Korenitek - instructions for use, dose, side effects, contraindications

Excipients: sodium bicarbonate 10.0 mg (weight allowance after drying 2.74 mg), lactose water 141.0 mg, corn starch 22.0 mg (weight allowance after drying 20.0 mg), pregelatinized starch 2.2 mg ( allowance for weight after drying 2.0 mg), iron oxide pigment yellow E172 0.5 mg, magnesium stearate 1.1 mg.

Description:Yellow, round, biconcave, with a corrugated edge of the tablet; on one side engraving "MSD 718", on another risk.

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

ATX: & nbsp

C.09.B.A.02 Enalapril in combination with diuretics

Pharmacodynamics:

The drug Korenitek® is a combination of an ACE inhibitor (enalapril) and a diuretic (hydrochlorothiazide).

Co-renitek® provides antihypertensive and diuretic action. Enalapril and hydrochlorothiazide can be used both in monotherapy and simultaneously for the treatment of arterial hypertension (AH). The antihypertensive effects of the components of the drug complement each other, the therapeutic effect persists for 24 hours.

Mechanism of action

Enalapril

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

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

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

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

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

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

Hydrochlorothiazide

The mechanism of antihypertensive action of thiazides is unknown. Usually, thiazides do not affect normal BP values. Hydrochlorothiazide is a diuretic and antihypertensive agent. It affects the mechanism of reabsorption of electrolytes in distal convoluted renal tubules. Hydrochlorothiazide increases the excretion of sodium and chloride in approximately equivalent amounts. Sodium-sulfur may be accompanied by some loss of potassium and bicarbonate ions. After ingestion diuresis begins within 2 hours, reaches a maximum for about 4 hours and lasts about 6-12 hours.

The combination of enalapril and hydrochlorothiazide

In clinical studies, it has been shown that the combination of enalapril and hydrochlorothiazide results in a more pronounced decrease in blood pressure than monotherapy with each drug alone and allows the anti-hypertensive effect of the drug KORENEKT® to be maintained for at least24 hours Enalapril reduces the loss of potassium ions caused by the use of hydrochlorothiazide. Enalapril and hydrochlorothiazide have a similar dosing regimen - a single dose per day, so the drug Korenitek® is a convenient dosage form for the combined use of enalapril and hydrochlorothiazide.

Pharmacokinetics:

Enalapril

After oral administration enalapril quickly absorbed in the gastrointestinal tract. The maximum concentration of enalapril in the blood serum is achieved within 1 hour after ingestion. The degree of absorption of enalapril when ingested is approximately 60%.

After suction enalapril rapidly hydrolyzed to form an active metabolite of the enalaprilatase inhibitor ACE. The maximum concentration of enalaprilate in serum is observed through 3-4 h after taking enalapril dose inside. Enalapril is excreted mainly through the kidneys. The main metabolites, determined in urine, are enalaprilate, which is approximately 40% of the dose, and unchanged enalapril. There are no data on other significant ways of metabolism of enalapril, other than hydrolysis to enalaprilate.The enalaprilate concentration curve in the blood plasma has a long final phase, apparently due to its binding to the ACE. In healthy volunteers with normal renal function, the equilibrium concentration of enalaprilat is reached by the 4th day from the start of enalapril intake. The half-life of enalaprilat with the oral administration of the drug is 11 hours. Eating does not affect the absorption of enalapril. The duration of absorption and hydrolysis of enalapril is similar for different recommended therapeutic doses.

Hydrochlorothiazide

Hydrochlorothiazide is not metabolized, but is quickly excreted by the kidneys. When the concentration of hydrochlorothiazide in the blood plasma was monitored for at least 24 hours, the half-life period varied from 5.6 to 14.8 hours. At least 61% of the ingested dose was excreted unchanged for 24 hours. Hydrochlorothiazide penetrates the placental barrier, but does not penetrate the blood-brain barrier.

The combination of enalapril and hydrochlorothiazide

Regular intake of a combination of enalapril and hydrochlorothiazide does not affect or slightly affects the bioavailability of each component of the drug.The drug Korenitek® is bioequivalent to the combination of hydrochlorothiazide and enalapril.

Indications:Treatment of arterial hypertension in patients who are shown combined therapy.

Contraindications:

- Anuria.

- Hypersensitivity to any of the components of the drug or other sulfonamide derivatives.

