Enalapril / Hydrochlorothiazide-Teva - instructions for use, dose, side effects, contraindications

Composition:1 tablet contains: active substances: Enalapril maleate 20.0 mg, hydrochlorothiazide 12.5 mg; Excipients: lactose monohydrate 140.0 mg, corn starch 6.0 mg, pregelatinized starch 16.0 mg, sodium hydrogen carbonate 11.6 mg, magnesium stearate 1.5 mg.

Description:Round biconvex tablets of white color.On one side - dividing risk and engraving "EL", "20", the other side is smooth.

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

ATX: & nbsp

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

Pharmacodynamics:

Combined antihypertensive drug, which includes enalapril an angiotensin-converting enzyme (ACE) inhibitor; and hydrochlorothiazide - Thiazide diuretic. Has antihypertensive and diuretic effect.

Enalapril catalyzes the conversion of angiotensin I to the pressor substance angiotensin II. After suction enalapril is converted by hydrolysis into enalaprilate, which inhibits ACE. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which leads to an increase in renin plasma activity (due to elimination of reverse negative reaction to changes in renin production) and a decrease in aldosterone secretion. The ACE is identical to the kinase II enzyme, so enalapril can also block the destruction of bradykinin, which has a vasodilating effect.The significance of this mechanism in the therapeutic action of enalapril requires refinement. Although enalapril reduces blood pressure (BP) by suppressing the renin-angiotensin-aldosterone system, which plays an important role in the regulation of blood pressure, enalapril reduces blood pressure even in patients with hypertension with a low concentration of renin. Decrease in blood pressure is accompanied by a decrease in total peripheral vascular resistance (OPSS), a slight increase in cardiac output and no changes or slight changes in heart rate (HR). As a result of enalapril, renal blood flow increases, the glomerular filtration rate remains unchanged. However, in patients with initially reduced glomerular filtration, its rate usually increases.

Hypotensive therapy with enalapril leads to a significant regression of left ventricular hypertrophy and preservation of left ventricular systolic function. Therapy with enalapril is accompanied by a favorable effect on the ratio of fractions of lipoproteins and the absence of influence or favorable effect on the content of total cholesterol.The use of enalapril in patients with hypertension leads to a decrease in blood pressure in both the "standing" and "lying" positions without a significant increase in heart rate.

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

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

Hydrochlorothiazide has a diuretic and antihypertensive effect, increases the activity of renin, stimulates the secretion of aldosterone, increases the concentration of angiotensin II, reduces the reabsorption of sodium and chlorine ions, to a lesser extent - potassium and bicarbonate ions in the proximal tubule of the kidneys, increases the excretion of magnesium ions and reduces - calcium ions, urinary acid.Oppresses the reactivity of the vascular wall with respect to the vasoconstrictive effects of mediators in connection with a decrease in the concentration of sodium ions in the cytoplasm of myocyte vessels, reduces the volume of circulating blood (BCC), lowers blood pressure. Diuretic effect occurs after 2 hours, reaches a maximum after 4 hours and lasts up to 12 hours.

The use of a combination of enalapril and hydrochlorothiazide results in a more pronounced decrease in blood pressure compared to monotherapy with enalapril or hydrochlorothiazide and allows the antihypertensive effect to be maintained for at least 24 hours. Enalapril reduces the loss of potassium ions caused by the use of hydrochlorothiazide.

Pharmacokinetics:

Enalapril

Suction. After oral administration, it is rapidly absorbed. Absorption is approximately 60% and is not dependent on food intake. The maximum concentration (C_max) in the blood serum is observed within 1 h after administration. After absorption, it rapidly hydrolyses to form an active metabolite of enalaprilate, an ACE inhibitor. FROM_max is observed 3-4 hours after taking the dose inside.

Distribution. 50-60% binds to blood plasma proteins.The constant concentration of enalaprilat in the serum is reached approximately on the 4th day. It penetrates the hematoplacental barrier and is excreted in breast milk.

