Renitek - instructions for use, doses, side effects, contraindications

auxiliary substances: sodium bicarbonate 10.0 mg (2.8 mg), lactose monohydrate 153.9 mg, corn starch 22.0 mg (20.0 mg), pregelatinized starch 2.2 mg (2.0 mg), magnesium stearate 1.1 mg, iron oxide red E172 0.05 mg, iron oxide yellow E172 0.13 mg.

Note:

1. The mass norm is given in parentheses - this is the mass after loss due to processing, for example, loss of water during drying and carbon dioxide release.

2. The content of excipients may vary ± 10%.

Description:

Tablets 5 mg: tablets of white color, triangular in shape, engraved on one side "MSD 712 ", on the other side - risk.

Tablets 10 mg: tablets pink color with patches, triangular shape, on one side engraved "MSD 713 ", on the other side - risk.

Tablets of 20 mg: tablets of light pink with a yellowish shade of color with impregnations, triangular in shape, engraved on one side "MSD714", on the other side - risk.

Pharmacotherapeutic group:Angiotensin-converting enzyme (ACE) inhibitor

ATX: & nbsp

C.09.A.A.02 Enalapril

Pharmacodynamics:

The preparation Renitek® (enalapril) refers to drugs that affect the renin-angiotensin-aldosterone system (RAAS) - ACE inhibitors. A drug Renitek® is used to treat essential hypertension (primary arterial hypertension (AH)) any degree of severity and Renovascular hypertension both in monotherapy and in combination with other antihypertensive agents, in particular with diuretics. Also, the drug Renitek® is used to treat or prevent the development of heart failure (HF).

A drug Renitek® (enalapril) is a derivative of two amino acids, L-alanine and L-prolin. After oral administration enalapril rapidly absorbed and hydrolyzed in enalaprilate, which is highly specific and long-term an ACE inhibitor, not containing a sulfhydryl group.

ACE (peptidyl-dipeptidase A) catalyzes the conversion of angiotensin I to pressor peptide angiotensin II. After suction enalapril hydrolyzed to enalaprilat, which inhibits ACE. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which leads to an increase in renin plasma activity (due to the elimination of negative feedback in response to the release of renin) and a decrease in aldosterone secretion.

The ACE is identical to the kinase II enzyme, so enalapril can also block the destruction of bradykinin-a peptide, which has a pronounced vasodilating effect. The significance of this effect in the therapeutic effect of enalapril needs clarification.

Despite the fact that the main mechanism by which enalapril lowers blood pressure (BP), suppression is considered activity RAAS, which plays an important role in the regulation of blood pressure, enalapril has an antihypertensive effect even in patients with hypertension and with a reduced activity renin blood plasma.

The use of enalapril in patients with hypertension leads to a decrease in blood pressure both in the "standing" and "lying" positions without a significant increase in the heart rate (heart rate).

Symptomatic postural hypotension develops infrequently. In some patients, achieving an optimal BP reduction may require several weeks of therapy. Interruption of enalapril therapy does not cause a sharp rise in blood pressure.

Effective inhibition of ACE activity usually develops 2-4 hours after a single dose of enalapril inside. Antihypertensive action develops within 1 h, the maximum decrease in blood pressure is observed 4-6 hours after taking the drug. The duration of action depends on the dose. However, when the recommended doses are used, the antihypertensive effect and hemodynamic effects persist for 24 hours.

Hypotensive therapy with enalapril leads to a significant regression of left ventricular hypertrophy and preservation of its systolic function.

In clinical studies of hemodynamics in patients with essential hypertension, a decrease in blood pressure was accompanied by a decrease in total peripheral vascular resistance, an increase in cardiac output and no changes or slight changes in heart rate. After receiving enalapril, there was an increase in renal blood flow.At the same time, the glomerular filtration rate (GFR) did not change, there were no signs of sodium retention or liquid. However, in patients with initially reduced glomerular filtration, its rate is usually increased.

Long-term use of enalapril in patients with essential hypertension and renal insufficiency can lead to an improvement in renal function, as evidenced by an increase GFR.

In short clinical studies in patients with renal insufficiency and with diabetes mellitus or without decreased albuminuria, excretion by the kidneys IgG. as well as a decrease in the total protein in the urine after enalapril intake.

With the simultaneous use of enalapril and thiazide diuretics, a more pronounced antihypertensive effect is observed. Enalapril reduces or prevents the development of hypokalemia caused by the administration of thiazides.

Therapy with enalapril is usually not associated with an undesirable effect on the concentration of uric acid in the blood plasma.

Therapy with enalapril is accompanied by a favorable effect on the ratio of lipoprotein fractions in blood plasma and the absence of influence or favorable effect on the concentration of total cholesterol.