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

- Simultaneous use with aliskiren or aliskirenoderzhaschimi drugs in patients with diabetes mellitus and / or renal dysfunction (GFR less than 60 ml / min / 1.73 m²) (see INTERACTION WITH OTHER DRUGS).

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

- Pregnancy and the period of breastfeeding.

- Severe renal impairment (creatinine clearance (CK) less than 30 ml / min).

- Severe liver function disorders (more than 9 on the Child-Pugh scale)

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

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

In some patients, therapy with thiazide diuretics can lead to the development of hyperuricemia and / or exacerbation of gout. but enalapril can increase the excretion of uric acid by the kidneys and thereby weaken the hyperuricemic effect of hydrochlorothiazide.

Pregnancy and lactation:

Use of the drug KORENEKT ® during pregnancy is not recommended. When diagnosing a pregnancy, taking Co-Renictec® should be stopped immediately, unless the drug is considered vital to the mother.

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

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

Perhaps the development of oligohydramnion is due to a decrease in the function of the kidneys of the fetus. This complication can lead to limb contracture, deformation of the skull bones, including its facial part, fetal lung hypoplasia.

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

Routine use of diuretics during pregnancy in healthy women is not recommended, since it exposes the mother and the fetus to unnecessary danger, namely the development of embryonic jaundice and jaundice of newborns, thrombocytopenia and other possible unwanted reactions that have been observed in adult patients.

When prescribing Co-Renictec® during pregnancy, the patient should be informed of the potential risk to the fetus. In those rare cases where the use of the drug during pregnancy is considered necessary, periodic ultrasound examinations should be performed to assess the amniotic fluid index. In case of detection during an ultrasound examination of oligohydramnion, it is necessary to stop taking the drug KORENEKT ®, unless the drug is considered to be vital for the mother. Nevertheless, both the patient and the doctor should know that the oligohydramnion develops with irreversible damage to the fetus.

If ACE inhibitors are used during pregnancy and the development of oligohydramnion is observed, depending on the week of pregnancy, in order to assess the functional state of the fetusit is necessary to carry out a stress test, a stress test, or a biophysical profile of the fetus. Newborns whose mothers took the drug KORENEKT® during pregnancy should be carefully examined for the detection of arterial hypotension, oliguria, and hyperkalemia. Enalapril penetrates the placental barrier. It can be partially removed from the bloodstream of a newborn with peritoneal dialysis. Theoretically, it can also be removed by means of exchange blood transfusion. There is no evidence of the possibility of removing a newborn hydrochlorothiazide from the blood, which also penetrates the placental barrier.

There is limited experience with the use of hydrochlorothiazide during pregnancy, especially in the first trimester. Hydrochlorothiazide penetrates the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide, it can be concluded that its use during the second and third trimesters can lead to a violation of fetoplacental perfusion and cause such effects on the fetus and the newborn as jaundice, a violation of the water-electrolyte balance and thrombocytopenia. Hydrochlorothiazide should not be used to treat gestational edema, gestational arterial hypertension or preeclampsia, as this may lead to a decrease in the volume of circulating blood and placental perfusion without a positive effect on the course of the disease.

Hydrochlorothiazide should not be used to treat hypertension in pregnant women except in rare cases when other therapy is not possible.

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

Dosing and Administration:

Tablets for oral administration.

Arterial hypertension

The recommended dose is 1 tablet 1 time per day. If necessary, the dose may be increased to a maximum daily dose of 2 tablets per day. Prior treatment with diuretics

After the first dose of Co-Renictec®, symptomatic arterial hypotension may develop. This effect is most likely in patients with impaired water-electrolyte balance due to previoustherapy with diuretics. Reception of diuretics should be stopped for 2-3 day before the start of therapy with Co-Renictec®.

Dosage for renal failure

Thiazides may not be effective diuretics in patients with impaired renal function, and when the QC is reduced to 30 ml / min or less (ie, with moderate or severe renal failure) are ineffective. In patients with SC greater than 30 ml / min, but less than 80 ml / min, the preparation of Co-Renictec® should be used only after preliminary selection of the doses of each component of the preparation.

In renal failure (QC more than 30 ml / min, but less than 80 ml / min), the recommended initial dose of enalapril when used in monotherapy is 5 to 10 mg.

Application the elderly patients

Clinical studies of the efficacy and safety of simultaneous use of enalapril and hydrochlorothiazide were similar in elderly (over 65 years) and younger patients with hypertension. It is not necessary to select the initial dose of the drug KORENEKT ® for elderly patients.

