Pharmacological properties

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

Enalapril maleate. APF is the peptidilovy dipeptidase catalyzing angiotensin transformation І in pressor substance angiotensin ІІ. After absorption, enalapril is hydrolyzed to enalaprilat which suppresses APF. Oppression of APF leads to decrease in level of angiotensin ІІ in blood plasma that leads to increase in activity of renin in blood plasma (because of 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 ІІ. 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 of decrease in the ABP of enalapril first of all connect system renin-angiotensin-aldosteronovoy which plays the main role in regulation of the ABP with oppression of activity, enalapril can show antihypertensive effect even at patients from lowrenine AG.

Hydrochlorothiazide is a diuretic and antihypertensive medicament which increases activity of renin in blood plasma.

Enalapril maleate/hydrochlorothiazide. Antihypertensive effects of two components are additive and, as a rule, last 24 h. In spite of the fact that separately enalapril shows hypotensive action even at patients from lowrenine AG, simultaneous use with a hydrochlorothiazide for such patients leads to more significant decrease in the ABP. Enapril as a part of drug, as a rule, reduces the potassium removal caused by reception of a hydrochlorothiazide.

Pharmacokinetics.

Enalapril maleate. After oral administration, enalapril is quickly absorbed, reaching the C _max in blood plasma for 1 h. Being based on a removal indicator with urine, 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 generally is emitted with kidneys. The main substance in urine is enalaprilat — about 40% of a dose, and enalapril in not changed look. Except for transformation into 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 caused by binding of APF. At persons with normal function of kidneys the equilibrium 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. When monitoring levels in blood plasma throughout at least 24 Parts T _½ made 5.6-14.8 h of blood plasma. The hydrochlorothiazide is not metabolized, but quickly allocated with kidneys. At oral administration of at least 61% of a dose it is removed in not changed look for 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 substances. The tablet containing a combination of two substances, a bioekvivalentna to its separate components which are applied at the same time.

Indication

Arterial hypertension at patients to whom combination therapy is shown.

Use

Arterial hypertension. tablets with the fixed combination of enalapril of a maleate and a hydrochlorothiazide are appointed to patients at whom hell is insufficiently controlled by use only of enalapril.

Use of the fixed combination of enalapril of a maleate and a hydrochlorothiazide is not suitable

for initial therapy and is usually recommended after titration of doses of separate components. At clinical expediency it is possible to pass from monotherapy to the fixed combination at once.

Mode of dosing is set individually depending on a condition of the patient and severity of AG. Treatment is begun with low doses of medicament with gradual increase in dosing. Drug is used inside irrespective of food. The established daily dose should be accepted in the morning, washing down with a large amount of liquid.

Usually the dose makes 1 tablet which is applied 1 time a day. If necessary the dose can be raised to 2 tablets a day in one step.

/ 25 mg and 20 mg / 12.5 mg can replace with

Tablet with the fixed combination of 10 mg the therapy consisting of reception separately of 10 or 20 mg of enalapril and 25 or 12.5 mg of a hydrochlorothiazide respectively at patients whose condition is stabilized by treatment by separate components.

Previous treatment by diuretics: symptomatic hypotension can arise at the beginning of therapy by drug. Reveal more often at patients in whom the previous therapy by diuretics caused disturbance of water and electrolytic balance. Therapy by diuretics has to be stopped in 2–3 days prior to therapy by the medicaments Enap-N, Enap-HL and Enap-20 HL.

Dosing in a renal failure. Clearance of creatinine of 30 ml/min. Dose adjustment of enalapril by titration is necessary for patients with disturbances of kidneys with clearance of creatinine of ≥30 ml/min. before transition to the fixed combination. Loopback diuretics are more acceptable for such patients, than a tiazida. The dose of enalapril and a hydrochlorothiazide has to be the lowest. Periodic control of potassium and creatinine, for example, is necessary each 2 months at stabilization of a condition of the patient.

Clearance of creatinine of 30 ml/min. Use of medicament is contraindicated.

Special populations. For patients with deficiency of electrolytes/liquid the initial dose of enalapril makes ≤5 mg and recommend titration of monocomponents.

