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

Excipients: lactose monohydrate 72.835 mg, potato starch 22 mg, sodium hydrogen carbonate 10 mg, sodium carboxymethyl starch 1.3 mg, magnesium stearate 1.3 mg, iron oxide dye yellow 0.065 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:

Enalapril-Acry® HJI - a combined drug, the effect of which is due to the components that make up its composition; has an antihypertensive effect.

Enalapril - inhibitor of angiotensin-converting enzyme (ACE). 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 degradation of bradykinin, which is accompanied by a decrease in systolic and diastolic blood pressure (BP), a decrease in the total peripheral resistance of blood vessels,increased 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 hypotensive 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 hypotensive effect. The mechanism of hypotensive 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 approximately 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 content of enalapril in the blood plasma is achieved after 1 h, enalaprilate - 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 - 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). It is removed during hemodialysis (rate 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, the average dose 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 time (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 h. 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-t-benzene disulfonamide (reduced in alkaline urine) - by glomerular filtration and active tubular secretion in the proximal nephron.

Indications:Arterial hypertension.

Contraindications:Hypersensitivity to the drug components (including other ACE inhibitors and sulfonamide derivatives), anuria, severe renal dysfunction (creatinine clearance <30 mL / min); angioedema in history, associated with the administration of ACE inhibitors, hereditary or idiopathic angioedema, lactose intolerance, lactase deficiency, glucose-galactose malabsorption, pregnancy, lactation, age under 18 years (efficacy and safety not established).

Carefully:

Impaired renal function (creatinine clearance> 30 ml / min); abnormal liver function; acute attack of angle-closure glaucoma; severe systemic diseases of connective tissue (incl.systemic lupus erythematosus, scleroderma), bilateral renal artery stenosis, single-kidney artery stenosis, hypertrophic obstructive cardiomyopathy, severe atherosclerosis, primary hyperaldosteronism, kidney transplantation condition, aortic stenosis, chronic heart failure, ischemic heart disease, bone marrow hematopoiesis depression, cerebrovascular diseases including insufficiency cerebral circulation), diabetes, hyperkalemia, restricted diet salt, hyperuricemia and gout, a condition associated with decreased blood volume (including diarrhea, vomiting), hemodialysis using vysokoprotochnyh polyacrylonitrile membranes (AN69®), lipoprotein apheresis low density (LDL-apheresis) with dextran sulfate holding allergen desensitization procedures venom gimenoptery (Hymenoptera), advanced age.

Pregnancy and lactation:

A drug contraindicated during 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 II and III trimester of pregnancy is associated with adverse effects on the fetus and 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.

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 adults.

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

Enalapril and hydrochlorothiazide penetrate into breast milk. Therefore, when using the drug during lactation, it is necessary to refuse breastfeeding.

Dosing and Administration:Inside, regardless of food intake, 1 tablet 1 time per day, if necessary, the dose can be increased to 2 tablets 1 time per day.

Dose with impaired renal function

In patients with renal insufficiency with a creatinine clearance of 30-75 ml / min, the drug should be used only after preliminary titration of doses of enalapril and hydrochlorothiazide alone, respectively, in doses in a combined

preparation Enalapril-Acry® NL. If there is no therapeutic effect, it is recommended to add another medication or change the therapy. The duration of treatment is determined by the doctor.

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, 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, confusion, depression, sleep disorders, drowsiness, "nightmarish" dreams; rarely - confusion, paresthesia, memory impairment, peripheral neuropathy, tremor, migraine, confusion.

Disturbances from the respiratory system: often - cough; infrequently - a rhinitis, zalozhennost a nose; very rarely - sore throat, hoarseness, bronchospasm; pulmonary infiltrates, allergic

alveolitis / eosinophilic pneumonia.

Violations of the blood and lymphatic system: rarely - reduction of hemoglobin and hematocrit, very rarely - suppression of bone marrow function, anemia, neutropenia; thrombocytopenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia, hemolytic anemia, lymphadenopathy, increased ESR.

Disorders from the digestive system: often - nausea; diarrhea, infrequently - abdominal pain, constipation; rarely - a violation of taste, 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 bile ducts: infrequently - increased activity of "liver" transaminases, increased bilirubin concentration; very rarely - a violation of the liver, hepatitis (hepatocellular or cholestatic), jaundice.

From the urinary system: often - renal dysfunction; 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 the hands, arthralgia, musculoskeletal pain, stiffness and swelling of the joints.

