for medical use
of ENAP® medicine – N
ЭНАП® – N
the International unlicensed name
Is not present
the Dosage form
of the Tablet of 10 mg / 25 mg
One tablet contains
active agents: enalapril maleate of 10.00 mg
hydrochlorothiazide of 25.00 mg,
excipients: Natrii hydrocarbonas, quinolinic yellow (E 104), lactoses monohydrate, corn starch, starch prezhelatinizirovanny, talc, magnesium stearate.
of the Tablet of yellow color of round shape, with a flat surface, with slanted edges and risky on one party.
the Drugs influencing renin-angiotenzinovuyu a system.
AKF inhibitors in a combination with diuretics.
The ATX C09BA02 code
Pharmacokinetics Enalapril properties is quickly absorbed from digestive tract. Extent
of absorption makes 60% and does not depend on meal. Within 1 hour
reaches peak concentration in blood serum, after 4 hours, concentration quickly goes down. Enalapril is metabolized in active drug enalaprilat in a liver. The peak of concentration of enalaprilat in serum is reached 3 – 4 hours later after reception of a dose of enalapril. At patients with normal renal function, stable concentration of enalaprilat in serum are reached for
the fourth day after the beginning of intake of enalapril.
Enalaprilat is distributed in the majority of tissues of body, mainly in lungs, kidneys and blood vessels, but there are no data that in therapeutic doses it reaches a brain. The half-life period is 4 hours. Communication with proteins of plasma of 50 – 60%. Enalapril and enalaprilat pass through a placental barrier and are emitted in breast milk.
Removal of enalapril is carried out mainly through kidneys. The main components in urine – enalaprilat (about 40% of a dose) and not changed enalapril. Removal is carried out by a combination of glomerular filtration and canalicular secretion. Clearance of enalapril and enalaprilat in kidneys – 0.005 ml / with (18 l/h) and from 0.00225 to 0.00264 ml / with (8.1 – 9.5 l/h), respectively. There are several phases of removal. Points long final elimination half-life to strong correlation between AKF of plasma and enalarpilaty. The effective half-life period for accumulation of enalaprilat after repeated oral doses of enalapril of a maleate is 11 hours. Elimination half-life of enalaprilat
makes 35 hours.
Enalaprilat can be removed from circulation with a hemodialysis or peritoneal dialysis. The clearance of a hemodialysis of enalaprilat of 0.63 – 1.03 ml / with (38 – 62 ml/minute), concentration of enalaprilat in blood plasma after a 4-hour hemodialysis decreases by 45 – 57%.
The hydrochlorothiazide, is generally absorbed in a duodenum and in an upper small intestine. Extent of absorption makes 70% and increases by 10% if the hydrochlorothiazide is accepted with food. The maximum concentration in blood plasma is reached within 1.5 – 5 hours.
The volume of distribution is about 3 l/kg. Communication with proteins of plasma about 40%. It also collects in erythrocytes the unknown mechanism. The hydrochlorothiazide gets through a placental barrier and collects in amniotic liquid. Hydrochlorothiazide level in breast milk very low.
The hydrochlorothiazide, generally remains nemetabolizirovanny and more than 95% are removed with urine in an invariable look.
Removal is carried out as a result of canalicular secretion. The renal clearance of a hydrochlorothiazide at patients with a hypertension with healthy kidneys is about 5:58 ml / with (335 ml/min.). Removal consists of two phases. The half-life period in plasma is about 2.5 hours and elimination half-life makes 5.6 – 14.8 hours.
Simultaneous use of enalapril and a hydrochlorothiazide has no effect on bioavailability and their pharmacokinetics separately.
of Enap®-N – the combined drug which effect is caused by properties of the components which are its part.
Enalapril – inhibitor of angiotenzinkonvertiruyushchy enzyme (AKF). In an organism it is quickly metabolized in enalaprilat which is the AKF powerful inhibitor.
Main effects of suppression of AKF: reduced concentration of angiotensin II and Aldosteronum in blood circulation, inhibition of activity of fabric of angiotensin II, increase in discharge of renin, stimulation of a vazodilatator of a kalikrein-kinin system, suppression of sympathetic nervous system, and the increased production of prostaglandins and the weakening factor of a vascular endothelium.
Энап®-Н, thus, blocks bradykinin disintegration – a potential vazadilatator of peptide. However, the bradykinin role in therapeutic effects of enalapril remains not until the end of explained. While the mechanism via which enalapril lowers arterial blood pressure as believe, is first of all suppression renin-angeotenzin-aldosteronovoy of a system which plays a major role in regulation of arterial blood pressure, enalapril is antihypertensive even for patients with a hypertension of low renin.
