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

Excipients: lactose 139.5 mg, microcrystalline cellulose 20.0 mg, povidone (polyvinylpyrrolidone) 6.0 mg, croscarmellose sodium 8.0 mg, silicon colloidal dioxide 2.0 mg, magnesium stearate 2.0 mg.

Description:Round tablets white or white with a beige shade of color, flat-cylindrical shape with a risk on one side and a facet on both sides.

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

ATX: & nbsp

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

Pharmacodynamics:Enalapril inhibits ACE that promotes the conversion of angiotensin 1 into angiotensin II, reduces the concentration of aldosterone in the blood plasma, increases the release of renin, improves the functioning of the kallikrein-kinin system, stimulates the release of prostaglandins and endothelial relaxants, and depresses the sympathetic nervous system. Together, these effects eliminate spasm and dilate the peripheral arteries, reduce overall peripheral vascular resistance, 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 antihypertensive effect is more pronounced with a high concentration of renin in the blood plasma,than with normal or reduced. 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 after 6-8 hours and persists up to 24 hours after ingestion.

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 to 2 hours, reaches a maximum after 4 hours, remains for 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 individually and allows preserving the antihypertensive effect of the drug Enalapril HJI for at least 24 hours.

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, enalaprilate - 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. 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, serum concentration of enalaprilat after 4-hour hemodialysis decreases by 45-57%.

In patients with reduced renal function, excretion slows, which requires a dose reduction in accordance with renal dysfunction, especially in patients with severe renal failure.

In patients with hepatic insufficiency, metabolism of enalapril can be slowed down without changing its pharmacodynamic effect.

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

Hydrochlorothiazide

It is absorbed mainly in the duodenum and the proximal part of the small intestine. Absorption is 70% and increases by 10% when taken 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 increases in direct proportion to the increase in dose, with application 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 part of the nephron. The renal clearance of hydrochlorothiazide in healthy volunteers and patients with arterial hypertension is approximately 5.58 ml / s (335 ml / min). Hydrochlorothiazide has a two-phase withdrawal profile. T_1/2 in the initial phase is 2 hours, in the final phase (10-12 hours after ingestion) - 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 hours; the renal clearance is 0.17-3.12 ml / s (10-187 ml / min) (averages of 1.28 ml / s (77 ml / min)).

In patients who underwent intestinal bypass surgery for obesity, 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 or other ACE inhibitors, hydrochlorothiazide or other sulfonamide derivatives or other components of the drug;

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

anuria;

- angioedema in the anamnesis (including those associated with the use of ACE inhibitors);

- hereditary and / or idiopathic angioedema;

- severe violations of the liver (more than 9 points on the scale Child-Pugh);

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

- Pregnancy;

- lactation period;

- age to 18 years (efficacy and safety of the drug are not established).

Carefully:

- bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney (risk of developing kidney failure);

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

- Stenosis of the aorta or hypertrophic obstructive cardiomyopathy;

- Chronic heart failure;

- severe atherosclerosis;

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

- oppression of bone marrow hematopoiesis;

- Diabetes mellitus, because. Thiazide diuretics can reduce glucose tolerance;

- Hyperkalemia;

- condition after kidney transplantation (no experience with the drug);

- impaired liver function (less than 9 on the Child-Pugh scale) (risk of hepatic coma);

- impaired renal function (QC more than 30 ml / min);

- conditions accompanied by a decrease in the volume of circulating blood (bcc) (as a result of diuretic therapy, with the restriction of consumption of table salt, diarrhea, vomiting);

- primary hyperaldosteronism;

acute attack of angle-closure glaucoma;

-elderly age;

- gout and / or hyperuricemia;

- arterial hypotension.

Pregnancy and lactation:

The use of the drug Enalapril NL during pregnancy is contraindicated. In the case of planning or diagnosing pregnancy during therapy with the drug Enalapril NL, the drug should be discontinued as soon as possible.

