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

Excipients:
lactose monohydrate	- 24.5 mg	- 18.5 mg	- 25 mg
potato starch	- 10 mg	- 10 mg	- 10 mg
microcrystalline cellulose	- 35 mg	- 31 mg	42 mg
povidone	- 2 mg	- 2 mg	- 2 mg
sodium hydrogen carbonate	- 2 mg	- 2 mg	- 2 mg
carboxymethyl starch sodium starch glycolate)	(sodium 2 mg	- 2 mg	- 2 mg
talc	- 1 mg	- 1 mg	- 1 mg
magnesium stearate	- 1 mg	- 1 mg	- 1 mg

Description:

Dosage of 12.5 mg + 10 mg: tablets of oblong form with rounded ends, biconvex, with a risk on one side of the tablet, white or almost white.

Dosage 12.5 mg + 20 mg: tablets are round, biconvex, white or almost white.

Dosage of 25 mg + 10 mg: tablets are round, biconvex, white or almost white.

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

ATX: & nbsp

C.09.A.A.02 Enalapril

Pharmacodynamics:

Combined drug, the effect of which is due to the properties of the components that make up its composition. Has antihypertensive effect.

Enalapril - an ACE inhibitor that promotes the conversion of angiotensin I into angiotensin II, reduces the concentration of aldosterone in the blood, increases the release of renin by juxtaglomerular cells in the walls of arterioles of the kidney glomeruli,improves the functioning of kallikrein-kinin system, stimulates the release of prostaglandins and endothelial relaxing factor, depresses the sympathetic nervous system. Together, these effects eliminate spasm and dilate the peripheral arteries, reduce the overall peripheral resistance blood vessels, systolic blood pressure and diastolic blood pressure / post- and preload of the myocardium. Expands arteries more than veins, with a reflex increase in frequency no cardiac contractions are noted.

The antihypertensive effect is more pronounced with a high concentration of renin in the blood plasma than with normal or decreased. Reducing blood pressure within therapeutic limits does not affect cerebral circulation. Improves the blood supply of the ischemic myocardium. Strengthens the renal blood flow, while the glomerular filtration rate does not change. In patients with initially reduced glomerular filtration, its rate usually increases. The maximum effect of enalapril develops in 6-8 hours and persists up to 24 hours.

Hydrochlorothiazide is a thiazide diuretic of moderate strength.Reduces the reabsorption of sodium ions (Na +) at the level of the cortical segment of the Henle loop, without affecting its site, passing in the medulla of the kidney. It blocks carbonic anhydrase in the proximal part of convoluted tubules, enhances the excretion of potassium ions (K +), hydrocarbonates and phosphates. Virtually does not affect the acid-base state. Increases the excretion of magnesium ions (Mg2 +). It delays calcium ions (Ca2 +) in the body. Increases excretion of urine ions Na +, SG, water, bicarbonate. Reduction of the Na + content in the vessel wall leads to their dilatation, reduces sensitivity to vasoconstrictor factors. The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, lasts 10-12 hours. The effect decreases with a decrease in the glomerular filtration rate and stops at a value of less than 30 ml / min.

Reduces blood pressure by reducing the volume of circulating blood (BCC), changes in the reactivity of the vascular wall.

Hydrochlorothiazide reduces the level of K + in the blood plasma, enalapril causes its delay; when these medicines are used together normal maintenance of the K + content in the blood plasma.

The use of a combination of enalapril and hydrochlorothiazide results in a more pronounced decrease in arterial pressure compared to monotherapy with each of the drugs alone and allows the antihypertensive effect of the drug to be maintained for at least 24 hours.

Pharmacokinetics:

Enalapril. After-ingestion absorption-60%. Food intake, does not affect suctioniesAni. In the liver is metabolized with the formation of an active metabolite Enalaprilat, which is a more effective ACE inhibitor than enalapril.

Binding to blood plasma proteins enalaprilata - 50-60%. Time to reach the maximum concentration in the blood plasma (TCam) enalapril-1 h, enalaprilat- 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 of Enalaprilat (T1 / 2) 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).It is removed during hemodialysis (speed 38-62 ml / min) and the peritoneal dialysis serum concentrations of enalaprilate after 4 hour hemodialysis reduced by 45-57%. In patients with reduced renal function iniesThe diet slows down, which requires a lower dose in accordance with the degree of impaired renal function, especially in patients with severe renal insufficiency. In patients with hepatic insufficiency, enalapril metabolism is slowed down without changing its pharmacodynamic effect. In patients with chronic heart failure (CHF), absorption and metabolism of enalaprilat slows down, and the steady-state volume of distribution (Vss) also decreases.