The peak effect of enalapril occurs in 6 – 8 hours. The effect usually remains within 24 hours, thus, allowing to take the drug one-two times a day.
The hydrochlorothiazide is diuretic and the antihypertensive agent who increases activity of renin in blood plasma. Though intake of enalapril separately, has antihypertensive effect even at hypertensive patients with low renin, the combined reception of a hydrochlorothiazide at these patients leads to a bigger lowering of arterial pressure. Therefore the accompanying intake of AKF inhibitor and a hydrochlorothiazide is reasonable when each drug is separately not rather effective. Such combined use gives the chance to increase efficiency of therapy at lower doses of enalapril and a hydrochlorothiazide and reduces side effects. The antihypertensive effect of a combination usually lasts for 24 hours therefore, one-two times a day are enough to take the drug.
– arterial hypertension (patients to whom combination
therapy is shown)
the Route of administration and doses
Drug is shown for oral administration.
The dosage of drug is based first of all on experience with its active agent enalapril a maleate. The usual dose makes one tablet once a day. Risk (a notch on tablets) it is not intended for a tablet razlamyvaniye, for swallowing simplification, or for division of a tablet into equal half.
If necessary, the dose can be increased to two tablets once a day. For most of patients of 20 mg of enalapril of a maleate and 50 mg of a hydrochlorothiazide a day it is enough therefore, it is recommended no more than two tablets Enap®-N a day. If positive reaction is not reached, addition of the second drug or change of therapy is recommended.
Preliminary therapy by diuretics
After an initial dose of drug can develop symptomatic hypotension, patients with deficit have liquids and/or salts as a result of preliminary therapy by diuretics. Therapy by diuretics needs to be cancelled in 2-3 days prior to therapy of Enapom®-N.
A dosage in a renal failure
Thiazide diuretics can be improper for patients with a renal failure. They are inefficient for patients with clearance of creatinine of 0.5 ml / with or less (that is with a moderate and heavy renal failure).
For patients with clearance of creatinine between 0.5 ml / with and 1.3 ml / with, treatment should be begun with a suitable dose of separate active agents.
A dosage for elderly patients
In clinical trials, the efficiency and the tolerance of enalapril
of a maleate and hydrochlorothiazide accepted at the same time were similar at elderly and at younger hypertensive patients.
Very often (≥ 1/10):
– illegibility of sight
– an asthenia
Often (from ≥ 1/100 to & lt, 1/10):
– a hypopotassemia, increase in cholesterol, increase in triglycerides,
– a headache, a depression, a faint, change of taste
– hypotension, orthostatic hypotension, disturbance of a rhythm, tachycardia,
– short wind
– diarrhea, an abdominal pain
– rash (dieback), an allergy/Quincke’s edema: edemas of face, extremities, lips, language,
a glottis and/or throat
– muscular spasms
– a stethalgia, fatigue
– a hyperpotassemia, increases in creatinine of serum
Infrequently (from ≥ 1/1000 to & lt, 1/100):
– anemia (including aplastic and hemolytic)
– a hypoglycemia, a hypomagnesiemia, gout
– confusion of consciousness, insomnia, drowsiness, nervousness, a parasthesia,
dizziness, decrease in a libido
– a ring in ears
– hyperaemia, a cardiopalmus, a myocardial infarction or a stroke,
a possibility of secondary excessive hypotension at patients with the increased
– a rhinorrhea, a sore throat and hoarseness, bronchospasm/asthma
– intestinal impassability, pancreatitis, vomiting, indigestion, a constipation,
anorexia, gastric irritations, dryness in a mouth, a peptic ulcer,
– an itching, sweating, baldness, urticaria
– an arthralgia
– renal dysfunction, a renal failure, a proteinouriya
– uneasiness, fever
– increases in urea of serum, a hyponatremia
Seldom (from ≥1/10,000 to & lt, 1/1000):
– a neutropenia, reduction of hemoglobin and a hematocrit, thrombocytopenia,
an agranulocytosis, a leukopenia, suppression of activity of marrow,
a pancytopenia, a hyperadenosis, autoimmune diseases
– sleep disorders, paresis (because of a hypopotassemia)
– Reynaud’s Phenomenon
– pulmonary infiltrates, breath disturbances (including pneumonia and pulmonary
hypostasis), rhinitis, allergic alviolit / eosinophilic pneumonia
– stomatitis / an aphthous ulcer, a glossitis
– a liver failure, liver necrosis (can be fatal), hepatitis – both
hepatocellular and cholestatic, jaundice, cholecystitis (in particular
at patients with earlier existing cholelithiasis)
– a polymorphic erythema, Stephens-Johnson’s syndrome, exfoliative
dermatitis, a toxic epidermal necrolysis, a purpura, a skin
lupus erythematosus, an erythrosis, a pempigus. The complex of symptoms was noted: fever, a serositis, a vasculitis, a myalgia/miositis, arthralgia/arthritis, positive ANA, the increased SOE, an eosinophilia and a leukocytosis. Also there can be rash, a photosensitization and other dermatological manifestations.