In patients with heart failure on the background of therapy with cardiac glycosides and diuretics, the use of enalapril caused a decrease in the total peripheral resistance and blood pressure. Cardiac output increased, while heart rate (usually elevated in patients with heart failure) decreased. The wedging pressure in the pulmonary capillaries also decreased. Tolerance to physical activity and severity of heart failure, assessed by the criteria of the New York Heart Association (NYHA), improved. These effects were observed at long-term therapy.

In patients with mild to moderate severity CH enalapril slowed the progression of cardiac dilatation and heart failure, which was confirmed by a decrease in end-diastolic and systolic volumes of the left ventricle and an improvement in the ejection fraction the left ventricle.

Clinical evidence has shown that enalapril reduces the incidence of ventricular arrhythmias in patients with CH, although the main mechanisms and the clinical significance of this effect are not known.

Pharmacokinetics:

Suction

After oral administration enalapril quickly absorbed in the gastrointestinal tract. The maximum concentration of enalapril in the blood serum is achieved within 1 hour after ingestion. The degree of absorption of enalapril when ingested is approximately 60%. Eating does not affect the absorption of enalapril.

After suction enalapril rapidly hydrolyzed to form an active metabolite enalaprilat-a powerful ACE inhibitor. The maximum concentration of enalaprilate in serum is observed about 4 hours after taking enalapril dose inside. The duration of absorption and hydrolysis of enalapril is similar for different recommended therapeutic doses. In healthy volunteers with normal renal function, the equilibrium concentration of enalaprilate in serum is reached by day 4 the start of enalapril.

Distribution

In the range of therapeutic doses, the binding of enalaprilat to plasma proteins does not exceed 60%.

Metabolism

There are no data on other significant ways of metabolism of enalapril, other than hydrolysis to enalaprilate.

Excretion

Enalapril is excreted mainly through the kidneys. The main metabolites, determined in urine, are enalaprilate, which is approximately 40% of the dose, and unchanged enalapril (approximately 20%).

The enalaprilate plasma concentration curve has a long final phase, apparently due to its binding to the ACE.The half-life of enalaprilat with the oral administration of the drug is 11 hours.

Pharmacokinetics in specific patient groups Patients from impaired renal function

Area under the curve "concentration-time" (AUC) Enalapril and enalaprilat increases in patients with renal insufficiency. In patients with mild and moderate severity of renal failure (creatinine clearance 40 to 60 ml / min) after enalapril administration at a dose of 5 mg once a day, the equilibrium value AUC Enalaprilat was approximately 2 times higher than in patients with unchanged renal function. In patients with severe renal failure (CC not more than 30 ml / min), the value AUC increased approximately 8-fold. The effective half-life of enalaprilate half-life after repeated use of enalapril in patients with severe renal insufficiency increased, and the onset of the equilibrium state of enalaprilate concentration was delayed (see section "Dosing and Administration"). Enalaprilat can be removed from the total blood flow by means of a hemodialysis procedure. The clearance for hemodialysis is 62 ml / min.

Lactation

After a single application of enalapril in a dose of 20 mg in patients in the puerperium, the average maximum enalapril concentration in breast milk was 1.7 μg / l (from 0.54 to 5.9 μg / l) 4-6 hours after ingestion. The mean maximum enalaprilate concentration was 1.7 μg / L (1.2 to 2.3 μg / L) and was observed at different times within 24 hours after administration. Given the data on the maximum concentrations in breast milk, the estimated maximum intake of enalapril the child who is fully breastfed is 0.16% of the dose, calculated taking into account the mother's body weight.

At the woman who accepted enalapril Inside at a dose of 10 mg once a day for 1 I months, the maximum concentrations of enalapril in breast milk were 2 μg / L 4 hours after administration, the maximum concentration of enalaprilate is 0.75 μg / l approximately 9 hours after ingestion. The average concentration in breast milk within 24 hours after ingestion of enalapril was 1.44 μg / l and enalaprilate 0.63 μg / l.

One woman who took enalapril in a dose of 5 mg once, and in two women who took enalapril in a dose of 10 mg once,the concentration of enalaprilate in breast milk was below the detectable level (less than 0.2 μg / l) 4 hours after ingestion. The concentration of enalapril in them was not determined.

Indications:

- Essential hypertension of any severity.

- Renovascular hypertension.

- Heart failure of any severity.

In patients with clinical manifestations of HF, the drug Renitek® also shown for:

- improved patient survival;

- slowing the progression of heart failure;

- decrease in the frequency of hospitalizations for HF.

- Prevention of the development of clinically significant heart failure.