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 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 during pregnancy is not recommended because they can cause jaundice fetus and newborn, thrombocytopenia and, possibly, other side effects observed in adults.

If the use of the drug during pregnancy is vital for the mother, the doctor should inform the patient about the potential risk to the fetus. In this case, an ultrasound examination of the intra-amniotic space should be performed periodically. When the oligohydramnion is detected, the drug is stopped, except when it is vitally important for the mother. The doctor should remember, as well as inform the patient that the oligohydramnion can develop after the irreversible damage to the fetus. If a decision is made to use ACE inhibitors already with the developed oligohydramnione, then, depending on the period of pregnancy, tests can be used to determine the functional state of the fetus (contractile stress test, non-stress test or fetal biophysical profile). Newborns whose mothers took the drug should be carefully monitored for the detection of arterial hypotension, oliguria, and hyperkalemia. In the case of development of oliguria, the attention of the doctor should be directed to the maintenance of blood pressure and renal perfusion.

Enalapril and thiazide diuretics enter the breast milk, so if they need to be used during lactation, breastfeeding while taking the drug Enalapril HJI should be discontinued. Also, the relationship between the use of thiazide diuretics during lactation and the reduction or even suppression of lactation, hypokalemia, as well as the emergence of hypersensitivity to sulfonamide derivatives.

Dosing and Administration:

A drug Enalapril HJI should be taken regularly at the same time, preferably in the morning, regardless of the time of ingestion, without chewing, squeezed with a small amount of liquid, once a day. The recommended dose is 1 tablet per day. If necessary, the dose can be increased to 2 tablets taken once a day, this dose is the maximum daily dose.

In patients taking diuretics, it is recommended to cancel them or reduce the dose, at least 3 days before the start of treatment with the drug Enalapril HJ1 to prevent the development of symptomatic arterial hypotension.

Impaired renal function

In patients with severe renal failure (CC less than 30 ml / min.), The drug Enalapril HJI is contraindicated.

In patients with renal insufficiency with a creatinine clearance of more than 30 ml / min., The drug Enalapril HJ1 can be used only after stabilization of blood pressure on the background of treatment with drugs enalapril and hydrochlorothiazide in separate dosage forms and the selection of their doses. The recommended initial dose of the drug Enalapril HJI - 1/2 tablets once a day. It should be regularly monitored (every 2 months) the content of potassium and creatinine.

Side effects:

In clinical studies 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.

The incidence of adverse events is classified according to the recommendations of the World Health Organization (WHO):

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), including individual messages.

Enalapril

From the hemopoietic system and lymphatic system:

LP 001994-080213

rarely: a decrease in hemoglobin and hematocrit;

very rarely - oppression of bone marrow function, anemia, thrombocytopenia, leukopenia, neutropenia and agranulocytosis, hemolytic anemia, lymphadenopathy, eosinophilia, autoimmune diseases;

From the endocrine system:

rarely: syndrome of inadequate secretion of antidiuretic hormone.

From the side of the nervous system:

often: headache, dizziness, fainting;

infrequently: insomnia, anxiety, panic, confusion, depression, sleep disturbance, "nightmarish" dreams, drowsiness;

rarely: paresthesia, memory impairment, peripheral neuropathy, tremor, migraine, confusion;

From the side of the organ of vision:

rarely: blurred vision, conjunctivitis, decreased visual acuity, dryness and burning eyes;

From the organ of hearing:

infrequently: vertigo, noise in the ears;

From the cardiovascular system:

often: marked decrease in blood pressure, orthostatic hypotension;

infrequent: palpitation, chest pain, arrhythmias (atrial fibrillation, sinus bradycardia, tachycardia, ventricular fibrillation), stenocardia, atrioventricular blockade of degree II, cerebral circulation disorder, myocardial infarction;

From the respiratory system:

often: cough;

infrequently: rhinitis, nasal congestion;

very rarely: sinusitis, pharyngitis, laryngitis, sore throat, hoarseness, dyspnea, bronchitis, lung infiltrates, bronchospasm / bronchial asthma;