Side effects:

The drug Korenitek®, as a rule, is well tolerated.In clinical trials, side effects were usually mild, transient, and did not require discontinuation of treatment.

When using the drug Korenitek®, the following adverse events were observed (very frequent: > 10% frequent: > 1% and <10%, infrequent: > 0.1% and <1%, rare: > 0.01% and <0.1%, very rare: <0.01%, the frequency is unknown: it is impossible to estimate the frequency based on available data):

Violations of the blood and lymphatic system

Infrequent: Anemia (including aplastic and hemolytic).

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

Disorders from the endocrine system

Frequency not set: syndrome of inadequate secretion of antidiuretic hormone. Disorders from the metabolism and nutrition

Frequent: hypokalemia, increased concentration of cholesterol and triglycerides in the blood, hyperuricemia.

Infrequent: hypoglycemia (see SPECIAL INSTRUCTIONS), hypomagnesemia, exacerbation of gout.

Rare: increase in the concentration of glucose in the blood.

Very rare: hypercalcemia (see SPECIAL INSTRUCTIONS).

Violations from the nervous system and mental disorders

Frequent: headache, depression, fainting, change in taste.

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

Rare: unusual dreams, sleep disturbances, paresis (due to hypokalemia).

Disturbances on the part of the organ of sight

Very Frequent: blurred vision.

Hearing disorders and labyrinthine disorders

Infrequent: noise in ears.

Violations from the heart and blood vessels

Very Frequent: dizziness.

Frequent: marked decrease in blood pressure. Orthostatic hypotension, rhythm disturbance, angina pectoris, tachycardia.

Infrequent: "tides" of blood to the skin of the face, palpitations, myocardial infarction or stroke **, possibly secondary to severe arterial hypotension in patients at high risk (see SPECIAL INSTRUCTIONS). Rare: Raynaud's syndrome.

Disturbances from the respiratory system, chest and mediastinal organs

Very Frequent: cough.

Frequent: dyspnea.

Infrequent: rhinorrhea, sore throat, hoarseness of the voice, bronchospasm / bronchial asthma.

Rare: pulmonary infiltrates, respiratory distress syndrome (including pneumonitis and

pulmonary edema), rhinitis, allergic alveolitis / eosinophilic pneumonia.

Disorders from the digestive system

Very Frequent: nausea.

Frequent: diarrhea, abdominal pain.

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

Rare: stomatitis / aphthous ulcers, glossitis.

Very rare: intestinal edema.

Disturbances from the liver and bile ducts

Rare: hepatic insufficiency, hepatic necrosis (possibly fatal), hepatitis (hepatocellular or cholestatic), jaundice, cholecystitis (especially in patients with cholelithiasis in the anamnesis).

Disturbances from the skin and subcutaneous tissues

Frequent: skin rash (exanthema), hypersensitivity reactions / angioedema, angioedema, swelling of the face, extremities, lips, tongue, vocal folds and / or larynx.SPECIAL INSTRUCTIONS).

Infrequent: increased sweating, itching, hives, alopecia.

Rare: erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, purpura, exacerbation of cutaneous lupus erythematosus, pemphigus, erythroderma.

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

Disorders from the musculoskeletal system

Frequent: muscle cramps ***.

Infrequent: convulsions *.

Disorders from the kidneys and urinary tract

Infrequent: impaired renal function, renal failure, proteinuria.

Rare: oliguria, interstitial nephritis.

Violations of the genitals and mammary gland

Infrequent: erectile disfunction.

Rare: gynecomastia.

General disorders

Very Frequent: asthenia.

Frequent: pain in the chest, increased fatigue.

Infrequent: a feeling of discomfort, fever.

Laboratory and instrumental data

Frequent: hyperkalaemia, increased serum creatinine concentration.

Infrequent: increased urea concentration in the blood, hyponatremia. Rare: an increase in the activity of "hepatic" transaminases, an increase in serum bilirubin concentration.

* Observed only with the dosage of hydrochlorothiazide 12.5 and 25 mg.

** The frequency of cases was comparable to the frequency observed in clinical

studies with a placebo or another comparator.

*** Frequent muscle cramps were observed with a dosage of hydrochlorothiazide 12.5 and 25 mg, infrequent muscle spasms were observed with a dosage of hydrochlorothiazide 6 mg.

