Renitek - instructions for use. Renitec is a highly specific long-acting ACE inhibitor.

Tablets yellow color, round, biconvex, with a ribbed edge, engraved "MSD 718" on one side and a line on the other.

Excipients: sodium bicarbonate, aqueous lactose, corn starch, pregelatinized corn starch, yellow iron oxide, magnesium stearate.

7 pcs. - blisters (2) - packs of cardboard.
7 pcs. - blisters (4) - packs of cardboard.
56 pcs. - polyethylene bottles (1) - cardboard packs.

Clinical and pharmacological group

pharmachologic effect

Combined antihypertensive drug, which includes an ACE inhibitor (enalapril maleate) and a thiazide diuretic (hydrochlorothiazide). It has antihypertensive and diuretic effects.

Enalapril is an ACE inhibitor that catalyzes the conversion of angiotensin I to the pressor substance angiotensin II. After absorption, enalapril is converted by hydrolysis into enalaprilat, which inhibits ACE. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in blood plasma, which entails an increase in plasma renin activity (due to the elimination of the reverse negative reaction to changes in renin production) and a decrease in aldosterone secretion.

ACE is identical to the enzyme kininase II, so enalapril can also block the destruction of bradykinin, a vasodilatory peptide. The significance of this mechanism in the therapeutic action of enalapril requires clarification. Despite the fact that enalapril reduces blood pressure by suppressing the renin-angiotensin-aldosterone system, which plays an important role in the regulation of blood pressure, the drug reduces blood pressure even in hypertensive patients with low renin content.

A decrease in blood pressure is accompanied by a decrease in TPVR, a slight increase in cardiac output, and no or slight changes in heart rate. As a result of taking enalapril, renal blood flow increases, the glomerular filtration rate remains unchanged. However, in patients with initially reduced glomerular filtration rate, its rate usually increases.

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

Therapy with enalapril is accompanied by a favorable effect on the ratio of lipoprotein fractions and no effect or a favorable effect on the content of total cholesterol.

The intake of enalapril by patients with arterial hypertension leads to a decrease in blood pressure both in the standing position and in the supine position without a significant increase in heart rate.

Symptomatic postural hypotension is rare. In some patients, achieving optimal blood pressure 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 oral dose of enalapril. The onset of antihypertensive action occurs within 1 hour, maximum reduction Blood pressure is observed 4-6 hours after taking the drug. The duration of action depends on the dose. However, when used at recommended doses, the antihypertensive effect and hemodynamic effects persist for 24 hours.

Hydrochlorothiazide has a diuretic and antihypertensive effect, increases renin activity. Although enalapril itself exhibits an antihypertensive effect even in patients with arterial hypertension against the background of low renin concentration, the concomitant use of hydrochlorothiazide in such patients leads to a more pronounced decrease in blood pressure.

Enalapril reduces the loss of potassium ions caused by the use of hydrochlorothiazide. Enalapril and hydrochlorothiazide have a similar dosing regimen. Therefore, Co-renitec is a convenient dosage form for the co-administration of enalapril and hydrochlorothiazide.

The use of a combination of enalapril and hydrochlorothiazide leads to a more pronounced decrease in blood pressure compared with monotherapy with each drug separately and allows you to maintain the antihypertensive effect of the drug Corenitec for at least 24 hours.

Pharmacokinetics

Enalapril

Suction

After oral administration, enalapril maleate is rapidly absorbed. C max enalapril in serum is observed within 1 hour after administration. After oral administration, absorption is approximately 60%.

Eating does not affect the absorption of enalapril. The duration of absorption and hydrolysis of enalapril is similar for various recommended therapeutic doses.

After absorption, enalapril is rapidly hydrolyzed to form the active substance enalaprilat, a potent ACE inhibitor. Cmax of enalaprilat in serum is observed 3-4 hours after taking a dose of enalapril inside.

breeding

Enalapril is excreted mainly by the kidneys. The main metabolites detected in urine are enalaprilat, accounting for approximately 40% of the dose, and unchanged enalapril. Data about others meaningful ways There is no metabolism of enalapril, with the exception of hydrolysis to enalaprilat. The enalaprilat plasma concentration curve has a long final phase, apparently due to its binding to ACE. In persons with normal renal function, a stable concentration of enalaprilat is reached on the 4th day from the start of enalapril. T 1/2 of enalaprilat with a course of the drug inside is 11 hours.

Hydrochlorothiazide

Metabolism and distribution

Does not undergo metabolism. Hydrochlorothiazide crosses the placental barrier, but does not cross the BBB.

breeding

T 1/2 hydrochlorothiazide from 5.6 to 14.8 hours. Rapidly excreted by the kidneys. At least 61% of an oral dose is excreted unchanged within 24 hours.

Combination of enalaprilat maleate and hydrochlorothiazide

Regular intake of a combination of enalapril and hydrochlorothiazide does not affect or slightly affects the bioavailability of each component of the drug. The use of a combination tablet of Co-renitec is bioequivalent to the simultaneous administration of its ingredients in separate dosage forms.

Indications for the use of the drug

- treatment arterial hypertension in patients for whom combination therapy is indicated.

Dosing regimen

The drug is administered orally, regardless of the meal.

At arterial hypertension initial dose - 1 tab. 1 time / day If necessary, the dose can be increased to 2 tab. 1 time / day

At the beginning of therapy with Corenitec, symptomatic arterial hypotension may develop, more often in patients with impaired water and electrolyte balance due to previous treatment with diuretics. Therapy with diuretics should be discontinued 2-3 days before the start of the use of Co-Renitec.

At CC ≤ 30 ml / min (i.e. with moderate to severe renal failure) are ineffective.

At CC 80-30 ml/min

At mild renal failure

Side effect

In clinical studies, side effects were usually mild, transient and in most cases did not require interruption of treatment.

From the side of cardio-vascular system: 1-2% - orthostatic effects, including arterial hypotension; rarely - fainting, arterial hypotension regardless of body position, palpitations, tachycardia, chest pain.

From the CNS and peripheral nervous system: often - dizziness, increased fatigue (usually passed with a decrease in dose and rarely required discontinuation of the drug); 1-2% - asthenia, headaches; rarely - insomnia, drowsiness, systemic dizziness, paresthesia, irritability.

From the side respiratory system: 1-2% - cough; rarely - shortness of breath.

From the side digestive system: 1-2% - nausea; rarely - pancreatitis, diarrhea, vomiting, dyspepsia, abdominal pain, flatulence, constipation, dry mouth.

From the musculoskeletal system: 1-2% - muscle cramps; rarely - arthralgia.

allergic reactions: rarely - angioedema of the face, limbs, lips, tongue, glottis and / or larynx. There are rare reports of the development of angioedema of the intestine in connection with the use of ACE inhibitors, including enalapril.