Dosing for patients of advanced age. Use of medicament for patients of advanced age is carried out in the same dose, as at young people. In case of a physiological renal failure before transition to the fixed combination the dose adjustment of enalapril by titration is necessary.

does not have

restriction in time concerning treatment duration.

Contraindication

Hypersensitivity to enalapril and other inhibitors apf, to a hydrochlorothiazide and other derivatives of sulfonamides or other components of medicaments enap-h or enap-hl; existence in the anamnesis of the Quincke's disease connected with the previous treatment by inhibitors apf; hereditary or idiopathic Quincke's disease; patients with heavy renal failures (the clearance of creatinine of 30 ml/min. or level of creatinine in blood serum exceeds 265 µmol/l (3 mg / 100 ml); renal artery stenosis; carrying out hemodialysis; a clinical state after transplantation of a kidney; heavy abnormal liver functions; anury, primary hyper aldosteronism; hypopotassemia, resistant to treatment, or hyperpotassemia; refractory hyponatremia; simptomny hyperuricemia (gout); the pregnant women or women who are going to become pregnant (see use during pregnancy and feeding by a breast); it is not necessary to apply enalapril with the medicaments containing aliskiren at patients with diabetes or a renal failure (skf 60 ml/min. / 1.73 sq.m).

Side effects

Most frequent side reactions were dizziness and increased fatigue which usually disappeared at a dose decline and seldom demanded medicament withdrawal.

Other side reactions (1–2%); headache, cough and impotence.

side reactions about which it was reported at use of one enalapril or one hydrochlorothiazide or during clinical trials, or after medicament entry into the market Are included by

.

from a cardiovascular system: orthostatic hypotension, palpitation, tachycardia, thorax pain.

from a GIT: pancreatitis, diarrhea, vomiting, dyspepsia, an abdominal pain, round ulcers, a meteorism, a constipation, dryness in a mouth, aphthous ulcers.

from nervous system / mentality: faints, insomnia, drowsiness, paresthesias, dizziness, fatigue, an indisposition, nervousness, paresis (owing to a hypopotassemia).

from respiratory organs: short wind, allergic alveolitis.

from skin: Stephens's syndrome — Johnson, rash, an itching, the increased sweating, a hyperhidrosis, a photosensitization or other dermatological reactions.

from blood: decrease in level of hemoglobin, a hematocrit and also reduction of quantity of thrombocytes and leukocytes, is rare — a neutropenia, thrombocytopenia, oppression of function of marrow.

from kidneys and urinary tract: renal failure, renal failure, proteinuria.

from a reproductive system: decrease in a libido.

Metabolic disturbances: gout.

from an organ of hearing and a vestibular mechanism: sonitus.

Others. 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.

Reaction of hypersensitivity: it was seldom reported about cases of a Quincke's disease of the face, extremities, lips, language, a glottis and/or throat (see. Special INSTRUCTIONS). It was very seldom reported about an intestinal Quincke's disease at use of APF inhibitors, including enalapril.

Change of laboratory indicators: hyperglycemia, hyperuricemia, hypopotassemia. Noted increase in level of nitrogen, urea and creatinine of blood serum, increase in level of liver enzymes and/or bilirubin in blood serum. These symptoms, as a rule, have reversible character at medicament withdrawal. Cases of a hyperpotassemia, a gipokhloremichesky alkalosis, a hypomagnesiemia, a hypercalcemia, increase in level XC and TG of blood were noted.

Influence on results of the following laboratory indicators:

• medicament can reduce the level of the iodine connected with proteins in blood plasma;
medicament is capable to raise
• concentration of free bilirubin in blood serum;
• through influence on exchange of calcium of a tiazida can affect results of assessment of function of epithelial bodies therefore before inspection of assessment of their function of treatment it is necessary to stop.

Additional side reactions which noted at use of separate components of medicament and can be potential side effects of the medicament Enap-N, Enap-HL or Enap-20HL.

