Enalapril-Acry H - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 128.9 mg, potato starch 22 mg, sodium hydrogen carbonate 10 mg, sodium carboxymethyl starch 2 mg, magnesium stearate 2 mg, iron oxide dye yellow 0.1 mg.

Description:Tablets from creamy to light yellow or yellow with interspersed, flat-cylindrical, with a 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 properties of the components that make up its composition.

Enalapril - ACE inhibitor. Pharmacological activity has a metabolite of enalapril - enalaprilate. Enalaprilat inhibits ACE that promotes the conversion of angiotensin I into angiotensin II. Reduction of the latter leads to a direct decrease in the production of aldosterone, an increase in renin activity of blood plasma, as well as suppression of bradykinin degradation, which is accompanied by a decrease in systolic and diastolic blood pressure (BP), a decrease in total peripheral vascular resistance, an increase in cardiac output at a constant heart rate. Enalapril reduces the tone of arterioles carrying out the glomeruli of the kidneys, thereby improving intra-cerebral hemodynamics, and inhibiting the development of diabetic nephropathy. The antihypertensive effect of enalapril is achieved after 24 hours. Enalapril does not affect the metabolism of glucose and lipoproteins.

Hydrochlorothiazide - Thiazide diuretic with moderate strength of action. Has a diuretic and antihypertensive effect. The mechanism of antihypertensive action is not fully understood. Acts at the level of the distal renal tubules, increasing the excretion of sodium and chlorine ions. Reduction of sodium ions in the vessel wall leads to their dilatation, reduces sensitivity to vasoconstrictor factors. Hydrochlorothiazide does not affect normal blood pressure. Diuretic effect develops after 2 hours, reaches a maximum after 4 hours and persists for about 6-12 hours. The combined use of enalapril and hydrochlorothiazide ensures the maintenance of a normal content of potassium ions in the blood.

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 plasma proteins enalaprilata - 50-60%. The maximum concentration of enalapril in the blood plasma is achieved after 1 hour, enalaprilata - after 3-4 hours. Enalaprilat easily passes through the histohematological barriers, excluding the blood-brain barrier, a small amount penetrates through the placenta and into breast milk. The half-life of enalaprilate is 11 hours. It is mainly excreted by the kidneys - 60% (20% in the form of enalapril and 40% in the form of enalaprilate), through the intestine - 33% (6% enalapril and 27% in the form of enalaprilate). Removed during hemodialysis (speed 62 ml / min) and peritoneal dialysis.

Hydrochlorothiazide

Absorbed quickly, but incomplete. Time to reach the maximum concentration in the blood plasma (TC_m_Oh) with oral administration in a dose of 100 mg - 1,5-2,5 h.

In the therapeutic range of doses, the average value AUC (the area under the "concentration-time" curve) increases in direct proportion to the increase in dose, with the appointment of once a day, cumulation is negligible. The connection with plasma proteins is 40-60%. Penetrates through the hematoplacental barrier and into breast milk. Half-life (T_1/2) - 6.4 h, with moderate chronic renal failure (CRF) - 11.5 h, with CRF with creatinine clearance less than 30 ml / min - 20.7 hours. It is not metabolized by the liver. It is excreted by the kidneys: basically unchanged and about 4% in the form of 2-amino-4-chloro-m-benzene disulfonamide (reduced in alkaline urine) by glomerular filtration and active tubular secretion in the proximal nephron.

Indications:Arterial hypertension.

Contraindications:Hypersensitivity to individual components of the drug, other ACE inhibitors, sulfonamide derivatives, anuria, severe renal dysfunction (creatinine clearance less than 30 ml / min), history of angioedema, associated with the administration of ACE inhibitors, hereditary or idiopathic angioedema, pregnancy, lactation, age under 18, lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Carefully:Renal / hepatic insufficiency, severe systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney,condition after kidney transplantation, aortic stenosis, chronic heart failure, ischemic heart disease, oppression of bone marrow hematopoiesis, cerebrovascular diseases (including cerebral circulatory insufficiency), diabetes mellitus, hyperkalemia, diet with restriction of table salt, hyperuricemia and gout, conditions, accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting), hypertrophic obstructive cardiomyopathy, severe atherosclerosis, primary hyperaldosteronism, heme Odilysis using high-flow AN69® membranes, desensitization, low-density lipoprotein (LDL) apheresis with dextran sulfate, old age.

