Enap-HL 20 - instructions for use, dose, side effects, contraindications

Excipients: sodium hydrogen carbonate¹ 10,20 mg, lactose monohydrate 122.16 mg, corn starch 28.70 mg, pregelatinized starch 6.00 mg, talc 6.00 mg, magnesium stearate 2.00 mg.

¹ In the production process, because of the chemical reaction between sodium bicarbonate and enalapril maleate, 5.36 mg of CO₂ and 2.20 mg of H₂0 per tablet, which evaporate during the production process and are not used to calculate the theoretical mass of the tablet.

Description:Round, flat tablets of white color with a facet on both sides and risk on one side.

Pharmacotherapeutic group:antihypertensive agent combined (angiotensin-converting enzyme (ACE) inhibitor + diuretic).

ATX: & nbsp

C.09.B.A.02 Enalapril in combination with diuretics

Pharmacodynamics:Combined drug, the effect of which is due to the components that make up its composition; has antihypertensive effect.

Enalapril inhibits ACE that promotes the conversion of angiotensin I into angiotensin II, reduces serum aldosterone concentration, increases the release of renin by juxtamglomerular cells in the walls of arterioles of the renal glomeruli, improves the functioning of the kallikrein kinin system, stimulates the release of prostaglandins and the endothelial relaxing factor (NO), depresses the sympathetic nervous system. Together, these effects eliminate spasm and dilate the peripheral arteries, reduce the overall peripheral vascular resistance (OPSS), systolic and diastolic blood pressure (BP), post- and preload on the myocardium.Expands arteries more than veins, while reflex increase in heart rate (heart rate) is not noted. The antihypertensive effect is more pronounced with high renin activity in blood plasma than with normal or decreased activity of renin. Reduction of blood pressure within therapeutic limits does not affect cerebral circulation. Improves the blood supply of the ischemic myocardium. It enhances kidney blood flow, while the glomerular filtration rate does not change. In patients with initially reduced glomerular filtration, its rate usually increases. The maximum effect of enalapril develops in 6-8 hours and persists up to 24 hours.

Hydrochlorothiazide - Thiazide diuretic with moderate strength of action. Reduces the reabsorption of sodium ions at the level of the cortical segment of the Henle loop, without affecting its area passing through the medulla of the kidney. It blocks carbonic anhydrase in the proximal part of convoluted tubules, increases the excretion of potassium ions, hydrocarbonates and phosphates by the kidneys. Virtually does not affect the acid-base state. Increases the excretion of magnesium ions. Delays in the body calcium ions.The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, lasts 10-12 hours. The effect decreases with a decrease in the glomerular filtration rate and stops when its value is less than 30 ml / min. Reduces blood pressure by decreasing the volume of circulating blood (BCC), changes in the reactivity of the vascular wall.

The use of a combination of enalapril and hydrochlorothiazide leads to a more pronounced decrease in blood pressure in comparison with the monotherapy of each of the components alone and allows the antihypertensive effect of the Enap®-HJI 20 preparation to be maintained for at least 24 hours.

Enalapril and hydrochlorothiazide is recommended to be applied once a day, therefore the combination preparation Enap®-HJI 20 represents a convenient dosage form for the simultaneous use of hydrochlorothiazide and enalapril.

Pharmacokinetics:

Enalapril. After ingestion, absorption is 60%. Food intake does not affect suction. In the liver is metabolized to form an active metabolite of enalaprilat, which is a more effective ACE inhibitor than enalapril. The connection with the proteins of the blood plasma enalaprilata - 50-60%.Time to reach the maximum concentration (TC_m_Oh) enalapril in blood plasma - 1 hour, enalaprilat - 3-4 hours. Enalaprilat easily passes through the histohematological barriers, excluding the blood-brain barrier, a small amount penetrates the placenta, as well as into breast milk. Renal clearance of enalapril and enalaprilate is 0.005 ml / s (18 l / h) and 0.00225-0.00264 ml / s (8.1-9.5 l / h), respectively. Half-life (T_1/2) enalaprilata - 11h. It is mainly excreted by the kidneys - 60% (20% in the form of enalapril and 40% in the form of enalaprilat), through the intestine - 33% (6% in the form of enalapril and 27% in the form of enalaprilate). Removed during hemodialysis (speed 38-62 ml / min) and peritoneal dialysis; The serum concentration of enalaprilat after 4-hour hemodialysis is reduced by 45-57%.

