Ko renitek indications for use. How to take Co-Renitec for the treatment of arterial hypertension? At what pressure is the medicine taken

Photo of the drug

Latin name: Co-Renitec

ATX code: C09BA02

Active substance: Enalapril maleate (Enalaprili maleates), Hydrochlorothiazide (Hydrochlorothiazide)

Manufacturer: Merck Sharp & Dohme B.V. (Netherlands)

The description applies to: 17.10.17

Ko-renitek is a drug combination drug that is used to treat arterial hypertension.

Release form and composition

Available in the form of round yellow tablets. They are sold in blisters of 7 tablets, placed in cardboard packaging, and in polyethylene bottles of 56 pieces.

Indications for use

Arterial hypertension.

Contraindications

hypersensitivity to the active and additional substances of the drug;
individual intolerance to sulfonamide derivatives;
angioedema in history;
anuria;
During pregnancy and breastfeeding.

With special care prescribed for the following diseases:

cardiac ischemia;
chronic heart failure;
diabetes;
aortic stenosis;
oppression of bone marrow hematopoiesis;
liver or kidney failure;
bilateral stenosis of the renal arteries;
cerebrovascular diseases;
severe autoimmune systemic connective tissue diseases;
hyperkalemia;
stenosis of the artery of a single kidney.

Use with caution in elderly patients, children, and those on a sodium-restricted diet.

Instructions for use Ko-renitek (method and dosage)

Tablets are taken regardless of food. The initial dosage is one tablet per day. The dose may be doubled.

A few days before the start of therapy, it is necessary to stop the use of diuretics, as symptomatic arterial hypotension may occur.

Side effects

Sometimes Ko-renitek can provoke the following side effects:

From the respiratory system: shortness of breath, cough.
From the side of the cardiovascular system: arterial hypotension, palpitations, fainting, chest pain, tachycardia.
From the gastrointestinal tract: pancreatitis, nausea, abdominal pain, vomiting, diarrhea, dry mouth, flatulence (bloating), constipation.
From the nervous system: headaches, fatigue, dizziness, asthenia, drowsiness or insomnia, irritability, paresthesia.
From the musculoskeletal system: arthralgia, muscle cramps.
From the reproductive system: decreased libido, impotence.
From the urinary system: impaired renal function and renal failure.
Allergic reactions: angioedema of the tongue, lips, extremities, larynx, glottis and face.
Dermatological reactions: pruritus, rashes, hyperhidrosis, Stevens-Johnson syndrome.
On the part of laboratory parameters: hyperuricemia, hyperglycemia, hyper- or hypokalemia, increased activity of liver enzymes, increased blood urea levels, decreased hematocrit and hemoglobin.
Others: gout, tinnitus, serositis, fever, myositis, myalgia, vasculitis, arthritis, ESR acceleration, leukocytosis, eosinophilia, photosensitivity.

Overdose

With an overdose of Co-renitek, the following is observed:

stupor;
severe arterial hypotension;
significant increase in adverse reactions.

Overdose treatment includes urgent drug withdrawal, gastric lavage, symptomatic and supportive therapy. Often resort to intravenous infusion of saline. Enalapril is removed from the systemic circulation by hemodialysis.

Analogues

Analogues according to the ATX code: Berlipril plus, Prilenal, Renipril GT, Enalapril N, Enal N.

Do not make the decision to change the drug yourself, consult your doctor.

pharmachologic effect

The main active ingredients of Co-renitec are enalapril maleate and hydrochlorothiazide. These substances have an antihypertensive and diuretic effect on the body.
Enalapril is an angiotensin-converting enzyme inhibitor that, by lowering blood pressure, significantly increases renal blood flow. This component leads to regression of hypertrophy and also preserves left ventricular systolic function. Improvement occurs both in the standing position and in the prone position without an excessive increase in heart rate.
Hydrochlorothiazide stimulates renin, and this contributes to a more pronounced decrease in pressure.
The drug is a convenient drug form for co-administration of hydrochlorothiazide and enalapril. Begins to act within an hour after oral administration. The maximum decrease in pressure is observed after five to six hours. The duration of exposure usually depends on the dosage used.

special instructions

To avoid symptomatic hypotension, preliminary (before treatment) and periodic (during treatment) monitoring of water and electrolyte balance indicators is necessary, especially in patients with concomitant cerebrovascular diseases and coronary artery disease.

In the case of use after diuretic therapy, an interval of 2-3 days is recommended. With an increase in the level of creatinine and urea in the blood, the intake should be discontinued. With caution appoint patients with liver failure, during major surgical operations, incl. with the use of anesthetics and other means that reduce blood pressure.

During pregnancy and breastfeeding

It is not recommended to prescribe during pregnancy, especially in the II-III trimester (due to the risk of developmental defects or fetal death). When pregnancy occurs, the intake should be discontinued. It is acceptable to use the drug in pregnant women for health reasons, but it is necessary to inform the patient about the possible consequences and conduct periodic ultrasound.

Lactating women should stop breastfeeding for the duration of treatment.

In childhood

For impaired renal function

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

For impaired liver function

Use with caution in liver failure.

drug interaction

Compatible with other antihypertensive drugs. With the simultaneous use of potassium-sparing diuretics, potassium supplements and potassium-containing salts, hyperkalemia is possible. Increases the likelihood of lithium intoxication.

Terms of dispensing from pharmacies

Released by prescription.

Terms and conditions of storage

Keep 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.

Price in pharmacies

The price of Ko-renitek for 1 pack is from 497 rubles.

Attention!

The description posted on this page is a simplified version of the official version of the annotation for the drug. The information is provided for informational purposes only and is not a guide for self-treatment. Before using the drug, you should consult with a specialist and read the instructions approved by the manufacturer.

Corenitec is a combination of an ACE inhibitor (enalapril maleate) and a diuretic (hydrochlorothiazide). Ko-renitek has an antihypertensive and diuretic effect. The hypotensive effects of its two components complement each other and persist for 24 hours. Most patients with hypertension (arterial hypertension) respond better to treatment with Corenitec than to the appointment of each of its components separately. The presence of enalapril maleate in the preparation reduces the loss of potassium associated with taking hydrochlorothiazide.
Mechanism of action. Enalapril maleate
ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the pressor substance angiotensin II. After absorption, enalapril is hydrolyzed to enalaprilat, which inhibits ACE. ACE blockade leads to a decrease in the concentration of angiotensin II in the blood plasma, resulting in an increase in the activity of plasma renin (due to inhibition of the negative feedback between the activity of angiotensin II and renin release), and a decrease in aldosterone secretion.
ACE is identical to kininase II. Enalapril also inhibits the breakdown of bradykinin, a potent vasodepressor peptide. The mechanism by which enalapril reduces blood pressure is primarily associated with inhibition of the activity of the renin-angiotensin-aldosterone system, which plays a significant role in the regulation of blood pressure; enalapril has an antihypertensive effect even in patients with low-renin hypertension.