From the digestive system:

often: nausea, diarrhea; infrequently: abdominal pain, constipation;

rarely: dryness of the oral mucosa, stomatitis, flatulence, vomiting, gastritis, taste disorder, peptic ulcer, aphthous ulcers;

very rarely: pancreatitis, intestinal obstruction, intestinal angioedema

edema:

From the liver and bile ducts:

infrequently: increased activity of "hepatic" transaminases, increased bilirubin concentration;

very rarely: a violation of the liver, hepatitis, hepatocellular or cholestatic, jaundice;

Allergic reactions:

infrequent: skin rash, itching;

rarely: angioedema, swelling of the face, limbs, lips, tongue, vocal cords and / or larynx, dysphonia, urticaria;

very rarely: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, photosensitivity;

From the skin:

rarely: alopecia, psoriasis, dermatitis, dry skin;

very rarely: pseudolymphoma, pemphigus;

From the genitourinary system:

often: impaired renal function;

rarely: uremia, acute renal failure, proteinuria; very rarely: oliguria, anuria;

From the musculoskeletal system:

often: muscle spasms, back pain, leg pain, myalgia;

infrequently: pain in hands, arthralgia, musculoskeletal pain, stiffness and swelling of the joints;

On the part of the reproductive system:

infrequently: impotence;

rarely: gynecomastia;

Other:

often: asthenia, fatigue, hyperkalemia;

infrequent: increased body temperature, a slight increase in the concentration of urea and creatinine;

rarely: hyponatremia;

very rarely: hyperglycemia, in patients with diabetes - hypoklikemia, epistaxis, vasculitis, Raynaud's syndrome, "flushes" of blood to the skin of the face described a symptom complex that may include fever, myalgia and arthralgia, serositis, vasculitis, increased erythrocyte sedimentation rate, leukocytosis and eosinophilia, skin rash, a positive test for antinuclear antibodies.

Hydrochlorothiazide

From the side of the blood and lymphatic system:

rarely: neutropenia and agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, leukopenia, oppression of bone marrow function.

From the side of metabolism and nutrition:

infrequently: anorexia, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia, hypomagnesemia, hypercalcemia and hypochloraemic alkalosis, increased concentrations of cholesterol and triglycerides, exacerbation of gout;

From the nervous system:

often: depression, sleep disturbance;

infrequently: insomnia, paresthesia, dizziness;

From the side of the organ of vision:

rarely: transient visual impairment, xantopsy;

From the organ of hearing:

rarely: vertigo;

From the cardiovascular system:

rarely: orthostatic hypotension, vasculitis, arrhythmia;

From the respiratory system:

infrequently: respiratory distress syndrome (including pneumonitis and non-cardiogenic pulmonary edema);

From the digestive system:

rarely: sialadenitis, constipation, diarrhea, irritation of the gastrointestinal mucosa;

very rarely: pancreatitis;

From the liver and bile ducts:

infrequently: jaundice (intrahepatic cholestasis), cholecystitis;

Allergic reactions:

rarely: photosensitization;

very rarely: urticaria, toxic epidermal necrolysis, Lyell's syndrome, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, anaphylactic reactions up to shock;

Other: decreased potency, fever.

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: gastric lavage and ingestion of activated charcoal; with a pronounced decrease in blood pressure - the patient to be moved to a horizontal position with raised legs, then to carry out measures aimed at stabilizing blood pressure - intravenous injection of plasma substitutes, infusion of 0.9% sodium chloride solution. The patient should monitor the blood pressure, respiratory rate, serum urea concentration, creatinine electrolytes and diuresis, if necessary - hemodialysis (the rate of excretion of enalaprilate is 62 ml / min).

Interaction:

ENALAPRIL

SIMULTANEOUS APPLICATION IS NOT RECOMMENDED

Potassium-sparing diuretics (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 electrocardiogram (see Fig. Special instructions).