– an oliguria, interstitial nephrite
– a gynecomastia
– increase in enzymes of a liver, increase in bilirubin of serum
Very seldom (& lt, 1/10.000):
– a hypercalcemia
– an intestinal Quincke’s edema
Isolated cases (it cannot be estimated from available data):
– the syndrome of inadequate secretion of antidiuretic hormone (SISAH)
At emergence of heavy side effects the treatment has to be stopped.
– hypersensitivity to active component or to any
– the Quincke’s disease connected with use before AKF inhibitors
– a hereditary or idiopathic Quincke’s disease
– hypersensitivity to sulphonamide drugs
– an anury
– a heavy renal failure (clearance of creatinine less than 30 ml/min.).
– a renal artery stenosis
– a heavy liver failure
– pregnancy and the period of a lactation
– children’s and teenage age up to 18 years (the efficiency and safety
are not established).
of Enalapril a maleate and a hydrochlorothiazide
Other antihypertensive means
the Accompanying use of other antihypertensive means
can increase hypotensive effects of enalapril and a hydrochlorothiazide.
The accompanying use of nitroglycerine and other nitrates, or other vazodilatator, can reduce arterial blood pressure further.
the Accompanying use of diuretics, AKF inhibitors and lithium can cause reversible increases in concentration of lithium in plasma and lithium toxicity. The accompanying use of thiazide diuretics can increase further the level of lithium and increases risk of lithium toxicity with AKF inhibitors. The accompanying use is not recommended, but if it is necessary, stringent control of level of lithium in plasma has to be carried out.
Non-steroidal anti-inflammatory drugs (NPVP)
Long reception of NPVP can reduce antihypertensive effect of AKF inhibitors or reduce diuretic, natriuretichesky and antihypertensive effects of diuretics.
Besides, as it was described, NPVP (including TsOG-2 inhibitors) and AKF inhibitors show aggregate effect increase in potassium in blood serum
whereas renal function can decrease, especially at patients with the damaged renal function (elderly people or patients with volume exhaustion, including those who accept diuretics). This effect, in principle, is reversible.
At some patients of NPVP can reduce diuretic and antihypertensive effects of diuretics.
Enalapril a maleate
the Effect of loss of potassium of thiazide diuretics usually decreases under the influence of enalapril. Potassium content in blood plasma usually remains within norm though there were cases and hyperpotassemias.
Use of kaliysberegayushchy diuretics (for example, Spironolactonum, Triamterenum or amiloride), the additives of potassium or solezamenitel containing potassium, especially at patients with the weakened function of kidneys can cause significant increases in level of potassium in blood plasma.
If the accompanying use any of these agents is considered expedient because of a hypopotassemia, they have to be used with care and with frequent control of potassium of serum.
Preliminary treatment by high doses of diuretics can result diuretics (thiazide or loopback diuretics) in deficiency of liquid and risk of hypotonia, after the beginning of intake of enalapril. Hypotensive effects can be reduced by the termination of intake of diuretics or increase in consumption of liquid or salt.
Tricyclic antidepressants / antipsychotic means / anesthetics
the Accompanying use of certain anesthetics, tricyclic antidepressants and antipsychotic means with AKF inhibitors can lead to a further lowering of arterial pressure.
Use of sympathomimetics can reduce antihypertensive
effects of AKF inhibitors, patients have to be under careful control for achievement of desirable effect.
Antidiabetic means (oral hypoglycemic means and insulin)
Simultaneous use of AKF inhibitors and antidiabetic drugs (insulin, oral hypoglycemic means), can cause the increased effect of reduction of glucose in blood with risk of development of a hypoglycemia. This phenomenon is more often observed within the first weeks of the combined
treatment and at patients with a renal failure. Long-term controlled clinical trials with enalapril did not confirm these results and do not exclude use of enalapril at patients with diabetes. However,
frequent monitoring of such patients is recommended.