Pregnancy and lactation:

The drug Enalapril-Acry® N is contraindicated in pregnancy.

The effect of ACE inhibitors on the fetus in the first trimester of pregnancy is not established. 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 bones of the skull. 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.

The use of diuretics in pregnancy is not recommended because it can cause jaundice of the fetus and newborn, thrombocytopenia and, possibly, other, unwanted reactions observed in adult patients.

In the case of planning or diagnosing pregnancy, Enalapril-Acry® H must be discontinued.

Enalapril and hydrochlorothiazide penetrate into breast milk. Therefore, when prescribing Enalapril-Acry® H during lactation, it is necessary to refuse breastfeeding.

Dosing and Administration:

Inside, regardless of food intake, 1 tablet 1 time per day.

In patients with a decrease in the glomerular filtration rate to 30 ml / min, the drug should be used only after preliminary titration of doses of enalapril and hydrochlorothiazide separately.

The duration of treatment depends on the effectiveness of therapy.

Side effects:Classification of the frequency of development of side effects of the World Health Organization: very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely (> 1/10000 and <1/1000), very rarely (<1/10000), the frequency is unknown.

With the use of the enalapril / hydrochlorothiazide combination, no adverse events specific to this combination drug were observed. Undesirable effects were limited to those reported earlier with enalapril and / or hydrochlorothiazide alone.

Enalapril

Disorders from the cardiovascular system: often - a marked decrease in blood pressure (including orthostatic hypotension); infrequent pain in the chest, stenocardia, atrioventricular blockade of the 2nd degree, cerebral circulation disorder, myocardial infarction or stroke, palpitation, arrhythmia (atrial fibrillation, sinus bradycardia, tachycardia, ventricular fibrillation); rarely - Raynaud's syndrome.

Disorders from the central nervous system and mental disorders: often - headache, dizziness, fainting; infrequently - insomnia, anxiety, panic, nervousness, confusion,depression, sleep disorders, drowsiness, nightmarish dreams, rarely paresthesia, memory impairment, peripheral neuropathy, tremor, migraine, confusion.

Disturbances from the respiratory system: often - cough; infrequently - rhinitis, nasal congestion, rhinorrhea; very rarely - sore throat, hoarseness, bronchospasm, pulmonary infiltrates, allergic alveolitis / eosinophilic pneumonia.

Violations of the blood and lymphatic system: rarely - reduced hemoglobin and hematocrit, leukopenia; very rarely - depression of bone marrow function, anemia, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia, hemolytic anemia, lymphadenopathy, increase soy.

Disorders from the digestive system: often - nausea, diarrhea; infrequently - abdominal pain, constipation; rarely - taste disorders, vomiting, dyspepsia, anorexia, irritation of the gastric mucosa, dryness of the oral mucosa, peptic ulcer; rarely - stomatitis, aphthous ulcers, glossitis; very rarely - intestinal obstruction, pancreatitis, intestinal angioedema.

From the liver and biliary tract: infrequently - increased activity of "liver" transaminases, increased bilirubin concentration; rarely - hepatic insufficiency, fulminant liver necrosis; very rarely - a violation of the liver, hepatitis (hepatocellular or cholestatic), jaundice.

From the urinary system: often - renal dysfunction; infrequently - proteinuria; rarely uremia, acute renal failure; very rarely - oliguria, anuria.

From the musculoskeletal and connective tissue: often - muscle spasm, back pain, leg pain, myalgia; infrequently - pain in hands, arthralgia, musculoskeletal pain, stiffness and swelling of the joints.

Disturbances on the part of the organ of sight: rarely - visual impairment, conjunctivitis, decreased visual acuity, dryness and burning eyes.

From the side of the hearing organ and labyrinthine disorders: infrequently - vertigo, noise in the ears.

Disorders from the reproductive system: infrequent - decreased potency; rarely - gynecomastia.

Disorders from the metabolism and nutrition: infrequently - hypoglycemia; rarely - the syndrome of impaired secretion of antidiuretic hormone.

Disturbances from the skin and subcutaneous tissue: rarely - alopecia, psoriasis, dermatitis, dry skin; very rarely - pseudolymphoma, pemphigus.