SIMULTANEOUS APPLICATION WITH CARE

Thiazide or "loop" diuretics: the previous treatment with diuretics in high doses may lead to a decrease in BCC and initiate the development of arterial hypotension at the beginning of enalapril therapy. Special instructions). The antihypertensive effect can be reduced if the diuretic is abolished, replenishes the BCC and normalizes the water-electrolyte baton, or starts 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: there may be a development of orthostatic hypotension.

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

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

Cimetidine: increased risk of developing collapse.

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

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

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.

Aliskiren-containing means: It is not recommended simultaneous use of ACE inhibitors or antagonistsreceptors of angiotensin II with aliskiren-containing preparations in patients with diabetes mellitus.

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

Antacids reduce the bioavailability of ACE inhibitors when used simultaneously. When used simultaneously with the drug gold (sodium aurotomy malate) for intravenous administration in patients were observed: "hot flashes" of the 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.

HYDROCHLOROTHYASIDE

SIMULTANEOUS APPLICATION WITH CARE

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 by 85 and 43%, respectively. Diuretics, which are derivatives of sulfonamide, 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: when they are taken together with hydrochlorothiazide, there may be an increase in electrolyte loss (in particular, 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 can cause piruet-type arrhythmia ("pirouette" - a special form of polymorphic ventricular tachycardia with a wave, screw or spindle-shaped configuration of ventricular complexes in combination with an increase or decrease in the amplitude of the teeth of the complex QRS. which can result in ventricular fibrillation or asystole): Because of the risk of developing hypokalemia, caution is required when hydrochlorothiazide is used together with certain antiarrhythmic (amiodarone, sotalol), antipsychotic (neuroleptics) (phenothiazines - chlorpromazine, thioridazine; ben bam idy - amisulpride, sulpiride, tiapride; butyrophenones - haloperidol) and other medicinal products, which are known to cause arrhythmia such as "pirouette": erythromycin (intravenous), pentamidine, sparfloxacin, moxifloxacin, astemizole.

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-gouty drugs (probenecid, sulfinpirazone, 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.

Atropine, biperidene: simultaneous application of thiazide diuretics may increase the bioavailability of thiazide diuretics, owing to decrease motility of the gastrointestinal tract and gastric emptying rate.

Carbamazepine: when used simultaneously with thiazide diuretics, there is a risk of developing hyponatremia.

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

Hypoglycemic agents for ingestion and insulin: it may be necessary to correct the dose of hypoglycemic drugs with simultaneous admission with thiazide diuretics.

Iodine-containing contrast agents: in patients with hypovolemia, diuretic therapy is associated with an increased risk of developing acute renal failure, especially when contrast media containing high doses of iodine are used. Before using these drugs, you should make up for the BCC.

Methyldopa: cases of hemolytic anemia with simultaneous application with methyldopa are described.

OTHER KINDS OF INTERACTION

Laboratory indicators: Because of the effect on calcium metabolism, thiazides can distort the result of the study of parathyroid function.

ENALAPRIL / HYDROCHLOROTHYASIDE IN THE COMBINATION SIMULTANEOUS APPLICATION IS NOT RECOMMENDED

Lithium: simultaneous use with thiazide diuretics can increase the already increased risk of lithium intoxication due to ACE inhibitors, so simultaneous use of the drug Enalapril HJI and lithium preparations are not recommended. If such a combination is still necessary, careful monitoring of the concentration of lithium in serum is also necessary.

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

SIMULTANEOUS APPLICATION WITH CARE

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, primarily 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.

Other antihypertensive drugs: simultaneous use can enhance the antihypertensive effect of enalaryl and hydrochlorothiazide. Concurrent with enalapril, the use of beta-blockers, alpha-blockers, 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.