In patients with impaired renal function excretion slows down, which requires a lower dose, especially in patients with severe renal insufficiency. In patients with liver failure, enalapril metabolism can be slowed down without changing its pharmacodynamic effect.

In patients with chronic heart failure (CHF), the absorption and metabolism of enalaprilat slows down, and the volume of distribution also decreases.

Hydrochlorothiazide absorbed, mainly in the duodenum and in the proximal part of the small intestine. Absorption is 70% and increases by 10% with simultaneous reception with food. The maximum concentration in the blood serum is achieved after 1.5-5 hours. The distribution volume is about 3 l / kg. Connection with blood plasma proteins - 40%. Bioavailability is 70%. In the therapeutic range of doses, the average area under the pharmacokinetic curve "concentration-time" increases in direct proportion to the increase in dose, when applied once a day, cumulation is negligible. Penetrates through the hematoplacental barrier and into breast milk. Accumulated in amniotic fluid. The serum concentration of hydrochlorothiazide in the blood of the umbilical vein is almost the same as in the maternal blood. Concentration in the amniotic fluid exceeds that in the blood serum from the umbilical vein (by 19 times). It is not metabolized in the liver and excreted mainly by the kidneys: 95% in an unmodified form and about 4% - in the form of a hydrolyzate - 2-amino-4-chloro-m-benzenedisulfonamida by glomerular filtration and tubular secretion of active in the proximal part of the nephron.The renal clearance of hydrochlorothiazide in healthy volunteers and patients with arterial hypertension is approximately 5.58 ml / s (335 ml / min). Hydrochlorothiazide has a two-phase withdrawal profile. T_1/2 in the initial phase is 2 hours, in the final phase (10-12 hours after taking) - about 10 hours.

In elderly patients hydrochlorothiazide does not adversely affect the pharmacokinetics of enalapril, but the serum concentration of enalaprilate is higher. When hydrochlorothiazide was used in patients with CHF, it was found that its absorption decreases in proportion to the development of CHF - by 20-70%. T_1/2 hydrochlorothiazide is extended to 28.9 hours; the renal clearance is 0.17-3.12 ml / s (10-187 ml / min) (averages of 1.28 ml / s (77 ml / min)).

In patients with obesity who have undergone intestinal bypass surgery, hydrochlorothiazide absorption can be reduced by 30%, and serum concentration by 50%, compared to healthy volunteers.

Simultaneous use of enalapril and hydrochlorothiazide does not affect the pharmacokinetics of each of them.

Indications:- Arterial hypertension (patients who are shown combined therapy).

Contraindications:

- Hypersensitivity to enalapril, hydrochlorothiazide (including other derivatives of sulfonamide) and other components of the drug;

- anuria, severe renal dysfunction (creatinine clearance (CK) less than 30 ml / min);

- severe violations of the liver (more than 9 points on the scale Child-Pugh, the risk of developing hepatic encephalopathy);

- angioedema in history, associated with the use of earlier ACE inhibitors, as well as hereditary or idiopathic angioedema;

- simultaneous application with aliskiren in patients with diabetes mellitus or moderate and severe renal dysfunction (CC less than 60 ml / min);

- pregnancy and the period of breastfeeding;

- age under 18 years (effectiveness and safety not established);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Carefully:

- severe stenosis of the aortic aorta, mitral stenosis, hypertrophic obstructive cardiomyopathy (GOKMP);

- ischemic heart disease (IHD) and cerebrovascular diseases (including cerebral circulatory insufficiency), since excessive reduction of blood pressure can lead to the development of myocardial infarction and stroke;

- chronic heart failure (CHF);

- severe atherosclerosis;

- bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney;

- severe autoimmune systemic diseases of connective tissue (including systemic lupus erythematosus, scleroderma);

- oppression of bone marrow hematopoiesis, diabetes mellitus, because thiazide diuretics can reduce glucose tolerance;

- hyperkalemia;

- condition after kidney transplantation;

- violations of the liver (1-8 points on the scale Child-Pugh) and / or kidney (KK <80 ml / min and> 30 ml / min);

- conditions, accompanied by a decrease in BCC (as a result of diuretic therapy, while limiting consumption of table salt, diarrhea and vomiting);

- angle-closure glaucoma;

- in elderly patients;

- hypercalcemia, hyperuricemia, and / or gout;

- in patients on dialysis using high-flow membranes (such as AN69®);

- surgical interventions;

- in patients of the Negroid race.

Pregnancy and lactation:

The drug Enap ® - HJI 20 is contraindicated in pregnancy.