Dermatological reactions: rarely - Stevens-Johnson syndrome, hyperhidrosis, skin rash, itching.

From the urinary system: rarely - impaired renal function, renal failure.

From the reproductive system: 1-2% - impotence; rarely - decreased libido.

From the side of laboratory indicators: hyperglycemia, hyperuricemia, hypo- or hyperkalemia, increased blood urea, serum creatinine, increased liver enzymes and / or increased serum bilirubin are possible (these indicators usually returned to normal after discontinuation of Co-renitec therapy); in some cases - a decrease in hemoglobin and hematocrit.

Others: rarely - tinnitus, gout. A symptom complex is described, the possible manifestations of which are fever, serositis, vasculitis, myalgia, myositis, arthralgia/arthritis, a positive test for antinuclear antibodies, accelerated ESR, eosinophilia and leukocytosis; photosensitivity may develop.

Contraindications to the use of the drug

- anuria;

- angioedema in history associated with the appointment of earlier ACE inhibitors, as well as hereditary or idiopathic angioedema;

— hypersensitivity to the components of the drug;

- Hypersensitivity to other sulfonamide derivatives.

FROM caution the drug should be prescribed for aortic stenosis, cerebrovascular diseases (including insufficiency cerebral circulation), IHD, chronic heart failure, severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), bone marrow hematopoiesis suppression, diabetes mellitus, hyperkalemia, bilateral renal artery stenosis, stenosis of the artery of a single kidney, condition after kidney transplantation , renal and / or liver failure, against the background of a sodium-restricted diet, in conditions accompanied by a decrease in BCC (including diarrhea, vomiting), elderly patients.

The use of the drug during pregnancy and lactation

The appointment of ACE inhibitors in the II and III trimesters of pregnancy can cause disease or death of the fetus or newborn. The negative effect of ACE inhibitors on the fetus and newborn is manifested by arterial hypotension, kidney failure, hyperkalemia and/or hypoplasia of the skull. Perhaps the development of oligohydramnios, apparently due to impaired renal function of the fetus. This complication can lead to contracture of the limbs, deformation of the skull, including its frontal part, to pulmonary hypoplasia.

The use of diuretics in women during pregnancy is not recommended, as there is a risk of jaundice in the fetus and newborn, thrombocytopenia, and possibly others. side effects seen in adult patients.

If Co-Renitec is prescribed during pregnancy, the patient should be warned of the potential risk to the fetus. In those rare cases when the appointment of the drug during pregnancy is considered necessary, periodic ultrasound examinations should be performed to assess the condition of the fetus, as well as the intra-amniotic space.

Newborns whose mothers have taken Corenitec should be carefully observed for the development of arterial hypotension, oliguria and hyperkalemia. Enalapril, which crosses the placental barrier, has been removed from the neonatal circulation by peritoneal dialysis with some clinical benefit, theoretically it can be removed by exchange transfusion.

Enalapril and thiazides, incl. hydrochlorothiazide, excreted from breast milk. If necessary, the use of the drug during lactation breast-feeding should be stopped.

Application for violations of liver function

FROM caution the drug should be prescribed for liver failure.

Application for violations of kidney function

At patients with impaired renal function thiazides may not be effective enough, and when CC less than or equal to 30 ml / min (i.e. with severe renal failure) are ineffective.

At CC 80-30 ml/min Ko-renitek should be used only after the preliminary selection of doses of each of the components.

At moderate renal failure The recommended dose of enalapril maleate taken alone is 5 mg to 10 mg.

special instructions

During treatment with Corenitec, as with any antihypertensive therapy, symptomatic hypertension may develop. Patients should be examined for clinical signs violations of water and electrolyte balance, i.e. dehydration of the body, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia, which may occur due to episodes of diarrhea or vomiting. In such patients, during therapy, periodic determination of the electrolyte composition of the blood should be carried out at regular intervals.

With extreme caution, the drug should be prescribed to patients with coronary artery disease or cerebrovascular diseases, because. an excessive decrease in blood pressure can lead to the development of myocardial infarction or stroke.

With the development of arterial hypotension, bed rest is indicated and, if necessary, intravenous administration of saline. Transient arterial hypotension when prescribing Co-renitec is not a contraindication to its further use. After normalization of blood pressure and BCC, therapy can be resumed either in slightly reduced doses, or each of the components of the drug can be used separately.

Corenitec should not be given to patients with renal insufficiency (QC

In some patients without any signs of kidney disease before treatment with enalapril in combination with a diuretic, there was usually a slight and transient increase in blood urea and serum creatinine. In such cases, treatment with Co-renitec should be discontinued. In the future, it is possible to resume therapy in reduced doses or to prescribe each of the components of the drug separately.

As with all drugs that have a vasodilatory effect, ACE inhibitors should be used with caution in patients who have difficulty in outflow of blood from the left ventricle of the heart.

In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, an increase in blood urea and serum creatinine was observed during treatment with ACE inhibitors. These changes were reversible, as a rule, the indicators returned to normal after the treatment was stopped.

Thiazide diuretics should be used with caution in patients with impaired liver function or with progressive liver disease, since even small changes in fluid and electrolyte balance can lead to hepatic coma.

When carrying out large surgical operations or during general anesthesia with the use of agents that cause arterial hypotension, enalaprilat blocks the formation of angiotensin II, caused by the compensatory release of renin. If, at the same time, severe arterial hypotension develops, explained by a similar mechanism, it can be corrected by an increase in BCC.

Thiazide diuretics may not be effective enough in patients with impaired renal function and are ineffective when CC ≤ 30 ml / min (i.e., with moderate to severe renal failure).

Thiazide diuretics can cause impaired glucose tolerance. Doses of hypoglycemic drugs, including insulin, may need to be adjusted.

Thiazide diuretics may decrease urinary calcium excretion and cause slight and transient increases in serum calcium. Severe hypercalcemia may be a sign of latent hyperparathyroidism. Thiazides should be discontinued before conducting a study of the function of the parathyroid glands.

An increase in cholesterol and TG levels may also be associated with thiazide diuretic therapy, however, with a dose of hydrochlorothiazide 12.5 mg contained in 1 tablet of Corenitec, such effects were either not observed or were insignificant.

Thiazide therapy may lead to hyperuricemia and/or gout in some patients. However, enalapril can increase the content of uric acid in the urine and thereby weaken the hyperuricemic effect of hydrochlorothiazide.