Disorders from the side of the organ of vision: 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: 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, edema of the face, limbs, lips, tongue, vocal folds, larynx; dysphonia, urticaria; very rarely - erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, erythroderma.

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

Other: often asthenia, fatigue; infrequently - muscle cramps, general malaise, fever; very rarely - epistaxis, vasculitis, Raynaud's phenomenon, "hot flashes" of blood to the skin of the face. With the use of ACE inhibitors, a symptom complex including

fever, serositis, vasculitis, myalgia, myositis, arthralgia, arthritis, a positive test for antinuclear antibodies, an increase in ESR, eosinophilia, leukocytosis, exanthema, reactions

photosensitivity or other dermatological disorders.With the simultaneous administration of ACE inhibitors and intravenous sodium aurotomyalate, a symptom complex including facial flushing, nausea, vomiting and arterial hypotension is described.

Hydrochlorothiazide

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

Impaired nervous system: often - anxiety, sleep disturbance, depression; infrequently - paresthesia, dizziness.

Disorders from the cardiovascular system: rarely - orthostatic hypotension, arrhythmias.

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, hypercholesterolemia and hypertriglyceridemia, gout.

From the side of the hearing organ: 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.

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: the patient is transferred to a horizontal position with raised legs. In mild cases, gastric lavage and ingestion of activated charcoal are indicated,in more serious cases - measures aimed at stabilizing blood pressure and heart rate: 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 (the rate of excretion of enalaprilate is 62 ml / min).

Interaction:

Enalapril

Simultaneous use is not recommended

Potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride) or potassium-containing salts, potassium supplements:

when used simultaneously with ACE inhibitors, hyperkalemia may develop. 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 withdiabetes mellitus and / or with moderate or severe renal dysfunction (glomerular filtration rate (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

Preparations containing aliskiren: at simultaneous application with ACE inhibitors and / or with angiotensin II receptor antagonists in patients with diagnosed atherosclerotic disease, heart failure or diabetes with target organ damage, a 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 renin-angio a tensin-aldosterone system. In this regard, a double blockade (for example, the appointment of an ACE inhibitor with an angiotensin II receptor antagonist) should be performed only in selected specific cases, constantly monitoring the kidney function, blood pressure.

Thiazide or "loop" diuretics: the 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. The hypotensive effect can be reduced if you cancel a diuretic, increase the flow of fluid or salts into 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.

Narcotic drugs / tricyclic antidepressants / psychotropic drugs / barbiturates: there may be a development orthostatic hypotension.

Other antihypertensive drugs (alpha and beta-adrenoblockers, blockers of "slow" calcium channels): the hypotensive 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.

Cyclosporine: while concomitant use with ACE inhibitors increases the risk of developing a violation of kidney function.

Allopurinol, procainamide, cytostatics or immunosuppressants: while simultaneous use with ACE inhibitors increases the risk of developing hypersensitivity reactions, leukopenia.

Hypoglycemic agents: in rare In some cases, ACE inhibitors can increase the hypoglycemic action of insulin and hypoglycemic agents for oral administration (eg, sulfonylureas) in diabetic patients. In these cases, simultaneous use of ACE inhibitors may require a reduction in the dose of hypoglycemic agent. Sympathomimetics can weaken the hypotensive effect of ACE inhibitors. To confirm the hypotensive effect of such patients should be under careful medical supervision.

Antacids reduce the bioavailability of ACE inhibitors when used simultaneously.

When applied simultaneously with the drug gold (sodium aurothiomalate) in injecting 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.

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 colstereol: simultaneous intake of anion-exchange drugs reduces the absorption of hydrochlorothiazide. Kolestyramine or kolstirol at their single reception connect 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 (ACTH), amphotericin B (intravenously), carbenoxolone, laxatives stimulating type: with simultaneous their admission with hydrochlorothiazide may lead to increased losses of electrolytes (especially, the development of hypokalemia).

Salts of calcium: It is possible to increase the content of calcium 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.

Medicinal products that are capable of cause arrhythmia such as "pirouette": simultaneous use of thiazide diuretics, including hydrochlorothiazide, with quinidine, disopyramide, amiodarone, sotalol, ibutilide, clopromazine, haloperidol, sulperid, erythromycin, pentamidine, terfenadine can cause hypokalemia and, thus, cause the development of pirouette type arrhythmias.

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

Nondepolarizing muscle relaxants (tubocurarine chloride): it is possible to increase the sensitivity to muscle relaxants when combined with hydrochlorothiazide application. Amantadine: Thiazides may increase the risk of side effects of amantadine.