Metabolism and excretion. After suction enalapril is converted by hydrolysis into enalaprilate, there are no data on other significant metabolic pathways. It is excreted mainly by the kidneys. The main metabolites, determined in urine, are enalaprilate, which is approximately 40% of the dose, and unchanged enalapril. The concentration curve of enalaprilate in blood plasma has a long final phase, which is apparently due to its binding to the ACE. In patients with normal renal function, the equilibrium concentration of enalaprilat is reached on the 4th day after the start of enalapril. The half-life (T_1/2) enalaprilata with the course use of enalapril inside is 11 hours.

Hydrochlorothiazide

Suction. After ingestion, 60-80% of the dose is absorbed from the gastrointestinal tract (GIT). Time to reach C_maxin the blood plasma -1,5-3 h.

Distribution. 40-60% binds to blood plasma proteins. It penetrates the hematoplacental barrier and is excreted in breast milk.

Metabolism and distribution. Not exposed to metabolism.It penetrates the hematoplacental barrier and is excreted in breast milk, does not penetrate the blood-brain barrier.

Excretion. T_1/2 differs in different patients and ranges from 6 to 25 hours. Kidney clearance is 90% of the total clearance, 95% is unchanged. In renal and heart failure, as well as in elderly patients, renal clearance of hydrochlorothiazide is reduced, T_1/2 and C_max increased.

Indications:Arterial hypertension (with ineffectiveness of ACE monotherapy with inhibitors, patients requiring combination therapy).

Contraindications:

Hypersensitivity to enalapril, hydrochlorothiazide, other derivatives of sulfonamide and other components of the drug; angioedema in history, associated with the administration of ACE inhibitors, as well as hereditary or idiopathic angioedema: anuria; renal failure of severe degree (QC less than 30 ml / min); hepatic failure of severe degree; simultaneous use with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and / or renal dysfunction (GFR less than 60 ml / min / 1.73 m²) (cm.Interaction with other medicinal products); age to 18 years; lactose intolerance, lactase deficiency. syndrome of glucose-galactose malabsorption; pregnancy and breastfeeding.

Carefully:Violation of the water-electrolyte balance (reduction of bcc, hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia), which can develop against a background of intercurrent diarrhea or vomiting, in patients observing a diet with restriction of table salt during dialysis; aortic or mitral stenosis: hypertrophic obstructive cardiomyopathy (GOKMP); cerebrovascular diseases, ischemic heart disease (IVS). systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), oppression of bone marrow hematopoiesis, immunosuppressive therapy, diabetes mellitus, bilateral stenosis of the renal arteries, stenosis of the single kidney artery, condition after kidney transplantation, treatment with allopurinol or procainamide; hyperkalemia, concomitant use with potassium-sparing substitutes for table salt and lithium preparations: low-density lipoprotein(LDL) -afferes with dextran sulfate; during desensitization with the allergen from the Hymenoptera venom; in patients undergoing dialysis with the use of high-flow membranes (such as AN69®); in patients after major surgery or in general anesthesia; in patients of the Negroid race.

Pregnancy and lactation:

The use of ACE inhibitors in the II and III trimesters of pregnancy can cause the disease or death of a fetus or newborn. It is not recommended to use the drug Enalapril / Hydrochlorothiazide-Teva during pregnancy. If pregnancy is established, use Enalapril / Hydrochlorothiazide-Teva immediately and consult a doctor.

According to the results of the epidemiological study of newborns whose mothers took ACE inhibitors in 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 use of ACE inhibitors during the II and III trimesters of pregnancy was accompanied by a negative effect on the fetus and newborn,including the development of arterial hypotension, renal failure, hyperkalemia and / or hypoplasia of the skull bones. In addition, it was reported on the development of prematurity, the retardation of intrauterine development and the non-proliferation of the arterial duct, but it was not clear whether these pathological conditions were due to the intake of the ACE inhibitor mother. Perhaps the development of oligohydramnion, apparently due to a decrease in the function of the kidneys of the fetus. This complication can lead to limb contracture, deformation of the bones of the skull, including its facial part, and lung hypoplasia. The use of diuretics during pregnancy is not recommended because it can cause jaundice of the fetus and newborn, thrombocytopenia and possibly other unwanted reactions observed in adult patients. In those rare cases when the use of the drug during pregnancy is considered necessary, periodic ultrasound examinations should be performed to assess the intra-amniotic space. In case of detection of oligohydramnion during ultrasound examination, it is necessary to stop taking the drug, unless its reception is not 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, a contractual stress test, a stress test, or a biophysical profile of the fetus may be necessary to assess the functional state of the fetus. Newborns whose mothers took the drug should be carefully monitored for the detection of arterial hypotension, oliguria, and hyperkalemia. In the case of development of oliguria, the attention of the doctor should be directed to the maintenance of blood pressure and renal perfusion.