Hydrochlorothiazide is a diuretic and antihypertensive drug that increases plasma renin activity. Although enalapril has an antihypertensive effect also in patients with low-renin hypertension, the simultaneous administration of hydrochlorothiazide leads to a more significant decrease in blood pressure in such patients.
Pharmacodynamics
Enalapril maleate
The appointment of enalapril in patients with hypertension (arterial hypertension) leads to a decrease in blood pressure in the horizontal and vertical position without a significant increase in heart rate. Symptomatic postural hypotension develops infrequently. In some patients, the achievement of the optimal level of blood pressure occurs within a few weeks of therapy. Sudden withdrawal of enalapril maleate did not lead to a sharp increase in blood pressure.
Effective inhibition of ACE activity is achieved within 2-4 hours after oral administration of a therapeutic dose of enalapril. The onset of the antihypertensive effect is usually noted after 1 hour, and the peak decrease in blood pressure is achieved within 4-6 hours after taking the drug. The duration of the hypotensive effect depends on the dose of the drug. When taken in recommended doses, the antihypertensive and hemodynamic effect persisted for 24 hours.
In the study of hemodynamics in patients with essential hypertension (arterial hypertension), a decrease in blood pressure was usually accompanied by a decrease in peripheral vascular resistance, some increase in cardiac output, and little or no change in heart rate. Enalapril maleate increases renal blood flow; glomerular filtration rate does not change. However, in patients with a low glomerular filtration rate before treatment, it usually increased during treatment.
Taking enalapril as an antihypertensive agent leads to a significant regression of left ventricular hypertrophy while maintaining its systolic function. Enalapril has a positive effect on the ratio of lipoprotein fractions and the level of total cholesterol in the blood plasma, or this effect does not appear.
Enalapril maleate - hydrochlorothiazide
In clinical studies, the degree of blood pressure reduction with the combined use of enalapril maleate and hydrochlorothiazide exceeded that with the separate use of these drugs. In addition, the antihypertensive effect of Co-renitec lasted for 24 hours.
Pharmacokinetics
Enalapril maleate
After oral administration, it is rapidly absorbed, reaching peak concentrations within 1 hour, based on data on urinary excretion, the degree of absorption is about 60%.
After absorption, enalapril is rapidly and largely hydrolyzed to form enalaprilat, a potent ACE inhibitor. Peak plasma concentrations of enalaprilat are determined 3-4 hours after an oral dose of enalapril maleate. Enalapril is excreted mainly by the kidneys in the form of metabolites, the main of which are enalaprilat, which accounts for about 40% of the dose, and unchanged enalapril. Excluding conversion to enalaprilat, there are no other signs of significant metabolism of enalapril. The serum concentration profile of enalaprilat is characterized by a prolonged terminal phase, which is apparently associated with ACE binding. In persons with normal renal function, a stable concentration of enalaprilat is achieved after 4 days of therapy when taken once a day. The half-life of enalapril in the course of the drug is 11 hours. Eating does not affect the absorption of enalapril in the gastrointestinal tract. The degree of absorption and hydrolysis of enalapril is similar for different doses of the recommended therapeutic range.
Hydrochlorothiazide
When assessing the concentration of hydrochlorothiazide in blood plasma for 24 hours, the half-life ranged from 5.6-14.8 hours. Hydrochlorothiazide is not metabolized, it is rapidly excreted by the kidneys. About 61% of the oral dose is excreted unchanged within 24 hours. Hydrochlorothiazide crosses the placental barrier and does not cross the BBB.
Enalapril maleate hydrochlorothiazide.
The simultaneous use of multiple doses of enalapril maleate and hydrochlorothiazide has little or no effect on the bioavailability of these drugs. Taking a combined tablet is bioequivalent to prescribing its components separately.

Indications for use of the drug Co-renitec

Treatment of hypertension (arterial hypertension) in patients who are indicated for combination therapy.

The use of the drug Co-renitec

AG (arterial hypertension)
Adults are usually prescribed 1 tablet 1 time per day. If necessary, the dose can be increased to 2 tablets per day for 1 dose.
Prior diuretic therapy
At the beginning of treatment with Co-renitec, symptomatic arterial hypotension may be noted; it is more often detected in patients in whom previous diuretic therapy has led to a violation of the water and electrolyte balance. Therapy with diuretics should be discontinued 2-3 days before the start of therapy with Corenitec.
Dosing in renal failure
Thiazide diuretics may not be effective enough in patients with impaired renal function and ineffective in patients with creatinine clearance of 30 ml / min and below (i.e., with moderate or severe renal insufficiency). In patients with creatinine clearance in the range of 30-80 ml / min, Co-renitec can be used only after prior selection of doses of each component.
The recommended starting dose of enalapril maleate taken alone for moderate renal impairment is 5 to 10 mg.

Contraindications to the use of Co-Renitec

Hypersensitivity to any of its components and a history of angioedema associated with previous ACE inhibitor therapy; hypersensitivity to other sulfonamide derivatives.

Side effects of Co-Renitec

Ko-renitek is generally well tolerated. The most common side effects were dizziness and fatigue, which usually resolved with dose reduction and rarely required discontinuation of therapy.
Other side effects (1-2%) were: muscle cramps, nausea, asthenia, orthostatic effects including arterial hypotension, headache, cough, impotence.
Rarely noted the following side effects:
from the cardiovascular system- syncope, non-orthostatic hypotension, palpitations, tachycardia, chest pain;
from the gastrointestinal tract- pancreatitis, diarrhea, vomiting, dyspepsia, abdominal pain, flatulence, constipation;
from the nervous system and psyche- insomnia, drowsiness, paresthesia, dizziness, irritability;
from the respiratory system- shortness of breath;
from the side of the skin- Stevens-Johnson syndrome, rash, itching, excessive sweating;
others- impaired renal function, renal failure, decreased libido, dry mouth, tinnitus, gout, arthralgia.
A complex of symptoms was noted, which may include fever, serositis, vasculitis, myalgia and myositis, arthralgia and arthritis, a positive test for antinuclear antibodies (ANA), accelerated ESR, eosinophilia, and leukocytosis. Rash, photosensitivity and other dermatological manifestations can be detected.
hypersensitivity and angioedema
Angioedema of the face, extremities, lips, tongue, glottis and / or larynx has rarely been noted (see).
From the side of laboratory indicators
When prescribing Co-renitec, clinically significant changes in laboratory parameters were rarely detected.
In rare cases, hyperglycemia, hyperuricemia and hypokalemia, an increase in the level of blood urea, serum creatinine, an increase in the activity of liver enzymes and / or an increase in the level of bilirubin in the blood serum were noted. After discontinuation of therapy with Co-renitec, these parameters usually returned to normal. Hyperkalemia, decreased hemoglobin and hematocrit have also been reported.