Double blockade of the renin-angiotensin-achestosterone system

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

Special instructions:

special instructions

ENALAPRIL

During the period of therapy with the drug Enalapril NL should regularly monitor the patient's condition, especially at the beginning of 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 renal impairment, as well as in patients with water disturbance Electrolyte balance, conditioned by previous therapy with diuretics, diet with restriction of consumption of table salt, diarrhea, vomiting, or on hemodialysis.

In patients with ischemic heart disease, severe cerebrovascular disease, stenosis of the aortic disorders of hemodynamics or other obstacles to outflow of blood from the left ventricle, a significant reduction in blood pressure can lead to myocardial infarction and / or stroke.

As with other medications with vasoconstrictive action, caution should be exercised in patients with aortic stenosis and hypertrophic obstructive cardiomyopathy with Enalapril NL.

Sudden abolition of treatment with Enalapril NL does not lead to the development of the syndrome "cancellation".

Transient arterial hypotension is not a contraindication to further therapy with Enalapril NL after BP stabilization. In the case of a re-expressed decrease in blood pressure, the dose should be reduced or the drug Enalapril NL should be withdrawn. With the development of a marked decrease in blood pressure, the patient should be in a horizontal position, if necessary, 0.9% sodium chloride solution and / or plasma-substituting solutions are administered.

With the use of ACE inhibitors in renovascular hypertension, there is also a high risk of a marked decrease in blood pressure, so treatment in such patients begins with a low dose of Enalapril NL under the supervision of a doctor

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 was treated with diuretics, then, if possible, they should be canceled 2-3 days before the start of treatment with Enalapril NL (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 plasma. Interaction with other medicinal products).

During the period of drug treatment Enalapril HJI it is possible to increase the potassium content in the blood serum, especially in patients with chronic renal failure, diabetes mellitus, while using potassium-sparing diuretics, potassium or potassium-containing salt substitutes, as well as in patients taking other drugs that lead to an increase in potassium in the blood serum for example, 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 blood serum is recommended (cf. Interaction with other medicinal products).

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 often 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, as well as 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 enalapril is used in such patients, it is desirable before the 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 suspected or detected neutropenia (less than 1 LLC / mm³), which is reversible, it is necessary to cancel the drug Enalapril NL and other concomitantly taken funds (see. Interaction with other medicinal products).

Before the planned surgical intervention, the anesthesiologist should be informed that the patient is receiving the Enalapril NL preparation, since there is a risk of developing arterial hypotension during surgical intervention under general anesthesia.If the ACE inhibitors can not be withdrawn, BCC should be carefully monitored.

It should be borne in mind that when treating with the drug Enalapril NL in patients who hemodialysis is shown, possibly anaphylactoid reactions (facial edema, hyperemia, marked decrease in blood pressure, dyspnea) due to the use of high-throughput filter membranes consisting of polyacrylonitrile (for example, high-flux membranes AN69). It is recommended to use other types of filter membranes for hemodialysis or alternative antihypertensive therapy with a drug from another pharmacotherapeutic group.

Do not apply the drug to patients who have undergone apheresis of low-density lipoproteins with dextran sulfate.

In the period of desensitizing therapy to aspen or bee venom in patients receiving the drug Enalapril HJ1, It is possible to develop reactions of hypersensitivity, representing a threat to life. To avoid the corresponding reactions, prior to each session of desensitizing therapy, the therapy with ACE inhibitors should be temporarily discontinued.

In case of angioedema development of the lips, face, neck (usually in the first weeks of treatment with ACE inhibitors) Enalapril HJ1 should immediately be canceled and continue treatment with an antihypertensive drug from another pharmacotherapeutic group. Angioedema with involvement of the tongue, vocal cords, or larynx can 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).

On the background of therapy with ACE inhibitors, cough may occur. Typically, this is a dry cough, is permanent and disappears after discontinuation of treatment. Cough associated with the use of ACE inhibitors should be considered in the differential diagnosis of cough. Enalapril, like other ACE inhibitors, has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races.