In the treatment of ACE inhibitors, including enalapril maleate, rare cases of angioedema of the face, extremities, lips, tongue, glottis and / or larynx have been described. These reactions can occur at any stage of therapy. In such cases, it is necessary to immediately stop taking enalapril maleate and establish careful monitoring of the patient's condition in order to control and correct clinical symptoms. Even in cases where there is only swelling of the tongue without swelling of the respiratory organs, patients may require long-term observation, since therapy antihistamines and corticosteroids may not be enough.

There have been rare reports of death due to angioedema accompanied by laryngeal edema or tongue edema. Swelling of the tongue, glottis, or larynx may lead to obstruction respiratory tract especially in patients undergoing respiratory surgery.

In cases where edema is localized in the area of ​​the tongue, glottis or larynx, which can lead to airway obstruction, 0.3-0.5 ml of a 0.1% solution of epinephrine (adrenaline) should be immediately injected subcutaneously and the airway should be quickly secured.

In black patients taking ACE inhibitors, angioedema was observed more often than in other patients.

With indications in the anamnesis of angioedema, not associated with the use of ACE inhibitors, the risk of developing angioedema during therapy with ACE inhibitors increases significantly.

In patients receiving thiazides, allergic reactions may occur regardless of the presence of a history of allergic conditions or bronchial asthma. Recurrence or worsening of SLE severity has been reported in patients treated with thiazides.

Rarely, patients receiving ACE inhibitors have developed life threatening anaphylactoid reactions during hyposensitization with an allergen from Hymenoptera venom. Such reactions can be avoided if the ACE inhibitor is temporarily stopped before the start of hyposensitization.

The appointment of Ko-renitek is contraindicated in patients with renal insufficiency who are on hemodialysis. Anaphylactoid reactions have been observed in patients on dialysis using high-throughput membranes (such as AN69) and receiving concomitant treatment with ACE inhibitors. In these patients, a different type of dialysis membrane or other classes of antihypertensive drugs should be used.

During ACE therapy, cases of coughing were noted. As a rule, the cough is dry, has a permanent character and disappears after the end of therapy. Cough associated with the use of ACE inhibitors should be considered in the differential diagnosis of cough.

results clinical research The efficacy and tolerability of enalapril maleate and hydrochlorothiazide, when co-administered, were similar in older and younger patients.

Pediatric use

The safety and efficacy of Co-Renitec in children have not been established, therefore pediatric use is not recommended.

Overdose

Symptoms: severe arterial hypotension, starting approximately 6 hours after taking the drug, and stupor. After taking enalapril maleate at doses of 330 mg and 440 mg, plasma concentrations of enalaprilat exceeded, respectively, 100 and 200 times its concentration at therapeutic doses.

With an overdose of hydrochlorothiazide, the most commonly observed symptoms are caused by hypokalemia, hypochloremia, hyponatremia and dehydration due to excessive diuresis. If previously treated with digitalis preparations, it is possible to exacerbate the course of arrhythmia due to hypokalemia.

Treatment: Ko-renitek should be canceled; close medical supervision is required. Gastric lavage is recommended if the drug has been taken recently; conducting symptomatic and supportive therapy in order to correct water and electrolyte imbalance and arterial hypotension. Data on specific overdose therapy are not available.

drug interaction

When prescribing enalapril in combination with other antihypertensive drugs, the summation of the effect is possible.

Potassium loss caused by thiazide diuretics is usually reduced by enalaprilat. Serum potassium concentration usually remains within the normal range.

The use of potassium supplements, potassium-sparing diuretics or potassium-containing salts, especially in patients with renal insufficiency, can lead to a significant increase in serum potassium.

Diuretics and ACE inhibitors reduce the excretion of lithium by the kidneys and increase the risk of lithium toxicity. Lithium preparations, as a rule, are not prescribed simultaneously with diuretics or ACE inhibitors.

NSAIDs, including selective COX-2 inhibitors, may reduce the effectiveness of diuretics and other antihypertensive drugs. Therefore, it is possible to reduce the hypotensive effect of ACE inhibitors when administered simultaneously with NSAIDs, including selective COX-2 inhibitors.

In patients with impaired renal function receiving NSAIDs, including selective COX-2 inhibitors, concomitant use of ACE inhibitors may further worsen renal function. These changes are usually reversible.

Thiazide diuretics may enhance the effect of tubocurarine.

The hypotensive effect of the drug is reduced by NSAIDs, estrogens, ethanol.

Immunosuppressants, allopurinol, cytostatics increase the risk of developing hematotoxicity.

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life for tablets in blister packs is 3 years, for tablets in high-density vials - 2 years.

INSTRUCTIONS
on medical use drug

REGISTRATION NUMBER: P N014039/01

TRADENAME: RENITEK ®

INTERNATIONAL NON-PROPRIETARY NAME: Enalapril

PHARMACEUTICAL FORM: tablets

COMPOUND:
1 tablet contains:
Active substance: enalapril maleate - 5 mg, 10 mg or 20 mg
Excipients: sodium bicarbonate, lactose monohydrate, corn starch, pregelatinized starch, magnesium stearate, red iron oxide E172 (Renitek 10 mg, 20 mg), yellow iron oxide E172 (Renitek 20 mg).

DESCRIPTION:
Tablets 5 mg: Tablets white color, triangular, engraved with "MSD 712" on one side and a line on the other side.
Tablets 10 mg: Pink, triangular, spotted tablets, debossed on one side with "MSD 713", on the other side with a score line.
Tablets 20 mg: Tablets light pink with a yellowish tint, triangular in shape, engraved "MSD 714" on one side and a line on the other side.