Allergic reactions: infrequently - skin rash, itchy skin; rarely - angioedema, swelling of the face, extremities, lips, tongue, vocal cords, larynx, dysphonia, urticaria; very rarely - erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, erythroderma.

Laboratory indicators: often - hyperkalemia; infrequently hypercreatinemia; rarely - hyponatremia; very rarely - hyperglycemia, hypercalcemia.

Other: often - asthenia, fatigue; infrequently - muscle cramps, general malaise, fever, epistaxis, vasculitis, the phenomenon of Raynaud, "hot flashes" of blood to the skin face.

With the use of ACE inhibitors, a symptom complex including fever, serositis, vasculitis, myalgia, myositis, arthralgia, arthritis, a positive antinuclear antibody test, an increase in ESR, eosinophilia, leukocytosis, exanthema, photosensitivity reactions or other dermatological disorders is described. With the simultaneous administration of ACE inhibitors and intravenous sodium aurotomy malate, a symptom complex is described, including facial flushing, nausea,vomiting and arterial hypotension.

Hydrochlorothiazide

Violations from the blood and lymphatic system: rarely - leukopenia, neutropenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, oppression of bone marrow hematopoiesis, pancytopenia.

Impaired nervous system: often - anxiety, sleep disturbance,

depression; infrequently - paresthesia, dizziness; rarely - paresis (due to hypokalemia).

Disorders from the cardiovascular system: rarely orthostatic hypotension, arrhythmia.

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - respiratory distress syndrome, pneumonitis, pulmonary edema.

Disorders from the gastrointestinal tract: rarely - anorexia, pain in the epigastric region, diarrhea, constipation, sialadenitis; very rarely - pancreatitis.

From the liver and biliary tract: infrequently - jaundice (intrahepatic cholestasis).

Disorders from the kidneys and urinary tract: infrequently - glucosuria, interstitial nephritis, renal failure.

Disturbances from the musculoskeletal and connective tissue: infrequently - muscle cramps, weakness.

From the side of metabolism and nutrition: infrequently - anorexia, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia, hypomagnesemia, hypercholesterolemia and hypertriglyceridemia, gout.

about the side of the organ of hearing: rarely - vertigo.

Disorders from the side of the organ of vision: rarely - xanthopsia, transient disruption of accommodation.

Allergic reactions: rarely - photosensitivity, anaphylactic reactions; very rarely - urticaria, toxic epidermal necrolysis, Lyell's syndrome, development of lupus-like syndrome, exacerbation of cutaneous systemic lupus erythematosus, necrotizing angiitis (vasculitis, cutaneous vasculitis).

Other: infrequently - fever, vasculitis.

Overdose:

Symptoms: increased diuresis, marked decrease in blood pressure with bradycardia or other cardiac arrhythmias, convulsions, impaired consciousness (including coma), acute renal failure, violation of the acid-base state and water-electrolyte balance of blood.

Treatment: In mild cases, gastric lavage and ingestion of activated charcoal are indicated. In more serious cases, the patient is transferred to a horizontal position with raised legs,aimed at stabilizing blood pressure - intravenous injection of plasma substitutes, infusion of 0.9% sodium chloride solution. The patient needs to control blood pressure, heart rate, respiratory rate, serum urea concentration, creatinine, electrolytes and diuresis, if necessary, intravenous angiotensin II, hemodialysis (enalaprilate removal rate - 62 ml / min).

Interaction:

Enalapril

Simultaneous use is not recommended

Potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride) or potassium-containing salts, potassium supplements: with simultaneous use with ACE inhibitors, it is possible to develop hyperkalemia. If, as a result of diagnosed hypokalemia, simultaneous application of these drugs is indicated, they should be used with caution, with regular monitoring of serum potassium and electrocardiograms.

Preparations containing aliskiren: when used concomitantly with ACE inhibitors and / or with angiotensin II receptor antagonists in patients with diabetes mellitus and / or with moderate or severe renal dysfunction (GFR) <60 mL / min / 1.73 m²), there was a higher incidence of adverse events, such as nonfatal stroke, kidney complications, hyperkalemia, and hypotension.