In patients without clinical symptoms of heart failure with left ventricular dysfunction, the drug Renitek® shown for:

- slowing the development of clinical manifestations of heart failure;

- decrease in the frequency of hospitalizations for HF.

- Prevention of coronary ischemia in patients with left ventricular dysfunction.

Preparation Renitek "is shown for:

- decrease the incidence of myocardial infarction;

decrease in the frequency of hospitalizations for unstable angina.

Contraindications:

- Hypersensitivity to any of the components of the drug.

- Angioedema in history, associated with the administration of ACE inhibitors, as well as hereditary or idiopathic angioedema.

- Simultaneous use with aliskiren or aliskiren containing preparations in patients with diabetes mellitus and / or impaired renal function (GFR less than 60 ml / min / 1.73 m2) (cm. section "Interaction with other drugs").

- Age to 18 years (effectiveness and safety not established).

- Pregnancy and the period of breastfeeding.

- Hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Carefully:Bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; condition after kidney transplantation; aortic or mitral stenosis; hypertrophic obstructive cardiomyopathy; cardiac ischemia or cerebrovascular diseases; kidney failure; Renovascular hypertension; oppression of bone marrow hematopoiesis; systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, etc.), immunosuppressive therapy,treatment with allopurinol or procainamide, or a combination of these complicating factors; liver failure; diabetes; hyperkalemia; when used simultaneously with potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for table salt and lithium preparations; when performing the procedure of apheresis of low-density lipoproteins (LDL-apheresis) using dextran sulfate; aggravated allergic anamnesis or angioedema in history; condition, accompanied by a decrease in the volume of circulating blood (including with diuretic therapy, adherence to diet with restriction of table salt, dialysis, diarrhea or vomiting); during desensitization with the allergen from the Hymenoptera venom; in patients on dialysis using high-flux membranes (such as AN 69 ); in patients after major surgical interventions or in general anesthesia; in patients of the Negroid race.

Pregnancy and lactation:

Application of the drug Renitek® during pregnancy is not recommended. When diagnosing a pregnancy, the drug Renitek⁸ should be immediately discontinued, unless the drug is considered vital to the mother.

In the published the results a retrospective epidemiological study of newborns whose mothers took ACE inhibitors during the first trimester of pregnancy, noted an increased risk of developing serious congenital malformations compared to newborns whose mothers did not take ACE inhibitors during the first trimester of pregnancy. The number of birth defects was low, and the results of this study were not re-confirmed.

ACE inhibitors can cause disease or death of the fetus or newborn when administered to pregnant women during the second and third trimesters of pregnancy. The use of ACE inhibitors in these periods was accompanied by a negative effect on the fetus and the newborn, which manifested itself in the form of arterial hypotension, renal failure, hyperkalemia and / or hypoplasia of the skull bones in a newborn. Preterm birth, intrauterine growth retardation, and non-spreading of the arterial (Botallova) duct were also reported, but it is unclear whether these cases were associated with the action of ACE inhibitors.

Perhaps the development of oligohydramnion is due to a decrease in the function of the kidneys of the fetus. This complication can lead to limb contracture, deformation of the skull bones, including its facial part, fetal lung hypoplasia. When the drug is prescribed Renitek® During pregnancy, the patient should be informed of the potential risk to the fetus.

These undesirable effects on the embryo and fetus do not appear to be the result of the intrauterine effect of ACE inhibitors during the first trimester of pregnancy.

In those rare cases where the use of an ACE inhibitor during pregnancy is considered necessary, periodic ultrasound examinations should be performed to assess the amniotic fluid index. In case of detection during an ultrasound examination of oligohydramnion, it is necessary to stop taking the drug Renitek®, unless the drug is considered vital to the mother. Nevertheless, both the patient and the doctor should know that the oligohydramnion develops with irreversible damage to the fetus.

If ACE inhibitors are used during pregnancy and the development of oligohydramnion is observed,then, depending on the week of pregnancy, a stress test, a stress test, or a biophysical profile of the fetus may be necessary to assess the functional state of the fetus.

Newborns whose mothers took the drug Renitek® during pregnancy, should be carefully examined for the detection of arterial hypotension, oliguria and hyperkalemia. With the development of oliguria, special attention should be paid to the maintenance of blood pressure and renal perfusion. Enalapril penetrates the placental barrier. It can be partially removed from the bloodstream of a newborn with peritoneal dialysis. Theoretically, it can also be removed by means of exchange blood transfusion.

Enalapril and enalaprilate are excreted in the breast milk of the mother in trace amounts. In case of need of application of a preparation during breast-feeding the patient should stop feeding by a breast.

Dosing and Administration:

A drug Renitek® take inside, regardless of food intake.