Use of antidiabetic drugs and thiazide diuretics can demand regulation of a dosage of antidiabetic drug.
Alcohol strengthens hypotensive effect of AKF inhibitors. Antacids can reduce bioavailability of AKF inhibitors.
Acetylsalicylic acid, trobmolitik and beta-blockers
Enalapril can be accepted safely together with acetylsalicylic acid (in cardiological doses), trombolitika and beta-blockers.
At patients to whom entered gold (sodium aurotiomalat) at the accompanying therapy AKF inhibitors, including enalapril, sometimes observed nitritoidny reactions (hyperaemia of the person, nausea, vomiting and hypotonia).
Tiazida’s muscle relaxants can increase susceptibility to tubocurarine.
Alcohol, barbiturates or opioid analgetics can strengthen orthostatic hypotension
Antidiabetic drugs (peroral agents and insulin)
adjustment of a dose of antidiabetic drug Can be necessary.
Holestiramin and kolestipolovy pitches (anionno-exchange pitches) can reduce absorption of a hydrochlorothiazide. The single dose and a holestiramina, and kolestipolovy pitches detains a hydrochlorothiazide, reduces its absorption from digestive tract to 85 and 43%, respectively.
Increase in QT of an interval (e.g. quinidine, procaineamide, Amiodaronum, sotalol)
Increase in risk of bidirectional tachycardia.
A glycoside the naperstyankigipokaliyemiya can sensibilize or increase reaction of heart to toxic influence of a digitalis (for example, to increase ventikulyarny sensitivity)
Simultaneous use with thiazide diuretics leads to the strengthened electrolyte exhaustion, especially gipokalemiya.
Potassiumuretic diuretics (for example, furosemide), karbenoksolon or abuse of laxatives
the Hydrochlorothiazide can increase loss of potassium and/or magnesium.
Pressor amines (for example, adrenaline)
Tiazida can reduce reaction to pressor amines.
Cytostatics (for example, cyclophosphamide, a methotrexate)
Tiazida can reduce renal removal of cytotoxic drugs and enhance their myelosuppressive effect.
instructions Hypotension and instability of electrolyte/liquid
As well as with other antihypertensive agents, some patients can have a symptomatic hypotension. It, in rare instances, happens at patients to the increased arterial blood pressure without complication, but it is more probable in the presence of instability of liquid or electrolyte (for example, deficiency of liquid, a hyponatremia, a gipokhloremichesky alkalosis, a hypomagnesiemia or a hypopotassemia) which can happen owing to preliminary therapy by diuretics, diets to restriction of salt, dialysis, or during accidental diarrhea or vomiting. At such patients in the corresponding intervals it is necessary to carry out the analysis of electrolytes in blood plasma.
Special attention has to be paid to patients with coronary heart disease or a cerebrovascular disease as the excessive lowering of arterial pressure can lead to a myocardial infarction or a stroke. At hypertensive patients with the heart failure connected with a renal failure or without it the symptomatic hypotension was observed.
When developing hypotension of the patient it is necessary to place in situation, lying on spin, and, in case of need, to enter intravenously isotonic solution of sodium chloride. Temporary hypotensive reaction is not a contraindication to further doses. After restoration of effective volume of blood and pressure, repeated prescribing of drug in the reduced dosage is possible, or any of components can be used in itself properly.
A renal failure
the Fixed combinations of enalapril and a hydrochlorothiazide should not be ordered to patients with a renal failure (clearance of creatinine & lt, 1.3 ml / with or 80 ml/min. and & gt, 0.5 ml / with or 30 ml/min.), there was no need of titration of separate active agents for the doses existing in the combined tablets yet. At some hypertensive patients without the obvious disease of kidneys existing earlier which accept enalapril together with diuretics insignificant and transitional increases in urea in serum and creatinine level can develop. If it happens during therapy to the fixed combination of enalapril and a hydrochlorothiazide, therapy has to be stopped. Perhaps repeated prescribing of drug in the reduced dosage, or any of components can be used in itself properly. This situation can increase a possibility of a stenosis of the main renal artery.
the Combination of enalapril and low doses of diuretics does not exclude a possibility of development of a hyperpotassemia
a lithium Combination with enalapril and diuretic drugs do not recommend.
