Enap-HL - instructions for use, doses, side effects, contraindications

Excipients: sodium bicarbonate * 5.10 mg, lactose monohydrate 130.08 mg, corn starch 32.10 mg, pregelatinized starch 6.00 mg, talc 6.00 mg, magnesium stearate 2.00 mg

* 2.68 mg CO₂ and 1.10 mg of H₂O, formed as a result of a chemical reaction between sodium bicarbonate and enalapril maleate,evaporate during the manufacturing process and are not included in the final weight of the tablet.

Description:Round, flat white tablets with a risk on one side and bevel.

Pharmacotherapeutic group:hypotensive combined agent (angiotensin-converting enzyme 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 an 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 to a greater extent than veins, with a reflex increase in heart rate (heart rate) is not noted. The hypotensive effect is more pronounced with high renin activity in the blood plasma than with normal or decreased. Reduction of blood pressure within therapeutic limits does not affect cerebral circulation. Improves the blood supply of the ischemic myocardium. Strengthens the renal 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 at a value of less than 30 ml / min. Reduces blood pressure by reducing the volume of circulating blood (BCC), changes in 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 drugs alone and allows the anti-hypertensive effect of the Enap®-HL 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 represents a convenient dosage form for simultaneous application of hydrochlorothiazide and enalapril.

Pharmacokinetics:Enalapril. After ingestion, absorption is 60%. Eating does not affect absorption. 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 - 1 h, enalaprilata - h. 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. The half-life (T_1/2Enalaprilat is 11 hours. It is mainly excreted by the kidneys - 60% (20% in the form of enalapril and 40% in the form of enalaprilate), 33% through the intestine (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 dose reduction, especially in patients with severe renal insufficiency. In patients with hepatic insufficiency, metabolism of enalapril 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 proximal part of the small intestine.Absorption is 70% and increases by 10% with simultaneous intake 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, with the appointment of 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, it is excreted mainly by the kidneys: 95% unchanged and about 4% in the form of hydrolyzate-2-amino-4-chloro-m-benzene disulfonamide by glomerular filtration and active tubular secretion in the proximal 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 administration) - about 10 hours.

In elderly patients hydrochlorothiazide does not adversely affect the pharmacokinetics of enalapril, but the serum concentration of enalaprilat is higher. When hydrochlorothiazide was prescribed, patients with CHF were found to have a decrease in proportion to the development of CHF by 20-70%. T_1/2 hydrochlorothiazide increased to 28.9 h; the renal clearance is 0.17-3.12 ml / s (10-187 ml / min) (averages of 1.28 ml / s (77 ml / min)).

In obese patients with 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

sulfonamide) and other components of the preparation;

- 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, risk of hepatic

encephalopathy);

- angioedema in history, associated with the use of previously ACE inhibitors, and

hereditary or idiopathic angioedema;

- simultaneous use with aliskiren in patients with diabetes mellitus or impaired

kidney function (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.

Carefully:

- pronounced stenosis of the aortic aorta, hypertrophic obstructive cardiomyopathy;

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

- Chronic heart failure;

- 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 are capable of

reduce glucose tolerance;

- Hyperkalemia;

- condition after kidney transplantation;

- violations of the liver and / or kidney function (CC <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);

- an angle-closure glaucoma; in elderly patients;

- hypercalcemia, hyperuricemia, and / or gout;

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

Pregnancy and lactation:

The drug Enap ® - HL is contraindicated in pregnancy. Epidemiological data

suggest a possible teratogenic effect on the fetus of ACE inhibitors in the first trimester

pregnancy. If therapy with an ACE inhibitor is not vital, then women planning a pregnancy should use other, hypotensive drugs that are approved during pregnancy, which have proven safety. The use of ACE inhibitors in the second and third trimesters of pregnancy was accompanied by negative

impact on the fetus and the newborn. Newborns developed arterial hypotension, renal failure, hyperkalemia, and / or 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.

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. 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 during an ultrasound of oligohydramnion, it is necessary to stop taking Enap®-HL. Patients and the physician should be aware 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 by peritoneal dialysis; in theory it can be removed by means of exchange blood transfusion. 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 the drug Enap ® - HL breastfeeding should be discontinued.

Dosing and Administration:

The drug Enap®-HL 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 to reduce the dose of diuretics at least 3 days before the start of treatment with Enap®-NL 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

Preparation Enap® - HL in patients with renal insufficiency (CC <80 ml / min and >30 ml / min) should be used only if the titration of enalapril dose showed the adequacy of the dose contained in the combination Enap®- HL.

Side effects:

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

frequency is unknown can not be

estimated on the basis of available data.

From the hematopoiesis:

infrequently: anemia (including aplastic and hemolytic);

rarely: neutropenia, decrease hemoglobin and hematocrit,

thrombocytopenia, leukopenia, suppression of bone marrow function, agranulocytosis, pancytopenia, lymphadenopathy.

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

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

From the sense organs:

very often: blurred vision perception;

infrequently: noise in the ears; frequency unknown: xanthopsy.