Enalapril and hydrochlorothiazide excreted in breast milk. If you need to use Enalapril / Hydrochlorothiazide-Teva during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, 1 time per day, at the same time of day, regardless of food intake. Before using Enalapril / Hydrochlorothiazide-Teva, diuretics should be discontinued.

The initial dose is 1 tablet once a day.If necessary, the dose can be increased to 2 tablets once a day.

In patients with severe renal insufficiency (CC less than 30 ml / min) The drug Enalapril / Hydrochlorothiazide-Teva is not used.

In patients with mild and moderate renal insufficiency (KC more than 30 ml / min) the drug Enalapril / Hydrochlorothiazide-Teva can be used only after the stabilization of blood pressure on the background of drug treatment enalapril and hydrochlorothiazide in separate dosage forms and the selection of their doses. The recommended initial dose of Enalapril / Hydrochlorothiazide-Teva is 1/2 tablet once a day. It should be regularly monitored (every 2 months) potassium content and creatinine concentration.

In elderly patients the recommended initial dose is 1/2 tablets once a day.

Side effects:

In clinical studies of the enalapril / hydrochlorothiazide combination, no adverse events specific to this combination drug were observed. Undesirable effects were limited to those reported earlier with enalapril and / or hydrochlorothiazide alone.

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - at least 10%; often - not less than 1%,but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - 0.01%, including individual reports.

Enalapril

From the side of the blood and lymphatic system: rarely - reduction of hemoglobin, decrease in hematocrit; very rarely - oppression of bone marrow function, anemia, thrombocytopenia, leukopenia, neutropenia and agranulocytosis, hemolytic anemia, lymphadenopathy, eosinophilia.

From the endocrine system: rarely - the syndrome of inadequate secretion of antidiuretic hormone.

From the nervous system: often - headache, dizziness, fainting; infrequently - insomnia, anxiety, panic condition, confusion, depression, sleep disturbance, drowsiness, "nightmarish" dreams; rarely - memory impairment, paresthesia, peripheral neuropathy, tremor, migraine, confusion.

From the side of the organ of vision: rarely - visual impairment, conjunctivitis, decreased visual acuity, dryness and burning eyes.

From the side of the hearing organ and labyrinthine disorders: infrequently - vertigo, noise in the ears.

From the cardiovascular system: often - marked decrease in blood pressure, orthostatic hypotension; infrequently - pain in the chest, stenocardia, atrioventricular blockade of the II degree, cerebral circulation,myocardial infarction, palpitation, arrhythmia (atrial fibrillation, sinus bradycardia, tachycardia, ventricular fibrillation).

From the respiratory system, chest and mediastinum: often - cough; infrequently - a rhinitis, zalozhennost a nose; very rarely - sinusitis, pharyngitis, laryngitis, sore throat, hoarseness, dyspnea, bronchitis, lung infiltrates, bronchospasm / bronchial asthma.

From the digestive system: often - nausea, diarrhea; infrequently - abdominal pain, constipation; rarely - dryness of the oral mucosa, stomatitis, flatulence, vomiting, gastritis; very rarely - pancreatitis, intestinal obstruction.

From the liver and bile ducts: infrequently - increased activity of "liver" transaminases, increased bilirubin concentration; very rarely - a violation of the liver, hepatitis (hepatocellular or cholestatic), jaundice.

From the skin and subcutaneous tissues: rarely - alopecia, psoriasis, dermatitis, dry skin; very rarely - pseudolymphoma, pemphigus.

Allergic reactions: infrequently - skin rash, itchy skin; rarely - angioedema, swelling of the face, extremities, lips, tongue,glottis and / or larynx, dysphonia, urticaria; very rarely - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, photosensitization.