Enalapril the maleate
the Aortal stenosis / a hypertrophic cardiomyopathy
As well as all vazodilatator, AKF inhibitors needs to be applied with care at treatment of patients with obstruction of a portable path of a left ventricle and to avoid cases of cardiogenic shock and hemodynamically significant obstruction of a portable path of a left ventricle.
A renal failure
the Renal failure connected with enalapril use, mainly, was noted at patients with heavy heart failure or diseases of kidneys of the latent form, including a renal artery stenosis. The renal failure connected with therapy by enalapril is usually reversible if it is distinguished quickly and treatment was carried out properly.
Exists the increased risk of developing arterial hypotension and renal failure when patients with a bilateral stenosis of renal arteries or a stenosis of an artery of the only functioning kidney accept treatment by AKF inhibitors.
Loss of function of kidneys can happen also at moderate changes of level of creatinine in blood plasma. Such patients should begin treatment under careful observation of the doctor and control of function of kidneys.
Experience of treatment by enalapril of patients with recent renal transplantation is absent. Therefore the use of enalapril is not recommended.
The patients who are on a hemodialysis
Enalapril it is not intended for treatment of the patients demanding dialysis for a renal failure. About development of hypersensitivity, anaphylactoid reaction (tumor of the person, hyperaemia, hypotension and difficulty of breath),
it was reported among the patients who are on a hemodialysis with
use of poliakrilnitrilovy membranes (AN 69) and at the same time accepting AKF inhibitors. Such combination needs to be avoided. In need of carrying out a hemodialysis it is necessary to use other type of membranes, or to transfer the patient to intake of suitable drug from other class
of antihypertensive agents.
A liver failure
during therapy by AKF inhibitors, in rare instances, development of a syndrome which begins with cholestatic jaundice is possible and then progresses to fulminantny necrosis of a liver and (sometimes) with a lethal outcome. The mechanism of development of this syndrome is not clear. The patients accepting AKF inhibitors at which jaundice develops or are marked out increases in enzymes of a liver, have to stop intake of AKF inhibitors and receive the corresponding medical observation.
At the patients accepting AKF inhibitors cases of development of a neutropenia/agranulocytosis, thrombocytopenia and anemia are noted. At patients with normal function of kidneys for lack of other complications, the neutropenia develops seldom.
Enalapril needs to be applied with very big care at the patients with collagenoses who are at the same time receiving therapy by immunodepressants, Allopyrinolum or procaineamide and also with a combination of these factors, especially at
the existing renal failures. At such patients the heavy infections which are not giving in to intensive antibiotic treatment can develop. When prescribing drug it is recommended to control periodically quantity of leukocytes in blood. The patient has to be warned that in case of any symptoms of an infection it is necessary to see a doctor immediately.
Increase in level of potassium in blood plasma were observed at some patients receiving AKF inhibitors including enalapril. Risk factors for development of a hyperpotassemia include a renal failure, deterioration in function of kidneys, age (& gt, 70 years), diabetes, intermediate events, in particular, dehydration, an acute heart failure, a metabolic acidosis and simultaneous use of kaliysberegayushchy diuretics (Spironolactonum, an eplerenona, Triamterenum or amiloride), potassium additives and potassium – the containing salt substitutes and also intake of other drugs increasing potassium level in blood plasma (for example heparin). Use of potassium additives or potassium – the containing substitutes of salt or kaliysberegayushchy diuretics can lead to significant increase in level of potassium in blood plasma, especially at patients with impaired renal function. The hyperpotassemia can cause heavy, sometimes fatal, arrhythmia. If simultaneous use of enalapril with any of above-mentioned agents,
it is considered expedient, then they should be applied with care, and to control potassium level in blood plasma more often.
Patients with diabetes
At the patients with diabetes receiving the anti-diabetic oral drugs or insulin beginning treatment with AKF inhibitors it is necessary to control carefully on a hypoglycemia, especially within the first month of the combined treatment.
Hypersensitivity / a Quincke’s disease
during intake of AKF inhibitors, including an elanapril a maleate, in rare instances there are edemas of face, extremities, lips, language, a glottis and/or throat. It can occur treatments at any time. When developing a Quincke’s edema, treatment has to be immediately stopped, and the patient has to be under control before the termination of manifestation of all symptoms. The patient cannot be released before complete cessation of manifestation of all symptoms.
Even when there is only a paraglossa without breath difficulty, long observation as treatment by antihistamines and corticosteroids can be insufficient can be required by patients.