Special instructions for the use of the drug Co-renitec

Hypotension and disturbance of water and electrolyte balance
As with other antihypertensive drugs, some patients may develop symptomatic hypotension. Patients should be evaluated for clinical signs of fluid and electrolyte imbalance, i.e. dehydration, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia, which may result from transient diarrhea or vomiting. In such patients, the level of electrolytes in the blood serum should be periodically determined at an appropriate time interval.
Particular attention should be paid to the treatment of patients with coronary artery disease or cerebrovascular disease, since a sharp decrease in blood pressure can lead to the development of myocardial infarction or stroke in such patients.
With the development of arterial hypotension, the patient should be given a horizontal position, if necessary, an isotonic solution of sodium chloride should be injected intravenously. Transient hypotension while taking the drug is not a contraindication to its further use. After normalization of blood pressure and BCC, therapy can be resumed at slightly reduced doses, or each of the components of the drug can be prescribed separately.
Aortic stenosis/hypertrophic cardiomyopathy
As with all vasodilators, ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction.
kidney failure
Thiazides may not be an effective diuretic for the treatment of patients with impaired renal function and are ineffective for creatinine clearance of 30 ml / min and below (i.e., with moderate or severe renal insufficiency).
Corenitec should not be administered to patients with renal insufficiency (creatinine clearance ≤80 ml/min) until the selection of the individual components of the drug shows that the required amount for this patient is combined in this dosage form (combination tablet).
In some patients with hypertension (arterial hypertension), who were not diagnosed with kidney disease before starting treatment, when treated with enalapril in combination with a diuretic, a slight and transient increase in the content of urea and creatinine in the blood serum may occur. In such cases, treatment with Co-renitec should be discontinued. In the future, you can resume therapy at reduced doses or prescribe each of the components of the drug separately.
In some patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney, an increase in serum urea and creatinine was noted during treatment with ACE inhibitors. As a rule, these changes were reversible and disappeared after treatment was stopped.
Liver disease
Thiazides should be used with caution in hepatic dysfunction or progressive liver disease, since even small changes in fluid and electrolyte balance can lead to hepatic coma.
Surgery / Anesthesia
During large-scale surgery and anesthesia using compounds that cause hypotension, enalaprilat blocks the formation of angiotensin II secondary to compensatory renin release. If at the same time arterial hypotension develops, explained by a similar mechanism, it can be corrected by increasing the volume of fluid.
Metabolic and endocrine effects
Thiazides are able to reduce glucose tolerance. Doses of antidiabetic drugs, including insulin, may need to be adjusted.
Thiazides can reduce urinary calcium excretion, resulting in a slight and transient increase in serum calcium concentration. Severe hypercalcemia may be a sign of latent hyperparathyroidism. Thiazides should be discontinued prior to testing parathyroid function.
An increase in serum cholesterol and triglycerides may also be associated with thiazide diuretic therapy. However, when used at a dose of 12.5 mg contained in Co-renitec, such an increase was not observed or was minimal.
Therapy with thiazide diuretics can lead to the development of hyperuricemia and / or gout in some patients, however, enalapril may increase the excretion of uric acid in the urine and thereby weaken the hyperuricemic effect of hydrochlorothiazide.
Hypersensitivity/angioedema
In the treatment of patients with ACE inhibitors, including enalapril maleate, isolated cases of angioedema of the face, extremities, lips, tongue, glottis and / or larynx have been described. This can happen at any time during treatment.
In such cases, it is necessary to immediately cancel the drug and establish strict medical supervision of the patient's condition in order to control clinical symptoms. Only after their complete disappearance, medical control can be stopped. In cases where swelling extends only to the face and lips, antihistamine therapy has a positive effect. Angioedema of the larynx can be fatal. In cases where edema is localized in the area of the tongue, glottis or larynx, which can lead to obstruction of the respiratory tract, you should immediately enter s / c solution of adrenaline 1:1000 (0.3-0.5 ml) and take appropriate therapeutic measures .
In patients of the Negroid race, when taking ACE inhibitors, angioedema developed more often than in other patients. Patients with a history of angioedema not associated with the use of ACE inhibitors are at risk of angioedema during therapy with ACE inhibitors (see).
In patients receiving thiazide diuretics, allergic reactions may occur with or without a history of allergic conditions or asthma. Relapse or more severe systemic lupus erythematosus has been reported in patients treated with thiazides.
Anaphylactoid reactions during hyposensitization with an allergen from Hymenoptera venom
In rare cases, patients treated with ACE inhibitors developed severe anaphylactoid reactions during hyposensitization with an allergen from Hymenoptera venom. In order to avoid the development of such reactions, it is recommended to temporarily stop treatment with ACE inhibitors until hyposensitization is carried out.
Patients on hemodialysis
Anaphylactoid reactions have been reported in patients on hemodialysis using high-capacity membranes (eg AN69) and concomitantly receiving an ACE inhibitor. Therefore, in such patients, the use of dialysis membranes of a different type or antihypertensive drugs of a different group is recommended.
Cough
There have been cases of cough during therapy with ACE inhibitors. Usually the cough is unproductive, is permanent and stops after the end of treatment. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.
Use during pregnancy
When pregnancy is established, Co-renitec should be discontinued immediately unless the drug is used for health reasons for the mother. ACE inhibitors can cause disease or death of the fetus or newborn when taken during the II and III trimester of pregnancy. The use of ACE inhibitors during these periods was accompanied by a negative effect on the fetus and newborn, caused the development of arterial hypotension, renal failure, hyperkalemia and / or skull hypoplasia in newborns. Perhaps the development of oligohydroamnion in the mother due to a decrease in fetal kidney function. This complication can lead to limb contractures, craniofacial deformity, and pulmonary hypoplasia. Such side effects, as a rule, did not occur in the first trimester of pregnancy due to the limited intrauterine effect of ACE inhibitors.
The conventional use of diuretics in apparently healthy women during pregnancy is not recommended because it exposes the mother and fetus to unnecessary risks, including fetal and neonatal jaundice, thrombocytopenia, and possibly other side effects that have been described in adult patients.
In the case of the use of Co-renitec during pregnancy, the patient should be warned of the potential risk to the fetus. In those rare cases when the use of the drug during pregnancy is considered necessary, repeated ultrasounds should be performed to assess the amniotic fluid. If oligohydramnios is detected, Co-renitec should be discontinued unless it is prescribed for health reasons. Both the doctor and the patient should be aware that oligohydroamnios can develop after the appearance of irreversible damage in the fetus. Newborns whose mothers have taken Corenitec should be carefully examined to exclude arterial hypotension, oliguria and hyperkalemia. Placental-crossing enalapril can be cleared from the neonatal circulation by peritoneal dialysis with some clinical benefit; theoretically, enalapril could also be removed by exchange transfusion. So far, there is no clinical experience in removing hydrochlorothiazide from the fetal circulation; this drug also crosses the placental barrier.
Use during breastfeeding
Enalapril and thiazides pass into breast milk. If the use of the drug is necessary, the patient should stop breastfeeding.
Application in pediatrics
The safety and efficacy of the drug in the treatment of children have not been established.
Use in elderly patients
In clinical studies, the efficacy and tolerability of enalapril maleate and hydrochlorothiazide, administered simultaneously, were comparable in patients with hypertension (arterial hypertension), both elderly and young.