Enalapril

from digestive system: Ilheus, anorexia, change of flavoring feelings, stomatitis, glossitis, nausea.

from a gepatobiliarny system: liver failure, hepatitis (hepatocellular or cholestatic), cholecystitis, hepatic necrosis, cholestasia.

from nervous system / mentality: depression, confusion of consciousness, sleep disorder, abnormal dreams, asthenia.

from respiratory organs: pulmonary infiltrates, bronchospasm / OH, sore throat and hoarseness of a voice, rhinorrhea.

from a cardiovascular system: disturbance of a warm rhythm, stenocardia, orthostatic hypotension, a myocardial infarction or a stroke (perhaps, owing to excessive arterial hypotension at patients of group of high risk), Reynaud's phenomenon.

from skin and mucous membranes: photosensitization, alopecia, erythrosis, toxic epidermal necrolysis, multiformny erythema, exfoliative dermatitis, bladderwort.

from blood: aplastic and hemolytic anemia, hyponatremia.

from the immune system: urticaria, acute anaphylaxis, autoimmune disorders.

Metabolic disturbances: hypoglycemia.

Others: illegibility of sight, lymphadenopathy, oliguria, syndrome of disturbance of secretion of ADG, muscular spasms.

Hydrochlorothiazide

from a cardiovascular system: arrhythmia.

from a gepatobiliarny system: jaundice (intra hepatic, cholestatic), hepatic necrosis, cholestasia, cholecystitis.

from digestive system: anorexia, irritation of a stomach, sialadenitis, change of flavoring feelings, nausea.

Metabolic disturbances: a glucosuria, a gipokhloremichesky alkalosis (that can induce hepatic encephalopathy or a hepatic coma), a hyperuricemia (that can provoke gout attacks at patients with an asimptomny course of the disease), a hypoglycemia, decrease in a glyukozotolerantnost (that can cause a demonstration of latent diabetes).

from blood: leukopenia, agranulocytosis, thrombocytopenia, aplastic and hemolytic anemia.

from the immune system: anaphylactic reactions, small tortoiseshell.

from skin and mucous membranes: photosensitivity, necrotizing angiitis (vasculitis), toxic epidermal necrolysis.

from an organ of sight: xanthopsia, passing disorder of vision.

from respiratory organs: a respiratory distress (including pneumonia and a fluid lungs).

from nervous system / mentality: concern, disorientation, changes of mood, exhaustion.

Change of laboratory indicators: an electrolytic imbalance (including a hyponatremia).

Others: fever, interstitial nephrite, spasms of muscles, spasms, thirst, sexual disorders.

Special instructions

Enalapril and hydrochlorothiazide

Arterial hypotension and imbalance of electrolytes. Symptomatic arterial hypotension is seldom noted at patients from uncomplicated AG. At patients from AG using drug, arterial hypotension develops more often at deficiency of electrolytes/liquid, for example owing to therapy by diuretics, restrictions of the use of salt, dialysis, diarrhea or vomiting. It is necessary to carry out regular control of level of electrolytes in blood plasma at such patients. Symptomatic arterial hypotension developed more often at patients with severe forms of heart failure which applied the maximum doses of loopback diuretics, with a hyponatremia or renal failures. At such patients the medicament treatment should be begun under observation of the doctor.

Patients needs to be surveyed rather clinical signs of a water and electrolytic imbalance, such as dehydration, a hyponatremia, a gipokhloremichesky alkalosis which can induce hepatic encephalopathy or a hepatic coma; a hypomagnesiemia or a hypopotassemia which can arise owing to diarrhea or vomiting. At such patients it is necessary to control periodically the level of electrolytes in blood serum.

Especially attentive.

At development of arterial hypotension of the patient should be put on a back and if it is necessary, to enter chloride sodium solution into 0.9%. Tranzitorny arterial hypotension at administration of medicament is not a contraindication for treatment which can be continued after normalization of the ABP and restoration of volume of liquid.

At some patients with heart failure and the normal or lowered arterial blood pressure medicament can lower the arterial blood pressure in addition. Such reaction to administration of medicament can be expected and it should not be regarded as the basis for the treatment termination. When arterial hypotension of a rezistentn to treatment, it is necessary to lower a dose and/or to stop treatment by diuretic and/or the medicament Enap-N, Enap-HL and Enap-20HL.

