Enaloside Forte tablets # 30

Enalopril instructions for use

Composition:

active ingredients : enalapril maleate, hydrochlorothiazide; 1 tablet contains in terms of 100% dry matter: enalapril maleate - 20 mg, hydrochlorothiazide - 12.5 mg;
auxiliary substances: sodium bicarbonate; corn starch; pregelatinized starch 1500; lactose monohydrate (200); iron oxide yellow (E 172); magnesium stearate.

Dosage form.

Pills.

Pharmacotherapeutic group.

Combined preparations of inhibitors of angiotensin-converting enzyme and diuretics. ATC code C09B A02.

Indications.

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

Contraindications.

Hypersensitivity to any of the components of the drug and to other derivatives of the sulfonamide. Angioedema, a history of angiotensin-converting enzyme (ACE) inhibitors, as well as a hereditary or idiopathic angioedema. Severe renal (creatinine clearance

<30 ml / min) or liver failure. Anuria. Stenosis of the renal arteries. During the hemodialysis. Condition after kidney transplantation. Significant disturbance of the electrolyte balance. Haemodynamically significant stenosis of the aorta.Pregnancy and lactation. Childhood.

Method of administration and dose.

Arterial hypertension. The initial dose of Enalozide Forte is 1 tablet once a day. If the desired effect is not achieved, then the daily dose is increased to 2 tablets once a day. The maximum dose is 2 tablets per day.

With renal failure. For patients with impaired renal function and moderate or severe renal failure (creatinine clearance level of 30 ml / min and below), thiazides may not be effective enough.

If the level of creatinine is in the range of 30 to 80 ml / min, Enaloside Forte is used only after a preliminary dose adjustment of each of the components.

With moderate renal failure, the recommended dose of enalapril maleate, which is taken alone, is 5 to 10 mg.

Prior therapy with diuretics. If the patient is already receiving diuretics, then it is recommended to cancel or reduce the dose of diuretics 2-3 days before the start of Enaloside Forte therapy, in order to avoid a sharp drop in blood pressure.Symptomatic arterial hypotension can occur at the beginning of therapy with the drug and is more often observed in patients in whom previous diuretic therapy caused a disturbance of the water-electrolyte balance.

Adverse reactions.

Treatment with Enalozide Forte, as a rule, is well tolerated.

The side effects that most often occurred-dizziness and increased fatigue-were minor and disappeared with a lower dose and only occasionally required the drug to be discontinued.

Side effects occurred with a frequency of 1-2% of cases: orthostatic effects, including arterial hypotension, headache, muscle cramps, nausea, asthenia, cough and impotence.

Side effects that rarely occurred:

From the cardiovascular system: fainting, arterial hypotension, severe palpitation, tachycardia, arrhythmia, chest pain.

On the part of the gastrointestinal tract: pancreatitis, diarrhea, vomiting, dyspepsia, abdominal pain, flatulence, constipation.

From the nervous system / psyche: insomnia, drowsiness, paresthesia, nervousness, fainting.

From the respiratory system: shortness of breath.

Dermatological reactions: erythema multiforme (Stevens-Johnson syndrome), toxic epidermal necrolysis, rash, photosensitization, pruritus, excessive sweating and other dermatological manifestations.

On the part of the hematopoiesis system: a positive test for antinuclear antibodies (ANA), an increase in the rate of erythrocyte sedimentation, eosinophilia and leukocytosis.

Allergic reactions: hypersensitivity, angioedema.

Laboratory data: hyperglycemia, hyperuricemia and hypo- or hyperkalemia, decreased hemoglobin and hematocrit, increased blood urea, serum creatinine, increased levels of hepatic enzymes and / or bilirubin in blood serum, hypoglycemia in patients taking hypoglycemic agents were rarely reported.

Other: renal dysfunction, kidney failure, decreased libido, dry mouth, gout, tinnitus, arthralgia, fever, serositis, vasculitis, myalgia, myositis, arthralgia / arthritis, syndrome of impaired secretion of antidiuretic hormone, anorexia.

Clinically significant changes in laboratory parameters during prescribing were rarely observed. These indicators usually returned to normal after discontinuation of therapy.

Adverse reactions that were observed with the use of individual components of the drug and may be potential side effects of Enalozide Forte.

Enalapril. Ileus, hepatic insufficiency, hepatitis (hepatocellular or cholestatic), jaundice, cholecystitis, depression, confusion, sleep disorder, dreaming, pulmonary infiltrates, bronchospasm / asthma, sore throat and hoarseness, heart rhythm disorder, angina pectoris, myocardial infarction or stroke (possibly due to excessive arterial hypotension in high-risk patients), Raynaud's phenomenon, rhinorrhea, alopecia, erythroderma, change in taste, blurred vision, urticaria, anaphylactic shock ok, lymphadenopathy, autoimmune disorders, stomatitis, glossitis, oliguria, exfoliative dermatitis, pemphigus, hyponatremia.