Aortic stenosis / hypertrophic obstructive cardiomyopathy - like all drugs that have a vasodilating effect, ACE inhibitors should be administered with caution to patients who have difficulty in draining blood from the left ventricle of the heart.

HYDROCHLOROTHYASIDE

In patients with kidney disease, thiazide diuretics can aggravate azotemia. In patients with impaired renal function hydrochlorothiazide can cumulate. With the progression of renal failure characterized by an increase in the nitrogen content in the blood plasma without increasing the protein nitrogen, the question of drug cancellation should be considered enalapril HJI. Each patient when taking diuretics requires a systematic control of the content of electrolytes in blood plasma.

Thiazide diuretics can cause a disturbance 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 risk of hypokalemia when taking thiazide diuretics increased in patients with cirrhosis, the increased urine output, as well as restricted diet salt, simultaneous application of corticosteroids or corticotropin (ACTH) (see. Interaction with other medicinal products). 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 examination of parathyroid gland function. Interaction with other medicinal products).

Thiazide diuretics increase the renal excretion of magnesium (risk of hypomagnesemia). In the treatment of thiazides, the development of a violation of glucose tolerance is possible. Correction may need a dose of insulin or hypoglycemic agents for oral administration (see. Interaction with other medicinal products). In the treatment of thiazides, latent-flowing 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 can cause a positive result in doping control.

Hydrochlorothiazide is a sulfonamide that can cause an idiosyncratic reaction leading to the development of a transient acute attack of angle-closure glaucoma. Symptoms include: sudden reduction in visual acuity or pain in the eyes, which appear, usually within a few hours or weeks from the initiation of hydrochlorothiazide therapy. In the absence of treatment, acute closed-angle glaucoma can lead to permanent loss of vision. Treatment: stop the hydrochlorothyroid as soon as possible. If intraocular pressure remains uncontrolled, immediate medical treatment or surgical intervention may be required.Risk factors for the development of acute closed-angle glaucoma are: an allergic reaction to sulfonamide or benzylpenicillin in the anamnesis.

In some patients, therapy with thiazide diuretics can lead to hyperureukemia and / or gout. but enalapril can increase the concentration of uric acid in the urine and thereby weaken the hyperurekemic effect of hydrochlorothiazide.

ENALAPRIL / HYDROCHLOROTIAZIP IN COMBINATION

The combination of ACE inhibitors with thiazide diuretics does not exclude the risk of hypokalemia, therefore, the level of potassium in the blood plasma should be monitored regularly. The drug should not be prescribed to patients with renal insufficiency (KC less than 80 ml / min), until the selection of individual components of the drug does not show that the necessary doses are present in this dosage form. In some patients with hypertension, without any signs of kidney disease in the history of enalapril in combination with a diuretic, an insignificant and transient increase in the urea concentration in blood serum and serum creatinine is possible, in such cases, treatment with Enalapril H should be discontinued.In some patients with bilateral stenosis of the renal arteries and stenosis of the artery of a single kidney in the treatment of ACE inhibitors, there was an increase in the concentration of urea in blood serum and serum creatinine, these changes were reversible, as a rule, the rates returned to normal after discontinuation of therapy.

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

The effect of Enalapril NL on the ability to drive vehicles and control mechanisms has not been specifically studied, therefore, during the treatment with Enalapril NL, caution should be exercised when driving vehicles and engaging in potentially dangerous activities requiring increased concentration and speed of psychomotor reactions (risk of dizziness ).

Form release / dosage:

Tablets 12.5 mg + 10 mg.

Packaging:For 10, 20 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered. By 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 tablets in cans of polymeric for medicines. One jar or 1, 2, 3,4, 5, 6, 8 or 10 contour mesh packages together with the instruction for use are placed in a pack ofcardboard.

Storage conditions:Store in a dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001994

Date of registration:08.02.2013

Date of cancellation:2018-02-08

The owner of the registration certificate:OZONE, LLC OZONE, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp11.01.2016

Illustrated instructions

Instructions

Enalapril NL (Enalapril-HL)