Co-Renitec drug interactions

Other antihypertensive drugs
When prescribing enalapril maleate in combination with other antihypertensive drugs, an increase in the hypotensive effect may be observed.
Serum potassium
Potassium loss during treatment with thiazide diuretics is reduced by enalapril; the content of potassium in the blood serum usually remains within the normal range. The use of potassium supplements, potassium-sparing diuretics or potassium salts, especially in patients with renal insufficiency, is not advisable, as it can lead to a significant increase in serum potassium.
Lithium preparations
Lithium preparations should generally not be given with diuretics or ACE inhibitors, as the latter reduce urinary excretion of lithium and increase the risk of lithium toxicity. It is necessary to study the instructions for the use of lithium preparations before prescribing them.
NSAIDs
In some patients with impaired renal function who are taking NSAIDs, the simultaneous administration of ACE inhibitors may lead to a further decrease in renal function. These disorders are usually reversible.
Non-depolarizing muscle relaxants
Thiazides may increase sensitivity to tubocurarine.

Overdose of the drug Co-renitec, symptoms and treatment

Symptoms: arterial hypotension, nausea, weakness, dizziness due to electrolyte imbalance.
In case of accidental overdose, it is necessary to wash the stomach (with a recent intake of tablets), correct dehydration, electrolyte disturbances and arterial hypotension in accordance with generally accepted methods.
Treatment of an overdose of Co-Renitec is symptomatic and supportive. The patient should be under strict medical supervision, the drug should be discontinued.
Enalapril maleate
The most characteristic symptoms of an overdose of enalapril, according to existing data, are severe arterial hypotension due to blockade of the renin-angiotensin system, which manifests itself within 6 hours after taking the drug, and stupor. Plasma levels of enalapril 100 and 200 times the maximum level achieved when taken in therapeutic doses were observed when taking 300 and 440 mg of enalapril maleate, respectively.
For the treatment of overdose, intravenous infusion of physiological solution of sodium chloride is recommended. The introduction of angiotensin II has a positive effect. Enalaprilat can be removed from the systemic circulation by hemodialysis.
Hydrochlorothiazide
The most common symptoms are those caused by the loss of electrolytes (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. If digitalis preparations are given concomitantly, hypokalemia may exacerbate the arrhythmia.

Storage conditions of the drug Ko-renitek

At a temperature of 15-30 °C.

List of pharmacies where you can buy Ko-renitek:

Saint Petersburg

Ko-renitek is a combined antihypertensive drug with a diuretic effect.

Release form and composition

Dosage form of Ko-renitek - tablets (round, biconvex, yellow), 7 pcs. in blisters, 2 or 4 blisters in a cardboard box; 56 pcs. in polyethylene bottles, 1 bottle in a cardboard box.

Active ingredients of the drug:

Enalapril maleate - 20 mg;
Hydrochlorothiazide - 12.5 mg.

Auxiliary components: corn starch, aqueous lactose, pregelatinized corn starch, sodium bicarbonate, magnesium stearate, iron oxide yellow dye.

Indications for use

Ko-renitek is prescribed for the treatment of arterial hypertension, if necessary, the use of combination therapy.

Contraindications

Absolute contraindications:

Angioedema in history, caused by previous use of angiotensin-converting enzyme (ACE) inhibitors;
Hereditary and idiopathic angioedema;
Anuria;
Renal failure in patients on hemodialysis;
Hypersensitivity to the drug or other sulfonamide derivatives.

Relative contraindications (special observation of the patient is required):

aortic stenosis;
Cerebrovascular diseases, including cerebrovascular insufficiency;
Cardiac ischemia;
Chronic heart failure;
Inhibition of bone marrow hematopoiesis;
Severe systemic autoimmune connective tissue diseases, incl. scleroderma and systemic lupus erythematosus;
Hyperkalemia;
Diabetes;
Bilateral stenosis of the renal arteries or stenosis of a single kidney;
Conditions after kidney transplantation;
Renal / liver failure;
Conditions accompanied by a decrease in circulating blood volume, including vomiting and / or diarrhea;
Sodium-restricted diet food;
Elderly age.

The efficacy and safety of the use of Co-renitec in pediatrics have not been established, so the drug is not recommended for children.

Method of application and dosage

Co-renitec should be taken by mouth with or without food.

The initial dose is 1 tablet 1 time per day, if necessary, it is increased to 2 tablets, which are also taken 1 time per day.