Essential hypertension

The initial dose is 10-20 mg, depending on the severity of hypertension and is applied 1 time per day. With a mild degree of hypertension, the recommended initial dose is 10 mg once a day.At other degrees of AH the initial dose is 20 mg once a day. The maintenance dose is 1 tablet 20 mg once a day. Dosage is selected individually for each patient, but the maximum dose should not exceed 40 mg per day.

Renovascular hypertension

Because in patients in this group, blood pressure and renal function may be particularly sensitive to ACE inhibition, therapy is initiated with a low initial dose of 5 mg or less. Then the dose is selected in accordance with the needs and condition of the patient. Usually an effective dose of 20 mg of the drug Renitek® 1 time per day with daily intake. Care should be taken when using the drug Renitek® in patients who had recently taken diuretics (see p. below Concomitant treatment of AH diuretics).

Concomitant treatment AG diuretics

After the first dose Renitek® symptomatic arterial hypotension may develop. This effect is most likely in patients who take diuretics. The drug should be used with caution, as these patients may have a disturbance of the water-electrolyte balance.Admission diuretikov should be stopped 2-3 days before the start of therapy with the drug Renitek®. If this is not possible, then the initial dose of the drug Renitek® should be reduced (up to 5 mg or less) to determine the primary effect of the drug on blood pressure. Further, the dosage should be selected taking into account the needs and conditions of the patient.

Dosage for renal failure

The interval between doses of the drug should be increased Renitek® and / or reduced dose.

Creatinine clearance, ml / min	Initial dose, mg / day
<80> 30 ml / min	5-10 mg
<or = 30> 10 ml / min	2.5 mg
<or = 10 ml / min	2.5 mg on dialysis days **

^*See the sections "With caution", "Special instructions".

^*^*Enalapril undergoes dialysis. Correction of the dose on days when dialysis is not performed, should be carried out depending on the level of blood pressure.

Cardiac insufficiency / asymptomatic dysfunction of the left ventricle

Initial dose of the drug Renitek® in patients with clinically severe heart failure or with asymptomatic left ventricular dysfunction is 2.5 mg. In this case, the drug should be administered under close medical supervision to determine the primary effect of the drug on blood pressure. A drug Renitek® can be used to treat HF with severe clinical manifestations, usually together with diuretics and, when necessary, with cardiac glycosides. In the absence of symptomatic arterial hypotension (resulting from the treatment with the drug Renitek®) or after its correction the dose of the drug should be gradually increased to the usual maintenance dose of 20 mg, which is applied either singly or divided into 2 doses depending on the patient's tolerance of the drug. The dose can be selected within 2-4 weeks or in shorter periods if there are residual signs and symptoms of heart failure. This therapeutic regimen effectively reduces the mortality rates of patients with clinically significant heart failure.

Both before and after initiation of drug treatment Renitek® should regular control of blood pressure and kidney function (see. section "Special instructions"), as it was reported about the development as a result of taking the drug of arterial hypotension with the subsequent (more rarely) occurrence of acute renal failure. In patients taking diuretics, the dose of diuretics should be reduced as far as possible before starting treatment with the drug Renitek®. Development of arterial hypotension after taking the first dose of the drug Renitek® does not mean that arterial hypotension will re-develop with long-term treatment, and does not indicate the need to stop taking the drug. When treating the drug Renitek® should also monitor the potassium content in the blood serum (see section "Interaction with other drugs").

Side effects:

In general, the drug Renitek® well tolerated. In clinical studies, the total frequency undesirable phenomena when using the drug Renitek® did not exceed the same when taking placebo. In most cases undesirable phenomena were mild, transient and did not require the abolition of therapy. When using the drug Renitek® the following undesirable phenomena (very frequent:> or = 10%, frequent:> or = 1% and <10%, infrequent:> or = 0.1% and <1%, rare:> or = 0.01% and <0 , 1%, very rare: <0.01%, the frequency is unknown: it is impossible to estimate the frequency based on available data):

Violations of the blood and lymphatic system

Infrequent: Anemia (including aplastic and hemolytic).

Rare: neutropenia, a decrease in hemoglobin, a decrease in hematocrit, thrombocytopenia, agranulocytosis, suppression of bone marrow function, pancytopenia, lymphadenopathy, autoimmune diseases.

Disorders from the endocrine system

Frequency not set: syndrome of inadequate secretion of antidiuretic hormone. Disorders from the metabolism and nutrition Infrequent: hypoglycemia (see section "Special instructions").

Violations from the nervous system and mental disorders

Frequent: headache, depression.

Infrequent: confusion, drowsiness, insomnia, increased nervousness, paresthesia, systemic dizziness.