PHARMACOTHERAPEUTIC GROUP:
Angiotensin converting enzyme (ACE) inhibitor

ATX CODE: C09AA02

PHARMACOLOGICAL PROPERTIES
RENITEC (enalapril maleate) belongs to the drugs that affect the renin-angiotensin system - ACE inhibitors and is a highly specific, long-acting, sulfhydryl-free ACE inhibitor.
It is used to treat arterial hypertension (AH) and heart failure (HF).
Pharmacodynamics
RENITEK (enalapril maleate) is a derivative of two amino acids: L-alanine and L-proline. Enalapril is an ACE inhibitor that catalyzes the conversion of angiotensin I to the pressor substance angiotensin II. After absorption, enalapril taken orally is converted by hydrolysis into enalaprilat, which inhibits ACE. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in blood plasma, which entails an increase in plasma renin activity (due to the elimination of the reverse negative reaction to changes in renin production) and a decrease in aldosterone secretion.
ACE is identical to the enzyme kininase II, so enalapril can also block the destruction of bradykinin, a vasodilatory peptide. The significance of this effect in the therapeutic action of enalapril requires clarification. Currently, it is believed that the mechanism by which enalapril lowers blood pressure (BP) is the suppression of the renin-angiotensin-aldosterone system, which plays an important role in the regulation of blood pressure. Enalapril exhibits an antihypertensive effect even in patients with reduced renin levels.
A decrease in blood pressure is accompanied by a decrease in total peripheral vascular resistance, an increase in cardiac output, and no or little change in heart rate. As a result of taking enalapril, renal blood flow increases, but the level of glomerular filtration remains unchanged. However, in patients with initially reduced glomerular filtration, its level usually increases.
Antihypertensive therapy with enalapril leads to a significant regression of left ventricular hypertrophy and preservation of its systolic function.
Therapy with enalapril is accompanied by a favorable effect on the ratio of lipoprotein fractions and no effect or a favorable effect on the concentration of total cholesterol.
The intake of enalapril by patients with hypertension leads to a decrease in blood pressure, regardless of body position: both in the standing position and in the supine position without a significant increase in heart rate (HR).
Symptomatic postural hypotension is rare. In some patients, achieving optimal blood pressure 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 oral dose of enalapril. The onset of hypotensive action occurs within 1 hour, 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 using the recommended doses, the antihypertensive effect and hemodynamic effects are maintained for 24 hours.
Enalapril reduces the loss of potassium ions caused by the use of hydrochlorothiazide.
Pharmacokinetics
After oral administration, enalapril is rapidly absorbed, the maximum concentration of enalapril in the blood serum is reached within 1 hour after ingestion.
The degree of absorption of enalapril maleate when taken orally is approximately 60%. Eating does not affect the absorption of enalapril.
After absorption, enalapril is rapidly hydrolyzed to form the active substance enalaprilat, a potent ACE inhibitor. The maximum concentration of enalaprilat in the blood serum is observed 3-4 hours after taking a dose of enalapril inside.
The duration of absorption and hydrolysis of enalapril is similar for various recommended therapeutic doses.
Excretion of enalapril is carried out mainly through the kidneys. The main metabolites detected in urine are enalaprilat, accounting for approximately 40% of the dose, and unchanged enalapril. There are no data on other metabolites of enalapril. The plasma concentration profile of enalaprilat has a long terminal phase, apparently due to the release of ACE-bound enalaprilat. In persons with normal renal function, a stable concentration of enalaprilat is reached on the 4th day from the start of enalapril. The half-life (T 1/2) of enalapril with a course of oral administration of the drug is 11 hours.

INDICATIONS FOR USE

Release form

Tablets

Compound

Active ingredient: Hydrochlorothiazide + Enalapril (Hydrochlorothiazide + Enalapril) Concentration active substance(mg): Enalapril maleate 20 mg, hydrochlorothiazide 12.5 mg

Pharmacological effect

Combined antihypertensive drug, which includes an ACE inhibitor (enalapril maleate) and a thiazide diuretic (hydrochlorothiazide). It has an antihypertensive and diuretic effect. Enalapril is an ACE inhibitor that catalyzes the conversion of angiotensin I into the pressor substance angiotensin II. After absorption, enalapril is converted by hydrolysis into enalaprilat, which inhibits ACE. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which entails an increase in plasma renin activity (due to the elimination of the reverse negative reaction to changes in renin production) and a decrease in aldosterone secretion. ACE is identical to the kininase II enzyme, therefore enalapril can also block the destruction of bradykinin , a peptide with a vasodilating effect. The significance of this mechanism in the therapeutic action of enalapril requires clarification. Despite the fact that enalapril reduces blood pressure by suppressing the renin-angiotensin-aldosterone system, which plays an important role in the regulation of blood pressure, the drug reduces blood pressure even in patients with arterial hypertension with low renin levels. A decrease in blood pressure is accompanied by a decrease in TPVR, a slight increase in cardiac output and no change or slight change in heart rate. As a result of taking enalapril, renal blood flow increases, the glomerular filtration rate remains unchanged. However, in patients with initially reduced glomerular filtration, its rate usually increases. Antihypertensive therapy with enalapril leads to a significant regression of left ventricular hypertrophy and preservation of systolic function of the left ventricle. Enalapril therapy is accompanied by a beneficial effect on the ratio of lipoprotein fractions and no effect or beneficial effect on total cholesterol. The intake of enalapril by patients with arterial hypertension leads to a decrease in blood pressure both in the standing position and in the supine position without a significant increase in heart rate. Symptomatic postural hypotension rarely develops. In some patients, achieving optimal blood pressure 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 oral dose of enalapril. The onset of antihypertensive action occurs within 1 hour, 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 used in recommended doses, the antihypertensive effect and hemodynamic effects persist for 24 hours. Hydrochlorothiazide has a diuretic and antihypertensive effect, increases renin activity. Although enalapril itself exhibits an antihypertensive effect even in patients with arterial hypertension against a background of low renin concentration, the concomitant use of hydrochlorothiazide in such patients leads to a more pronounced decrease in blood pressure. Enalapril reduces the loss of potassium ions caused by the use of hydrochlorothiazide. Enalapril and hydrochlorothiazide have a similar dosing regimen. Therefore, Corenitec is a convenient dosage form for the co-administration of enalapril and hydrochlorothiazide. The use of a combination of enalapril and hydrochlorothiazide leads to a more pronounced decrease in blood pressure compared to monotherapy with each drug alone and allows you to maintain the antihypertensive effect of Core-renitec for at least 24 h.

Pharmacokinetics

Enalapril Absorption After oral administration, enalapril maleate is rapidly absorbed. Cmax of enalapril in serum is observed within 1 hour after administration. After oral administration, absorption is approximately 60%. Eating does not affect the absorption of enalapril. The duration of absorption and hydrolysis of enalapril is similar for various recommended therapeutic doses. After absorption, enalapril is rapidly hydrolyzed to form the active substance enalaprilat, a potent ACE inhibitor. Cmax of enalaprilat in serum is observed 3-4 hours after taking a dose of enalapril inside. Excretion Enalapril is excreted mainly by the kidneys. The main metabolites detected in urine are enalaprilat, accounting for approximately 40% of the dose, and unchanged enalapril. Data on other significant pathways of metabolism of enalapril, with the exception of hydrolysis to enalaprilat, are not available. The enalaprilat plasma concentration curve has a long final phase, apparently due to its binding to ACE. In persons with normal renal function, a stable concentration of enalaprilat is reached on the 4th day from the start of enalapril. T1 / 2 of enalaprilat with the course use of the drug inside is 11 hours. Hydrochlorothiazide Metabolism and distribution Does not undergo metabolism. Hydrochlorothiazide crosses the placental barrier, but does not cross the BBB. Excretion T1 / 2 hydrochlorothiazide from 5.6 to 14.8 hours. Rapidly excreted by the kidneys. At least 61% of the dose taken orally is excreted unchanged within 24 hours. The combination of enalaprilat maleate and hydrochlorothiazide Regular intake of the combination of enalapril and hydrochlorothiazide does not affect or slightly affects the bioavailability of each component of the drug. The use of a combination tablet of Co-renitec is bioequivalent to the simultaneous administration of its ingredients in separate dosage forms.

