Pharmacodynamics and pharmacokinetics
This drug reduces the level of sodium ions in the vascular wall, blood pressure , arterial vascular tone, peripheral , and also increases diuresis . The hypotensive effect lasts throughout the day.
Thus, the drug is effective in cases of arterial hypertension . The hypotensive effect of the active components of the drug complements each other. Therapy with this drug is more effective in most cases for arterial hypertension than the use of enalapril maleate and hydrochlorothiazide separately.
Enalapril is an ACE inhibitor . Once absorbed it is metabolized to enalaprilat . Its action leads to a decrease in the level of angiotensin II in plasma, which increases the activity renin and decreases the secretion of aldosterone . In addition, enalapril prevents the destruction of bradykinin .
The decrease in blood pressure is accompanied by a decrease in total peripheral vascular resistance and a slight increase in cardiac output. The drug increases renal blood flow . the glomerular filtration rate does not change , unless it was initially reduced in patients.
Hydrochlorothiazide is a diuretic and antihypertensive agent that helps increase renin . Thus, when combined with enalapril , it results in a greater reduction in blood pressure . Discontinuation of the drug does not cause its sharp increase.
The maximum effect, as a rule, appears 2-4 hours after application. The hypotensive effect is noticeable within an hour. The duration of action of the medicine largely depends on the dosage. As a rule, it lasts throughout the day.
Pharmacological properties of the drug Ko-renitek
Corenitec is a combination of an ACE inhibitor (enalapril maleate) and a diuretic (hydrochlorothiazide). Ko-Renitek has antihypertensive and diuretic effects. 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 Korenitek than to the administration of each of its components separately. The presence of enalapril maleate in the drug 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, as a result of which the activity of plasma renin increases (due to inhibition of the negative feedback between the activity of angiotensin II and the release of renin), 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. Enalapril maleate - hydrochlorothiazide Hydrochlorothiazide is a diuretic and antihypertensive agent that increases the activity of plasma renin. Although enalapril also has an antihypertensive effect in patients with low-renin hypertension, simultaneous administration of hydrochlorothiazide leads to a more significant reduction in blood pressure in such patients. Pharmacodynamics of Enalapril maleate Prescribing enalapril to patients with hypertension (arterial hypertension) leads to a decrease in blood pressure in horizontal and vertical positions without a significant increase in heart rate. Symptomatic postural hypotension occurs infrequently. In some patients, achievement of optimal blood pressure levels occurs within several 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 within 1 hour, and the peak reduction 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. When studying hemodynamics in patients with essential hypertension (arterial hypertension), a decrease in blood pressure was usually accompanied by a decrease in peripheral vascular resistance, a slight increase in cardiac output and a slight change in heart rate or without it. Taking enalapril maleate increases renal blood flow; the rate of glomerular filtration 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. Taking 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 Korenitek lasted for 24 hours. Pharmacokinetics of Enalapril maleate After oral administration, it is rapidly absorbed, reaching peak concentrations within 1 hour, based on data regarding urinary excretion, the degree of absorption is about 60%. After absorption, enalapril is quickly and significantly hydrolyzed to form enalaprilat, a potent ACE inhibitor. Peak plasma concentrations of enalaprilat are determined 3–4 hours after taking an oral dose of enalapril maleate. Enalapril is excreted primarily 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 is no other evidence 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 individuals 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 during a course of use of the drug is 11 hours. Food intake does not affect the absorption of enalapril in the gastrointestinal tract. The extent 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 over 24 hours, the half-life ranged from 5.6 to 14.8 hours. Hydrochlorothiazide is not metabolized and is rapidly excreted by the kidneys. About 61% of an orally administered dose is excreted unchanged within 24 hours. Hydrochlorothiazide penetrates the placental barrier and does not penetrate 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 combination tablet is bioequivalent to taking its components separately.
Contraindications
Co-Renitec should not be used in case of hypersensitivity to its components, childhood , anuria , history of angioedema , as well as hereditary or idiopathic angioedema .