Rare: unusual dreams, sleep disturbances.

Disturbances on the part of the organ of sight Very Frequent: blurred vision.

Violations from the heart and blood vessels Very Frequent: dizziness.

Frequent: marked decrease in blood pressure, fainting, chest pain, rhythm disturbance, angina pectoris, tachycardia.

Infrequent: Orthostatic hypotension, palpitations, myocardial infarction, or stroke *, possibly secondary to severe arterial hypotension in patients at high risk (see section "Special instructions").

Rare: Raynaud's syndrome.

Disturbances from the respiratory system, chest and mediastinal organs

Very Frequent: cough.

Frequent: dyspnea.

Infrequent: rhinorrhea, sore throat, hoarseness of the voice, bronchospasm / bronchial asthma. Rare: pulmonary infiltrates, rhinitis, allergic alveolitis / eosinophilic

pneumonia.

Disorders from the digestive system

Very Frequent: nausea.

Frequent: diarrhea, abdominal pain, taste disorder.

Infrequent: intestinal obstruction, pancreatitis, vomiting, indigestion, constipation, anorexia, stomach irritation, dryness of the oral mucosa, stomach and duodenal ulcer.

Rare: stomatitis / aphthous ulcers, glossitis.

Very rare: intestinal edema.

Disturbances from the liver and bile ducts

Rare: hepatic insufficiency, hepatitis (hepatocellular or cholestatic), hepatitis (including necrosis), cholestasis (including jaundice).

Disturbances from the skin and subcutaneous tissues

Frequent: skin rash, hypersensitivity reactions / angioedema:

angioedema, swelling of the face, extremities, lips, tongue, vocal cords and / or larynx (see section "Special instructions").

Infrequent: increased sweating, itching, hives, alopecia.

Rare: erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma.

The development of the symptom complex, which may include all or some of the following symptoms, has been reported: fever, serositis, vasculitis, myalgia / myositis, arthralgia / arthritis, positive antinuclear antibody test, increase sedimentation rate of erythrocytes (ESR), eosinophilia and leukocytosis. Skin rashes, photosensitivity and other skin reactions may also occur.

Disorders from the kidneys and urinary tract

Infrequent: impaired renal function, renal failure, proteinuria.

Rare: oliguria.

Violations of the genitals and mammary gland

Infrequent: erectile disfunction.

Rare: gynecomastia.

General disorders Very Frequent: asthenia.

Frequent: increased fatigue.

Infrequent: muscle cramps, "tides" of blood to the skin of the face, tinnitus, a sense of discomfort, fever.

Laboratory and instrumental data

Frequent: hyperkalaemia, increased serum creatinine concentration.

Infrequent: increased urea concentration in the blood, hyponatremia.

Rare: an increase in the activity of "hepatic" transaminases, an increase in serum bilirubin concentration.

* The incidence was comparable to the frequency observed in clinical trials with placebo or another comparator.

Listed below undesirable phenomena were revealed during post-registration observation, but the causal relationship with the drug intake Renitek® not established: urinary tract infection, upper respiratory tract infection, bronchitis, cardiac arrest, atrial fibrillation, herpes zoster, melena, ataxia, pulmonary artery thromboembolism and pulmonary infarction, hemolytic anemia, including hemolysis cases in patients with deficiency of glucose-6-phosphate dehydrogenase .

Overdose:

Information on overdose is limited. The most characteristic symptoms of an overdose are a marked decrease in blood pressure, beginning approximately 6 hours after taking the drug concomitantly with RAAS blockade, and stupor. Concentrations of enalaprilate in serum, exceeding in 100 and 200 times the concentrations observed with the use of therapeutic doses, appeared after intake of 300 and 440 mg of enalapril, respectively.

Recommended overdose treatment: intravenous infusion of 0.9% sodium chloride solution.If the drug was taken recently, provocation of vomiting. Enalaprilat can be removed from the systemic circulation by hemodialysis (see Fig. section "Special instructions, Patients on hemodialysis ").

Interaction:

Other antihypertensives

Additive effect can be observed with simultaneous application of the drug Renitek® and other antihypertensive therapy.

When using the drug Renitek® simultaneously with other antihypertensive agents, especially with diuretics, an increase in the antihypertensive effect may be observed.

Simultaneous use of the drug Renitek® with beta-adrenoblockers, methyldopa or blockers of "slow" calcium channels increased the severity of the antihypertensive effect.

