine allowed for use for pregnant women.

Feeding by a breast. Enalapril and thiazide diuretics get into breast milk. Use of the medicament Enalozid Forte during feeding by a breast is not recommended.

Ability to influence speed of response at control of vehicles or work with other mechanisms. Some of the undesirable effects specified in the section SIDE EFFECTS can affect ability to run vehicles and/or mechanisms.

Children. Researches of medicinal interactions were conducted only with participation of adult patients.

Interaction

Double blockade raas. in clinical trials it is shown that double blockade raas at simultaneous use of inhibitors apf, antagonists of receptors of ii angiotensin or an aliskiren is connected with the increased risk of by-effects (hypotensions, hyperpotassemias and deterioration in function of kidneys, including opn) in comparison with use of one medicament raas (see contraindications, special instructions).

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 the return increase in concentration of lithium in blood plasma and toxicity at simultaneous use of lithium with APF inhibitors. Simultaneous use of thiazide diuretics can increase in addition the level of lithium and increase risk of toxic effect of lithium if to apply APF inhibitor.

Use of the medicament Enalozid Forte 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 (see. Special INSTRUCTIONS).

NPVP, including selection TsOG-2 inhibitors. NPVP, including selection inhibitors TsOG-2 inhibitors, can weaken antihypertensive effects of APF inhibitors, effects of diuretics and/or other antihypertensive drugs. 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. The renal failure, in particular at patients with a renal failure can seldom develop (for example at patients of advanced age or patients with dehydration, including the patients receiving treatment by diuretics). Therefore such combination of medicaments should be applied with care to patients with the weakened function of kidneys.

Enalapril maleate

Kaliysberegayushchy diuretics or additives of potassium. APF inhibitors reduce the potassium loss 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 (see. Special INSTRUCTIONS).

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. It is possible to weaken hypotensive effect by diuretic cancellation, increase in volume of liquid in an organism or increase in consumption of salt.

Tricyclic antidepressants / neuroleptics / anesthetics. Simultaneous use of certain anesthetics, tricyclic antidepressants and neuroleptics with APF inhibitors can lead to additional decrease in the ABP (see. Special INSTRUCTIONS).

Sympathomimetics. Sympathomimetics can reduce antihypertensive effect of APF inhibitors.

Antidiabetic drugs. Results of epidemiological researches indicate that simultaneous use of APF inhibitors and antidiabetic means (insulin, oral hypoglycemic means) can lead to decrease in level of glucose in blood with risk of development of a hypoglycemia. Such effect will probably be noted within the first weeks of the accompanying treatment and at patients with a renal failure (see. Special INSTRUCTIONS).

Alcohol. Alcohol exponentiates hypotensive effect of APF inhibitors.

Acetylsalicylic acid, thrombolytic medicaments and blockers of β-adrenoceptors. Enalapril can be applied with care together with acetylsalicylic acid (in cardiological doses), thrombolytic means and blockers of β-adrenoceptors.

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, including enalapril.

Accompanying therapy by APF inhibitor and the antagonist of receptors of angiotensin. It was reported that at patients with the confirmed atherosclerotic disease, heart failure or diabetes the accompanying therapy by APF inhibitor and the antagonist of receptors of angiotensin is associated with damage of target organs with high frequency emergence of arterioles