Double blockade system renin-angiotensin-aldosteronovoy (SRAA). Double blockade (for example at addition of APF inhibitor to the antagonist of a receptor of angiotensin II) has to be limited only to separate cases with careful control of the ABP, function of kidneys and level of electrolytes. During several researches it was reported that at patients with the established atherosclerotic defeat of vessels, heart failure or diabetes double blockade of RAAS is connected with final defeat of bodies with high frequency arterial hypotension, faints, a hyperpotassemia and deterioration in function of kidneys (including OPN) in comparison with that at use of one medicament operating on RAAS. It is not necessary to apply enalapril with aliskireny at patients with diabetes or a renal failure (glomerular filtration rate of 60 ml/min. / 1.73 m ² ) (see CONTRAINDICATIONS or SPECIAL INSTRUCTIONS).

Renal failure. It was reported about the renal failure caused by enalapril, especially in patients with heavy heart failure or diseases of kidneys including a stenosis of renal arteries. If the diagnosis is established quickly and the corresponding treatment is carried out, the renal failure connected with therapy by enalapril is usually reversible.

At some patients with AG without the previous renal failure at intake of enalapril with diuretic reveal increase in urea and creatinine in blood plasma. The dose decline of enalapril and/or the termination of intake of diuretics can be necessary. In that case it is necessary to consider a possibility of a stenosis of renal arteries at the patient.

Hyperpotassemia. At use of a combination of enalapril and diuretic in low doses there can be a hyperpotassemia.

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

Patients of advanced age. The efficiency and tolerance of enalapril of a maleate and hydrochlorothiazide at a concomitant use are similar to that at young adult patients with AG.

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

Enalapril

Aortal or mitral stenosis / hypertrophic cardiomyopathy. As well as all vazodilatator, APF inhibitors need to be applied with care at patients with a stenosis of the mitral valve and blockade of outflow from a left ventricle. Their use should be avoided in case of cardiogenic shock and obstruction of an exhaust outlet of a left ventricle.

Renovascular hypertensia. The increased risk of developing arterial hypotension is characteristic of patients with a bilateral stenosis of renal arteries or with a stenosis of an artery of the only kidney which accept APF inhibitors. Even at minor changes of creatinine in blood plasma the function of kidneys can worsen. At these patients the treatment should be begun under stringent medical control, with low doses and at careful correction of doses and control of function of kidneys.

Patients who are on a hemodialysis. At the patients who are on dialysis with use of membranes with high-permeability (for example AN 69) and simultaneous treatment by APF inhibitors, anaphylactoid reactions in certain cases developed. Therefore at such patients recommend use of dialysis membranes of other type or antihypertensive medicaments of other group.

Transplantation of a kidney. There is no experience of use of medicament for patients with recently postponed renal transplantation. Therefore medicament treatment for them is not recommended.

Abnormal liver function. Very seldom using APF inhibitors connect the syndrome beginning with cholestatic jaundice and progressing to liver necrosis, sometimes with a lethal outcome. The mechanism of this syndrome is unknown. At patients who receive APF inhibitors when developing jaundice or substantial increase of liver enzymes it is necessary to stop reception of the last and to begin the corresponding treatment.

Neutropenia/agranulocytosis. Patients who receive therapy by APF inhibitors had messages about development of a neutropenia/agranulocytosis, thrombocytopenia and anemia. The neutropenia seldom arises at patients with normal function of kidneys and without special risk factors. Enalapril should be applied very carefully at patients with collagenoses, at immunonodepressivny therapy, at treatment by Allopyrinolum or procaineamide, or at a combination of the above-stated risk factors, especially at earlier established renal failure. At some of such patients heavy infections which sometimes rezistentna to intensive care by antibiotics develop.

recommend to

At use of enalapril for such patients periodic monitoring of quantity of leukocytes, and the patient should be warned concerning informing the doctor on any symptoms of an infection.