Indications

Treatment of arterial hypertension in patients for whom combination therapy is indicated

Contraindications

Anuria Hypersensitivity to any of the components of the drug Hypersensitivity to sulfonamide derivatives History of angioedema associated with the appointment of earlier ACE inhibitors, as well as hereditary or idiopathic angioedema.

Precautionary measures

Do not exceed the recommended doses. With caution, the drug should be prescribed for aortic stenosis, cerebrovascular diseases (including cerebrovascular insufficiency), coronary artery disease, chronic heart failure, severe autoimmune systemic diseases of the connective tissue (including systemic lupus erythematosus, scleroderma ), depression of bone marrow hematopoiesis, diabetes mellitus, hyperkalemia, bilateral renal artery stenosis, stenosis of the artery of a single kidney, condition after kidney transplantation, renal and / or liver failure, on the background of a sodium-restricted diet, in conditions accompanied by a decrease in BCC (incl. including diarrhea, vomiting), elderly patients.

Use during pregnancy and lactation

The use of Co-Renitec during pregnancy is not recommended. When pregnancy is established, the drug should be stopped immediately. The appointment of ACE inhibitors in the II and III trimesters of pregnancy can cause disease or death of the fetus or newborn. The negative effect of ACE inhibitors on the fetus and newborn is manifested by arterial hypotension, renal failure, hyperkalemia and / or skull hypoplasia. Perhaps the development of oligohydramnios, apparently due to impaired renal function of the fetus. This complication can lead to contracture of the extremities, deformation of the skull, including its facial part, to pulmonary hypoplasia. The use of diuretics in women during pregnancy is not recommended, since there is a risk of developing jaundice in the fetus and newborn, thrombocytopenia, and possibly other side effects, observed in adult patients. If Co-renitec is prescribed during pregnancy, then the patient should be warned about the existing potential risk to the fetus. In those rare cases when the appointment of the drug during pregnancy is considered necessary, periodic ultrasound examinations should be performed to assess the condition of the fetus, as well as the intra-amniotic space. Newborns whose mothers took Corenitec should be carefully monitored for the development of arterial hypotension, oliguria and hyperkalemia. Enalapril, which crosses the placental barrier, has been removed from the neonatal circulation by peritoneal dialysis with some clinical benefit, theoretically it can be removed by exchange transfusion. Enalapril and thiazides, incl. hydrochlorothiazide are excreted in breast milk. If necessary, the use of the drug during lactation, breastfeeding should be discontinued.

Dosage and administration

Arterial hypertension: Initial dose 1 tablet 1 time per day. If necessary, the dose can be increased to 2 tablets 1 time per day. Inside, regardless of the meal

Side effects

From the side of the cardiovascular system: 1-2% - orthostatic effects, including arterial hypotension; rarely - fainting, arterial hypotension regardless of body position, palpitations, tachycardia, chest pain. From the side of the central nervous system and peripheral nervous system: often - dizziness, increased fatigue (usually disappeared with a decrease in dose and rarely required discontinuation of the drug); 1-2% - asthenia, headaches; rarely - insomnia, drowsiness, systemic dizziness, paresthesia, irritability. From the respiratory system: 1-2% - cough; rarely - shortness of breath. From the digestive system: 1-2% - nausea; rarely - pancreatitis, diarrhea, vomiting, dyspepsia, abdominal pain, flatulence, constipation, dry mouth. From the musculoskeletal system: 1-2% - muscle cramps; rarely - arthralgia. Allergic reactions: rarely - angioedema of the face, extremities, lips, tongue, glottis and / or larynx. There are rare reports of the development of angioedema of the intestine in connection with the use of ACE inhibitors, including enalapril. Dermatological reactions: rarely - Stevens-Johnson syndrome, hyperhidrosis, skin rash, itching. From the urinary system: rarely - impaired renal function, renal failure. side of the reproductive system: 1-2% - impotence; rarely - a decrease in libido. From the side of laboratory parameters: hyperglycemia, hyperuricemia, hypo- or hyperkalemia, an increase in the concentration of urea in the blood, serum creatinine, an increase in the activity of liver enzymes and / or an increase in serum bilirubin are possible (these indicators usually returned to normal after discontinuation of Corenitek therapy ); in some cases - a decrease in hemoglobin and hematocrit. Others: rarely - tinnitus, gout. A symptom complex is described, the possible manifestations of which are fever, serositis, vasculitis, myalgia, myositis, arthralgia/arthritis, a positive test for antinuclear antibodies, accelerated ESR, eosinophilia and leukocytosis; photosensitivity may develop.

Overdose

Symptoms: severe arterial hypotension, starting approximately 6 hours after taking the drug, and stupor. After taking enalapril maleate at doses of 330 mg and 440 mg, plasma concentrations of enalaprilat exceeded its concentrations at therapeutic doses by 100 and 200 times, respectively. With an overdose of hydrochlorothiazide, symptoms caused by hypokalemia, hypochloremia, hyponatremia and dehydration due to excessive diuresis are most often observed. If previously treated with digitalis preparations, the arrhythmia may worsen due to hypokalemia. Treatment: Corenitec should be discontinued; close medical supervision is required. Gastric lavage is recommended if the drug has been taken recently; conducting symptomatic and supportive therapy in order to correct water and electrolyte imbalance and arterial hypotension. There are no data on specific overdose therapy. In case of an overdose of enalapril maleate, intravenous infusion of saline is recommended, angiotensin II administration is effective. Enalaprilat can be removed from the systemic circulation by hemodialysis.