Use with caution at the same time

Thiazide or "loop" diuretics: previous treatment with diuretics in high doses may lead to a decrease in the volume of circulating blood (BCC) at the beginning of enalapril therapy and promote the development of arterial hypotension.

Antihypertensive effect can be reduced if you cancel a diuretic, increase the flow of fluid or salts in the body, or start therapy with low doses of enalapril.

Preparations for general anesthesia: when used with ACE inhibitors may lead to aggravation of orthostatic hypotension.

Drugs / tricyclic antidepressants / psychotropic drugs / barbiturates / anesthetics: Orthostatic hypotension may occur.

Other antihypertensive drugs (alpha and beta adrenoblockers, blockers of "slow" calcium channels): the antihypertensive effect can be summed up or potentiated.

Care is required when treating with nitroglycerin in various dosage forms and other nitrates or other vasodilators.

Cimetidine: increased risk of collapse.

Cyclosporin: when used concomitantly with ACE inhibitors, the risk of renal impairment increases.

Allopurinol, procainamide. cytostatics or immunosuppressants: when used simultaneously with ACE inhibitors, the risk of developing hypersensitivity reactions, leukopenia, increases.

Hypoglycemic agents: In rare cases, ACE inhibitors can increase the hypoglycemic action of insulin and hypoglycemic agents for oral administration (eg, sulfonylureas) in patients with diabetes mellitus. In these cases, simultaneous use of ACE inhibitors may require a reduction in the dose of hypoglycemic agent.

Sympathomimetics can attenuate the antihypertensive effect of ACE inhibitors. To confirm antihypertensive action, such patients should be under careful medical supervision.

Simultaneous administration of ACE inhibitors and lovastatin increased the risk of hyperkalemia.

Antacids reduce the bioavailability of ACE inhibitors when used simultaneously.

When used simultaneously with the drug gold (sodium aurotomyalate) in the injection form patients were observed: "hot flashes" of blood to the skin of the face, nausea, vomiting, as well as arterial hypotension. Arterial hypotension can be regarded as an increase in the effect of ACE inhibitors under the influence of the gold preparation.

Double blockade of the renin-angiotensin-aldosterone system

In patients with diagnosed atherosclerotic disease, heart failure or diabetes with target organ damage, the double blockade of the renin-angiotensin-aldosterone system is associated with an increased incidence of arterial hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal failure), when compared with the use of one drug that affects the renin-angiotensin-aldosterone system. In this regard, a double blockade (for example, the appointment of an ACE inhibitor with an angiotensin II receptor antagonist or aliskiren) should be performed only in certain specific cases, constantly monitoring the kidney function, blood pressure.

Acetylsalicylic acid, thrombolytics and beta-blockers

Enalapril can be used simultaneously with acetylsalicylic acid (as an antiplatelet agent), thrombolytics and beta-blockers.

Hydrochlorothiazide

Use with caution at the same time

Kolestyramine and colestipol: simultaneous intake of anion-exchange drugs reduces the absorption of hydrochlorothiazide. Kolestyramine or colestipol in their single admission are associated hydrochlorothiazide and reduce its absorption from the gastrointestinal tract (GIT) by 85 and 43%, respectively. Diuretics, which are derivatives of sulfonamides, should be taken at least 1 hour before or 4-6 hours after taking these drugs.

Glucocorticosteroids. corticotropin (ACTT), amphotericin B (intravenously), carbenoxolone, calcitonin, laxatives of stimulating type: with their simultaneous administration with hydrochlorothiazide, there may be an increase in electrolyte losses (in particular, the development of hypokalemia).

Salts of calcium: it is possible to increase the calcium content in the blood serum due to a decrease in its excretion while simultaneous use with thiazide diuretics.

Cardiac glycosides: hypokalemia or hypomagnesemia caused by thiazides, contribute to the occurrence of arrhythmias caused by cardiac glycosides.

Drugs that can cause arrhythmia of the "pirouette" type: simultaneous use of thiazide diuretics, including hydrochlorothiazide, with quinidine, disopyramide, amiodarone, sotalol, ibutilide, chlorpromazine, haloperidol, sulpiride, erythromycin, pentamidine, terfenadine can cause hypokalemia and, thus, cause the development of pirouette type arrhythmias.