Hydrochlorothiazide. Irritation of the stomach, jaundice (intrahepatic, cholestatic), sialadenitis, xantopsy, leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, purpura, fever, urticaria, respiratory distress (including pneumonia and pulmonary edema), interstitial nephritis, anaphylactic reaction, glucosuria, electrolyte imbalance, including hyponatremia, anxiety, temporary blurred vision, hypoglycemia.

Overdose.

Symptoms of an overdose: arterial hypotension, nausea, weakness, dizziness against electrolyte imbalance.Hypokalemia, hyponatremia and dehydration due to increased diuresis. If a digitalis preparation is used, hypokalemia may exacerbate cardiac arrhythmia.

Treatment of an overdose Enalozide Forte is symptomatic and supportive. In case of unintentional overdose, it is necessary to cancel the drug, wash the stomach if the drug was taken recently, and also to correct the water and electrolyte balance and arterial hypotension. Enalapril can be removed from the systemic blood flow by hemodialysis.

Use during pregnancy or lactation.

Enaloside Forte is contraindicated during pregnancy and during lactation. At the first sign of pregnancy should immediately stop taking the drug. The appointment of ACE inhibitors in the I and III trimesters of pregnancy can cause disease or death of the fetus (newborn). If the drug is prescribed during pregnancy, the patient should be warned about the risk to the fetus. In single cases, when the prescription of the drug during pregnancy is considered necessary, periodic periodic ultrasound examinations should be performed to assess the fetal condition as well as the intra-amniotic space. If oligohydramnios are diagnosed, Enaloside Forte should be discontinued, except when the drug is vital to the mother. However, it should be remembered that oligohydramnios can occur only after the fetus has sustained irreversible changes. If an ACE inhibitor is used during pregnancy and an oligohydramnion is detected, it is appropriate to carry out tests such as a stress test for uterine contraction and a stress test or fetal biophysical profile test, depending on the pregnancy week.

If it is necessary to prescribe the drug during lactation, breast-feeding should be stopped.

Children.

It is not recommended for children.

Features of application.

Some patients may develop symptomatic arterial hypotension, as with other antihypertensive therapy. Patients should be examined for clinical signs of abnormal water-electrolyte balance, such as hyponatremia, lack of fluid, hypochloraemic alkalosis, hypomagnesemia, or hypokalemia that may occur as a result of episodes of diarrhea or vomiting. In such patients, it is necessary to periodically determine the serum content of electrolytes.

Excessive reduction in blood pressure can lead to myocardial infarction or stroke in patients with coronary heart disease or cerebrovascular disease.

Transient arterial hypotension in prescribing the drug is not a contraindication for further therapy. Therapy can be resumed in smaller doses or with the use of each component of the drug separately after the normalization of blood pressure and the volume of the circulating fluid.

With caution apply the drug in patients with obstruction of the outflow of blood from the left ventricle (aortic stenosis, hypertrophic cardiomyopathy).

With moderate or severe renal failure (when the creatinine clearance level is 30 ml / min and below), thiazides may not be effective diuretics. At creatinine clearance <80 ml / min Enaloside Forte should be used only after previous dose selection of each component.

In the treatment with enalapril in combination with diuretin, in some patients, with no signs of kidney disease at the beginning of treatment, there was a slight and transient increase in the level of urea and creatinine in the serum. In such cases, treatment with Enaloside Forte should be discontinued with possible further resumption of therapy in reduced doses or the administration of each component of the drug separately.

In the treatment of ACE inhibitors in patients with bilateral renal artery stenosis or with stenosis of the single kidney artery, an increase in urea and creatinine in the serum was observed. These changes were reversible and normalized after discontinuation of treatment.

Thiazides should be used with caution in patients with impaired function or with progressive liver disease, since even minor changes in the water-electrolyte balance can cause hepatic coma.

During large surgical interventions or during anesthesia with the use of drugs that cause arterial hypotension, enalaprilat blocks the formation of angiotensin II secondary to compensatory release of renin. If the arterial hypotension develops, which is explained by a similar mechanism, it can be corrected by increasing the volume of the fluid.

Thiazides are capable of:

• change the tolerance to glucose (possible correction of doses of antidiabetic drugs, including insulin);
• reduce urinary calcium excretion, which leads to a slight and reversible increase in serum calcium levels (pronounced hypercalcemia may be a sign of latent hyperparathyroidism). Before the study of the functions of the parathyroid glands, the use of thiazides should be discontinued;
• increase the level of cholesterol and triglycerides, which may also be associated with therapy with diuretics of the thiazide series, but with a dose of hydrochlorothiazide of 12.5 mg, similar effects were either not observed at all, or were insignificant;
• may cause hyperuricemia and / or gout in some patients, but enalapril may increase the level of uric acid in the urine and thereby reduce the hyperuricemic effect of hydrochlorothiazide.