Overdose:

Enalapril

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

The most common symptoms and signs caused by loss of electrolytes (hypokalemia, hypochloraemia, hyponatremia) and dehydration due to excessive diuresis. If cardiac glycosides were previously used, the flow of arrhythmias may be aggravated by hypokalemia.

Treatment

Data on specific therapy with an overdose of Körnitek® no. Treatment is symptomatic and supportive. The patient should be under close medical supervision, drug therapy should be discontinued. Gastric lavage is recommended if the drug is taken recently, as well as treatment of dehydration, water-electrolyte balance disorders and arterial hypotension with standard measures.

Recommended overdose treatment: intravenous infusion of 0.9% sodium chloride solution. Enalaprilat can be removed from the systemic circulation by hemodialysis (see SPECIAL INSTRUCTIONS, Patients on hemodialysis).

Interaction:

Potassium of blood serum

With the simultaneous use of enalapril with diuretics that cause the loss of potassium ions (thiazides or looped diuretics), the symptoms of hypokalemia can be leveled.The potassium content in the serum usually remains within the normal range. The use of potassium supplements, potassium-sparing diuretics or potassium-containing salts, especially in patients with impaired renal function, can lead to a significant increase in potassium in the serum. If you need to simultaneously use the potassium-containing or potassium-raising drugs listed above, you should be careful and regularly monitor the potassium content in the blood serum.

Lithium preparations

Diuretics and ACE inhibitors reduce the excretion of lithium by the kidneys and increase the risk of developing lithium intoxication. Simultaneous use of the drug Korenitek® and lithium preparations are not recommended. Before using lithium drugs, you should read the instructions for using these drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs)

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

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

An interaction with enalapril may be observed with simultaneous use with the following drugs.

Other antihypertensives

Additive effect can be observed with simultaneous use of enalapril and other antihypertensive therapy.

Simultaneous use of enalapril with β-adrenoblockers, methyldopa or blockers of "slow" calcium channels increased the severity of the antihypertensive effect.

The simultaneous use of enalapril with α-, β-adrenoblockers and ganglion blockers should be performed under close medical supervision.

Simultaneous use of the drug Korenitek® with nitroglycerin, other nitro drugs or other vasodilators increases the antihypertensive effect.

Double blockade of the renin-angiotensin-aldosterone system

Double blockade of RAAS with APA II, ACE inhibitors or aliskiren (renin inhibitor) is associated with an increased risk of developing arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy. Regular monitoring of blood pressure, kidney function and electrolyte content in the blood in patients taking both the preparation of Co-renitek® and other drugs that affect RAAS are necessary. The drug Korenitek® should not be used concurrently with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus

and / or with impaired renal function (GFR less than 60 mL / min / 1.73 m² ).

Preparations of gold

Symptomocomplex (nitrate-like reactions), including a "tide" of blood to the skin of the face,nausea, vomiting and arterial hypotension, was observed in rare cases with simultaneous use of gold preparations for parenteral administration (sodium aurotomy malate) and ACE inhibitors, including enalapril.

Tricyclic antidepressants / antipsychotics / general anesthetics / drugs

Simultaneous use of certain means for general anesthesia, tricyclic antidepressants and neuroleptics with ACE inhibitors may lead to an increase in antihypertensive effect (see SPECIAL INSTRUCTIONS).

Ethanol

Ethanol enhances the antihypertensive effect of ACE inhibitors.

Acetylsalicylic acid, thrombolytics and β-blockers

Enalapril can be used simultaneously with acetylsalicylic acid (as an antiplatelet agent), thrombolytic agents and β-blockers.

Sympathomimetics

Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors. Hypoglycemic agents

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

Interactions with hydrochlorothiazide can be observed with simultaneous use with the following drugs.

Muscle relaxants of a non-depolarizing action type (eg, tubocurarine) -

it is possible to enhance the effect of muscle relaxants.

Ethanol, barbiturates and narcotic analgesics - may potentiate the risk of developing orthostatic hypotension.

Hypoglycemic agents (for oral administration and insulin) - dosage correction of hypoglycemic agents may be required.

Kolestyramine and colestipol - in the presence of anion exchange resins, hydrochlorothiazide absorption is impaired. Kolestyramine and colestipol in a single dose bind hydrochlorothiazide and reduce its absorption in the gastrointestinal tract by 85% and 43%, respectively.