From the side of the musculoskeletal and connective tissue: often - muscle spasm, back pain, leg pain, myalgia; infrequently - pain in the hands, arthralgia, musculoskeletal pain, tight mobility and swelling of the joints.

From the urinary system: often - renal dysfunction; rarely uremia, acute renal failure; very rarely - oliguria, anuria.

On the part of the reproductive system: infrequently - impotence; rarely - gynecomastia.

Other: often - asthenia, fatigue, hyperkalemia; infrequent - increased body temperature, a slight increase in the concentration of urea and creatinine; rarely - hyponatremia; very rarely - hyperglycemia, epistaxis, vasculitis, the phenomenon of Raynaud, "hot flashes" of blood to the skin of the face.

Hydrochlorothiazide

From the side of the blood and lymphatic system: rarely - neutropenia and agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, leukopenia, oppression of bone marrow function.

From the side of metabolism and nutrition: infrequently - anorexia, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia, increased cholesterol and triglycerides, gout.

From the nervous system: often - depression, sleep disturbance; infrequently - insomnia, paresthesia, dizziness.

From the side of the organ of vision: rarely - transient visual impairment, xantopsy.

From the organ of hearing: rarely - vertigo.

From the cardiovascular system: rarely - orthostatic hypotension.

From the respiratory system, chest and mediastinum: infrequently - respiratory distress syndrome, pneumonitis, pulmonary edema.

From the digestive system: rarely - sialadenitis, constipation, diarrhea, irritation of the gastrointestinal mucosa; very rarely - pancreatitis.

From the liver and bile ducts: infrequently, ehtuha (intrahepatic cholestasis).

Allergic reactions: rarely - photosensitivity; very rarely - hives, toxic epidermal necrolysis, Lyell's syndrome.

From the side of the musculoskeletal and connective tissue: infrequently - muscular spasm.

From the urinary system: infrequently - glucosuria, interstitial nephritis, renal failure.

Other: infrequently - fever, hyperkalemia, vasculitis.

Overdose:

Symptoms: marked decrease in blood pressure, collapse, water-electrolyte disorders, increased diuresis, renal failure, cough, palpitations, tachycardia, bradycardia, heart rhythm disturbance, dizziness, anxiety, confusion, convulsions, paresis.

Treatment: induction of vomiting, gastric lavage, reception of activated charcoal, intravenous (iv) administration of 0.9% sodium chloride solution, electrolytes, symptomatic therapy, if necessary - hemodialysis. The specific antidote is unknown.

Interaction:

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.

ACE inhibitors and diuretics can reduce renal clearance of lithium and increase the risk of its toxic effects. It is not recommended simultaneous use of enalapril / hydrochlorothiazide and lithium preparations.

In some cases, the use of non-steroidal anti-inflammatory drugs drugs

(NSAIDs), including cyclooxygenase-2 inhibitors (COX-2), can reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics and other antihypertensive agents, including ACE inhibitors. In patients with impaired renal function taking NSAIDs, including COX-2 inhibitors, treatment with ACE inhibitors, including enalapril, can cause further impairment of kidney function, including acute kidney failure, which is usually reversible. Simultaneous use of ACE inhibitors. including enalapril, with potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium-containing additives or potassium salts, including in patients with impaired renal function or diabetes mellitus, can lead to an increase in serum potassium. Simultaneous use of enalapril with beta-blockers, methyldopa or blockers of "slow" calcium channels increased the severity of the antihypertensive effect.

Simultaneous use of enalapril with alpha, beta-adrenoblockers and ganglion blockers should be carried out under the supervision of a doctor.

Simultaneous use of enalapril / hydrochlorothiazide with nitroglycerin, other nitro drugs or other vasodilators enhances the antihypertensive effect.

Double blockade of RAAS using angiotensin II receptor antagonists (ARA II), ACE inhibitors or aliskiren (inhibitor renin) 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 enalapril / hydrochlorothiazide and other medicines. influencing RAAS. Enalapril / hydrochlorothiazide should not be used concomitantly with aliskiren or aliskiren containing and preparations in patients with diabetes mellitus and / or renal dysfunction (GFR less than 60 ml / min / 1.73 m²).