Simultaneous use of the drug Renitek® from alpha-, beta-blockers and ganglion blockers should be carried out under careful medical control. Simultaneous use of the drug Renitek® with nitroglycerin, other nitro drugs or other vasodilators increases the antihypertensive effect. Potassium of blood serum

In clinical studies, the serum potassium content was usually within normal limits. In patients with hypertension taking the drug Renitek® in monotherapy for more than 48 weeks, there was an increase in serum potassium average on 0.2 mmol / l.

With the simultaneous use of the drug Renitek® with diuretics causing loss of potassium ions (thiazides or "loop" diuretics), The hypokalemia caused by the action of diuretics is usually weakened by the effect of enalapril. Risk factors for the development of hyperkalemia are renal failure, diabetes mellitus, concomitant use of potassium-sparing diuretics (eg, spironolactone, eplerenone, triamterene or amiloride), as well as potassium-containing supplements and salts. The use of potassium supplements, potassium-sparing diuretics or potassium-containing salts, especially in patients with impaired renal function, can lead to a significant increase in potassium in the serum. If you need to simultaneously use the potassium-containing or potassium-raising drugs listed above, you should be careful and regularly monitor the potassium content in the blood serum.

Hypoglycemic agents

Epidemiological studies have shown,that simultaneous use of ACE inhibitors and hypoglycemic agents (insulin, hypoglycemic agents for oral administration) can enhance the hypoglycemic effect of the latter with the risk of developing hypoglycemia. This phenomenon, as a rule, was most often observed during the first weeks of combined therapy, as well as in patients with impaired renal function. In patients with diabetes mellitus taking hypoglycemic agents for ingestion or insulin, the blood glucose concentration should be monitored regularly, especially during the first month of simultaneous use with ACE inhibitors.

Lithium preparations

Like other drugs that affect the excretion of sodium, ACE inhibitors can reduce the excretion of lithium by the kidneys, so when using lithium drugs and ACE inhibitors simultaneously, regularly monitor the concentration of lithium in the blood serum.

Tricyclic antidepressants / antipsychotics / general anesthetics / narcotics

The simultaneous use of certain anesthetic drugs, tricyclic antidepressants and neuroleptics with ACE inhibitors may lead to a further reduction in blood pressure (see section "Special instructions").

Ethanol

Ethanol enhances the antihypertensive effect of ACE inhibitors.

Acetylsalicylic acid, thrombolytics and beta-blockers

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

Sympathomimetics

Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors. Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs, including selective inhibitors of cyclooxygenase-2 (COX-2), can reduce the effect of diuretics and other antihypertensive agents. As a result, the antihypertensive effect of angiotensin II receptor antagonists (APA II) or ACE inhibitors can be weakened when used simultaneously with NSAIDs, including selective COX-2 inhibitors.

In some patients with impaired renal function (eg, in elderly patients or patients with dehydration, including those taking diuretics) receiving NSAID therapy, including selective COX-2 inhibitors, concomitant use of ARA II or ACE inhibitors may cause further impairment of function kidney, including the development of acute renal failure.These effects are usually reversible, so the simultaneous use of these medicines should be carried out with caution in patients with impaired renal function.

Double blockade of the renin-angiotensin-aldosterone system

Double blockade of RAAS with the use of ARA II, ACE inhibitors or aliskiren (renin inhibitor) is associated with an increased risk of arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy. Requires regular monitoring of blood pressure, renal function and blood electrolytes in patients taking the drug at the same time Renitek® and other drugs that affect RAAS. A drug Renitek® It should not be applied simultaneously with aliskiren or aliskirensoderzhaschimi drugs in patients with diabetes mellitus and / or impaired renal function (GFR of less than 60 ml / min / 1.73 m2).

Preparations of gold

Symptom (nitratopodobnye reaction) comprising the "rush" of blood to the skin, nausea, vomiting, and hypotension was observed in rare cases while applying gold preparations for parenteral administration (sodium aurotomy malate) and ACE inhibitors. including enalapril.

Other medicines

There was no clinically significant pharmacokinetic drug interaction between the drug Renitek® and the following drugs: hydrochlorothiazide, furosemide, digoxin, timolol, methyldopa, warfarin, indomethacin, sulindac and cimetidine. With the simultaneous use of the drug Renitek® and propranolol reduced enalaprilat concentration in serum, but this effect is not clinically significant.

Special instructions:

Symptomatic arterial hypotension

Symptomatic arterial hypotension is rarely observed in patients with uncomplicated hypertension. In patients with hypertension taking the drug Renitek®, arterial hypotension develops more often on the background of dehydration, resulting, for example, as a result of diuretic therapy, consumption restriction cookery salts, in patients on dialysis, and in patients with diarrhea or vomiting. sections "Side effect"; "Interaction with other drugs"). Symptomatic arterial hypotension was also observed in patients with HF with or without renal failure.Arterial hypotension develops more often in patients with a more severe degree of HF with hyponatremia or impaired renal function, which have higher doses of "loop" diuretics. In these patients, drug treatment Renitek® should be started under medical supervision, which should be particularly careful when changing the dose of the drug Renitek® and / or diuretic. Similarly, patients with ischemic heart disease or cerebrovascular disease should be monitored, in whom excessive BP reduction can lead to myocardial infarction or stroke.