This drug is prescribed with caution for:
- bilateral renal artery stenosis ;
- coronary heart disease;
- aortic stenosis;
- severe systemic connective tissue diseases;
- diabetes mellitus;
- condition after kidney transplantation;
- a diet with limited sodium content;
- old age;
- cerebrovascular diseases;
- chronic heart failure ;
- renal failure;
- inhibition of bone marrow hematopoiesis;
- conditions accompanied by a decrease in circulating blood volume;
- liver failure;
- hyperkalemia;
- stenosis of the artery of a single kidney.
Side effects
Negative side effects, according to research, are usually moderate in nature. They usually do not require discontinuation of therapy. Side effects may be as follows:
- respiratory system – shortness of breath, cough;
- CVS - palpitations, orthostatic effects, fainting, arterial hypotension , chest pain, tachycardia ;
- musculoskeletal system - the appearance of muscle cramps, pain in the joints;
- kidneys – development of renal failure , problems with kidney function;
- laboratory indicators – hyperglycemia , hyperkalemia , hypokalemia , hyperuricemia , decreased hematocrit and hemoglobin ;
- CNS – dizziness , increased excitability, asthenia , paresthesia , increased fatigue, drowsiness , headache , sleep disturbances ;
- digestive system - dyspepsia , diarrhea , nausea, flatulence , dry mouth, vomiting, abdominal pain, constipation , pancreatitis ;
- allergies – itching , rash;
- reproductive system – development of impotence , decreased libido;
- others – tinnitus, gout .
In addition, in rare cases, when taking the medicine, undesirable manifestations such as angioedema of the glottis, limbs, tongue, face, larynx, lips, Stevens-Johnson syndrome , intestinal Quincke's edema , hyperhidrosis .
Overdose of the drug Ko-Renitek, symptoms and treatment
Symptoms: arterial hypotension, nausea, weakness, dizziness due to electrolyte imbalance. In case of accidental overdose, it is necessary to rinse the stomach (if you have recently taken pills), correct dehydration, electrolyte disturbances and arterial hypotension in accordance with generally accepted methods. Treatment of an overdose of Ko-renitek is symptomatic and supportive. The patient should be under strict medical supervision and 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 at therapeutic doses were observed with 300 and 440 mg of enalapril maleate, respectively. To treat an overdose, intravenous infusion of physiological sodium chloride solution is recommended. The administration of angiotensin II has a positive effect. Enalaprilat can be removed from the systemic circulation by hemodialysis. Hydrochlorothiazide The most common symptoms that occur are those caused by loss of electrolytes (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excess diuresis. If digitalis is co-administered, hypokalemia may worsen the arrhythmia.
Instructions for use Co-Renitek (Method and dosage)
This medication is taken orally , one tablet once a day. If necessary, the dosage can be increased to two tablets per day.
Instructions for use Co-Renitek recommends monitoring water and electrolyte balance data. If the patient has previously taken diuretics , you must wait 2-3 days before using Co-Renitec tablets. In cases where there is an increase in urea and creatinine in the blood, the use of the drug should be discontinued.