Anti-arthritis 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 enhances action and toxicity of other antihypertensive drugs.

Hypoglycemic agents

At simultaneous reception hydrochlorothiazide with hypoglycemic means for ingestion decreases their effectiveness, can develop hyperglycemia.

Atropine, biperiden

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

Salicylates

Hydrochlorothiazide can increase the toxic effects of salicylates on the central nervous system when used in high doses.

Methyldopa

Possible development of hemolytic anemia when combined hydrochlorothiazide and methyldopa.

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

Enalapril-Acry® NL

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® NL 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 drugs (NSAIDs) (including acetylsalicylic acid at a dose> 3 g / day, including cyclooxygenase-2 inhibitors (COX-2)): The use of NSAIDs may reduce the hypotensive 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 hypotensive 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 developing hematotoxicity increases.

Special instructions:

Enalapril

During the period of therapy with the drug Enalapril-Acry® NL, the patient's condition (BP) should be regularly monitored, 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 the first dose) in patients with severe chronic heart failure, expressed violations of kidney function, as well as in patients with a violation of water-electrolyte balance, due to previous therapy diuretics, diet with reduced intake of table salt, diarrhea, vomiting, or who are on hemodialysis.In patients with ischemic heart disease, severe cerebrovascular disease, stenosis of the aortic aorta with hemodynamic disturbances or other obstructions to outflow of blood from the left ventricle, 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 who have jaundice or marked increase in the activity of "hepatic" transaminases in treatment with ACE inhibitors should abolish ACE inhibitors and conduct medical surveillance. If a patient with hypertension is treated with diuretics, they should, if possible, be canceled 2-3 days before the start of treatment with Enalapril-Acry® HL (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 treatment with Enalapril-Acry® HL, potassium may be raised in the blood serum, especially in patients with chronic renal failure (CRF), diabetes mellitus, while using potassium-sparing diuretics, potassium or potassium-containing salt substitutes, as well as in patients taking other means leading 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 can often occur in patients with reduced renal function, especially if there is a 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 1000 / mm3), which is reversible, you should cancel the drug Enalapril-Acry® NL and other concurrently taken funds.Before the planned surgical procedure, the anesthetist should be informed that the patient is receiving the Enalapril-Acry® NL preparation because there is a risk of developing arterial hypotension at surgical intervention under general anesthesia. If the ACE inhibitors can not be withdrawn, BCC should be carefully monitored.

It should be noted that in patients treated with Enalapril-Acry® NL in patients on hemodialysis using high-throughput filter membranes consisting of polyacrylonitrile (high-flow membranes) or low-density lipoprotein (LDL-apheresis) apheresis with dextran- sulfate, the development of anaphylactoid reactions (facial edema, hyperemia, marked decrease in blood pressure, dyspnea) is possible. It is recommended to use other types of filter membranes for dialysis or alternative antihypertensive therapy with the drug of another pharmacotherapeutic group. In the period of desensitizing therapy to aspen or bee venom in patients receiving the drug Enalapril-Acry® NL, the development of reactions with increased sensitivity,

posing a threat to life. To avoid the corresponding reactions, before of each session

desensitizing therapy should temporarily discontinue therapy with ACE inhibitors. If angioedema develops in the lips, face, neck (usually in the first weeks of treatment with ACE inhibitors), Enalapril-Acry® NL 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 stenosis of the renal arteries,stenosis of the artery of a single kidney, in a state after kidney transplantation, and with primary hyperaldosteronism, the drug Enalapril-Acry® HL is administered with caution, such patients should be under constant medical supervision.

Among patients of the Negroid race receiving therapy with ACE inhibitors, the frequency the occurrence 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 the progression of renal failure, characterized by an increase in the total blood in the blood of nitrogen without increasing the protein nitrogen, consideration should be given to the abolition of Enalapril-Acry® HL. 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 inadequate 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.

Should to avoid the use of hydrochlorothiazide in patients with bilateral stenosis of the renal arteries or stenosis of the renal artery of a single kidney.

Hydrochlorothiazide can cause a positive result in 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.

Enalapril-Acry® HL

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® HL, there may be a marked decrease in blood pressure, dizziness and drowsiness, which may reduce the ability to drive vehicles and engage in other potentially hazardous activities requiring increased attention 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 12.5 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-000009

Date of registration:25.02.2010

Date of cancellation:2016-10-14

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

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Information update date: & nbsp14.10.2016

Illustrated instructions

Instructions

Enalapril-Acry® NL (Enalapril-Akri® HL)