From the side of cardiovascular system:

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

infrequently: faint, sensation heart palpitations, chest pain, heart attack myocardium or brain damage blood circulation (as a consequence severe arterial hypotension patients with high risk);

rarely: Raynaud's syndrome.

From the respiratory system:

very often: cough;

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

rarely: rhinitis, allergic alveolitis / eosinophilic pneumonia, respiratory distress syndrome

(including pneumonitis and pulmonary edema), drug-induced lesions lungs (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 mucous membrane of the stomach, intestinal obstruction, pancreatitis, peptic ulcer;

rarely: cholestatic jaundice, fulminant hepatic 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 face, 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, hives;

rarely: erythema multiforme, exfoliative dermatitis, toxic epidermal necrolysis, thrombocytopenic purpura, exacerbation of the systemic red lupus, erythroderma, pemphigus.

From the genitourinary system:

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

rarely: oliguria, interstitial nephritis, gynecomastia.

From the side of the locomotor system apparatus:

often: muscle spasms **; infrequently: arthralgia *.

Laboratory indicators: often: hypokalemia, hyperuricemia, increased concentration of cholesterol and triglycerides in the blood serum; infrequently: hypoglycemia, hypomagnesemia; rarely: hyperglycemia (in patients with diabetes mellitus), hyperkalemia, hyponatremia, increased urea and creatinine concentrations in the blood serum, increased activity of "hepatic" transaminase, increase in concentration bilirubin, glucose in the blood serum; very rarely: hypercalcemia; frequency unknown: glucosuria.

Other:

often: increased fatigue; rarely: general malaise, fever. A symptom complex is described, which 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 applied hydrochlorothiazide at 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. It is necessary to carry out symptomatic and maintenance therapy.

Symptoms: a pronounced decrease in blood pressure with bradycardia or other cardiac arrhythmias, dizziness, cough, increased diuresis, which causes hypokalemia, hypochloremia,hyponatremia, convulsions, feelings of anxiety, impaired consciousness (including coma), acute renal failure, violation of the acid-base state and water-electrolyte balance of blood.

Treatment: patient is transferred to a horizontal position with raised legs. In mild cases, gastric lavage and ingestion of activated charcoal are shown, in more serious cases, measures aimed at stabilizing blood pressure are administered intravenously introduction of plasma substitutes, 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 application can strengthen the hypotensive effect of enalapril and hydrochlorothiazide. Simultaneous with enalapril application of beta-blockers, alpha-adrenoblockers, ganglion blocking agents, methyldopa, blockers of "slow" calcium channels, nitroglycerin or other nitrates can further reduce blood pressure. Hydrochlorothiazide can enhance the 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. delayed lithium removal (increased cardiotoxic and neurotoxic action of lithium).

Simultaneous application of Enap®- HL 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)

Simultaneous application of NSAIDs (including selective inhibitors

cyclooxygenase-2) can reduce the hypotensive effect of ACE inhibitors. NSAIDs 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 hypotensive effects of diuretics.

Drug Interactions for Enalapril

Double blockade of the renin-angiotensin-aldosterone system (RAAS)

The risk of developing arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) is higher in the case of a double blockade of RAAS, i.e. while concomitantly using angiotensin II receptor antagonists, ACE inhibitors, in comparison with the use of the drug of one of the listed groups. If it is necessary to simultaneously use drugs, it is recommended to monitor blood pressure, kidney function and water-electrolyte balance. The simultaneous use of enalapril with aliskiren in patients with diabetes mellitus or renal dysfunction (KC less than 60 ml / min) is contraindicated. 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 potassium content in the serum usually remains within the normal range.

Diuretics (thiazide or "looped") 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 hypotensive effect can be reduced by eliminating the diuretic, increasing bcc or applying sodium salts.

Sympathomimetics can reduce the hypotensive effect of ACE inhibitors.

Hypoglycemic agents for oral administration and insulin

Epidemiological studies suggest that simultaneous use of ACE inhibitors and hypoglycemic agents (insulin and hypoglycemic agentsfor oral administration) may lead to an increase in the 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 not confirm these data 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 hypotensive effect of ACE inhibitors, which can cause orthostatic hypotension.

Acetylsalicylic acid, thrombolytics and beta-blockers Safely simultaneous use of enalapril with acetylsalicylic acid (in doses of antiplatelet) thrombolytics and beta- adrenoblockers.

Nonsteroidal anti-inflammatory drugs

NSAIDs 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.

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

Simultaneous application with ACE inhibitors may increase the risk of developing leukopenia. When used simultaneously with allopurinol, the risk of developing an allergic reaction increases, especially in patients with impaired function of the kidneys.

Cyclosporin

Simultaneous application with ACE inhibitors may increase the risk development of hyperkalemia.

Antacids

Antacids can reduce bioavailability of ACE inhibitors.

With simultaneous application ACE inhibitors and preparations of gold (sodium aurotomy malate) intravenously, describes a symptom complex, including hyperemia of the facial skin, nausea, vomiting and arterial hypotension.

Drug interactions for hydrochlorothiazide

Non-depolarizing muscle relaxants

Thiazide diuretics can enhance the effect of tubocurarine chloride.