Interaction with other drugs

When prescribing enalapril in combination with other antihypertensive drugs, a summation of the effect is possible. Potassium loss caused by thiazide diuretics, as a rule, decreases under the influence of enalaprilat. Serum potassium concentration usually remains within the normal range. The use of potassium supplements, potassium-sparing diuretics or potassium-containing salts, especially in patients with renal insufficiency, can lead to a significant increase in serum potassium. Diuretics and ACE inhibitors reduce the excretion of lithium by the kidneys and increase the risk of developing intoxication lithium. Lithium preparations, as a rule, are not prescribed simultaneously with diuretics or ACE inhibitors. NSAIDs, including selective COX-2 inhibitors, may reduce the effectiveness of diuretics and other antihypertensive drugs. Therefore, it is possible to reduce the hypotensive effect of ACE inhibitors when administered simultaneously with NSAIDs, including selective COX-2 inhibitors. In patients with impaired renal function receiving NSAIDs, including selective COX-2 inhibitors, with concomitant use of ACE inhibitors, further deterioration of kidney function is possible. These changes are usually reversible. Thiazide diuretics can enhance the effect of tubocurarine. The antihypertensive effect of the drug is reduced by NSAIDs, estrogens, ethanol. Immunosuppressants, allopurinol, cytostatics increase the risk of hematotoxicity.

special instructions

During treatment with Corenitec, as with any antihypertensive therapy, symptomatic hypertension may develop. Patients should be examined for clinical signs of fluid and electrolyte imbalance, i.e. dehydration of the body, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia, which may occur due to episodes of diarrhea or vomiting. In such patients, during therapy, periodic determination of the electrolyte composition of the blood at regular intervals should be carried out. an excessive decrease in blood pressure can lead to the development of myocardial infarction or stroke. With the development of arterial hypotension, bed rest is indicated and, if necessary, intravenous administration of saline. Transient arterial hypotension when prescribing Co-renitec is not a contraindication to its further use. After normalization of blood pressure and BCC, therapy can be resumed either in slightly reduced doses, or each of the components of the drug can be used separately. Corenitec should not be prescribed to patients with renal insufficiency (CC

Renitek is a remedy whose action is aimed at eliminating the symptoms of high blood pressure. The drug is based on enalapril maleate, which is the active ingredient.

The antihypertensive effect of the drug develops within the first hour, and its peak is observed 4-6 hours after taking the medication. The duration of action is determined by the dose taken.

When using therapeutic doses given in the instructions for use, the antihypertensive effect is maintained throughout the day.

Clinical and pharmacological group

ACE inhibitor.

Terms of sale from pharmacies

Can be bought with a doctor's prescription.

Price

How much does Renitek cost in pharmacies? The average price is at the level of 80 rubles.

Composition and form of release

The drug Renitek is available in dosage form oral tablets (oral). They have a triangular shape and several colors, depending on the dosage of the main active ingredient - white (5 mg), pink (10 mg) and light pink with a yellowish tint (20 mg) color.

Composition of 1 tablet:

• active ingredient: enalapril maleate - 5, 10 or 20 mg;
• auxiliary components (5/10/20 mg): sodium bicarbonate - 2.5/5/10 mg; lactose monohydrate - 198.1 / 164.1 / 153.9 mg; pregelatinized starch - 5.06 / 2.2 / 2.2 mg; corn starch - 22.77 / 22 / 22 mg; magnesium stearate - 0.9 / 1 / 1.1 mg; yellow iron oxide (E172) - 0/0/0.13 mg; red iron oxide (E172) - 0 / 0.5 / 0.05 mg.

Tablets are packaged in a blister of 7 pieces. The cardboard pack contains 1, 2 and 4 blisters with tablets, as well as instructions for the preparation. For dosages of 10 and 20 mg, there is also a packing of tablets in a dark glass bottle in the amount of 100 pieces. In this case, the carton pack contains 1 bottle of tablets.

Renitek and Co-Renitek - what's the difference?

More effective drug, similar in action to Renitek, is considered the combined antihypertensive drug Ko-Renitek. In addition to elanapril 20 mg, it contains the diuretic hydrochlorothiazide (12.5 mg).

The combined effect of the drug is based on a combination of vasodilating and diuretic effects. Co-Renitec is usually prescribed for severe hypertension to reduce the load on the heart and blood vessels.

pharmachologic effect

The medicine is an antihypertensive agent. Active ingredient The drug is converted in the body to enalaprilat, which inhibits ACE (angiotensin-converting enzyme). This prevents the conversion of angiotensin I to angiotensin II and the synthesis of aldosterone, and also increases plasma renin activity. In addition, the drug increases the level of prostaglandin E and nitric oxide, reduces the excretion of potassium ions to a small extent, accelerates the excretion of sodium ions, and also reduces the level of circulating catecholamines.

The active substance Renitec helps to reduce blood pressure. In people with essential hypertension, it also interferes with total peripheral vascular resistance and increases cardiac output. In patients with kidney problems and proteinuria, there is a decrease in albuminuria, urinary excretion of IgG and total urine protein. And in the case of heart failure, the frequency of ventricular arrhythmias decreases.

Enalaprilat helps in the regression of left ventricular hypertrophy with the maintenance of systolic function.

After using the tablets inside, the action develops over 1-4 hours, they remain effective throughout the day. The drug is rapidly absorbed and then cleaved to enalaprilat. The time of eating does not affect their action.

Maximum reduction blood pressure observed approximately 5 hours after drug administration.

Indications for use

• renovascular;
• essential hypertension;
• any stage of CH.

In the presence of clinical manifestations of HF, Renitec is also prescribed to achieve the following goals:

• improving patient survival;
• slowing the progression of HF.

In the absence of clinical symptoms of heart failure in patients with impaired left ventricular function, Renitec is prescribed to achieve the following goals (prevention of the development of clinically significant heart failure):

• reduction in the frequency of hospitalizations associated with heart failure;
• slowing down the onset of clinical manifestations of heart failure.

With dysfunction of the left ventricle, Renitek is prescribed to achieve the following goals (prevention of coronary ischemia):

• reducing the frequency of hospitalizations associated with unstable angina;
• reduction in the frequency of occurrence.

At what pressure is the medicine taken?

Since the drug Renitek is declared as an antihypertensive drug, it should be used only according to the instructions for use, which indicates arterial hypertension as a target group of diseases in the treatment with Renitek.

Arterial hypertension is diagnosed when the pressure tends to reach and exceed 140/90 mm Hg. Art. Therefore, it is possible to say exactly at what pressure the instructions for use for Renitek recommend using the drug.

Contraindications

Medical contraindications to the use of Renitek tablets are several pathological and physiological conditions of the body, which include:

1. Individual intolerance to any of the components of the drug.
2. The development of angioedema, provoked by taking any drugs pharmacological group ACE inhibitors, including in the past.
3. Hereditary (due to a genetic defect transmitted from parents to children) or idiopathic (the cause of the pathological process cannot be established) angioedema is the release of blood plasma into the intercellular substance of soft tissues due to an increase in the permeability of the walls of blood vessels.
4. Age up to 18 years, since the effectiveness and safety of the drug in this situation is not reliably proven.

Before you start taking Renitek tablets, it is important to make sure that there are no contraindications to their use.

Dosage and method of application

As indicated in the instructions for use, Renitec is taken orally, regardless of food intake, since the absorption of tablets ye depends on food intake.