Epidemiological data indicate a possible teratogenic effect on the fetus of ACE inhibitors in the first trimester of pregnancy. If therapy with an ACE inhibitor is not vital, then women planning a pregnancy should use other,allowed in pregnancy, hypotensive drugs that have proven safety.

The use of ACE inhibitors in the second and third trimesters of pregnancy was accompanied by a negative effect on the fetus and the newborn. Newborns developed arterial hypotension, renal failure, hyperkalemia, hypoplasia of the skull bones. Perhaps the development of oligohydramnion, apparently due to impaired renal function of the fetus. This can lead to limb contracture, deformation of the skull bones, including its facial part, and lung hypoplasia. If a woman took an ACE inhibitor in the second and third trimesters of pregnancy, it is recommended to perform ultrasound examination of the kidneys and fetus / newborn skull and to monitor blood pressure.

In those rare cases when the use of an ACE inhibitor during pregnancy is considered necessary, periodic ultrasound (ultrasound) should be performed to assess the amniotic fluid index. In case of detection of oligohydramnion during ultrasound, it is necessary to stop taking Enap®-HJI 20. Patients and the doctor should know that the oligohydramnion develops with irreversible damage to the fetus.If ACE inhibitors are used during pregnancy and the development of oligohydramnion is observed, depending on the week of pregnancy, it may be necessary to perform a stress test, a stress test, or a biophysical profile of the fetus to assess the functional state of the fetus. Newborns whose mothers took ACE inhibitors during pregnancy should be monitored taking into account the risk of developing arterial hypotension, oliguria, and hyperkalemia.

Enalapril, which penetrates the placenta, can be partially removed from the bloodstream of the newborn with peritoneal dialysis, in theory it can be removed by exchange blood transfusion.

The use of hydrochlorothiazide in pregnancy is not recommended because it can worsen perfusion of the placenta and cause jaundice of the fetus / newborn, thrombocytopenia, disturbance of the water-electrolyte balance, and possibly other unwanted reactions observed in adults.

There is no evidence of the possibility of removing a newborn hydrochlorothiazide from the blood, which also penetrates the placental barrier.

Application in the period of breastfeeding

Enalapril and hydrochlorothiazide penetrate into breast milk, so if you need to use Enap®-HL 20, breastfeeding should be discontinued.

Dosing and Administration:

The Enap®- HL20 should be taken regularly at the same time, preferably in the morning, during or after a meal, without chewing, squeezed with a small amount of liquid. The recommended dose is 1 tablet per day. If necessary, the dose can be increased to the maximum daily dose - 2 tablets, taken once a day.

In patients who are on diuretic therapy, it is recommended to cancel treatment or reduce the dose of diuretics, at least 3 days before the start of treatment with Enap®- HL 20 to prevent the development of symptomatic arterial hypotension. Before the beginning of treatment, the function of the kidneys should be investigated. The duration of treatment is determined by the doctor.

Dose with impaired renal function

Side effects:

Classification of the frequency of development of side effects of the World Organization

Health (WHO):

Often >1/10

often from > 1/100 to <1/10

infrequently from> 1/1000 to <1/100

rarely from > 1/10000 to <1/1000

very rarely from <1/10000

the frequency of the unknown can not be estimated from the available data.

From the hematopoiesis:

infrequently: anemia (including aplastic and hemolytic);

rarely: neutropenia, a decrease in hemoglobin and hematocrit, thrombocytopenia, leukopenia,

oppression of bone marrow function, agranulocytosis, pancytopenia, lymphadenopathy,

autoimmune diseases.

Metabolic and nutritional disorders:

infrequent: exacerbation of gout.

From the endocrine system:

very rarely: syndrome of inadequate secretion of antidiuretic hormone.

From the nervous system: very often: dizziness, weakness;

often: headache, asthenia, depression, fainting, taste disorder;

infrequently: confusion, insomnia, drowsiness, paresthesia, increased excitability, nervousness, vertigo;

rarely: sleep disturbance, "nightmarish" dreams, paresis (due to hypokalemia).

From the sense organs:

very often: blurred vision;

infrequently: noise in the ears;

frequency unknown: xanthopsy.

From the cardiovascular system:

often: orthostatic hypotension, marked decrease in blood pressure, violation of the rhythm of the heart, angina pectoris, tachycardia;

infrequently: "tides" of blood to the skin of the face, fainting, a feeling of palpitations, pain in the chest,

Myocardial infarction or cerebrovascular accident (as a consequence of pronounced

arterial hypotension in high-risk patients);

rarely: Raynaud's syndrome.