Special instructions for the use of the drug Ko-Renitek
Hypotension and electrolyte imbalance As with other antihypertensive drugs, some patients may develop symptomatic hypotension. Patients should be assessed for clinical signs of fluid and electrolyte imbalance, i.e. dehydration, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia, which may occur due to transient diarrhea or vomiting. In such patients, serum electrolyte levels should be determined periodically at appropriate intervals. A particularly careful approach should be taken to the treatment of patients with coronary artery disease or cerebrovascular pathology, since a sharp decrease in blood pressure can lead to the development of myocardial infarction or stroke in such patients. If arterial hypotension develops, the patient should be placed in a horizontal position and, if necessary, isotonic sodium chloride solution should be administered intravenously. Transient hypotension when taking the drug is not a contraindication to its further use. After normalization of blood pressure and blood volume, therapy can be resumed in slightly reduced doses or each component 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. Renal impairment Thiazides may not be effective diuretics for the treatment of patients with impaired renal function and are ineffective when creatinine clearance is 30 ml/min or lower (that is, with moderate or severe renal impairment). Korenitek should not be prescribed to patients with renal failure (creatinine clearance ≤80 ml/min) until the selection of individual components of the drug shows that the required amount for a given patient is combined in a given dosage form (combined tablet). In some patients with hypertension (arterial hypertension) who were not diagnosed with kidney disease before starting treatment, a slight and transient increase in serum urea and creatinine may occur when treated with enalapril in combination with a diuretic. In such cases, treatment with Corenitec should be discontinued. In the future, you can resume therapy in 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 solitary kidney, an increase in serum urea and creatinine was observed when treated with ACE inhibitors. As a rule, these changes were reversible and disappeared after cessation of treatment. Liver disease Thiazides should be used with caution in patients with impaired liver function or progressive liver disease, since even small changes in fluid and electrolyte balance can lead to hepatic coma. Surgery/Anesthesia During large surgical procedures and anesthesia using compounds that cause hypotension, enalaprilat blocks the formation of angiotensin II secondary to compensatory renin release. If arterial hypotension, explained by a similar mechanism, develops, it can be corrected by increasing the volume of fluid. Metabolic and endocrine effects Thiazides can reduce glucose tolerance. Doses of antidiabetic medications, including insulin, may need to be adjusted. Thiazides may reduce urinary calcium excretion, resulting in a slight and transient increase in serum calcium concentrations. Severe hypercalcemia may be a sign of latent hyperparathyroidism. Thiazides should be discontinued before testing parathyroid function. Increases in serum cholesterol and triglyceride levels may also be associated with thiazide diuretic therapy. However, when used at a dose of 12.5 mg contained in Ko-Renitek, such an increase was not noted or was minimal. Thiazide diuretic therapy may lead to the development of hyperuricemia and/or gout in some patients, but enalapril may increase uric acid excretion in the urine and thereby reduce the hyperuricemic effect of hydrochlorothiazide. Hypersensitivity/angioedema When treating 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 discontinue the drug and establish strict medical supervision of the patient’s condition in order to control clinical symptoms. Only after their complete disappearance can medical control be stopped. In cases where swelling extends only to the face and lips, therapy with antihistamines has a positive effect. Angioedema of the larynx can be fatal. In cases where the swelling is localized in the area of the tongue, glottis or larynx, which can lead to obstruction of the respiratory tract, you should immediately administer a subcutaneous solution of adrenaline 1:1000 (0.3–0.5 ml) and carry out 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 developing angioedema during therapy with ACE inhibitors (see CONTRAINDICATIONS). In patients receiving thiazide diuretics, allergic reactions may occur with or without a history of allergic conditions or asthma. Relapse or more severe cases of systemic lupus erythematosus have been reported in patients receiving thiazides. Anaphylactoid reactions during hyposensitization with an allergen from Hymenoptera venom In rare cases, patients receiving ACE inhibitors developed severe anaphylactoid reactions during hyposensitization with an allergen from Hymenoptera venom. To avoid the development of such reactions, it is recommended to temporarily discontinue treatment with ACE inhibitors until hyposensitization is carried out. Patients on hemodialysis Anaphylactoid reactions have been reported in patients on hemodialysis using high-flow 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 Cases of cough development have been observed during therapy with ACE inhibitors. Usually the cough is non-productive, persistent and stops after treatment. ACE inhibitor-induced cough must be considered in the differential diagnosis of cough. Use during pregnancy If pregnancy is established, use of Korenitek should be stopped 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 second and third trimester of pregnancy. The use of ACE inhibitors during these periods was accompanied by a negative effect on the fetus and newborn, causing the development of arterial hypotension, renal failure, hyperkalemia and/or cranial hypoplasia in newborns. The development of oligohydroamnion in the mother is possible due to decreased fetal renal function. This complication can lead to limb contractures, craniofacial deformation and pulmonary hypoplasia. Such side effects, as a rule, did not occur in the first trimester of pregnancy due to the limited intrauterine influence of ACE inhibitors. Traditional use of diuretics in otherwise 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 reported in adult patients. If Corenitec is used during pregnancy, the patient should be warned about the potential risk to the fetus. In those rare cases when the use of the drug during pregnancy is considered necessary, repeat ultrasounds should be performed to assess the amniotic environment. If oligohydramnios is detected, use of Korenitek should be discontinued, except when it is prescribed for health reasons. Both the doctor and the patient should be aware that oligohydroamnion can develop after irreversible damage has occurred in the fetus. Newborns whose mothers took Korenitek should be carefully examined to exclude arterial hypotension, oliguria and hyperkalemia. Enalapril, which crosses the placental barrier, can be removed from the neonatal circulation by peritoneal dialysis with some beneficial clinical effect; theoretically, enalapril can also be removed by exchange transfusion. There is no clinical experience yet on removing hydrochlorothiazide from the fetal circulation; this drug also penetrates 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. Use in pediatrics The safety and effectiveness of the drug in the treatment of children have not been established. Use in elderly patients In clinical studies, the effectiveness and tolerability of enalapril maleate and hydrochlorothiazide, prescribed simultaneously, were comparable in patients with hypertension (arterial hypertension) of both elderly and young age.