Side effects

Cardiovascular system: orthostatic effects, including arterial hypotension; rarely - palpitations, chest pain, arterial hypotension, regardless of body position, fainting, tachycardia;
Digestive system: nausea; rarely - dyspepsia, vomiting, abdominal pain, diarrhea, flatulence, dry mouth, pancreatitis, constipation;
Central and peripheral nervous system: often - increased fatigue and dizziness (these symptoms usually disappear with a decrease in dose and rarely require discontinuation of the drug), headaches, asthenia; rarely - systemic dizziness, drowsiness, paresthesia, insomnia, irritability;
Musculoskeletal system: muscle cramps; rarely - arthralgia;
Respiratory system: cough; rarely - shortness of breath;
Reproductive system: impotence; rarely - decreased libido;
Urinary system: rarely - impaired renal function, renal failure;
Dermatological reactions: rarely - skin rash, itching, hyperhidrosis, Stevens-Johnson syndrome;
Allergic reactions: rarely - angioedema of the extremities, face, tongue, lips, glottis and / or larynx; in isolated cases - angioedema of the intestine;
Other: gout, tinnitus, photosensitivity. There is evidence of the development of a symptom complex, which includes myalgia, vasculitis, myositis, serositis, arthralgia / arthritis, fever, eosinophilia, leukocytosis, accelerated ESR, a positive test for antinuclear antibodies;
Laboratory indicators: hypo- or hyperkalemia, hyperuricemia, hyperglycemia, increased serum creatinine, blood urea concentration, liver enzyme activity and / or serum bilirubin (these indicators usually normalize after discontinuation of the drug); in some cases - a decrease in hemoglobin and hematocrit.

In clinical studies, the side effects of Corenitec were usually mild, transient and did not require interruption of treatment.

special instructions

At the beginning of therapy, there is a possibility of developing symptomatic arterial hypotension, especially in patients with impaired water and electrolyte balance (hyponatremia, hypomagnesemia, hypokalemia, body dehydration, hypochloremic alkalosis), including due to previous intake of diuretics. For this reason, before prescribing Corenitec, diuretic drugs should be canceled (2-3 days in advance), the patient should be examined for clinical signs of such disorders, and also periodically, at certain intervals, during the treatment period, determine the electrolyte composition of the blood.

In the case of the development of arterial hypotension, bed rest is indicated, if necessary, intravenous administration of saline. With transient arterial hypotension, Co-renitec should be discontinued. After normalization of blood pressure and circulating blood volume, therapy can be resumed, but in this case, the dose of the drug is reduced or each of its active components is prescribed separately.

Thiazide diuretics (in this case, hydrochlorothiazide) can impair glucose tolerance, so dose adjustment of insulin and hypoglycemic drugs may be required.

drug interaction

With the simultaneous use of other antihypertensive drugs, the summation of the effect is possible.

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

Diuretics and ACE inhibitors help to reduce the excretion of lithium by the kidneys, thereby increasing the likelihood of developing intoxication, so lithium preparations are not recommended to be taken in combination with Corenitec.

Non-steroidal anti-inflammatory drugs can reduce the effectiveness of diuretics and other antihypertensive drugs, which may reduce the hypotensive effect of ACE inhibitors. In patients with impaired renal function, this combination may further worsen renal function (usually reversible).

The hypotensive effect of Co-renitec is also reduced by estrogens and ethanol.

Hydrochlorothiazide may enhance the effect of tubocurarine.

With the simultaneous administration of cytostatics, immunosuppressants and allopurinol, hematotoxicity increases.

Terms and conditions of storage

Store at temperatures up to 30 ºС out of the reach of children.

The shelf life of tablets in vials is 2 years, in blisters - 3 years.

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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 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.

Instructions for use Ko-renitek ®
Composition of Co-renitec ®
Indications for Co-renitec ®
Storage conditions for Co-renitec ®
Shelf life of Co-renitec ®

ATC Code: Cardiovascular system (C) > Drugs affecting the renin-angiotensin system (C09) > ACE inhibitors in combination with other drugs (C09B) > ACE inhibitors in combination with diuretics (C09BA) > Enalapril in combination with diuretics (C09BA02)

Release form, composition and packaging

tab. 20 mg + 12.5 mg: 14, 28 or 56 pcs.
Reg. No: 1156/95/2000/05/10 dated 06/15/2010 - Valid

Pills yellow, 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. - high-density polyethylene bottles (1) - cardboard packs.

Description of the medicinal product CO-RENITECH ® created in 2011 on the basis of instructions posted on the official website of the Ministry of Health of the Republic of Belarus. Date of update: 03/14/2011

pharmachologic effect

Enalapril maleate. The use of enalapril maleate by patients with arterial hypertension leads to a decrease in blood pressure when measured in horizontal and vertical positions without a significant increase in heart rate.

Symptomatic postural hypotension occurs infrequently. In some patients, several weeks of therapy may be necessary to achieve optimal blood pressure reduction. Sudden discontinuation of enalapril maleate did not lead to a rapid increase in blood pressure levels.

Effective inhibition of ACE activity is usually achieved 2-4 hours after oral administration of an individual dose of enalapril. The onset of antihypertensive action, as a rule, is observed after 1 hour, and the maximum decrease in blood pressure is achieved 4-6 hours after taking the drug. The duration of the effect depends on the dose. When using the recommended doses, the antihypertensive and hemodynamic effects persisted for at least 24 hours.

In hemodynamic studies in patients with essential hypertension, a decrease in blood pressure was usually accompanied by a decrease in peripheral arterial resistance with some increase in cardiac output and little or no change in heart rate. After the use of enalapril maleate, renal blood flow increased; glomerular filtration rate, as a rule, did not change. However, in patients with a low glomerular filtration rate before treatment, this indicator, as a rule, increased.

Antihypertensive therapy with enalapril leads to a significant regression of left ventricular hypertrophy while maintaining its systolic function. Enalapril treatment is accompanied by a positive effect on plasma lipoprotein fractions and a favorable effect (or no effect) on total cholesterol levels.

Enalapril maleate - hydrochlorothiazide. In clinical studies, the degree of blood pressure reduction with the combination of enalapril maleate and hydrochlorothiazide was more pronounced than with the separate use of each of the components. In addition, the antihypertensive effect of Co-Renitec persisted for at least 24 hours.

Pharmacokinetics

Enalapril maleate. After oral administration, enalapril is rapidly absorbed, reaching Cmax in serum within one hour. Based on the rate of excretion in the urine, the absorption of enalapril when administered orally is approximately 60%.

After absorption, enalapril is rapidly and extensively hydrolyzed to enalaprilat, a potent ACE inhibitor. Cmax of enalaprilat in serum is achieved 3-4 hours after oral administration of enalapril maleate. Enalapril is excreted mainly by the kidneys. The main components in the urine are enalaprilat, which is approximately 40% of the dose, and unchanged enalapril. With the exception of conversion to enalaprilat, there are no signs of significant metabolism of enalapril. The serum concentration profile of enalaprilat is characterized by a prolonged terminal phase, probably due to ACE binding. In individuals with normal renal function, the equilibrium state of enalaprilat serum concentrations is reached on the fourth day of oral administration of enalapril maleate. The effective half-life of accumulation of enalaprilat after repeated oral administration of enalapril is 11 hours. Food intake does not affect the absorption of enalapril maleate from the gastrointestinal tract (GIT). The volume of absorption and hydrolysis of enalapril is similar at different doses within the recommended therapeutic range.