With the simultaneous use of ACE inhibitors, including enalapril, with tricyclic antidepressants and, baclofen, amifostine, the risk of a sudden drop in blood pressure increases. At simultaneous application of ACE inhibitors, including enalapril, with preparations of gold (sodium aurotomy malate) it is possible to develop nitrate-like reactions (headache that usually occurs at the beginning of treatment, tachycardia, orthostatic hypotension, manifested by dizziness, weakness and even short-term loss of consciousness). Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors. including enalapril. With simultaneous use of ACE inhibitors, including enalapril, with other antihypertensive agents, observationadditive effect is given. With the simultaneous use of ACE inhibitors, including enalapril, with insulin and other hypoglycemic agents for oral administration, the risk of hypoglycemia increases, especially in patients with renal insufficiency. With the simultaneous use of ACE inhibitors, including enalapril, with allopurinol, cytostatics, procaine-house, immunosuppressive drugs, their myelosuppressive effect is increased and the risk of developing renal failure increases.

With simultaneous use of ACE inhibitors, including enalapril, with cyclosporine, lovastatin, the risk of renal dysfunction and the development of hyperkalemia is increased.

According to reports, rifampicin and fluconazole reduce the concentration of the active metabolite of enalapril, the clinical significance of this interaction has not been studied.

Simultaneous application gidrohlorogiazida with corticosteroids, corticotropin, carbenoxolone, amphotericin B, trimethoprim can lead to a marked reduction in the content of electrolytes, in particular, can cause hypokalemia.

Simultaneous use of hydrochlorothiazide with calcium preparations can cause hypercalcemia. This should be taken into account also when examining the function of parathyroid glands.

With the simultaneous use of thiazide diuretics, including hydrochlorothiazide. with cardiac glycosides, because of the possible development of hypokalemia, the likelihood of the toxic effect of cardiac glycosides, in particular, arrhythmias, increases.

Anion exchange resins, as well as colestramine or colestipol in single doses bind hydrochlorothiazide and reduce its absorption from the digestive tract by 85% and 43%, respectively.

It is possible to enhance the action of nondepolarizing muscle relaxants (tubocurarine) against hydrochlorothiazide. With simultaneous application with atropine,biperidenom may increase the bioavailability of thiazide diuretics, including hydrochlorothiazide, due to a decrease in gastrointestinal motility and the rate of gastric emptying.

Simultaneous use of thiazide diuretics. including hydrochlorothiazide, with quinidine, disopyramide, amiodarone, sotalol, ibutilide, chlorpromazine, haloperidol, sulpiride, erythromycin, pentamidine, terfenadine can cause hypokalemia and thereby cause the development of pirouette type arrhythmias. Individual cases of development have been reportedhemolytic anemia at one-timeuse of thiazide diuretics and methyldopy.

With the simultaneous use of thiazidediuretics, including hydrochlorothiazide, with carbamazepine there is a risk development of hyponatremia. With the development of dehydration against the background ofchanges in thiazide diuretics, includingle hydrochlorothiazide, there is a possibilitythe development of acute renal insufficiencyaccuracy, especially with simultaneous application with iodine preparations.

Thiazide diuretics, including hydrochlorothiazidechlorothiazide, can enhance toxic effects of salicylates on the central nervous system when applied to youdoses.

With the simultaneous use of thiazidediuretics, including hydrochlorothiazide, with barbiturates, opioid analgesics, ethanol is possiblerisk of orthostatic gipotency.

In clinical studies of pharmacologynoits was not clinically knowninteraction of enalapritela / hydrochlorothiazide with warfarin, cimehydin, phenobarbital, ketoconazole and erythromycin.