Interaction
Co-Renitec can be used with other antihypertensive drugs. Then the summation of the action is observed. In combination with potassium supplements, potassium-containing salts and potassium-sparing diuretics hyperkalemia is likely .
When interacting with lithium drugs, lithium excretion through the kidneys is reduced. lithium intoxication increases .
NSAIDs reduce the effect of the drug. And if they are taken by patients with kidney function problems, this combination can lead to a deterioration in kidney function. But these changes are reversible.
The hypotensive effect of the drug is reduced by estrogens and ethanol . Immunosuppressants , cytostatics and Allopurinol increase the likelihood of hematotoxicity .
Interactions of the drug Ko-Renitek
Other antihypertensive drugs When enalapril maleate is prescribed in combination with other antihypertensive drugs, an increased hypotensive effect may be observed. Serum potassium Potassium loss during treatment with thiazide diuretics is reduced by enalapril; serum potassium levels usually remain within normal limits. The use of potassium supplements, potassium-sparing diuretics, or potassium salts, especially in patients with renal failure, is not advisable because it may lead to a significant increase in serum potassium levels. Lithium preparations Lithium preparations, as a rule, should not be prescribed with diuretics or ACE inhibitors, since the latter reduce the excretion of lithium in the urine and increase the risk of developing lithium toxicity. It is necessary to study the instructions for use of lithium preparations before prescribing them. NSAIDs In some patients with impaired renal function who are taking NSAIDs, coadministration of ACE inhibitors may result in a further decrease in renal function. These disorders are usually reversible. Non-depolarizing muscle relaxants Thiazides may increase sensitivity to tubocurarine.
Analogues of Ko-Renitek
Level 4 ATX code matches:
Akkuzid
Enap-N
Iruzid
Co-Diroton
Enalozide
Enap NL
Enapril-N
Capozide
Tritace Plus
Enzix
Liprazid
Hartil N
Hartil D
Noliprel
Ko-Perineva
Kaptopres
The following analogues of Co-Renitek are sold in pharmacies:
- Enalapril-HL-Health;
- Berlipril Plus;
- Ena Sandoz Compositum;
- Enalapril-H-Health;
- Enalozide;
- Enalozid Forte;
- Enap-N;
- Enap-HL;
- Enapril-N.
Co-Renitek price, where to buy
The price of Co-Renitek, which contains 28 tablets per package, is on average about 340 rubles.
- Online pharmacies in RussiaRussia
- Online pharmacies in UkraineUkraine
ZdravCity
- KO-Renitek tablets 20mg+12.5mg 28 pcsMerck Sharp & Dohme BV
RUB 548 order
Pharmacy Dialogue
- Co-Renitek (tab. 20/12.5 mg No. 28) Merck Sharp
RUR 534 order
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Pharmacy24
- Tablets Co-Renitek 20/12.5 mg No. 28 Merck Sharp i Dome B.V./Merck Sharp i Dome Limited, Netherlands/Great Britain
189 UAH order