Hydrochlorothiazide. It absorbed primarily in the duodenum and proximal small intestine: The absorption is 70% and increases to 10% when taken with food. The maximum concentration in blood plasma (Сmах) is reached in 1,5-5 hours. Vss - about 3 l / kg. Binding to blood plasma proteins is 40%. Bioavailability is 70%. In the therapeutic dose range of the average value of the area under the curve of the concentration of drug in blood plasma of time (AUC) increases in direct proportion to the dose, the application 1 time the cumulation is insignificant. It 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 serum from the umbilical vein (19 times). It is not metabolized in the liver, it is excreted predominantly kidneys: 95% in unchanged form and about 4% in the form of hydrolyzate-2-amino-4-chloro-m-benzene disulfonamide by glomerular filtration and active tubular secretion in the proximal nephron. The renal clearance of hydrochlorothiazide in healthy volunteers and patients with arterial hypertension is approximately 5.58 ml / s (335 ml / min). Hydrochlorothiazide has a two-phase withdrawal profile. T1 / 2 in the initial phase is 2 hours, in the final phase (10-12 hours after administration) - about 10 hours.

In elderly patients hydrochlorothiazide does not adversely affect the pharmacokinetics of enalapril, but the serum concentration of enalaprilate in this case higher. When hydrochlorothiazide was used in patients with CHF, it was found that its absorption decreases in proportion to the development of CHF- 20-70%.T ½ hydrochlorothiazide increased to 28.9 h; renal clearance is 0.17-3.12 ml / s (10-187 ml / min); mean values of -1.28 ml / s (77 ml / min).

In patients undergoing surgery, intestinal bypass surgery for obesity, hydrochlorothiazide absorption can be reduced by 30%, and serum concentration by 50% compared to healthy volunteers. Simultaneous the appointment of enalapril and hydrochlorothiazide does not affect the pharmacokinetics of each of them.

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

Contraindications:

Hypersensitivity (including to individual components of the drug or sulfonamide derivative); anuria, severe disorders, renal function (creatinine clearance <30 mL / min); angioedema in history, associated with the use of other ACE inhibitors and derivatives of sulfonamide, and hereditary or idiopathic angioedema; lactose intolerance, lactase deficiency or glucose-galactose malabsorption; pregnancy; the period of breastfeeding; age to 18 years (effectiveness and safety not established)

Carefully:

With caution use a combination drug under the following conditions: bilateral stenosis of the renal arteries, stenosarches of the single kidney expressed aortic and mitral stenosis or hypertrophic obstructive cardiomyopathy; ischemic heart disease and cerebrovascular diseases (including cerebral circulatory insufficiency), because of the lack of cerebral circulation. excessive reduction in blood pressure can lead to the development of myocardial infarction and stroke; 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; violations of the liver and / or kidneys (creatinine clearance 30-75 ml / min); conditions, accompanied by a decrease in BCC (as a result of diuretic therapy, while limiting consumption of table salt, diarrhea and vomiting); primary hyperaldosteronism; elderly age.

Pregnancy and lactation:

The drug 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 II and III trimesters, pregnancy was accompanied by a negative effect on the fetus and the newborn. In newborns, arterial hypotension developed, renal failure, hyperkalaemia insufficiency and/ or hypoplasia, 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 adults.

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

Dosing and Administration:

Inside, during or after a meal, without chewing, squeezed a small amount of liquid. Initially, adequate doses of individual components should be determined.Dosage should always be selected individually for each patient. The recommended dose is 1 tablet per day. Patients should enter at habit of taking the drug regularly, at the same time, preferably in the morning.

In patients who are on diuretic therapy, it is recommended to cancel treatment or reduce the dose of diuretics at least 3 days before the start of treatment, a drug to prevent the development of symptomatic arterial hypotension.

Before the beginning of treatment, the function of the kidneys should be investigated. The duration of treatment is determined by the doctor.

In case of missed intake of a regular dose of the drug, it must be taken as soon as possible, if a sufficiently large amount remains until the next dose time. If several hours are left before taking the next dose, you should wait and take only this dose. Never double the dose.

Dose with impaired renal function.

In patients with renal failure 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 the combined preparation Enalapril N.

If there is no therapeutic effect, it is recommended to add another medication or change the therapy. The duration of treatment is unlimited

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.

Violations from the blood and lymphatic system: infrequently - anemia (including aplastic and hemolytic); rarely - neutropenia; reduction of hemoglobin and hematocrit, thrombocytopenia, agranulocytosis, oppression of bone marrow function, pancytopenia, leukopenia, lymphadenopathy, autoimmune diseases.