Hyperpotassemia. At some patients at intake of APF inhibitors, including enalapril, increase in potassium concentration in blood plasma is noted. The renal failure or depression of function of kidneys, age (70 years), diabetes, intercurrent states, such as dehydration, an acute heart failure, a metabolic acidosis and simultaneous use of kaliysberegayushchy diuretics (for example Spironolactonum, eplerenon, Triamterenum or amiloride are more senior), nutritional supplements which contain potassium, or salt substitutes with potassium belongs to risk factors of emergence of a hyperpotassemia; or other medicaments causing increase in potassium concentration in blood plasma (for example heparin). Use of the nutritional supplements containing potassium, kaliysberegayushchy diuretics or substitutes of salt with potassium, especially at patients with renal failures, can lead to substantial increase of level of potassium in blood plasma. The hyperpotassemia can cause emergence serious, sometimes lethal arrhythmia. At simultaneous use of medicament and any of the specified means it is regularly necessary to control potassium level in blood plasma (see INTERACTIONS).

Hypoglycemia. At patients with diabetes who take the oral anti-diabetic medicaments or insulin the careful glycemic control, especially in the first month of treatment by APF inhibitors is necessary.

Hypersensitivity / Quincke's disease. At the patients accepting APF inhibitors, including Enap-N, Enap-HL or Enap 20 HL, in certain cases arose a Quincke's disease of the face, extremities, lips, language, a throat, narrowing of a glottis. It can arise throughout treatment at any time. In that case use of medicament needs to be stopped and established immediately constant observation of the patient before total disappearance of symptoms. Even if note only a paraglossa in the absence of respiratory a distress syndrome, long observation as treatment by antihistaminic and corticosteroid means can be insufficient can be necessary for the patient.

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it was Very seldom reported about a lethal Quincke's disease of a throat or language. When developing a paraglossa, a throat, narrowing of a glottis the emergence of obstruction of airways, especially at the patients who underwent an operation on respiratory organs is probable. In these cases the use of emergency treatment which can include p / to administration of solution of adrenaline 1:1000 (0.3-0.5 ml) and/or measures for ensuring free passability of airways is necessary.

representatives of negroid race who applied APF inhibitors had a Quincke's disease in comparison with patients of other races more often.

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At patients in whose anamnesis there is an instruction on the Quincke's disease which is not connected with use of APF inhibitors increased risk of its emergence and at use of APF inhibitors.

Anaphylactoid reactions when performing the desensibilizing therapy. Sometimes at the patients applying APF inhibitors during performing desensitization by allergen from poison of hymenopterous insects, anaphylactoid reactions which could be life-threatening developed. Similar reactions can be avoided if prior to the beginning of desensitization it is temporary to stop intake of APF inhibitor.

Anaphylactoid reactions at a LDL afereza. Seldom at a LDL afereza by means of dextransulphate the patients accepting APF inhibitors can have life-threatening anaphylactoid reactions. Such reactions can be avoided by means of temporary cancellation of therapy by APF inhibitor before each aferez.

Cough. It was reported about developing of cough at treatment by APF inhibitors. Usually cough unproductive, resistant also stops after medicament withdrawal. The cough connected with intake of APF inhibitors needs to be considered at differential diagnosis of cough.

Surgeries/anesthesia. During extensive surgeries or at anesthesia using the medicaments causing arterial hypotension, enalapril blocks formation of angiotensin ІІ again before compensatory release of renin. If at the same time arterial hypotension which can be explained with these mechanisms of interaction develops, it korrigirutsya by increase in volume of liquid.

Racial factor. As it was reported for other APF inhibitors, enalapril can be less effective concerning decrease in the ABP at patients of negroid race with AG, than at patients of other race what, perhaps, is explained by the low level of renin in blood of these patients.

Hydrochlorothiazide

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

Drug Enap-N, Enap-HL or Enap 20 HL patients should not appoint

with a renal failure (clearance of creatinine of 80 ml/min.) until by means of titration of doses of separate components the expediency of use of the doses which are contained in the combined medicament is proved.

Abnormal liver function. Tiazida it is necessary to apply with care at patients with an abnormal liver function or the progressing liver disease as even at insignificant disturbances of water and electrolytic balance the hepatic coma can develop.