It was very seldom reported about the Quincke’s edemas connected with a throat or language. Patients with hypostases of language, a glottis or throat will probably experience obstruction of airways, especially patients who have in the anamnesis an operation of airways. In paraglossas, a glottis or throat which can cause obstruction of airways the treatment which can include hypodermic administration of solution of adrenaline 1:1000 (0.3 ml – 0.5 ml) is appointed and/or to take operational measures for ensuring passability of airways.
The black patients accepting AKF have inhibitors, there is higher incidence of a Quincke’s disease in comparison with patients of other race. For patients with the Quincke’s edema which is not connected with therapy of AKF inhibitors in the anamnesis, there is an increased risk of a Quincke’s edema at intake of AKF inhibitors.
Anaphylactoid reactions during desensitization
the Patients accepting AKF inhibitors can sometimes experience life-threatening allergic (anaphylactoid) reactions during desensitization with poison of a bee or wasp. These reactions can be avoided, temporarily stopping intake of AKF inhibitor before each session of desensitization.
Anaphylactoid reactions during LDL of an aferez
the Patients accepting AKF inhibitors can sometimes experience life-threatening allergiyapodobny (anaphylactoid) reactions during an anaferez of lipoproteins of the low density (LDL) with dextran sulfate. These reactions can be avoided, temporarily stopping intake of AKF inhibitor before each session of an aferez.
during intake of AKF inhibitors can begin steady dry unproductive cough which passes after the treatment termination. It is necessary to consider it as a part of the distinctive diagnosis of cough.
At patients who underwent a serious operation or during anesthesia with agents who cause a gipotenniya enalapril can block the angiotensin-II forming secondary to compensatory release of renin. If assume that hypotension happens because of this mechanism, it can be corrected by expansion of volume of the circulating blood.
As well as other inhibitors of angiotensin-converting enzyme, enalapril is less effective in a lowering of arterial pressure at black people, than at the others, it is possible because of higher prevalence of the status of low renin.
Pregnancy and the period of a lactation
during pregnancy it is not necessary to begin intake of AKF inhibitors. Until treatment by AKF inhibitors is necessary, the patients planning pregnancy have to pass to intake of alternative antihypertensive drugs which have the established safety profile for use during pregnancy. When diagnosing pregnancy, treatment by AKF inhibitors needs to be stopped immediately, and if it is reasonable, to begin alternative treatment.
Enalapril is not recommended for use in the period of a lactation.
the Renal failure
of Tiazida can be improper diuretics for use at patients with impaired renal function and are inefficient at clearance of creatinine of 30 ml/min. and below (that is, a moderate or heavy renal failure).
Diseases of a liver
of Tiazida have to be used with care at patients with the weakened hepatic function, or the progressing liver disease as minor changes of balance of electrolyte can accelerate a hepatic coma.
Metabolic and endocrine effects
Therapy of a tiazidama can weaken tolerance of glucose. Regulation of a dosage of anti-diabetic agents, including insulin can be required.
Increases in cholesterol and level of triglyceride can be connected with thiazide diuretic therapy, however, at a dose of 12.5 mg of a hydrochlorothiazide, this action minimum or is absent. Besides, in clinical trials from 6 mg of a hydrochlorothiazide it was not reported about any clinically significant impact on glucose, cholesterol, triglycerides, sodium, magnesium or potassium.
Therapy of a tiazidama can accelerate a hyperuricemia and/or gout at certain patients. This impact on a hyperuricemia, perhaps, is connected with a dose, and is not clinically significant at a dose of a hydrochlorothiazide of 6 mg. Besides, enalapril can increase renal uric acid and thus reduce giperurikemichesky effect of a hydrochlorothiazide.
As for any patient receiving diuretic therapy the periodic definition of electrolytes in blood plasma, in the corresponding intervals has to be carried out.
Tiazida (including a hydrochlorothiazide) can cause instability of liquid or electrolyte (hyperpotassemia, a hyponatremia, and a gipokhloremichesky alkalosis). Signs of instability of liquid or electrolyte – xerostomia, thirst, weakness, a lethargy, drowsiness, excitement, muscle pain or spasms, muscular fatigue, hypotonia, an oliguria, tachycardia, and gastrointestinal disorders, such as nausea and vomiting.
Though the hypopotassemia can develop in a usage time of thiazide diuretics, parallel therapy with enalapril can reduce the hypopotassemia caused by diuretic. The risk of a hypopotassemia is the biggest for patients with cirrhosis, for the patients testing a brisk diuresis for patients with inappropriate oral administration of electrolytes and for a patsa