Arterial hypertension

The initial dose is 10-20 mg, depending on the severity of arterial hypertension, and is prescribed 1 time / day. With a mild degree of arterial hypertension, the recommended initial dose is 10 mg / day. For other degrees of arterial hypertension, the initial dose is 20 mg / day in a single dose. Maintenance dose - 1 tab. 20 mg 1 time / day. The dosage is selected individually for each patient, but the dose should not exceed 40 mg / day.

Renovascular hypertension

Since blood pressure and renal function may be particularly sensitive to ACE inhibition in this group of patients, therapy is started with a low initial dose of 5 mg or less. The dose is then adjusted according to the needs of the patient. A dose of 20 mg/day taken daily is usually effective. Caution should be exercised when treating patients who have recently received diuretic treatment.

Concomitant treatment of arterial hypertension with diuretics

After the 1st dose of Renitec, arterial hypotension may develop. This effect is most likely in patients treated with diuretics. The drug is recommended to be prescribed with caution, because. these patients may be fluid or sodium deficient. Treatment with diuretics should be discontinued 2-3 days before the start of treatment with Renitec. If this is not possible, then the initial dose of Renitec should be reduced (to 5 mg or less) to determine the primary effect of the drug. Further, the dosage should be selected taking into account the patient's condition.

The initial daily dose of Renitec depending on creatinine clearance:

• 30–80 ml/min (minor disorders): 5–10 mg;
• 10–30 ml/min (moderate impairment): 2.5–5 mg;
• < 10 мл/мин (выраженные нарушения; такие больные, как правило, находятся на гемодиализе): 2,5 мг в дни диализа (коррекция дозы в дни, когда гемодиализ не проводится, должна проводиться в зависимости от уровня АД).

Heart failure/asymptomatic left ventricular dysfunction

The initial dose of Renitec in patients with heart failure or asymptomatic left ventricular dysfunction is 2.5 mg, while the drug should be prescribed under close medical supervision to establish the primary effect of the drug on blood pressure. Renitec can be used to treat severe heart failure, usually in conjunction with diuretics and, when necessary, with cardiac glycosides. In the absence of symptomatic hypotension (due to treatment with Renitec) or after its appropriate correction, the dose should be gradually increased to the usual maintenance dose of 20 mg, which is administered either once or divided into 2 doses, depending on the patient's tolerance to the drug. Dose adjustments may be made over 2-4 weeks, or shorter if there are residual signs and symptoms of heart failure. Such a therapeutic regimen effectively reduces the mortality rates of patients with symptomatic heart failure.

Both before and after the start of treatment with Renitec, careful monitoring of blood pressure and renal function in patients with heart failure should be carried out, since there have been reports of the development of arterial hypotension as a result of taking the drug, followed by (which is much less common) the occurrence of renal failure. In patients receiving diuretics, the dose of diuretics, if possible, should be reduced before starting treatment with Renitec. The development of arterial hypotension after taking the first dose of Renitec does not mean that arterial hypotension will persist during long-term treatment, and does not indicate the need to stop taking the drug. Serum potassium levels should also be monitored during treatment with Renitec.

Side effect

The drug is usually well tolerated by patients, most side effects are mild and do not require discontinuation of the drug.

1. From the hemopoietic system: thrombocytopenia, neutropenia, agranulocytosis.
   From the urinary system: impaired renal function, oliguria, acute renal failure.
2. From the side of the cardiovascular system: arterial hypotension, including orthostatic hypotension, palpitations, arrhythmia, angina pectoris, chest pain. In isolated cases, mainly in patients at risk, myocardial infarction or stroke may develop.
3. From the gastrointestinal tract and liver: nausea, vomiting, impaired stool, pain in the epigastric region, loss of appetite. In isolated cases, the development of hepatitis, jaundice, intestinal obstruction, pancreatitis.
4. From the side of the central and peripheral nervous system: headache, dizziness, fatigue, tinnitus, convulsions, asthenia, emotional lability, disturbed sleep and wakefulness, paresthesia. In isolated cases, depression and confusion may develop.
5. On the part of laboratory parameters: an increase in the level of urea, creatinine, bilirubin and liver enzymes in the blood plasma. In isolated cases, it is possible to develop an increase in the level of potassium and a decrease in the level of sodium in the blood, as well as a decrease in hematocrit and hemoglobin. Allergic reactions: skin rash, itching, urticaria, angioedema, bronchospasm, allergic rhinitis, Stevens-Johnson syndrome.
6. Others: dry cough, pharyngitis, excessive sweating, alopecia, erectile dysfunction, visual impairment.

Overdose

At dosages above the norm, pronounced arterial hypotension appears, which is noticeable six hours after ingestion and coincides with the blockade of the renin-angiotensin system. Stupor may also occur.

As a therapy, an isotonic solution is administered intravenously. If an overdose has occurred recently, it is recommended to do a gastric lavage. The active substance can also be removed from the systemic circulation by hemodialysis.

special instructions

The development of clinically significant arterial hypotension in patients with uncomplicated arterial hypertension is rare. During therapy in patients with arterial hypertension, this disease often develops against the background of hypovolemia, which is associated with diuretic therapy, restriction of salt intake, in patients on hemodialysis, as well as diarrhea or vomiting. Clinically significant arterial hypotension can also be observed in patients with heart failure with or without renal insufficiency. In case of development of arterial hypotension, the patient must take a supine position, if necessary, a saline solution of sodium chloride is administered intravenously.

When taking Renitec, transient arterial hypotension for further treatment is not a contraindication, after replenishing the volume of fluid and normalizing blood pressure, the drug can be continued. In some patients with heart failure and normal/low blood pressure, the use of Renitec may cause an additional decrease in blood pressure. Such a reaction to taking the drug is expected, and there is no need to regard it as a reason for stopping therapy. In cases where arterial hypotension becomes stable, a dose reduction and / or withdrawal of the diuretic / Renitek is indicated.

In patients with a history of angioedema, which is not associated with the use of ACE inhibitors, it is possible to increase the likelihood of its occurrence when using Renitec. The incidence of angioedema in patients of the Negroid race is higher than in representatives of other races.

There are reports of rare cases of the development of life-threatening anaphylactic reactions during hyposensitization with an allergen from Hymenoptera venom. Such reactions can be avoided if Renitek is temporarily canceled before the onset of hyposensitization.

There is information about the occurrence of cough during the use of the drug. In most cases, the cough is unproductive, permanent, and after the abolition of Renitec it stops (must be taken into account when carrying out differential diagnosis cough).

The main risk factors for the development of hyperkalemia are renal failure, diabetes mellitus, combined use with potassium-sparing diuretics (spironolactone, triamterene or amiloride). The risk also increases with the use of potassium-containing supplements and salts. It must be taken into account that hyperkalemia can lead to serious (in some cases fatal) disorders. heart rate. In cases of need combined application with the above potassium-containing or potassium-increasing drugs, care must be taken and regular monitoring of serum potassium in the blood should be carried out.