Hydrochlorothiazide. When monitoring plasma levels for at least 24 hours, T 1/2 from blood plasma was 5.6-14.8 hours. Hydrochlorothiazide is not metabolized, but is rapidly excreted by the kidneys. When administered orally, at least 61% of the dose is excreted unchanged within 24 hours. Hydrochlorothiazide crosses the placental and does not penetrate the blood-brain barrier.

Enalapril maleate - hydrochlorothiazide. The simultaneous repeated use of enalapril and hydrochlorothiazide has little or no effect on the bioavailability of these drugs. The combination tablet is bioequivalent to its individual components, which are used simultaneously.

Dosing regimen

Arterial hypertension

In arterial hypertension, the initial dose is half a tablet once a day. If necessary, the dose can be increased to 2 tablets once a day.

Prior treatment with diuretics

When using the first dose of the drug Corenitec, symptomatic arterial hypotension may occur. More often, hypotension occurs in patients with impaired water or salt balance as a result of previous use of diuretics. Therapy with diuretics should be discontinued 2-3 days before the start of the use of the drug Co-Renitec.

Dosage for impaired renal function

Thiazides may not be an effective diuretic for patients with impaired renal function and are ineffective at creatinine clearance of 30 ml / min and below (i.e., with moderate or severe renal impairment). In patients with creatinine clearance > 30 to< 80 мл/мин препарата Ко-ренитек следует применять только после подбора дозы каждого из компонентов отдельно. Рекомендованная начальная доза эналаприла малеата, применяющегося отдельно, при нарушении функции почек легкой степени тяжести составляет от 5 до 10 мг.

Side effects

Ko-renitek is usually well tolerated. In clinical studies, adverse reactions were generally mild and transient, and in most cases no temporary discontinuation of therapy was required.

The most common clinical adverse reactions were dizziness and fatigue, which, in most cases, disappeared with a decrease in the dose of the drug, and rarely required discontinuation of the drug.

Other adverse reactions (1-2%) were: muscle spasms, nausea, asthenia, orthostatic effects including arterial hypotension, headache, cough and impotence.

Less common side effects of the drug when it was used in controlled studies or post-marketing use were as follows.

From the side of the cardiovascular system: syncope, non-orthostatic arterial hypotension, palpitation, tachycardia, chest pain.

From the endocrine system: syndrome of inappropriate secretion of antidiuretic hormone.

From the digestive tract: pancreatitis, diarrhea, vomiting, dyspepsia, abdominal pain, flatulence, constipation.

From the nervous system / psyche: insomnia, drowsiness, paresthesia, vertigo, irritability.

From the respiratory tract: dyspnea.

From the side of the skin: Stevens-Johnson syndrome, rash, itching, increased sweating.

Other reactions: impaired renal function, renal failure, decreased libido, dry mouth, gout, tinnitus, arthralgia.

A symptom complex has been reported that may include some or all of the following symptoms: fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, positive antinuclear antibody (AHA) test, increased ESR, eosinophilia, leukocytosis. Rash, photosensitivity or other dermatological reactions may occur. Hypersensitivity/angioedema

Rarely, cases of angioedema of the face, extremities, lips, tongue, glottis and/or larynx have been reported. Very rarely, intestinal angioedema has been reported with ACE inhibitors, including enalapril.

Lab test data

Clinically significant changes in standard laboratory values have rarely been observed with Co-Renitec. Rarely, hyperglycemia, hyperuricemia and hypokalemia have been reported. Elevations in blood urea nitrogen and serum creatinine, elevations in liver enzymes and/or serum bilirubin have been observed. These symptoms are usually reversible when Corenitec is discontinued. There have been cases of hyperkalemia.

Decreases in hemoglobin and hematocrit have been reported.

Clinical adverse reactions for which a causal relationship has not been established

Other adverse reactions have been observed in clinical studies with Corenitec or enalapril maleate alone or in combination with other drugs, but a causal relationship has not been established. Reactions include:

transient ischemic disorders of cerebral circulation, dystonia, oral ulcers, burning sensation in the mouth, back pain, urinary tract infections.

Laboratory tests

A decrease in the number of platelets and leukocytes has been reported, rarely - neutropenia, thrombocytopenia, bone marrow suppression, but a causal relationship with the use of Co-renitec has not been established.

Potential adverse reactions

Additional adverse reactions that have been observed with the use of individual components of the drug, and may be potential side effects of the drug Corenitec, are as follows.

Enalapril

Ileus, liver failure, hepatocellular or cholestatic hepatitis, jaundice, depression, confusion, abnormal dreams, pulmonary infiltrates, bronchospasm/asthma, sore throat and hoarseness, cardiac arrhythmias, angina pectoris, myocardial infarction or stroke, possibly as a result of severe arterial hypotension in high-risk patients, Raynaud's phenomenon, rhinorrhea, photosensitivity, alopecia, flushing, changes in taste, anorexia, blurred vision, urticaria, stomatitis, glossitis, oliguria, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, pemphigus.

Laboratory tests. Hyponatremia.

Hydrochlorothiazide

Anorexia, gastric irritation, jaundice (intrahepatic cholestatic jaundice), sialadenitis, xanthopsia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia, purpura, photosensitivity, fever, urticaria, necrotizing angiitis (vasculitis), respiratory distress (including pneumonia and pulmonary edema) , interstitial nephritis, anaphylactic reaction, toxic epidermal necrolysis, glucosuria, electrolyte imbalance including hyponatremia, restlessness, muscle spasms, temporary blurred vision.

Use during pregnancy and lactation

Pregnancy

The use of Co-Renitec during pregnancy is not recommended. If pregnancy is diagnosed, Co-Renitec should be discontinued as soon as possible, unless the use of the drug is considered life-saving for the mother.

A published retrospective epidemiological study indicated that newborns whose mothers used an ACE inhibitor during the first trimester of pregnancy have an increased risk of developing major birth defects compared with newborns who did not have an ACE inhibitor during the first trimester. The incidence of birth defects is small and the data from this study have not been re-validated.