From the respiratory system:

very often: cough;

infrequently: rhinorrhea, shortness of breath, sore throat, hoarseness of the voice, bronchospasm / bronchial asthma;

rarely: rhinitis, allergic alveolitis / eosinophilic pneumonia, respiratory

distress syndrome (including pneumonitis and pulmonary edema), drug-induced

lung lesions (infiltrates in the lungs);

From the digestive system:

very often: nausea;

often: diarrhea, abdominal pain;

infrequent: vomiting, indigestion, flatulence *, constipation, dryness of the oral mucosa, anorexia, irritation of the gastric mucosa, intestinal obstruction, pancreatitis, peptic ulcer;

rarely: cholestatic jaundice, fulminant liver necrosis (hepatic insufficiency - in patients without existing violations of the liver function), stomatitis / aphthous ulcers, glossitis, hepatocellular or cholestatic hepatitis,cholecystitis (especially in patients with cholelithiasis); frequency unknown: sialadenitis.

Allergic reactions:

infrequently: Stevens-Johnson syndrome;

rarely: angioedema (including facial, lips, pharynx and / or larynx and extremities);

very rarely: intestinal angioedema.

From the skin: often: skin rash (exanthema);

infrequently: itchy skin, increased sweating, skin necrosis, alopecia, urticaria; rarely: erythema multiforme, exfoliative dermatitis, toxic epidermal necrolysis, thrombocytopenic purpura, exacerbation of systemic lupus erythematosus, erythroderma, pemphigus, photosensitivity.

From the genitourinary system:

infrequently: impaired renal function, acute renal failure, proteinuria, impotence, decreased libido *;

rarely: oliguria, interstitial nephritis, gynecomastia.

From the side of the musculoskeletal system:

often: muscle spasms **;

infrequently: arthralgia *.

Laboratory indicators:

often: hypokalemia, hyperuricemia, increased serum cholesterol and triglyceride levels; infrequently: hypoglycemia, hypomagnesemia;

rarely: hyperglycemia (in patients with diabetes mellitus), hyperkalemia, hyponatremia,

increased urea and creatinine levels in serum, increased

activity of "hepatic" transaminases, an increase in the concentration of bilirubin, glucose in

blood serum;

very rarely: hypercalcemia;

frequency unknown: glucosuria.

Other:

often: increased fatigue; rarely: general malaise, fever.

A symptom complex is described that may include fever, myalgia / myositis and arthralgia / arthritis, serositis, vasculitis, increased erythrocyte sedimentation rate, leukocytosis and eosinophilia, skin rash, positive antinuclear antibody test. Can be observed: skin rash, photosensitivity reactions or other skin manifestations.

* These undesirable effects are noted only when hydrochlorothiazide is used in doses of 12.5 mg and 25 mg.

** Cramps in the muscles are often found with hydrochlorothiazide at doses of 12.5 mg and 25 mg.

With simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate) intravenously, a symptom complex is described, which includes facial flushing, nausea, vomiting and arterial hypotension.

Overdose:

In case of an overdose, it is necessary to stop using Enap®-HL 20. Symptomatic and maintenance therapy is necessary.

Symptoms: marked reduction of blood pressure with bradycardia or other cardiac arrhythmias, dizziness, cough, increased diuresis, giving rise to hypokalemia, chloropenia, hyponatremia, seizures, anxiety, impaired consciousness (including to whom), acute renal failure, acid-base status and water-electrolyte balance.

Treatment: the patient is transferred to a horizontal position with raised legs. In mild cases shown gastric lavage ingestion and the activated carbon, in more serious cases - actions to stabilize blood pressure: intravenous plasma expander, infusion of 0.9% sodium chloride solution. The patient should monitor blood pressure, heart rate, respiratory rate, serum urea concentration, creatinine, electrolytes and diuresis, if necessary - hemodialysis (the rate of excretion of enalaprilate is 62 ml / min). With bradycardia, refractory to drug therapy, cardiac stimulation is performed.

Interaction:

General drug interactions for enalapril and hydrochlorothiazide

Other antihypertensive drugs

Simultaneous use can enhance the antihypertensive effect of enalapril and hydrochlorothiazide. Concurrent with enalapril, the use of beta adrenoblockers, alpha-blockers, ganglion blocking agents, methyldopa, slow calcium channel blockers (BCCC), nitroglycerin or other nitrates can further reduce blood pressure. Hydrochlorothiazide can enhance hyperglycemic effect of beta-blockers and diazoxide.