Corticosteroids, adrenocorticotropic hormone (corticotropin) - marked decrease in electrolytes, in particular, the risk of hypokalemia.

Pressor amines (e.g., epinephrine)- it is possible to reduce the severity of the response to the introduction of pressor amines, but does not exclude the possibility of their simultaneous application.

Increase the interval QT (eg, quinidine, procainamide, amiodarone, sotalol) - increased risk of developing pirouette ventricular tachycardia.

Cardiac glycosides - hypokalemia may increase the heart response to toxic effects of cardiac glycosides (eg, increased ventricular excitability). Overdose of "loop" diuretics (eg, furosemide), carbenoxolone, laxatives - hydrochlorothiazide can increase the loss of potassium and / or magnesium.

Cytostatics (e.g. cyclophosphamide, methotrexate)- Thiazides can reduce the excretion of cytotoxic drugs by the kidneys and enhance their mielosupressive effects.

NSAIDs (including COX-2 inhibitors)- In some patients, NSAIDs, including selective inhibitors of COX-2, can reduce the diuretic, natriuretic and antihypertensive effect of diuretics (loop diuretics, potassium-sparing diuretics and thiazides). In this regard, while using the drug Korenitek® and NSAIDs.including COX-2 inhibitors, careful monitoring of the patient is necessary to determine whether a desired diuretic effect is present.

Special instructions:

Arterial hypotension and disturbance of water-electrolyte balance

When using antihypertensive drugs in some patients may develop symptomatic hypotension. Patients should be monitored in order to timely identify clinical signs of a disturbance of the water-electrolyte balance, for example, dehydration, hyponatremia, hypochloraemic alkalosis, hypomagnesemia or hypokalemia, which may develop against the background of concomitant diarrhea or vomiting. Such patients need control of the content of electrolytes in the blood serum.

With special care, the drug should be prescribed to patients with coronary heart disease or cerebrovascular disease, in which excessive reduction in blood pressure can lead to myocardial infarction or stroke.

With the development of arterial hypotension, the patient should be laid and, if necessary, to enter a 0.9% solution of sodium chloride. Transient arterial hypotension with the drug Korenitek® is not a contraindication to its further application. After normalizing blood pressure and replenishing the volume of circulating blood, therapy can be resumed in smaller doses, or each of the components of the drug can be used separately.

Aortic or mitral stenosis / hypertrophic obstructive cardiomyopathy

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

Impaired renal function

Thiazide diuretics can be ineffective in patients with impaired renal function and are ineffective with QC 30 ml / min and lower (ie, with moderate or severe renal failure).

The drug Korenitek® should not be prescribed to patients with renal insufficiency (KC less than 80 ml / min) until the selection of individual active ingredients of the drug will not show that the necessary dose is contained in one tablet of the combined preparation.

In some patients with hypertension without any signs of a history of kidney disease in the treatment of enalapril in combination with a diureticthere was usually an insignificant and transitory increase in the concentration of urea in the blood and creatinine in the blood serum. In such cases, treatment with Co-Renitek®must be terminated. In the future, it is possible to resume therapy in smaller doses, or each of the components of the drug can be used separately. In some patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney in the treatment of ACE inhibitors, there was an increase in the concentration of urea in the blood and creatinine in serum. The changes were usually reversible, and the indicators returned to their initial values after the cessation of treatment. This pattern of changes is most likely in patients with renal insufficiency.

Liver failure

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

Surgical interventions / general anesthesia

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

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

Very rarely reported a lethal outcome due to angioedema, associated with laryngeal edema or edema of the tongue. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction, especially in patients undergoing surgical procedures on the respiratory organs. In cases where edema is localized in the area of the tongue, vocal folds or larynx and can cause airway obstruction, immediate treatment should be prescribed, which may include subcutaneous administration of 0.1% epinephrine (adrenaline) solution (0.3-0.5 ml) and / or provide airway patency. In patients of the Negroid race who took ACE inhibitors, angioedema was observed more often than in patients of other races.

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

In patients taking thiazide diuretics, hypersensitivity reactions can occur even in the absence of an anamnesis of allergic reactions or bronchial asthma.Reported relapses or worsening of the severity of systemic lupus erythematosus in patients taking thiazide diuretics.