Hyperkalemia. Hyperalemia is associated with kidney failure, diabetes mellitus, and concomitant use of potassium-sparing diuretics (eg, spironolactone, triamterene or amiloride), and the use of nutritional supplements or salt substitutes containing potassium. If concomitant administration of Enaloside Forte and the aforementioned agents is considered necessary, they should be used with caution and under frequent monitoring of potassium levels in serum.

Allergic reactions. During the treatment with ACE inhibitors, including enalapril maleate, individual cases of angioedema of the face, extremities, lips, tongue, glottis and / or larynx have been described. In such cases, it is necessary to immediately stop taking the drug, apply antihistamines and establish careful monitoring of the patient's condition in order to control clinical symptoms. Only with their disappearance, medical supervision can be stopped.

Angioedema, accompanied by swelling of the larynx, can lead to death. If the edema in the area of the tongue, glottis or larynx is localized, which can lead to airway obstruction, adrenaline solution 1: 1000 (0.3-0.5 ml) should be injected subcutaneously and other appropriate medical measures should be performed.

Patients with a history of cases of angioedema, not associated with the administration of ACE inhibitors, are more likely to develop angioedema along with therapy with ACE inhibitors.

In patients with thiazide therapy, allergic reactions can occur regardless of the history of allergic conditions or bronchial asthma. There is evidence of relapses or worsening of the course of systemic lupus erythematosus in patients taking thiazides.

Occasionally, patients receiving ACE inhibitors developed severe anaphylactoid reactions during hyposensitization with an allergen from Hymenoptera venom. Such reactions can be avoided by temporarily stopping the intake of ACE inhibitors by the time of hypensensitivity.

Anaphylactoid reactions were observed in patients who were on dialysis using high-throughput membranes (such as AN 69®) and were simultaneously treated with ACE inhibitors. In these patients, dialysis membranes of a different type or hypotensive drugs of other classes should be used.

Cough. Coughing was observed against the background of therapy with ACE inhibitors. Usually the cough is unproductive, permanent and stops after the drug is discontinued. The possibility of cough in connection with treatment with ACE inhibitors should be considered as part of the differential diagnosis of cough.

Patients of advanced age. The efficacy and tolerability of enalapril maleate and hydrochlorothiazide with simultaneous use are similar to effects in elderly and younger patients.

The composition of Enaloside Forte tablets includes lactose, therefore this drug is not recommended for patients with congenital intolerance to galactose, with deficiency of lactase or impaired absorption of glucose or galactose.

Do not consume alcohol during treatment with Enaloside Forte.

The ability to influence the reaction rate when driving or working with other machinery. Specific data are not available.Some of the unwanted effects listed in the "Adverse Reactions" section may affect the ability to drive vehicles or work with other mechanisms.

Interaction with other drugs and other types of interactions.

In the appointment of enalapril maleate in combination with other antihypertensive drugs, there may be an increase in the effect.

The loss of potassium under the influence of thiazide diuretics is usually weakened by enalapril. The level of potassium in the serum usually remains within normal limits.

The use of additives containing potassium, potassium-sparing diuretics or salts containing potassium, especially in patients with renal insufficiency, is impractical, since it can lead to a significant increase in potassium levels in serum.

Lithium preparations, as a rule, are not prescribed together with diuretics or ACE inhibitors. Diuretics and ACE inhibitors reduce the excretion of lithium by the kidneys and increase the risk of developing lithium intoxication; joint application is not recommended.

In some patients with impaired renal function who are treated with non-steroidal anti-inflammatory drugs, simultaneous use of ACE inhibitors can lead to further impairment of kidney function. These changes are usually reversible. Thiazides can increase susceptibility to tubocurarine.

When used with thiazide diuretics:

• alcohol, barbiturates or narcotic analgesics - can potentiate the development of orthostatic hypotension;
• antidiabetic drugs (oral and insulin) - there may be a need to adjust the dose of the antidiabetic drug, since the combined use of ACE inhibitors and antidiabetic drugs can cause a decrease in blood glucose levels;
• resins colestyramine and colestipol - the absorption of hydrochlorothiazide decreases in the presence of anion exchange resins.

Pharmacological properties.