Disorders from the metabolism and nutrition: often-hypercholesterolemia, hypertriglyceridemia; infrequently - hypoglycemia, hypomagnesemia, exacerbation of gout; rarely - hyperglycemia; very rarely - hypercalcemia.

Disorders from the endocrine system: the frequency is unknown - syndrome of impaired secretion of antidiuretic hormone.

Disorders from the central nervous system and mental disorders: often - headache,depression, faint; infrequently - confusion, drowsiness, insomnia, nervousness; paresthesia, dizziness; rarely - sleep disturbances, paresis (due to hypokalemia).

Disorders from the side of the eye: very often - visual impairment; frequency unknown - xantopsy.

Disorders from the cardiovascular system: often - marked reduction in blood pressure (including orthostatic hypotension), chest pain, disorders rhythm, tachycardia, angina pectoris; not often - myocardial infarction or stroke, palpitation: rarely - Raynaud's syndrome; frequency unknown - necrotizing angiitis (vasculitis, cutaneous vasculitis).

Disturbances from the respiratory system: very often - cough; often shortness of breath; infrequently - rhinorrhea, sore throat, hoarseness, bronchospasm; rarely; - pulmonary infiltrates, (rhinitis, allergic alveolitis / eosinophilic pneumonia, Respiratory distress syndrome (including pneumonitis and pulmonary edema).

Disorders from the digestive system: very often - nausea; often - diarrhea, abdominal pain, taste disorders; infrequently - intestinal obstruction, pancreatitis, vomiting; dyspepsia, constipation, anorexia, stomach irritation,dryness of the mucous membrane, oral cavity, peptic ulcer; rarely - stomatitis, aphthous ulcers, glossitis, hepatic insufficiency, hepatitis (hepatocellular, or hemolytic cholestasis, fulminant liver necrosis, very rarely - intestinal angioedema.

Disturbances from the skin and subcutaneous tissue: often - skin rash, angioedema, edema of the face, limbs, lips, tongue, glottis, larynx; infrequently increased sweating, itching, hives, alopecia; rarely: erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic

epidermal necrolysis, pemphigus, erythroderma, lupus-like skin reactions, exacerbation of systemic lupus erythematosus.

Disorders from the musculoskeletal system: often - muscle cramps; infrequently, arthralgia.

Disorders from the urinary system: infrequently - impaired renal function, acute renal failure, proteinuria; rarely oliguria, interstitial nephritis.

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

Other: very often - asthenia; often fatigue; infrequently - muscle cramps, noise in the ears; general malaise, fever;frequency unknown (for hydrochlorothiazide) - fever; weakness.

Laboratory studies: often - hyperkalemia, hypercreatininaemia; infrequently - ghyperuricemia, hyponatremia; rarely - increased activity of "hepatic" transaminases, hyperbilirubinemia.

With the use of ACE inhibitors, a symptom complex including fever, serositis, vasculitis, myalgia, myositis, arthralgia, arthritis, positive antinuclear antibody test, increase, COE, 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 flushing of the facial skin, nausea, vomiting and arterial hypotension.

Overdose:

Symptoms: increased diuresis, marked decrease in blood pressure with bradycardia or other cardiac arrhythmias, convulsions of disturbance of consciousness (including to whom), acute renal failure, violation of 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 carbon are shown, in more serious cases, measures aimed at stabilizing blood pressure and heart rhythm: intravenous administration of plasma substitutes, infusion of 0.9% solution of sodium chloride. The patient must monitor 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:

Arterial hypotension with all clinical consequences can be observed after the first intake of Enalapril H tablets in patients with severe CHF and hyponatremia, expressed by renal failure or left ventricular dysfunction and, in particular, in patients with hypovolemia, as a result of therapy diuretics, salt-free diets, diarrhea, vomiting or hemodialysis.

In case of arterial hypotension, it is necessary to lay the patienta back with a low headboard and, if necessary, adjust the BCC by infusion 0.9% solution of sodium chloride. Arterial hypotension, which occurred after taking the first doses is not a contraindication for further treatment. Required be careful in patients with ischemic heart disease; severe cerebrovascular disease, aortic, stenosis, or idiopathic hypertrophic obstructive subaortic stenosis, preventing the outflow of blood from the left ventricle, pronounced atherosclerosis in elderly patients as a result of the risk of developing arterial hypotension and worsening blood supply to the heart, brain and kidneys. A regular monitoring of the serum concentration of electrolytes during the period treatment to identify possible imbalances and timely take the necessary measures. Determination of the serum concentration of electrolytes is mandatory for patients with prolonged diarrhea, vomiting.