Amines with vasoconstrictive action (epinephrine): a possible reduction in the response to vasoconstrictor amines, although not as pronounced, to exclude their use with hydrochlorothiazide.

Muscle relaxants of nondepolarizing type (tubocurarine chloride): it is possible to increase the sensitivity to muscle relaxants in conjunction with hydrochlorothiazide application.

Amantadine: Thiazides may increase the risk of side effects of amantadine.

Anti-gouty drugs (probenecid, sulfinpyrazone, allopurinol): it may be necessary to correct the dose of the hypo-uricemic drug (increasing the dose of probenecid or sulfinpyrazone), since hydrochlorothiazide can increase the concentration of uric acid in the serum. Simultaneous use with thiazide diuretics can increase the frequency of development of hypersensitivity reactions to allopurinol.

Other antihypertensives: with simultaneous application hydrochlorothiazide strengthens the action and toxicity of other antihypertensive drugs.

Hypoglycemic agents: with the simultaneous administration of hydrochlorothiazide with hypoglycemic agents for oral administration, their effectiveness decreases, hyperglycemia may develop.

Atropine, biperidene: with simultaneous administration with atropine and biperidenum bioavailability of hydrochlorothiazide may increase, due to a decrease in the motility of the gastrointestinal tract and the rate of gastric emptying.

Salicylates: hydrochlorothiazide can enhance the toxic effects of salicylates on the central nervous system when used in high doses.

Methyldopa: it is possible to develop hemolytic anemia with the combined use of hydrochlorothiazide and methyldopa.

Iodine-containing contrast media: in the case of hypovolemia caused by the use of thiazide diuretics,the risk of acute renal failure increases with the introduction of large doses of iodine-containing contrast agents.

Carbamazepine: simultaneous use with carbamazepine may lead to symptomatic hyponatremia.

Laboratory indicators: due to the effect on calcium metabolism, thiazides can distort the result of the investigation of parathyroid gland function.

Enalapril Acry® H

Simultaneous use is not recommended

Lithium: simultaneous use with thiazide diuretics may increase the already high risk of lithium intoxication caused by ACE inhibitors, so the combined use of Enalapril-Acry® H and lithium preparations is not recommended. If such a combination is still necessary, careful monitoring of lithium content in serum is also necessary.

Laboratory indicators: Thiazides can reduce the iodine content associated with the protein without causing symptoms of thyroid dysfunction.

Use with caution at the same time

Non-steroidal anti-inflammatory drugs (NSAIDs) (including acetylsalicylic acid at a dose> 3 g / day, including cyclooxygenase-2 inhibitors (COX-2)): the use of NSAIDs may reduce the antihypertensive effect of ACE inhibitors and diuretics.In addition, there are reports that the effects of NSAIDs and ACE inhibitors that increase potassium levels in the blood serum can be summarized, while kidney function may be reduced. The corresponding effects are reversible and they develop in patients with existing renal dysfunction. In rare cases, acute renal failure may develop - especially in patients with impaired renal function (elderly or dehydrated patients).

Ethanol: enhances the antihypertensive effect of ACE inhibitors and hydrochlorothiazide. Trimethoprim: simultaneous use with ACE inhibitors and thiazides increases the risk of hypercalcemia.

Cytotoxic drugs and immunosuppressants: when used simultaneously with immunosuppressants and cytostatics (cyclophosphamide, methotrexate, cyclosporine), the risk of hematotoxicity increases.

Special instructions:

Enalapril

During the period of therapy with Enalapril-Acry® H, the patient's condition (BP) should be monitored regularly, especially at the beginning of the treatment. As with other ACE inhibitors, one should keep in mind the possibility of developing symptomatic arterial hypotension(even a few hours after taking the first dose) in patients with severe chronic heart failure, expressed renal dysfunction, as well as in patients with a disturbance of the electrolyte electrolyte balance caused by previous therapy with diuretics, a diet with restricted intake of table salt, diarrhea, vomiting, or on hemodialysis.

In patients with coronary artery disease, severe cerebrovascular disease, stenosis of the aortic aorta with hemodynamic disturbances or other obstructions to outflow of blood from the left ventricle, hypertrophic cardiomyopathy, a significant reduction in blood pressure can lead to myocardial infarction and / or stroke.

Arterial hypotension with severe consequences is rare and transient. Transient arterial hypotension is not a contraindication to further therapy with the drug.