With the development of arterial hypotension, the patient should be laid and, if necessary, to enter a 0.9% solution of sodium chloride. Transient arterial hypotension when taking the drug Renitek® is not a contraindication to further application and an increase in the dose of the drug, which can be continued after replenishing the volume of fluid and normalizing blood pressure.

In some patients with HF and with normal or reduced BP, the drug Renitek® may cause an additional decrease in blood pressure.This reaction to taking the drug is expected and is not a basis for discontinuing treatment. In those cases where arterial hypotension assumes a stable character, the dose should be reduced and / or discontinued with a diuretic and / or drug Renitek®.

Aortic or mitral stenosis / hypertrophic obstructive cardiomyopathy

Like all medicines, which have a vasodilating effect, ACE inhibitors should be administered with caution to patients with obstruction of the outflow path from the left ventricle.

Impaired renal function

In some patients, arterial hypotension, which develops after the initiation of treatment with ACE inhibitors, can lead to further impaired renal function. In some cases, the development of acute renal failure, usually reversible, has been reported.

Patients with renal insufficiency may need to reduce the dose and / or frequency of taking the drug (see p. See section "Dosing and Administration"). In some patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, there was an increase in the concentration of urea in the blood and creatinine in the serum.The changes were usually reversible, and the indicators returned to their initial values after the cessation of treatment. This pattern of changes is most likely in patients with renal insufficiency.

In some patients who did not show any kidney disease before treatment, the drug Renitek® in combination with diuretics caused a usually minor and transient increase in the concentration of urea in the blood and creatinine in the blood serum. In such cases, a dose reduction and / or cancellation of the diuretic and / or Renitek® may be required.

Kidney Transplantation

There is no experience of use in patients after kidney transplantation, so treatment with the drug Renitek® It is not recommended in patients after kidney transplantation. Liver failure

The use of ACE inhibitors has rarely been associated with the development of a syndrome that begins with cholestatic jaundice or hepatitis and progresses to fulminant liver necrosis, sometimes with a fatal outcome. The mechanism of this syndrome has not been studied. When jaundice or a significant increase in the activity of "liver" transaminases against the background of the use of ACE inhibitors should be canceled taking the drugand appoint appropriate supportive therapy, the patient should be under appropriate supervision.

Neutropenia / agranulocytosis

Neutropenia / agranulocytosis, thrombocytopenia and anemia have been observed in patients taking ACE inhibitors. Neutropenia occurs rarely in patients with normal renal function and without other complicating factors. Enalapril should be used with extreme caution in patients with systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, etc.) taking immunosuppressive therapy, allopurinol or procainamide, or a combination of these complicating factors, especially if there are already existing impairments of kidney function. Some of these patients developed serious infectious diseases, which in some cases did not respond to intensive antibiotic therapy. If such patients are used enalaprilit is recommended that the number of white blood cells be regularly monitored and lymphocytes in the blood and patients should be warned about the need to report any signs of an infectious disease.

Hypersensitivity reactions / angioedema

With the use of ACE inhibitors, including the drug Renitek®, rare cases of angioneurotic edema of the face, limbs, lips, tongue, vocal folds and / or larynx that occurred during different periods of treatment were observed. In very rare cases, the development of intestinal edema was reported. In such cases, stop taking the drug immediately Renitek® and carefully monitor the patient's condition in order to monitor and correct clinical symptoms. Even in cases where there is only swelling of the tongue without the development of respiratory distress syndrome, patients may need long-term follow-up, since therapy with antihistamines and corticosteroids may not be sufficient.

Very rarely reported a lethal outcome due to angioedema, associated with laryngeal edema or edema of the tongue. Edema of the tongue, vocal wrinkles or larynx can lead to airway obstruction, especially in patients undergoing surgical procedures on respiratory organs. In cases where edema is localized in the area of the tongue, vocal cords or larynx and can cause airway obstruction,immediate treatment should be prescribed, which may include subcutaneous administration of 0.1% epinephrine (epinephrine) solution (0.3-0.5 ml) and / or provide airway patency.

In patients of the Negroid race, taking ACE inhibitors. angioedema was observed more often than in patients of other races.

Patients who have a history of angioedema, not associated with the administration of ACE inhibitors, may be more at risk of developing angioedema due to therapy with ACE inhibitors (see. section "Contraindications").