In patients taking. The drug Enalapril H, it is necessary to identify signs of disturbance of the water-electrolyte balance, such as dryness of the oral mucosa, thirst, weakness, drowsiness, increased excitability, myalgia and convulsions (mainly the calf muscles), lowering blood pressure, tachycardia, oliguria and gastrointestinal disorders (nausea, vomiting).

The drug Enalapril H in patients with renal insufficiency (creatinine clearance 30-75 ml / min) should be used only after preliminary titration of doses enalapril and hydrochlorothiazide alone, respectively, in doses in the combined preparation Enalapril N.

The drug Enalapril H should be used with caution in patients with liver failure or progressive liver disease, because hydrochlorothiazide can cause hepatic coma even with minimal disturbances of the water-electrolyte balance. Several cases have been reported, the development of acute hepatic insufficiency with cholestatic jaundice, fulminant liver necrosis and death (rarely) during treatment with ACE inhibitors. If jaundice occurs and the activity of "hepatic" transaminases increases, treatment with Enalapril H should be stopped immediately, patients should to be under observation.

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

Thiazide diuretics can reduce the excretion of calcium by the kidneys and cause a slight and transient increase in serum calcium.

Expressed hypercalcemia may be a sign of latent hyperparathyroidism. Before the study of parathyroid function, thiazide diuretics you must cancel

Against the background of treatment, cholesterol and triglyceride concentrations in the blood serum (the property of thiazide diuretics) can increase.

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

When an angioedema develops in the face, it is usually sufficient to cancel therapy and prescribe antihistamines to the patient.

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

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

Patients with an angioneurotic edema in a history not associated with ACE inhibitors have an increased risk of developing angioedema while taking any ACE inhibitor.

In patients taking thiazide diuretics, hypersensitivity reactions can develop both in the presence of, and in the absence of an anamnesis of allergic reactions. Reported worsening of the course of systemic lupus erythematosus.

Due to the risk of anaphylactic reactions, the drug Enalapril H should not be administered to patients on hemodialysis using

High-flow polyacrylonitrile membranes (AN69®) undergoing low-density lipoprotein (LDL-apheresis) apheresis with dextran sulfate, and immediately before the procedure of desensitization by the allergen from the venom of the hymenoptera (Hymenoptera).

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

During surgical interventions or general anesthesia with agents that cause arterial hypotension, ACE inhibitors can block the formation of angiotensin II in response to compensatory release of renin. If this develops a marked decrease in blood pressure, explained by such mechanism, you can correct by increasing the BCC.

Cough was used in the use of ACE inhibitors. Cough is dry, prolonged, which disappears after discontinuation of ACE inhibitors. With the differential The diagnosis of a cough should also take into account the cough caused by the use of ACE inhibitors.

The drug can cause a positive result when conducting anti-doping tests.

Special instructions:

In patients taking. Preparation Enalapril H, it is necessary to identify signs of disturbance of the water-electrolyte balance,such as dryness of the oral mucosa, thirst, weakness, drowsiness, increased excitability, myalgia and convulsions (mainly the calf muscles), lowering blood pressure, tachycardia, oliguria and gastrointestinal disturbances (nausea, vomiting).

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

Thiazide diuretics can reduce v excretion of calcium by the kidneys and cause a slight and transient increase in serum calcium.

Expressed hypercalcemia may be a sign of latent hyperparathyroidism. Before the study of parathyroid function, thiazide diuretics you must cancel

Against the background of treatment, cholesterol and triglyceride concentrations in the blood serum (the property of thiazide diuretics) can increase.

When an angioedema develops in the face, it is usually sufficient to cancel therapy and prescribe antihistamines to the patient.

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

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

Patients with an angioneurotic edema in a history not associated with ACE inhibitors have an increased risk of developing angioedema while taking any ACE inhibitor.

Due to the risk of anaphylactic reactions, the drug Enalapril H should not be administered to patients on hemodialysis using

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

The drug can cause a positive result when conducting anti-doping tests.

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

At the beginning of treatment with Enalapril H, 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 dangerous activities requiring 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 12.5 mg + 10 mg, 12.5 mg + 20 mg, 25 mg + 10 mg.

Packaging:

For 10, 15, 20, 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 1,2, 3, 4, 5, 6 contour mesh packages together with instructions for use 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 printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001285

Date of registration:25.11.2011

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Information update date: & nbsp22.10.2015

Illustrated instructions

Instructions

Enalapril H (Enalapril H)