Special instructions:

During treatment with Enalapril / Hydrochlorothiazide-Teva, as with any antihypertensive therapy, there may be a marked decrease in blood pressure. Patients should be examined from the point of view of revealing the clinical signs of disturbance of the water-electrolyte balance, i.e. dehydration of the body, hyponatremia, hypo-chloremicemic alkalosis, hypomagnesemia or hypokalemia that may occur as a result of episodes of diarrhea or vomiting. as a result of diuretic therapy, while limiting intake of table salt. Treatment of patients with the drug Enalapril / Hydrochlorothiazide-Teva should be carried out under medical supervision and regular analysis of the water-electrolyte blood composition.Caution should be exercised when performing physical exercises or in hot weather (the risk of dehydration and a marked decrease in blood pressure due to a decrease in BCC). Transient arterial hypotension is not a contraindication for continuing treatment with Enalapril / Hydrochlorothiazide-Teva after stabilization of blood pressure. In the case of a re-expressed decrease in blood pressure should reduce the dose or cancel the drug Enalapril / Hydrochlorothiazide-Teva. With the development of a marked decrease in blood pressure, the patient should be in a horizontal position, if necessary, 0.9% solution of sodium chloride and / or plasma-substituting solutions are administered.

Precautions should be taken with Enalapril / G Hydrochlorothiazide-Teva in patients with ischemic heart disease, CHF, and cerebrovascular diseases. a marked decrease in blood pressure can lead to the development of myocardial infarction, stroke, or impaired renal function.

As with other medications with vasodilator action, caution should be exercised in patients with aortic and mitral stenosis or GOKMP with Enalapril / Hydrochlorothiazide-Teva.

The sudden withdrawal of Enalapril / Hydrochlorothiazide-Teva does not lead to a withdrawal syndrome. Before surgery (including dentistry), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors, including Epalapril / Hydrochlorothiazide-Teva. The drug Enalapril / Hydrochlorothiazide-Teva should not be taken with mild and moderate renal failure (QC more than 30 ml / min) until the dosage of the medicinal preparations enalapril and hydrochlorothiazide has been selected in separate dosage forms. In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney during treatment with ACE inhibitors, an insignificant and transient increase in serum urea and creatinine levels may occur. In such cases, treatment with Enalapril / Hydrochlorothiazide-Teva should be discontinued. In the future, it is possible to resume therapy with the drug Enalapril / Hydrochlorothiazide-Teva in reduced doses or the use of individual dosage forms of drugs enalapril and hydrochlorothiazide. An increase in the concentration of creatinine and urea in the blood plasma against the background of treatment with ACE inhibitors in patients with hypertension without kidney disease is also a signal to cancel the drug Enalapril / Hydrochlorothiazide-Teva and revision of the regimen for the treatment of hypertension.

Simultaneous use of ACE inhibitors, ARA II or aliskiren increases the risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure). Double blockade of RAAS with the use of ACE inhibitors, APA II or aliskiren is not recommended (see section "Interaction with other drugs").

If a double blockade of RAAS is considered absolutely necessary, then treatment should only be performed under the supervision of specialists and should be accompanied by careful and frequent monitoring of kidney function. the content of electrolytes and blood pressure. ACE inhibitors and APA II, should not be used simultaneously in patients with diabetic nephropathy. With the use of ACE inhibitors in renovascular hypertension, there is also a high risk of a marked decrease in blood pressure.so treatment in such patients begins with a low dose of Enalapril / Hydrochlorothiazide-Teva under the supervision of a doctor. Caution should be applied to ACE inhibitors in patients with impaired hepatic function or with progressive liver disease, since even small disturbances of the water-electrolyte balance can lead to the development of hepatic coma.

There are reports that ACE inhibitors were the cause of the development of the symptom complex, which began with cholestatic jaundice and quickly progressed to liver necrosis (in some cases, fatal). The drug Enalapril / Hydrochlorothiazide-Teva should be discontinued if jaundice has developed during treatment or the activity of "liver" enzymes has increased.

In the treatment of ACE inhibitors, rare cases of angioneurotic edema of the face, extremities, lips, tongue, vocal folds and / or larynx have been described that may lead to airway obstruction, especially in patients undergoing surgical procedures on respiratory organs. There are rare reports of death in connection with angioedema, accompanied by edema of the larynx or edema of the tongue.These reactions can occur at any stage of therapy. In such cases, it is necessary to immediately stop taking Enalapril / Hydrochlorothiazide-Teva and to carefully monitor the patient's condition in order to monitor and correct clinical symptoms. With a history of angioedema, unrelated to ACE inhibitors, the risk of angioedema developing significantly increases with the use of Enalapril / Hydrochlorothiazide-Teva. There are reports of life-threatening anaphylactic reactions against the background of treatment with ACE inhibitors that have arisen from the bites of Hymenoptera (for example, bees, wasps). In rare cases, patients receiving ACE inhibitors during LDL-apheresis with dextran sulfate developed life-threatening anaphylactic reactions. The use of high-flow dialysis membranes (such as AN69) increases the risk of developing an anaphylactic reaction with ACE inhibitors during the hemodialysis procedure.