Metabolic and endocrine effects. Therapy of a tiazidama can change tolerance to glucose. Correction of doses of anti-diabetic drugs, including insulin can be necessary.

levels of sodium, magnesium and potassium in blood plasma can reduce Tiazida's

.

Increase in levels XC and TG can be associated with therapy by thiazide diuretics; however at use in low doses (12.5 mg) it was reported about the minimum effect or about its absence.

Tiazida's

can reduce calcium discharge with urine and cause periodic slight increase of level 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 of function of a thyroid gland.

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.

Despite the lack of these controlled clinical trials at the patients taking the medicament Enap of N, Enap of HL, Enap 20 HL as well as at the patients accepting diuretics should control regularly levels of electrolytes in blood plasma through certain periods.

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 are xerostomia, thirst, weakness, a lethargical sleep, drowsiness, fatigue, myalgia or spasms, muscle weakness, arterial hypotension, an oliguria, tachycardia, disturbances from a GIT (nausea, vomiting).

Though throughout use of thiazide diuretics the hypopotassemia can arise, the combined therapy with enalapril can reduce expressiveness of the hypopotassemia caused by diuretic use. The risk of a hypopotassemia can increase at patients with the cirrhosis raised by a diuresis, the insufficient use of electrolytes and at the persons who were at the same time receiving therapy by corticosteroids or AKTG.

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

Tiazida's

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

Drug can affect results of the following laboratory analyses:

• medicament can reduce the level of the iodine connected with proteins in blood plasma;
• treatment should be stopped before carrying out laboratory inspection for assessment of function of epithelial bodies;
• medicament is capable to increase concentration of free bilirubin in blood serum;
• a hydrochlorothiazide which can yield positive take in the anti-doping test.

Hypersensitivity. The patients predisposed to an allergy or at patients OH in the anamnesis can have hypersensitivity reactions to a hydrochlorothiazide.

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

Special preventions of rather inactive components of drug. Drug contains lactose. To patients with rare hereditary diseases: galaktazny insufficiency, a lactose intolerance of Lapp or a syndrome glucose-galaktoznoy of malabsorption it is not necessary to use this drug.

Period of pregnancy and feeding by a breast. It is contraindicated to apply APF inhibitors at pregnant women and women who plan pregnancy (see CONTRAINDICATIONS).

Patients, planning pregnancy, it is necessary to transfer 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, alternative therapy.

Epidemiological conclusions concerning risk of teratogenecity after influence of APF inhibitors in the I trimester of pregnancy are ambiguous

; however it is impossible to exclude some increase in risk. It is known 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).

When prescribing medicament needs to inform the patient of rather potential harm for a fruit.

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If needs use of APF inhibitors during pregnancy, it is necessary to carry out periodic ultrasonography for assessment of intraamniotichesky space. However the doctor and the patient need to know about what oligoamnion can develop after emergence at a fruit of irreversible damages.

At use of APF inhibitors in ІІ a trimester of pregnancy ultrasonography of kidneys and a skull of an embryo recommend to carry out

.

Newborns whose mothers accepted APF inhibitors should be surveyed carefully concerning developing of arterial hypotension, an oliguria and a hyperpotassemia. Enalapril gets through a placenta, but he can be brought partially from the newborn's organism by peritoneal dialysis; theoretically he can be brought by exchange blood transfusion though there is no experience concerning holding the last procedure.

Hydrochlorothiazide. Experience of use of a hydrochlorothiazide during pregnancy, especially in І a trimester, is limited. Researches on animals are not enough. The hydrochlorothiazide gets through a placental barrier. At use in II and III trimester of pregnancy the hydrochlorothiazide can break fetoplacental blood circulation and cause jaundice in a fruit or in the newborn, an electrolytic imbalance and thrombocytopenia.

Hydrochlorothiazide cannot be applied to treatment of hypostases, AG or a preeclampsia at pregnant women as instead of beneficial influence on a course of the disease it increases risk of reduction of volume of blood plasma and worsens placentary blood supplies.

Hydrochlorothiazide should not be used for treatment of essential AG at pregnant women.

Hydrokhlorotia