Rarely with the treatment with ACE inhibitors, there is a syndrome that begins with cholestatic jaundice, which progresses to fulminant liver necrosis, sometimes with a fatal outcome. The mechanism of this syndrome is unclear. Patients,which, when treated with ACE inhibitors, jaundice or a marked increase in the activity of "hepatic" transaminases, ACE inhibitors should be withdrawn and medical surveillance performed.

If a patient with hypertension is treated with diuretics, then, if possible, they should be canceled 2-3 days before the start of treatment with Enalapril-Acry® H (because of the risk of developing arterial hypotension).

Before the beginning of treatment and during therapy, it is necessary to monitor the kidney function (determine the protein content in the urine with the help of test strips in the first dose of morning urine), tk. proteinuria can occur both in patients with already existing renal dysfunction and in those taking relatively high doses of ACE inhibitors.

In patients with diabetes mellitus receiving treatment with hypoglycemic agents for ingestion or insulin, the first month of treatment with ACE inhibitors should regularly monitor the concentration of glucose in the blood.

During the period of treatment with Enalapril-Acry® H, potassium may be raised in the blood serum, especially in patients with chronic renal failure (CRF), diabetes mellitus,with the simultaneous use of potassium-sparing diuretics, potassium or potassium-containing salt substitutes, as well as in patients taking other drugs that lead to an increase in serum potassium (heparin); this effect is usually weakened by thiazide diuretics because of increased excretion of potassium. If the simultaneous use of the above mentioned means is necessary, then regular monitoring of the potassium content in the serum is recommended. There are reports of the development of neutropenia / agranulocytosis, thrombocytopenia and anemia in patients receiving treatment with ACE inhibitors. The risk of neutropenia is likely to depend on the dose and clinical state of the patient. Neutropenia may occur more frequently in patients with impaired renal function, especially if there is concomitant connective tissue disease (systemic lupus erythematosus, scleroderma) or in the treatment of immunosuppressants, allopurinol or procainamide, and a combination of these risk factors. Some of these patients developed severe infectious diseases, in which in some cases there was no response to intensive antibiotic therapy.

When used in such patients, enalapril is desirable before treatment, every 2 weeks in the first three months of treatment, and then regularly monitor blood leukocytes and a detailed blood test. It should be strongly recommended that the patient be informed of any symptom of an infectious disease (sore throat, fever); In this case, the leukocyte blood count should be monitored. If you suspect or detect neutropenia (less than 1 000 / mm3), which is reversible, you should cancel the drug Enalapril-Acry® H and other concomitant drugs. Before the planned surgical procedure, the anesthetist should be informed that the patient is receiving the Enalapril-Acry® H preparation, since there is a risk of developing arterial hypotension during surgical intervention under general anesthesia. If the ACE inhibitors can not be canceled, the volume of circulating blood (BCC) should be carefully monitored.

It should be borne in mind that when treated with Enalapril-Acry® H in patients on hemodialysis using high-throughput filter membranes consisting of polyacrylonitrile (high-flow membrane),or low density lipoprotein apheresis (LDL-apheresis) with dextran sulfate, anaphylactoid reactions may develop (facial edema, hyperemia, marked decrease in blood pressure, dyspnea). It is recommended to use other types of filter membranes for dialysis or alternative antihypertensive therapy with a drug from another pharmacotherapeutic group.

During the period of desensitizing therapy to aspen or bee venom in patients receiving the Enalapril-Acry® H preparation, it is possible to develop hypersensitivity reactions that are life threatening. To avoid the corresponding reactions, prior to each session of desensitizing therapy, the therapy with ACE inhibitors should be temporarily discontinued.

If angioedema develops in the lips, face, neck (usually in the first weeks of treatment with ACE inhibitors), Enalapril-Acry® N should be immediately withdrawn and continued with an antihypertensive drug from another pharmacotherapeutic group. However, in rare cases, severe angioedema with involvement of the tongue, vocal cords or larynx can also develop after long-term use of ACE inhibitors and lead to death.In this case, emergency measures should be taken, including at least (but not necessarily this limited): immediate subcutaneous injection of 0.3-0.5 ml of epinephrine (adrenaline) 1: 1000 solution or slow intravenous injection of epinephrine 1 mg / ml ( dilute according to the instructions!) under close supervision of the ECG and blood pressure. The patient should be hospitalized and observed for at least 12-24 hours (until the symptoms disappear completely).