Discontinuation of therapy with Enalapril / Hydrochlorothiazide-Teva in each of the cases of threat of anaphylactic reaction may prevent such reactions.

On the background of therapy with ACE inhibitors, cough may appear. As a rule, it is a dry cough, has a permanent character and disappears after the cessation of treatment. Cough associated with the use of ACE inhibitors should be considered in the differential diagnosis of cough. Neutropenia / agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function, neutropenia is very rare. Neutropenia and agranulocytosis are reversible after discontinuation of ACE inhibitors.

In patients with severe autoimmune systemic diseases of connective tissue (including systemic lupus erythematosus, scleroderma) against the background of treatment with ACE inhibitors, severe infectious diseases developed which are resistant to intensive antibiotic therapy. Use with caution the drug Enalapril / Hydrochlorothiazide-Teva in this category of patients. The use of hydrochlorothiazide may cause impaired glucose tolerance. When treatment with Enalapril / Hydrochlorothiazide-Teva, dosages of hypoglycemic agents, including insulin, may be required. Treatment with hydrochlorothiazide can

reduce the excretion of calcium by the kidneys, and also cause a slight and transient increase in the serum calcium level. Expressed hypercalcemia may be a sign of latent hyperparathyrosis. The intake of Enalapril / Hydrochlorothiazide-Teva should be discontinued before the study of parathyroid function.

Therapy with hydrochlorothiazide can lead to hyperuricemia and / or gout in some patients. Enalapril can increase the excretion of uric acid by the kidneys and thereby weaken the hyperuricemic effect. It is necessary to carry out periodic monitoring of the concentration of uric acid in order to prevent exacerbation of the gout during treatment with the drug Enalapril / Hydrochlorothiazide-Teva.

The risk of developing 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-containing

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

If it is necessary to simultaneously use enalapril / hydrochlorothiazide and the medicines listed above, care should be taken and the serum potassium content is regularly monitored. Hydrochlorothiazide can lead to false-positive analytical results during the anti-doping test.

Hydrochlorothiazide, which is a sulfonamide derivative, can induce an idiosyncratic reaction in the form of acute transient myopia and acute closed-angle glaucoma, which may manifest an unexpected decrease in vision or pain in the eyes, and typically occurs a few hours to several weeks after the start of the drug . If therapy is not performed, acute angle-closure glaucoma can lead to loss of vision. It is necessary to cancel as soon as possible hydrochlorothiazide. In the event that intraocular pressure remains uncontrollable, immediate surgical or surgical treatment may be required.The risk factors for the development of acute closed-angle glaucoma include information on allergy to sulfonamides and penicillin in history.

Effect on the ability to drive transp. cf. and fur:Caution should be exercised when using Enalapril / Hydrochlorothiazide-Teva because of the possible development of adverse reactions (dizziness), which can adversely affect the ability to drive vehicles and perform potentially dangerous activities requiring increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets 20 mg + 12.5 mg.

Packaging:

For 10 tablets per blister of OPA / Al / PVC film and aluminum foil.

By 2, 3, 5, 6, 9 or 10 blisters together with instructions for use in a cardboard box.

For 7 tablets per blister of OPA / Al / PVC film and aluminum foil.

For 2, 4 or 8 blisters together with instructions for use in a cardboard box.

Storage conditions:Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001099

Date of registration:03.11.2011

The owner of the registration certificate:TEVA, LLC TEVA, LLC Russia

Manufacturer: & nbsp

TEVA Pharmaceutical Works Private, Ltd. Co. Hungary

Information update date: & nbsp24.12.2015

Illustrated instructions

Instructions

Enalapril / Hydrochlorothiazide-Teva (Enalapril / Hydrochlorothiazide-Teva)