Influence on the ability to drive vehicles

Due to the likelihood of dizziness (especially after taking the initial dose of Renitec in patients taking diuretics), caution should be exercised when driving vehicles during the period of therapy.

Interaction with other drugs

Antihypertensive and diuretic drugs, when used in combination with Renitec, enhance the hypotensive effect. With the combined use of the drug with potassium-sparing diuretics and potassium preparations, the risk of developing hyperkalemia increases. The drug, when used simultaneously, reduces the excretion of lithium and increases the toxicity of lithium preparations. With the simultaneous use of the drug with non-narcotic analgesics increased risk of nephrotoxicity.

Instructions for use
Ko-renitek tab. 20mg + 12.5mg №28

Dosage forms
tablets 12.5mg+20mg

Synonyms
Berlipril Plus
Renipril GT
Enalapril N

Enap-NL
Enap-NL 20

Group
Combination of angiotensin-converting enzyme inhibitors and diuretics

International non-proprietary name
Hydrochlorothiazide + Enalapril

Compound
Active ingredients: enalapril maleate and hydrochlorothiazide.

Manufacturers
Merck Sharp & Dome (Netherlands), Merck Sharp & Dome, packaged by Merck Sharp & Dome B.V. (Great Britain)

pharmachologic effect
Antihypertensive drug. It is a combination of an ACE inhibitor (enalapril maleate) and a thiazide diuretic (hydrochlorothiazide). The mechanism of the antihypertensive action of enalapril maleate is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II (which has a pronounced vasoconstrictor effect and stimulates the secretion of aldosterone in the adrenal cortex). Due to its vasodilating action, enalapril maleate reduces total peripheral vascular resistance (afterload), pulmonary capillary wedge pressure (preload), and pulmonary vascular resistance; increases cardiac output and exercise tolerance. Hydrochlorothiazide disrupts the reabsorption of sodium, chloride and water ions in the distal tubules of the nephron. Helps reduce high blood pressure. Increases the excretion of potassium, magnesium, bicarbonate ions; retains calcium ions in the body.

Side effect
From the side of the cardiovascular system: orthostatic effects, including arterial hypotension; possible fainting, arterial hypotension, not associated with the position of the body, palpitations, tachycardia, chest pain. From the side of the central nervous system: often - dizziness, increased fatigue (usually passed with a decrease in dose and rarely required discontinuation of the drug); asthenia, headaches; possible insomnia, drowsiness, paresthesia, increased nervous excitability and irritability. From the respiratory system: cough; possible difficulty breathing. From the digestive system: nausea; possible diarrhea, vomiting, indigestion, abdominal pain, flatulence, constipation, dry mouth, pancreatitis. From the musculoskeletal system: muscle cramps; possible arthralgia. Allergic reactions: possible skin rash, itching; rarely - angioedema of the face, limbs, lips, tongue, glottis and / or larynx. Dermatological reactions: possible Stevens-Johnson syndrome, profuse sweating, skin rash. From the urinary system: possible violations of kidney function, renal failure. From the reproductive system: impotence; possibly decreased libido. On the part of laboratory parameters: rarely - hyperglycemia, hyperuricemia, hypokalemia, increased levels of urea in the blood, serum creatinine, increased activity of liver enzymes and / or increased serum bilirubin, hyperkalemia; in some cases - a decrease in hemoglobin and hematocrit. Other: possible tinnitus, gout.

Indications for use
Arterial hypertension in patients who are more effective combination therapy.

Contraindications
anuria; hypersensitivity to the components of the drug; a history of angioedema associated with the use of ACE inhibitors; hypersensitivity to other sulfonamide derivatives. The use of the drug during pregnancy is not recommended. When pregnancy is established, the drug should be stopped immediately, except in cases of vital need for therapy for the mother.

Method of application and dosage
With arterial hypertension, 1 tablet is prescribed 1 time / day. If necessary, the dose can be increased to 2 tablets 1 time / day. In patients with impaired renal function, Corenitec should be used only after prior selection of doses of each of the components. In moderate renal failure, the recommended dose of enalapril maleate taken alone is 5 mg to 10 mg.

Overdose
Symptoms: The most pronounced symptoms of an overdose of enalapril are severe arterial hypotension, starting approximately 6 hours after taking the drug, and stupor. With an overdose of hydrochlorothiazide, the most commonly observed symptoms are caused by hypokalemia, hypochloremia, hyponatremia and dehydration due to excessive diuresis. If previously treated with digitalis preparations, arrhythmias may increase due to hypokalemia. Treatment: the drug should be discontinued; gastric lavage is recommended if the drug has been taken recently; conducting symptomatic and supportive therapy in order to correct water and electrolyte imbalance and arterial hypotension. In case of an overdose of enalapril maleate, intravenous infusion of saline is recommended; in the presence of angiotensin II, its administration may be useful. Enalaprilat can be removed from the systemic circulation by hemodialysis.

Interaction
When prescribing enalapril maleate in combination with other antihypertensive drugs, the summation of the effect is possible. Potassium loss caused by thiazide diuretics is usually reduced by enalaprilat. The content of potassium in serum usually remains within the normal range. The use of potassium supplements, potassium-sparing diuretics or potassium-containing salts, especially in patients with renal insufficiency, can lead to a significant increase in serum potassium. Diuretics and ACE inhibitors reduce the excretion of lithium by the kidneys, and increase the risk of developing lithium intoxication. Lithium preparations, as a rule, are not prescribed simultaneously with diuretics or ACE inhibitors. In patients with impaired renal function receiving NSAIDs, in some cases, the use of ACE inhibitors may further worsen renal function. Thiazides may increase sensitivity to tubocurarine.

special instructions
At the beginning of therapy, symptomatic arterial hypotension may develop, more often in patients with impaired water and electrolyte balance due to previous treatment with diuretics. Therapy with diuretics should be discontinued 2-3 days before the start of the drug. In the course of treatment, patients should be examined to identify clinical signs of impaired water and electrolyte balance, i.e. dehydration of the body, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia, which may occur due to episodes of diarrhea or vomiting. In such patients, periodic determination of the electrolyte composition of the blood should be carried out at appropriate intervals. With extreme caution, the drug should be prescribed to patients with coronary artery disease or cerebrovascular diseases, because. an excessive decrease in blood pressure can lead to the development of myocardial infarction or stroke. For more information, see the instructions for use of the drug.

Storage conditions
List B. The drug should be stored at a temperature not exceeding 30°C.