Lithium

With simultaneous use with lithium preparations, a reversible increase in the concentration of lithium in the blood serum occurs, as lithium removal (enhancement of cardiotoxic and neurotoxic action of lithium) slows down.

Simultaneous application of Enap® - HL20 with lithium preparations is not recommended. If simultaneous application is necessary, the serum concentrations of lithium should be carefully monitored.

Non-steroidal anti-inflammatory drugs (NSAIDs) (including selective inhibitors of cyclooxygenase-2 (COX-2))

Simultaneous application of NSAIDs (including selective inhibitors of COX-2) can weaken the antihypertensive effect of ACE inhibitors.

NSAIDs (including selective COX-2 inhibitors) and ACE inhibitors have an additive effect on potassium levels in the blood serum, which can lead to impaired renal function, especially in patients with impaired renal function. This effect is reversible.

In rare cases, the development of acute renal failure, especially in patients with impaired renal function (for example, in elderly patients or with hypovolemia, including with the use of diuretics) is possible.

NSAIDs can reduce the diuretic, natriuretic and antihypertensive effects of diuretics.

Drug Interactions for Enalapril

Double blockade of angiotensin-aldosterone system (RAAS)

The simultaneous use of enalapril with aliskiren in patients with diabetes mellitus or moderate and severe renal dysfunction (CC less than 60 ml / min) is contraindicated.

In the literature it was reported that the double blockade of RAAS in patients with established diagnosis of atherosclerosis, heart failure or diabetes with target organ damage is associated with a higher incidence of arterial hypotension, fainting,hyperkalemia and changes in kidney function (including the development of acute renal failure) compared with the use of a one-component blockade of RAAS. The question of the application of a double blockade of RAAS (for example, by combining an ACE inhibitor with angiotensin II receptor antagonists (ARA II)) should be addressed in each case individually with careful monitoring of kidney function.

Potassium of blood serum

The use of potassium supplements, potassium-sparing diuretics (triamterene, spironolactone, amiloride, eplerenone) or potassium-containing salt substitutes, especially in patients with renal insufficiency, can lead to a significant increase in serum potassium levels. If the simultaneous application to the background of hypokalemia is indicated, care should be taken, and it is also recommended to monitor the potassium content in the blood serum. The loss of potassium on the background of taking thiazide diuretics, as a rule, decreases under the action of enalapril. The content of potassium in the serum usually remains within normal limits.

Diuretics (thiazide or "loop")

Prior therapy with high doses of diuretics can lead to a decrease in BCC and an increased risk of developing arterial hypotension after enalapril.The antihypertensive effect can be reduced by canceling the diuretic, increasing bcc or applying sodium salts.

Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors. Hypoglycemic agents for ingestion and insulin

Epidemiological studies suggest that simultaneous use of ACE inhibitors and hypoglycemic agents (insulin and hypoglycemic agents for ingestion) can lead to an increase in hypoglycemic effect with a risk of hypoglycemia. More often, hypoglycemia develops in the first weeks of therapy in patients with impaired renal function. Long-term and controlled clinical studies of enalapril do not confirm these findings and do not limit the use of enalapril in patients with diabetes mellitus. However, such patients should be under regular medical supervision.

Ethanol enhances the antihypertensive effect of ACE inhibitors, which can cause orthostatic hypotension.

Acetylsalicylic acid, thrombolytics and beta-blockers Safe simultaneous use of enalapril with acetylsalicylic acid (in doses,antiaggregant effect), thrombolytics and beta-blockers.

NSAIDs (including selective inhibitors of COX-2)

Allopurinol, cytostatics and immunosuppressants (incl. methotrexate, cyclophosphamide)

Simultaneous use with ACE inhibitors may increase the risk of developing leukopenia. With simultaneous application with allopurinol, the risk of developing an allergic reaction increases, especially in patients with impaired renal function.

Cyclosporin

Simultaneous use with ACE inhibitors may increase the risk of developing

hyperkalemia.

Antacids

Antacids can reduce the bioavailability of ACE inhibitors.

With simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate) The symptom complex is described intravenously, which includes facial flushing, nausea, vomiting and arterial hypotension.

Drug Interactions for Hydrochlorothiazide

Non-depolarizing muscle relaxants

Thiazide diuretics can enhance the effect of tubocurarine chloride.

Ethanol, barbiturates increase the antihypertensive effect of thiazide diuretics.