Enalozide Forte is a combination of an ACE inhibitor (enalapril maleate) and a diuretic (hydrochlorothiazide). The hypotensive effects of both components complement each other and persist for 24 hours. A higher percentage of hypertensive patients respond better to treatment Enalozidom Forte than the appointment of each of its components individually. The presence of a component of enalapril maleate to reduce the potassium loss associated with taking hydrochlorothiazide.

Mechanism of action.

Enalapril maleate. ACE - piptidilovaya peptidase which catalyzes the conversion of angiotensin I to the pressor substance angiotensin II. After absorption hydrolyzed to enalapril enalaprilat, which inhibits ACE. Inhibition of ACE reduces levels of angiotensin II in the blood plasma, which leads to an increase in plasma renin activity (via inhibition of negative feedback between the activity of angiotensin II and renin release) and reduced aldosterone secretion.

Enalapril may also block the breakdown of bradykinin, which is a potent vasodepressor peptide. The mechanism by which enalapril reduced blood pressure, especially associated with the inhibition of the renin-angiotensin-aldosterone system, which plays an important role in regulating blood pressure; enalapril can detect an antihypertensive effect even in patients with low-renin hypertension.

Enalapril maleate - hydrochlorothiazide. Hydrochlorothiazide - diuretic and antihypertensive agent which increases plasma renin activity. Although enalapril has antihypertensive effect even in patients with low-renin hypertension, concomitant administration of hydrochlorothiazide leads to greater reduction in blood pressure in these patients.

Pharmacodynamics. Enalapril in patients with hypertension leads to lower blood pressure in the horizontal and vertical positions without a substantial increase in heart rate. Postural hypertension occurs infrequently.

Abrupt withdrawal of enalapril maleate has not led to a rapid increase in blood pressure.

Effective inhibition of ACE activity is normally achieved within 2-4 hours after oral administration of the individual dose of enalapril. Starting antihypertensive activity normally recorded after one hour, and the maximum reduction in blood pressure is achieved within 4-6 hours after drug application. The duration of effect is dose-dependent. However, it recommended doses antihypertensive and hemodynamic effects were maintained for 24 hours.

In hemodynamic studies in patients with essential hypertension, blood pressure reduction is usually accompanied by a reduction in peripheral arterial resistance with slight increase in cardiac output and heart rate minor changes or no such changes. After receiving enalapril maleate typically increased renal blood flow; glomerular filtration rate usually not changed. Nevertheless, patients with a low glomerular filtration rate prior to treatment is generally increased.

enalapril antihypertensive therapy leads to a significant regression of left ventricular hypertrophy with preserved systolic function of the latter.

Enalapril maleate - hydrochlorothiazide

In clinical studies, the degree of decrease in blood pressure was observed with the combination of enalapril and hydrochlorothiazide, greater than that of the case of separate application of the individual components. In addition, the antihypertensive effect Enalozida forte was maintained for 24 hours.

Pharmacokinetics.

enalapril maleate

Hour Following oral enalapril is rapidly absorbed, its maximum concentration achieved within one hour. Based on the allocation data in the urine extent of absorption of enalapril is approximately 60%.

After absorption, enalapril rapidly and largely hydrolyzed to enalaprilat - powerful ACE inhibitor. Maximum concentration in blood serum enalaprilat recorded 3-4 hours after oral reception of enalapril maleate. Enalapril excreted mainly by the kidneys. The main components in urine is enalaprilat, constituting 40% of the dose, and unmodified enalapril. Except for conversion to enalaprilat, there is no significant evidence of metabolism of enalapril. The profile of serum concentrations of enalaprilat is characterized by a prolonged terminal phase, which is obviously associated with the binding of ACE. In individuals with normal renal function, a constant concentration of enalaprilat were reached before the fourth day of receiving enalapril maleate once a day.food presence in the gastrointestinal tract does not affect the absorption of enalapril maleate. The degree of absorption and hydrolysis of enalapril are similar for different doses of the recommended therapeutic range.

hydrochlorothiazide

The half-life ranges from 5.6 to 14.8 hours. Hydrochlorothiazide is not metabolized but is rapidly excreted by the kidneys. About 61% of the dose after oral administration is allocated in an unmodified state within 24 hours. Hydrochlorothiazide crosses the placental but not pass through the blood-brain barrier.

Enalapril maleate - hydrochlorothiazide

Simultaneous administration of multiple doses of enalapril and hydrochlorothiazide has little impact or has no influence on the bioavailability of these drugs.

Pharmaceutical characteristics.

Basic physical and chemical properties:

Valium pills yellow with a facet and Valium. On the surface of tablets allowed blotches.

Shelf life.

2 years. Do not use the product after the expiration date printed on the package.

Storage conditions.

Store in a dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Packaging.

10 tablets in a blister pack. 2 blisters, nested in a pack.

Category vacation.

On prescription.