Ethanol, barbiturates reinforce hypotensive effect of thiazide diuretics.

Narcotic drugs analgesics / antipsychotics

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

Hypoglycemic agents for admission Inside and insulin

Simultaneous application hypoglycemic agents for admission Inside and insulin with thiazide

diuretics may require correction of their doses.

Anion exchange resins (colestramine and colestipol)

Absorption of hydrochlorothiazide 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.

Preparations that extend the RT interval (quinidine, procainamide, amiodarone, sotalol) - increased risk of developing 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 effectiveness of adrenomimetics (epinephrine, norepinephrine).

Glucocorticosteroids (GCS), calcitonin, adrenocorticotropic hormone (ACTH)

Simultaneous application with GCS, calcitonin, ACTH can lead to violations of water-electrolyte balance, in particular to development hypokalemia.

Iodine-containing contrast media

In patients with hypovolemia in the background diuretic therapy exists increased risk of acute kidney failure, especially when use of contrast agents,

containing high doses of iodine. Before these drugs should be replenish the BCC.

Non-steroidal anti-inflammatory drugs drugs

NSAIDs (eg, acetylsalicylic acid and indomethacin) can reduce diuretic and hypotensive effects thiazide diuretics.

Methyldopa

Cases of hemolytic anemia are described when used simultaneously with methyldopa.

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 administration of Enap®-NL in patients with severe CHF and hyponatremia, severe renal failure or left ventricular dysfunction and, in particular, in patients with hypovolemia, as a result of diuretic therapy, diets with restricted cooking salt, diarrhea, vomiting or hemodialysis.

In case of arterial hypotension, it is necessary to place the patient on the back with a low headboard and, if necessary, make up for the BCC by intravenous infusion of a solution of 0.9% sodium chloride. Arterial hypotension, which occurred after taking the first dose, is not a contraindication for further treatment. The use of Enap®-NL can be continued after recovery of blood pressure and bcc.

Care should be taken in patients with coronary heart disease, expressed cerebrovascular diseases, aortic stenosis, hypertrophic obstructive cardiomyopathy, preventing blood outflow from the left ventricle, pronounced atherosclerosis, in elderly patients as a result of the risk of arterial hypotension and impaired blood flow to the heart, brain and kidneys.

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®- HL, it is necessary to identify signs of disturbance of the water-electrolyte balance, such as: dryness of the oral mucosa, thirst, weakness, drowsiness, increased excitability, myalgia and convulsions (predominantly gastrocnemius muscles), excessive decrease in blood pressure, tachycardia, oliguria and gastrointestinal disturbances (nausea , vomiting).

Renal impairment

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

Dysfunction of the liver

The drug Enap®-NL 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. If jaundice occurs and the activity of "liver" transaminases is increased, treatment with Enap®-NL should be stopped immediately, 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 number 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 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. There was reported exacerbation of the systemic lupus erythematosus.

Due to the increased risk of anaphylactic reactions, the Enap® - HL patients on hemodialysis using high-flow polyacrylonitrile membranes (AN69®), hypersensitivity to low-density lipoproteins with dextran sulfate, and immediately before the procedure of desensitization to the venom of Hymenoptera (hymenoptera).

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 hypotensive effect in patients of the Negroid race compared with representatives of other races. Hyperkalemia

It 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

Hydrochlorothiazide, which is part of the Enap®-NL preparation, can be the cause of a positive anti-doping test.

Acute myopia and secondary acute closed angle glaucoma

Hydrochlorothiazide is a sulfonamide that can cause 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 a permanent loss of vision.

Treatment: stop hydrochlorothiazide as soon as possible. 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.

Effect on the ability to drive transp. cf. and fur:At the beginning of therapy with Enap®-NL, there may be a marked decrease in blood pressure, dizziness and drowsiness, so at the beginning of treatment it is not recommended to drive vehicles and engage in other potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions; Care should be taken in the future.

Form release / dosage:Tablets 12.5 mg + 10 mg.

Packaging:

When manufacturing at JSC "Krka, dd, Novo mesto", Slovenia:

10 tablets per blister (contour mesh packaging) from a combined material polyamide / aluminum foil / PVC - aluminum foil (Coldforming OPA/A1/PVC-A1). 2, 3, 6 or 9 blisters (contour cell packs) together with the instruction for use are placed in a cardboard pack.

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

At packing on the Russian enterprise of Joint-Stock Company "Vector-medica":

2, 3, 6 or 9 blisters (contour cell packs) together with the

application put in a pack of cardboard.

When produced at OOO Krka-Rus, Russia:

10 tablets per contour mesh package (blister) from the combined material polyamide / aluminum foil / PVC - aluminum foil (Coldforming OPA/A1/PVC-A1). 2, 3, 6 or 9 contour squares (blisters) together with instructions for use are placed in a cardboard pack.

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

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N013029 / 01

Date of registration:23.12.2010

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: & nbsp30.12.2015

Illustrated instructions

Instructions

Enap®-HL (Enap®-HL)