ACE inhibitors can cause fetal and neonatal morbidity and mortality when these drugs are used by pregnant women during the second and third trimesters of pregnancy. The use of ACE inhibitors during this period was accompanied by negative effects on the fetus and newborn, including arterial hypotension, renal failure, hyperkalemia, and / or hypoplasia of the skull bones in the newborn. As a result of a decrease in fetal kidney function, the development of oligohydramnios is possible. This complication can lead to limb contracture, craniofacial deformity, and lung hypoplasia. Such a side effect on the embryo and fetus was not observed with the use of ACE inhibitors during only the first trimester of pregnancy. The routine use of diuretics in apparently healthy women during pregnancy is not recommended because the mother and fetus are at an unnecessary risk of complications, including fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have been observed in adult patients.

If Co-Renitec is used during pregnancy, the patient should be informed of the potential adverse effects on the fetus. In those rare cases where the use of an ACE inhibitor during pregnancy is considered necessary, ultrasound examination should be performed frequently to assess growth retardation and the state of the intra-amniotic environment. If oligohydramnios is diagnosed, Corenitec should be discontinued unless the drug is essential for the mother. However, patients and clinicians should be aware that oligohydramnios can occur after the fetus has sustained irreversible damage.

Newborns whose mothers used Corenitec should be carefully examined for the development of arterial hypotension, oliguria and hyperkalemia. Enalapril crosses the placenta and is excreted from the neonatal circulation during peritoneal dialysis with some favorable clinical effect, and theoretically can be excreted from the body by exchange transfusion.

There is no experience of removing hydrochlorothiazide (also crosses the placenta) from the circulating blood in newborns.

Lactation

Enalapril and thiazide diuretics pass into human breast milk. If the use of the drug is considered necessary, breast-feeding should be discontinued.

Application for violations of kidney function

Contraindicated in severe renal failure (creatinine clearance ≤ 30 ml / min), anuria.

Use in elderly patients

special instructions

Arterial hypotension and electrolyte/water imbalance

As with other antihypertensive drugs, some patients may develop symptomatic hypotension. Patients should be evaluated for clinical signs of fluid or electrolyte imbalance such as dehydration, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia, which may result from diarrhea or vomiting. In such patients, serum electrolyte levels should be checked periodically. Particular care should be taken in the treatment of patients with ischemic heart disease or cerebrovascular disease, since excessive lowering of blood pressure can lead to myocardial infarction or stroke. With the development of arterial hypotension, the patient should be placed on his back and, if necessary, administered intravenously infusion with saline sodium chloride solution. Temporary hypotension is not a contraindication to the use of the following doses of the drug. After normalization of the volume of circulating blood and blood pressure, therapy can be resumed at reduced doses or using each of the components of the drug separately.

Aortic stenosis/hypertrophic cardiomyopathy

As with all other vasodilators, ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction.

Impaired kidney function

Thiazides may be inappropriate for use in patients with impaired renal function, as well as ineffective at creatinine clearance values \u200b\u200bof 30 ml / min or below (i.e. moderate and severe renal impairment). Corenitec should not be administered to patients with impaired renal function (creatinine clearance< 80 мл/мин), пока титрация дозы каждого из компонентов препарата не достигнет доз данного комбинированного препарата.

In some patients with arterial hypertension without signs of existing kidney disease, while using enalapril and a diuretic, as a rule, a slight and temporary increase in the level of blood urea and serum creatinine occurs. If this phenomenon occurs during the use of Co-Renitec, this combination drug should be discontinued. Treatment with the drug can be resumed in reduced doses or using each of the components of the drug separately.

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 levels was observed with the use of ACE inhibitors, which are usually reversible upon discontinuation of the drug.

Liver disease

Thiazides should be used with caution in patients with hepatic impairment or progressive liver disease, since minimal changes in fluid or electrolyte balance may lead to the development of hepatic coma.

Surgery / Anesthesia

In patients undergoing major surgery or anesthesia using drugs that lead to the development of arterial hypotension, enalapril can block the formation of angiotensin II as a result of compensatory renin release. If arterial hypotension occurs, which is explained by a similar mechanism, it can be corrected by increasing the volume of circulating blood.

Metabolic and endocrine effects

Therapy with thiazides can lead to a deterioration in glucose tolerance. Dose adjustments of antidiabetic agents, including insulin, may be necessary. Thiazides can reduce the excretion of calcium in the urine, and also cause a periodic and slight increase in the level of calcium in the blood serum. Severe hypercalcemia may indicate latent hyperparathyroidism. The use of thiazides should be discontinued before conducting a study of the function of the parathyroid glands.

Elevated cholesterol and triglyceride levels may be associated with thiazide diuretic treatment; however, minimal or no effects have been reported with Co-Renitec containing the 12.5 mg dose. Thiazide therapy may lead to the development of hyperuricemia and/or gout in certain patients. However, enalapril may increase the excretion of uric acid in the urine and thus weaken the hyperuricemic effect of hydrochlorothiazide.

Hypersensitivity/angioedema

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been rarely reported in patients treated with ACE inhibitors, including enalapril maleate. These reactions may occur at any time during treatment. In such cases, the use of enalapril maleate should be immediately discontinued and appropriate monitoring of the patient's condition should be established to ensure the complete disappearance of symptoms before the patient is discharged. Even in cases where there is only swelling of the tongue without respiratory distress, long-term monitoring of the patient's condition is necessary, since treatment with antihistamines and corticosteroids may not be enough. Very rarely, fatal cases have been reported due to angioedema, which was accompanied by swelling of the larynx or tongue. Patients with swelling of the tongue, glottis, or larynx are more likely to develop airway obstruction, especially in patients with a history of airway surgery. In cases where swelling of the tongue, glottis, or larynx may lead to airway obstruction, appropriate therapy should be initiated immediately, which may include subcutaneous injection of epinephrine 1 solution:

1000 (0.3-0.5 ml) and / or measures to maintain airway patency.

The development of angioedema was more often reported in patients of the black race than in patients of other races.

Patients with a history of angioedema that is not associated with the use of ACE inhibitors may have a higher risk of angioedema during the use of an ACE inhibitor.

In patients treated with thiazides, sensitivity reactions may occur regardless of a history of allergy or asthma. With the use of thiazides, exacerbation or activation of systemic lupus erythematosus has been reported.

Anaphylactoid reactions during desensitization with Hymenoptera venom

Life-threatening anaphylactoid reactions have rarely occurred in patients treated with ACE inhibitors during desensitization with hymenoptera venom. The occurrence of such reactions can be avoided by temporarily stopping the use of the ACE inhibitor before starting desensitization.