Anaphylactoid reactions during desensitization with an allergen from Hymenoptera venom

In rare cases, patients with ACE inhibitors developed life-threatening anaphylactoid reactions during desensitization with an allergen from Hymenoptera venom. Undesirable reactions can be avoided if the ACE inhibitor is temporarily discontinued before desensitization begins. Anaphylactoid reactions during LDL-apheresis

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

Patients on hemodialysis

The use of the drug Co-renitek® is not recommended for patients with renal insufficiency located on hemodialysis. Anaphylactoid reactions were observed in patients on dialysis using high-flux membranes (such as AN 69®) and concomitantly receiving therapy with ACE inhibitors.These patients need to use dialysis membranes of a different type or antihypertensive drugs of other classes.

Kidney transplantation

There is no experience with enalapril in patients after kidney transplantation. Treatment with enalapril patients after kidney transplantation is not recommended. Neutropenia / agranulocytosis

Neutropenia / agranulocytosis, thrombocytopenia and anemia have been observed in patients taking ACE inhibitors. In patients with normal renal function and in the absence of other complicating factors, neutropenia develops rarely. Enalapril should be used with extreme caution in patients with systemic connective tissue diseases receiving immunosuppressive therapy, allopurinol or procainamide therapy, or having a combination of these complicating factors, especially if there are abnormalities in kidney function in the anamnesis. Some of these patients developed serious infectious diseases, which in some cases did not respond to intensive antibiotic therapy. If enalapril is used in such patients, it is recommended to carry out periodic monitoring of the number of white blood cells and patients should be warned about the need to report any signs of infection.

Lithium preparations

It is not recommended simultaneous use of drugs lithium, enalapril and diuretics (see INTERACTION WITH OTHER DRUGS).

Cough

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

Hyperkalemia (see INTERACTION WITH OTHER DRUGS)

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

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

If it is necessary to simultaneously use the drug Korenitek® and the medicines listed abovemeans should be careful and regularly monitor the potassium content in the blood serum.

Metabolic and endocrine effects

Thiazide therapy may impair glucose tolerance. In some cases, a dose adjustment of hypoglycemic agents, including insulin, may be required. Thiazides can reduce the excretion of calcium by the kidneys and cause a short-term and insignificant increase in serum calcium. Expressed hypercalcemia may be a sign of latent hyperparathyroidism. In connection with the effect of thiazides on calcium metabolism, their reception may distort the results of the study of parathyroid gland function, therefore, before the study of parathyroid function, the thiazide diuretic should be canceled.

An increase in the concentration of cholesterol and triglycerides in the blood can also be associated with therapy with thiazide diuretics, however, with the dose of hydrochlorothiazide 12.5 mg contained in 1 tablet of the drug Korenitek®, similar effects were not observed or were of minor character.

Diseases of the liver

Thiazide diuretics should be used with caution in patients with impaired liver function or progressive liver disease, because even small changes in the water-electrolyte balance can lead to a "hepatic" coma. Anti-doping test

Hydrochlorothiazide can lead to false-positive analytical results

when conducting an anti-doping test.

Acute myopia and secondary closed angle glaucoma

Hydrochlorothiazide, being a sulfonamide derivative, can cause an idiosyncratic reaction in the form of acute transient myopia and acute closed-angle glaucoma. Symptoms of these disorders are an unexpected reduction in visual acuity or eye pain, which typically occurs within a few hours to several weeks after starting the drug. If therapy is not available, acute angle-closure glaucoma can lead to loss of vision. The main treatment consists in the fastest possible removal of hydrochlorothiazide.It should be borne in mind that if intraocular pressure remains uncontrolled, urgent surgical or surgical treatment may be required. The risk factors for the development of acute closed-angle glaucoma include information about allergies to sulfonamides or penicillin in the anamnesis.

Effect on the ability to drive transp. cf. and fur:When driving vehicles or working with machinery, the possibility of developing dizziness or weakness should be considered (see ADVERSE EFFECTS).

Form release / dosage:

Tablets 12.5 mg + 20 mg.

Packaging:

For 7 tablets in PVC / Al blister. For 2 or 4 blisters together with the instructions for use are placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 30 ° C. Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N013201 / 01

Date of registration:03.10.2011

Manufacturer: & nbsp

MERCK SHARP & DOHME, B.V. Netherlands

Representation: & nbspMSD Pharmaceuticals Ltd.MSD Pharmaceuticals Ltd.

Information update date: & nbsp27.12.2018

Illustrated instructions

Instructions

Co-Renitek® (Co-renitec®)