Anaphylactoid reactions during desensitization with an allergen from Hymenoptera venom

In rare cases, patients with ACE inhibitors developed life-threatening anaphylactoid reactions during desensitization with an allergen from Hymenoptera venom. Unwanted reactions can be avoided if prior to the initiation of desensitization temporarily stop taking an ACE inhibitor.

Anaphylactoid reactions during LDL-apheresis

In patients taking ACE inhibitors during LDL-apheresis using dextran sulfate, there were rarely observed life-threatening anaphylactoid reactions. The development of these reactions can be avoided if the ACE inhibitor is temporarily discontinued before the beginning of each LDL-apheresis procedure.

Patients on hemodialysis

Anaphylactoid reactions were observed in patients on dialysis using high-flux membranes (such as AN 69 ") and at the same time receiving therapy with ACE inhibitors.In these patients it is necessary to use dialysis membranes of another type or antihypertensive drugs of other classes.

Cough

There were cases of coughing on the background of therapy with ACE inhibitors. As a rule, cough is unproductive, permanent and stops after the abolition of therapy. Cough associated with the use of ACE inhibitors. should be taken into account in the differential diagnosis of cough.

Surgical interventions / general anesthesia

During major surgical interventions or general anesthesia with the use of agents that cause antihypertensive Effect, enalaprilate blocks the formation of angiotensin II, caused by compensatory release of renin.If this results in a pronounced decrease in blood pressure, explained by such a mechanism, it can be corrected by increasing the volume of circulating blood.

Hyperkalemia (cm. section "Interaction with other drugs") The risk of hyperkalemia is observed in renal failure, diabetes, as well as with the simultaneous use of potassium-sparing diuretics (eg spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium salts.

The use of potassium supplements, potassium-sparing diuretics or potassium-containing salts, especially in patients with impaired renal function, can lead to a significant increase in potassium in the serum. Hyperkalemia can lead to serious, sometimes fatal, arrhythmias.

If it is necessary to simultaneously apply the drug Renitek® and the medicines listed above, caution should be exercised and the serum levels of potassium regularly monitored.

Hypoglycaemia

Patients with diabetes mellitus taking hypoglycemic agents for ingestion or insulin,before starting the use of ACE inhibitors should be informed of the need regular control of glucose concentration at blood (hypoglycemia), especially during the first month of simultaneous application of the data medicines (cm. section "Interaction with other drugs").

Lithium preparations

It is not recommended simultaneous use of drugs of lithium and enalapril (see the section "Interaction with other drugs").

Double blockade renin-angiotensin-aldosterone system

The development of arterial hypotension, fainting, stroke, hyperkalemia, and renal dysfunction (including acute renal failure) in susceptible patients has been reported, especially if combined therapy with drugs affecting the RAAS is used (see "Interactions with Other Drugs"). . It is not recommended to perform a double blockade of RAAS by the combined use of ACE inhibitors with ARA II or aliskiren. Contraindicated simultaneous use of the drug Renitek '¹ with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and / or with impaired renal function (GFR less than 60ml / min / 1.73 m²) (see the section "Contraindications").

Application in elderly patients

Clinical studies of the efficacy and safety of enalapril were similar in elderly and younger patients with AG.

Race

As with other ACE inhibitors, enalapril, apparently, less effectively reduces blood pressure in patients of the Negroid race than in patients of other races, which may be explained by the higher prevalence of conditions with low renin activity of blood plasma in the population of patients of negroid race with hypertension.

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

Effect of the drug Renitek® on the ability to drive vehicles and work with mechanisms have not been studied. However, some undesirable phenomena (for example, dizziness), which were observed when taking the drug Renitek®, can affect the ability to drive vehicles and work with mechanisms (see. section "Side effect").

Form release / dosage:

Tablets 5 mg, 10 mg or 20 mg

Packaging:

Tablets 5 mg, 10 mg or 20 mg: 7 tablets per aluminum blister. For 1, 2 or 4 blisters together with instructions for use in a cardboard box.

Tablets 10 mg or 20 mg: 100 tablets per bottle of dark glass. For the first bottle, along with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years and 6 months.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N014039 / 01

Date of registration:15.04.2008

The owner of the registration certificate:Merck Sharp and Doum B.V.Merck Sharp and Doum B.V. Netherlands

Manufacturer: & nbsp

MERCK SHARP & DOHME, Ltd. United Kingdom

Representation: & nbspMSD Pharmaceuticals Ltd.MSD Pharmaceuticals Ltd.

Information update date: & nbsp21.10.2015

Illustrated instructions

Instructions

Renitek® (Renitec®)