Anaphylactoid reactions during LDL apheresis

Life-threatening anaphylactoid reactions have rarely occurred in patients treated with ACE inhibitors during LDL apheresis using dextran sulfate. The occurrence of such reactions can be avoided by temporarily stopping the use of the ACE inhibitor before each apheresis.

Patients undergoing hemodialysis

The use of Co-Renitec is contraindicated in patients requiring hemodialysis for renal insufficiency. Anaphylactic reactions have been reported in patients undergoing dialysis using high permeability membranes (eg AN 69®) and concomitant treatment with an ACE inhibitor. For such patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.

Cough

Cough has been reported with the use of ACE inhibitors. As a rule, the cough is unproductive, persistent and disappears after cessation of therapy. Cough that occurs as a result of the use of ACE inhibitors should be considered in the differential diagnosis of cough.

Hyperkalemia

Risk factors for developing hyperkalemia include impaired renal function, diabetes mellitus, and concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, or amiloride), potassium supplements, or salt substitutes containing potassium.

If co-administration of Co-Renitec and the above agents is considered necessary, they should be used with caution, frequently monitoring serum potassium levels.

Lactose

Co-Renitec contains less than 200 mg of lactose per tablet. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not use this medicinal product.

kidney transplant

There is no experience with the use of enalapril in patients with recent kidney transplantation. Therefore, treatment with enalapril is not recommended.

Use in elderly patients

In clinical studies, the efficacy and tolerability of enalapril maleate and hydrochlorothiazide, used simultaneously, were similar in elderly patients and in younger patients with arterial hypertension.

Use in children

The safety and efficacy of the drug in children have not been established.

Influence on the ability to drive vehicles and other mechanisms

When driving vehicles and mechanisms, it should be taken into account that occasionally dizziness or fatigue may occur.

Overdose

There is no specific information regarding the treatment of overdose with Co-Renitec. Treatment is symptomatic and supportive. The use of Co-Renitec should be discontinued and the patient carefully examined. Suggested activities include:

inducing vomiting if the drug has been taken recently, as well as correcting dehydration, electrolyte imbalance and arterial hypotension according to generally accepted procedures.

Enalapril maleate

The main manifestation of an overdose, which has been reported so far, is severe arterial hypotension, which occurs within 6 hours after taking the drug and is accompanied by blockade of the renin-angiotensin system, and stupor. It was reported that after taking enalapril maleate at doses of 300 and 440 mg, serum enalaprilat levels were 100 and 200 times higher, respectively, than levels when using therapeutic doses of the drug.

The recommended treatment for overdose is intravenous administration of isotonic sodium chloride solution. If necessary, angiotensin II infusion may also be considered. Enalapril can be removed from the systemic circulation by hemodialysis.

Hydrochlorothiazide

The most commonly observed signs and symptoms of overdose are symptoms of electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. With the simultaneous use of digitalis preparations, hypokalemia can exacerbate cardiac arrhythmias.

drug interaction

Additional effects may occur when enalapril is used concomitantly with other antihypertensive drugs.

Serum potassium

As a rule, enalapril weakens the effect of thiazide diuretics, such as excretion of potassium from the body. Usually, serum potassium levels remain within the normal range.

The use of potassium supplements, potassium-sparing drugs or salt substitutes containing potassium, especially in patients with impaired renal function, can lead to a pronounced increase in serum potassium levels. Hyperkalemia can cause serious, sometimes fatal, arrhythmias. If co-administration of Co-Renitec and the above agents is considered necessary, they should be used with caution, frequently monitoring serum potassium levels.

Lithium

Diuretics or ACE inhibitors reduce the renal clearance of lithium and increase the risk of lithium toxicity, so concomitant use is not recommended. Before using this combination, you should read the instructions for the lithium preparation.

Non-steroidal anti-inflammatory drugs (NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors)

NSAIDs, including selective COX-2 inhibitors, may reduce the effects of diuretics or other antihypertensive drugs. Therefore, the antihypertensive effect of angiotensin II receptor antagonists or ACE inhibitors may be weakened by the use of NSAIDs, including COX-2.

In some patients with impaired renal function (for example, elderly patients or patients with dehydration, including those taking diuretics) who are treated with NSAIDs, including COX-2 inhibitors, the simultaneous use of angiotensin II receptor antagonists and ACE inhibitors may lead to a subsequent deterioration in renal function including possible acute renal failure. Such effects are usually reversible. Therefore, the combination of these drugs should be used with caution in patients with impaired renal function.

Double blockade of the renin-angiotensin-aldosterone system

In patients with diagnosed atherosclerotic disease, heart failure, or diabetes with end organ damage, dual blockade of the renin-angiotensin-aldosterone system has been reported in the literature to be associated with an increased incidence of arterial hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) when compared with the use of a single drug that affects the renin-angiotensin-aldosterone system. Double blockade (for example, the appointment of an ACE inhibitor with an angiotensin II receptor antagonist) should be carried out only in certain certain cases, constantly monitoring kidney function.

Non-depolarizing muscle relaxants

Thiazides may increase susceptibility to tubocurarine.

Preparations of gold

Rarely, nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) have been reported in patients treated with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitors, including enalapril.

Potential interactions with other drugs

Other antihypertensive drugs

The combination of enalapril maleate and beta-blockers, methyldopa, or calcium channel blockers improves blood pressure lowering efficacy.

Ganglioblockers or adrenoblockers in combination with enalapril should be used only under the condition of careful monitoring of the patient's condition.

With the simultaneous use of the following drugs, their interaction with thiazide diuretics is possible.

Alcohol, barbiturates, or narcotic analgesics- can potentiate the development of orthostatic hypotension.

Antidiabetic drugs (oral agents and insulin)- dose adjustment of the antidiabetic drug may be necessary.

Resins of cholestyramine and colestipol- absorption of hydrochlorothiazide is reduced in the presence of anion exchange resins. A single dose of colestyramine or colestipol resin binds to hydrochlorothiazide and reduces its absorption from the gastrointestinal tract by 85% and 43%, respectively.

Corticosteroids, adrenocorticotropic hormone (ACTH)- increased loss of electrolytes, in particular, hypokalemia.

Pressor amines (e.g. adrenaline)- a decrease in response to pressor amines is possible, but not enough to exclude their use.

Contacts for appeals

MERK SHARP and DOME IDEA Inc., representative office, (Swiss Confederation)

Representation JSC " Merck Sharp & Dohme IDEA Inc."
in the Republic of Belarus