Patients with bilateral renal artery stenosis, single-kidney artery stenosis, in a condition after kidney transplantation, and with primary hyperaldosteronism, Enalapril-Acry® H is administered with caution, such patients should be under constant medical supervision.

Among patients of the Negroid race receiving therapy with ACE inhibitors, the incidence of angioedema is higher than in patients of other race.

Hydrochlorothiazide

In patients with kidney disease, thiazides can aggravate azotemia. In patients with impaired renal function hydrochlorothiazide can cumulate. With progression of renal failure characterized by an increase

the content in the blood of total nitrogen without increasing the nitrogen of the protein should be considered to cancel the drug Enalapril-Acry® H. Each patient when taking diuretics requires a systematic control of the content of electrolytes in blood plasma. Thiazides can cause a violation of the water-electrolyte balance (hypokalemia, hyponatremia and hypochloraemic alkalosis). Symptoms-precursors are: dryness of the oral mucosa, thirst, weakness, stupor, drowsiness, anxiety, muscle pain or cramps, muscle weakness, arterial hypotension, oliguria, tachycardia, nausea or vomiting.

With the use of thiazide diuretics, it is possible to detect signs of a deficiency in potassium, but simultaneous use of enalapril helps to reduce hypokalemia caused by diuretics. The highest degree of risk of hypokalemia exists in patients with cirrhosis of the liver, increased diuresis, as well as insufficient intake of table salt inward, simultaneous use of glucocorticosteroids or corticotropin (ACTH). In hot weather, diluted hyponatremia may occur in patients with edema.Chloride deficiency usually is not expressed and does not require treatment.

Thiazides can reduce the excretion of calcium by the kidneys and cause a transient increase in serum calcium without visible disturbances in its metabolism. Expressed hypercalcemia may be a sign of latent hyperparathyroidism. Thiazides should be discontinued before the study of parathyroid function. Thiazides increase the excretion of magnesium by the kidneys (risk of hypomagnesemia). In the treatment of thiazides, the development of a violation of glucose tolerance is possible. You may need to adjust the dose of insulin or hypoglycemic agents for oral administration. In the treatment of thiazides, latent diabetes mellitus can manifest.

The relationship between increased cholesterol and triglyceride concentrations and the use of thiazide diuretics has been established. Treatment with thiazides can cause hyperuricemia and / or exacerbation of gout.

Hydrochlorothiazide should be avoided in patients with bilateral renal artery stenosis or renal artery stenosis of a single kidney. Hydrochlorothiazide may cause a positive result in the conduct of doping control.

Hydrochlorothiazide can cause acute transient myopia and acute closed-angle glaucoma. Symptoms of development include decreased vision, eye pain, and can develop several hours or weeks after starting the drug. Closed-angle glaucoma can lead to a complete loss of vision. When complications develop, it is recommended to stop taking hydrochlorothiazide. Increased intraocular pressure may require surgical intervention. Caution should be exercised in the treatment of patients with impaired liver function or progressive impairment of liver function, as small fluctuations in the water or electrolyte balance may cause hepatic coma.

Enalapril-Acry® H

The combination of ACE inhibitors with thiazide diuretics does not exclude the risk of hypokalemia, therefore, the content of potassium in the blood should be monitored regularly.

Effect on the ability to drive transp. cf. and fur:

At the beginning of treatment with Enalapril-Acry® H, there may be a marked decrease in blood pressure, dizziness and drowsiness, which may reduce the ability to drive vehicles and occupy other potentially dangerousActivities that require increased concentration and speed of psychomotor reactions.

Therefore, at the beginning of treatment it is not recommended to drive vehicles and engage in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 25 mg + 10 mg.

Packaging:For 10 tablets in a contour mesh package made of aluminum foil and a combined three-layer material for drug packaging.

2 or 3 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:In a dry, protected from light place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000008

Date of registration:25.02.2010

Date of cancellation:2016-10-04

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Information update date: & nbsp04.10.2016

Illustrated instructions

Instructions

Enalapril-Acry® H (Enalapril-Akri® N)