Narcotic analgesics / antipsychotics

The simultaneous use of thiazide diuretics, narcotic analgesics or phenothiazine derivatives may lead to a further decrease in blood pressure.

Hypoglycemic agents for ingestion and insulin

Simultaneous use of hypoglycemic agents for ingestion and insulin with thiazide diuretics may require correction of their doses.

Anion exchange resins (colestramine and colestipol)

The absorption of hydrochlorothiazide is significantly reduced in the presence of anion-exchange resins. A single dose of colestyramine or colestipol reduces the absorption of hydrochlorothiazide in the gastrointestinal tract by 85% and 43%, respectively.

Drugs that extend the interval QT (quinidine, procainamide, amiodarone, sotalol), increase the risk of ventricular tachycardia such as pirouette.

Cardiac glycosides

Hypokalemia with thiazide diuretics may increase the toxicity of cardiac glycosides (eg, increased excitability of the ventricles).

Vitamin D and calcium salts

The simultaneous use of thiazide diuretics with vitamin D or calcium salts helps increase the serum calcium content.

Diuretics and laxatives

With the simultaneous use of hydrochlorothiazide with furosemide, carbenoxolone or when used with laxatives it is possible to increase the excretion of potassium / magnesium ions.

Sympathomimetics (pressor amines, for example, epinephrine and norepinephrine)

Thiazide diuretics can reduce the effectiveness of adrenomimetics (epinephrine, norepinephrine).

Glucocorticosteroids (GCS), calcitonin, adrenocorticotropic hormone (ACTH) Simultaneous application with GCS, calcitonin, ACTH can lead to disturbances in the water-electrolyte balance, in particular, to the development of hypokalemia.

Iodine-containing contrast media

In patients with hypovolemia during therapy with diuretics, there is an increased risk of developing acute renal failure, especially in the application of contrast agents containing high doses of iodine. Before using these drugs, you should make up for the BCC. NSAIDs

NSAIDs (for example, acetylsalicylic acid and indomethacin) can reduce

diuretic and antihypertensive effects of thiazide diuretics.

Methyldopa

The cases of development of hemolytic anemia with simultaneous application with methyldopa are described.

Metformin should be used with caution in connection with the risk of developing lactic acidosis against a background of kidney damage caused by hydrochlorothiazide.

Special instructions:

Arterial hypotension

Symptomatic arterial hypotension develops rarely in patients with uncomplicated arterial hypertension. Arterial hypotension with all clinical manifestations can be observed after the first intake of Enap® - HL20 in patients with CHF III-IV functional class by classification NYHA and hyponatremia, severe renal failure or left ventricular dysfunction, and especially in patients with hypovolemia, as a result of diuretic therapy, diets with restriction of table salt, diarrhea, vomiting or hemodialysis. With extreme caution, the drug should be used in patients with ischemic heart disease or cerebrovascular disease, because excessive reduction in blood pressure can lead to the development of myocardial infarction or stroke.

In case of development of arterial hypotension, it is necessary to place the patient on the back with a low headboard and, if necessary, make up BCC by intravenous infusion of 0.9% sodium chloride solution. Transient arterial hypotension, which occurred after taking the first dose, is not a contraindication for further treatment. After replenishment of BCC and normalization of blood pressure, therapy with Enap®- HL 20 can be resumed in smaller doses or each of the components of the drug can be administered separately.

Violations of the water-electrolyte balance

It is necessary to regularly monitor the serum electrolyte content during the treatment period to identify possible imbalances and timely take the necessary measures. Determination of the serum content of electrolytes is mandatory for patients with prolonged diarrhea, vomiting.

In patients taking the drug Enap ® - HL20, it is necessary to detect signs of disturbance of the water-electrolyte balance, such as: dryness of the oral mucosa, thirst, weakness, drowsiness, increased excitability, myalgia and convulsions (mainly gastrocnemius muscles), excessive lowering of blood pressure, tachycardia, oliguria and gastrointestinal disturbances (nausea, vomiting).

Aortic stenosis / mitral stenosis / GOKMP

Like all drugs that have a vasodilating effect, ACE inhibitors should be used with caution in patients with stenosis of the aortic and / or mitral valve, obstruction of the outflow tract of the left ventricle.

Renal impairment

Preparation Enap® - HL 20 in patients with renal insufficiency (CC <80 ml / min and >30 ml / min) should be used only if the preliminary titration of enalapril dose showed the adequacy of the dose contained in the combination Enap®-NL20. With simultaneous use of enalapril and diuretic in some patients with hypertension, there was an increase in the concentrations of urea and creatinine in the blood serum. In this case, therapy with Enap® - HL 20 should be discontinued. This situation indicates the possibility of latent stenosis of the renal artery.

Renovascular hypertension

With the use of ACE inhibitors in patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, there is an increased risk of developing arterial hypotension and renal failure. In patients with elevated serum creatinine concentration in the blood plasma, kidney function may worsen.In such patients therapy with ACE inhibitors should start with low doses, carefully select the dose of the drug and monitor the kidney function.

Double blockade of RAAS

Simultaneous use with aliskiren in patients with diabetes mellitus or

moderate and severe renal dysfunction (CC <60 mL / min or speed

glomerular filtration (GFR) <60 ml / min / 1.73 m²) is contraindicated.

The risk of developing arterial hypotension, hyperkalemia and renal dysfunction (in

including acute renal failure) is higher in the case of a double blockade of the RAAS, i.e.,

with the simultaneous use of ARA II, ACE inhibitors, compared with the use of

preparation of one of the listed groups. This combination is not recommended.

If it is necessary to simultaneously use drugs, it is recommended

monitor kidney function (including periodic monitoring of potassium content

and the concentration of creatinine in the blood serum).

Dysfunction of the liver

Preparation Enap® - HL20 should be used with caution in patients with hepatic insufficiency or progressive liver disease, since hydrochlorothiazide can cause hepatic coma even with minimal disturbances in the water-electrolyte balance. Several cases of development of acute hepatic insufficiency with cholestatic jaundice, fulminant liver necrosis and lethal outcome (rarely) during treatment with ACE inhibitors have been reported. The mechanism of this syndrome is not established. When jaundice occurs and the activity of "liver" transaminases increases, treatment with Enap® - HL 20 should be immediately discontinued, patients should be monitored.

Neutropenia / agranulocytosis

In patients taking ACE inhibitors, there may be cases of development of neutropenia / agranulocytosis, thrombocytopenia and anemia. In patients with normal renal function in the absence of other complications, neutropenia develops rarely and passes on its own after the withdrawal of ACE inhibitors.

Enalapril should be used with great care in patients with connective tissue diseases and simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially with existing impairments of kidney function.Such patients can develop severe infections that are not amenable to intensive antibiotic therapy. In the case of enalapril it is recommended to periodically monitor the amount of white blood cells in the blood. The patient should be warned that in case of any signs of an infectious disease (sore throat, fever), you should immediately consult a doctor.

Metabolic and endocrine effects

Caution is needed in all patients receiving treatment with hypoglycemic agents for ingestion or insulin, since hydrochlorothiazide can weaken, and enalapril - strengthen their action.

Thiazide diuretics can reduce the excretion of calcium by the kidneys and cause a slight and transient increase in serum calcium. Expressed hypercalcemia may be a sign of latent hyperparathyroidism. Before the study of the function of parathyroid glands, thiazide diuretics should be discontinued.

Against the background of treatment with thiazide diuretics, the concentrations of cholesterol and triglycerides in serum can increase.

Therapy with thiazide diuretics in some patients may exacerbate hyperuricemia and / or aggravate the course of gout. But, enalapril enhances the excretion of uric acid by the kidneys, thereby counteracting the hyperuricemic effect of hydrochlorothiazide.

Allergic reactions / angioedema

With the development of angioneurotic edema of the face, it is usually enough to cancel therapy and prescribe antihistamines to the patient.

Angioedema, edema of the tongue, throat or larynx can be lethal. With angioedema, swelling of the tongue, throat or larynx, which can lead to airway obstruction, you must immediately enter epinephrine (0.3-0.5 ml epinephrine (adrenaline) solution subcutaneously in a ratio of 1: 1000) and maintain airway patency (intubation or tracheostomy).

Among patients of the Negroid race receiving ACE inhibitor therapy, the incidence of angioedema is higher than among patients of other race.

Patients with a history of angioedema not associated with the use of ACE inhibitors have an increased risk of developing angioedema due to the administration of any ACE inhibitor.

In patients taking thiazide diuretics, hypersensitivity reactions can develop both in the presence and in the absence of an anamnesis of allergic reactions.

Anaphylactoid reactions during desensitization with an allergen from Hymenoptera venom

In rare cases, patients receiving ACE inhibitors developed life-threatening anaphylactoid reactions during hyposensitization with an allergen from Hymenoptera venom. Such reactions can be avoided if the use of an ACE inhibitor is temporarily discontinued prior to the initiation of hyposensitization.

Patients on hemodialysis

The use of the drug is not indicated in patients with renal failure who are on hemodialysis. Anaphylactoid reactions were observed in patients on dialysis using high-flux membranes (such as AN69®), simultaneously receiving treatment with ACE inhibitors. These patients need to use a different type of dialysis membrane or antihypertensive drugs of other classes.

Surgical interventions / general anesthesia

Before surgery (including dentistry), an anesthesiologist should be warned about the use of ACE inhibitors.

During surgical interventions or general anesthesia with the use of drugs that cause arterial hypotension, ACE inhibitors can block the formation of angiotensin II in response to compensatory release of renin. If this results in a pronounced decrease in blood pressure, explained by a similar mechanism, it can be corrected by an increase in BCC.

Cough

With the use of ACE inhibitors, there was a dry, prolonged cough, which disappears after discontinuation of ACE inhibitors. With a differential diagnosis of cough, one should also consider a cough caused by the use of ACE inhibitors.

Ethnic Features

Enalapril (as well as other ACE inhibitors) has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races. Hyperkalemia

Hyperkalemia can develop during treatment with ACE inhibitors, including enalapril. Risk factors for hyperkalemia are: renal failure, advanced age, diabetes mellitus, certain concomitant conditions (decreased BCC, acute heart failure in decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), as well as preparations of potassium or potassium-containing salt substitutes and the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin). Hyperkalemia can lead to serious heart rhythm disturbances, sometimes with a fatal outcome. The simultaneous use of the above drugs should be done with caution. Simultaneous use of enalapril and hydrochlorothiazide in a low dose does not exclude the possibility of developing hyperkalemia.

Anti-doping test

The hydrochlorothiazide, which is part of the Enap®- HL20, may be the reason

positive anti-doping test.

Are common

In patients with or without allergies or bronchial asthma, a history of hypersensitivity reactions hydrochlorothiazide, but their risk is higher in the presence of an allergy or bronchial asthma in the anamnesis. In the treatment of thiazide diuretics, including hydrochlorothiazide, cases of exacerbation or worsening of the systemic lupus erythematosus are described.

Acute myopia and secondary acute closed-angle glaucoma

Hydrochlorothiazide is a sulfonamide that can induce an idiosyncratic reaction leading to the development of transient acute myopia and acute closed-angle glaucoma. Symptoms include: sudden reduction in visual acuity or eye pain, which usually appears within a few hours or weeks of initiating hydrochlorothiazide therapy. In the absence of treatment, acute closed-angle glaucoma can lead to persistent loss of vision.

Treatment: as soon as possible stop taking hydrochlorothiazide. If intraocular pressure remains uncontrolled, immediate medical treatment or surgery may be required. Risk factors for the development of acute closed-angle glaucoma are: an allergic reaction to sulfonamide or benzylpenicillin in the anamnesis.

Special information on excipients

Preparation Enap® - HL 20 contains lactose, so the drug is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

Effect on the ability to drive transp. cf.and fur:At the beginning of therapy with Enap® - HL20 possible a marked reduction in blood pressure, dizziness and drowsiness, so early treatment is not recommended to drive and engage in other potentially hazardous activities that require high concentration and psychomotor speed reactions, in the future you should be careful.

Form release / dosage:

Tablets, 12.5 mg + 20 mg.

Packaging:

In production at JSC "KRKL, dd, Novo mesto", Slovenia:

10 tablets in a blister (contour cell package) of the composite material OPA / Al / PVC and aluminum foil.

2, 3, 6, 9 or 10 blisters (packages contour cell) together with instructions for use placed into cardboard pack.

When packaging and packaging at a Russian company LLC "Krka-RUS":

10 tablets per blister (contour mesh package) of the combined material

OPA / Al / PVC and aluminum foil.

2, 3, 6, 9 or 10 blisters (packages contour cell) together with instructions for

application is placed in a pack of cardboard.

When produced at OOO Krka-Rus, Russia:

10 tablets in blisters (blister) of the composite material OPA / Al / PVC and aluminum foil.

By 2, 3, 6, 9 or 10 contour squares (blisters) together with the instruction for use are placed in a pack of cardboard.

Storage conditions:At a temperature of no higher than 25 ° C, in the original packaging. Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000966

Date of registration:23.11.2010

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

KRKA-RUS, LLC Russia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp01.01.2016

Illustrated instructions

Instructions

Enap®-HL 20 (Enap®-HL 20)