Enap-N pills 25mg+10mg, 60pcs

Composition

For 1 tablet:

Active ingredients:

Hydrochlorothiazide 25.00 mg

Enalapril Maleate 10.00 mg

Auxiliary substances:  

sodium bicarbonate 5.10 mg,

lactose monohydrate 120.02 mg,

corn starch 29.60 mg,

pregelatinized starch 6.00 mg,

talc 6.00 mg,

magnesium stearate 2.00 mg,

quinoline yellow dye, E 104 0.06 mg

Clinical pharmacology

A combined drug, the action of which is determined by the properties of the components that make up its composition.

Enalapril, an ACE inhibitor, is a prodrug: as a result of its hydrolysis, enalaprilate is formed, which inhibits ACE.

Hydrochlorothiazide is a thiazide diuretic. It acts at the level of the distal renal tubules, increasing the excretion of sodium and chlorine ions.

At the beginning of treatment with hydrochlorothiazide, the volume of fluid in the vessels decreases as a result of increased sodium and fluid excretion, which leads to a decrease in blood pressure and a decrease in cardiac output.

Due to hyponatremia and decreased body fluids, the renin-angiotensin-aldosterone system is activated. A reactive increase in the concentration of angiotensin II partially limits the decrease in blood pressure. With continued therapy, the antihypertensive effect of hydrochlorothiazide is based on a decrease in the total peripheric resistance of blood vessels. Activation of the renin-angiotensin-aldosterone system results in metabolic effects on blood electrolyte balance, uric acid, glucose, and lipids, which partially neutralizes the effectiveness of antihypertensive treatment.

Despite the effective reduction of blood pressure, thiazide diuretics do not reduce structural changes in the heart and blood vessels. Enalapril enhances the antihypertensive effect: it inhibits the renin-angiotensin-aldosterone system, i. e. the production of angiotensin II and its effects. Additionally, it reduces the production of aldosterone and enhances the action of bradykinin and prostaglandin release. Since it often has its own diuretic effect, this may increase the effect of hydrochlorothiazide.

Enalapril reduces pre-and post-loading, which relieves the left ventricle, reduces regression of hypertrophy and overgrowth of collagen, and prevents damage to myocardial cells. As a result, the heart rate slows down and the load on the heart decreases) improves coronary blood flow and reduces oxygen consumption by cardiomyocytes. Thus, the sensitivity of the heart to ischemia decreases, and the number of dangerous ventricular arrhythmias decreases. It has a beneficial effect on cerebral blood flow in patients with arterial hypertension and chronic cardiovascular diseases. Prevents the development of glomerulosclerosis, supports and improves kidney function, and slows down the course of chronic kidney disease, even in patients who have not yet developed hypertension.

The antihypertensive effect of ACE inhibitors is known to be higher in patients with hyponatremia, hypovolemia, and elevated serum renin levels, whereas the effect of hydrochlorothiazide is independent of serum renin levels. Therefore, the simultaneous use of enalapril and hydrochlorothiazide has an additional antihypertensive effect. In addition, enalapril prevents or reduces the metabolic effects of diuretic therapy and has a beneficial effect on structural changes in the heart and blood vessels.

Simultaneous use of an ACE inhibitor and hydrochlorothiazide is used when each drug alone is not effective enough or monotherapy is carried out using the maximum doses of the drug, which increases the frequency of undesirable effects. This combination allows you to get a better therapeutic effect with lower doses of enalapril and hydrochlorothiazide and reduce the development of undesirable effects.

The antihypertensive effect of the combination usually persists for 24 hours.

Indications

Arterial hypertension (patients who are indicated for combination therapy).

Contraindications

– hypersensitivity (including to individual components of the drug or a derivative of sulfonamide); – anuria, severe renal dysfunction (creatinine clearance (CC) of less than 30 ml/min); – a history of angioedema associated with the use of earlier ACE inhibitors, and hereditary or idiopathic angioedema; bilateral renal artery stenosis, stenosis of the artery to a solitary kidney; – pregnancy and lactation period; – age under 18 years (effectiveness and safety not established); – lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Side effects

World Health Organization (WHO)classification of the incidence of side effects:  – very often (> 1/10) – often (>> 1/100 and-infrequently (>>>1/1000 and-rarely (>>>>1/10000 and-very rarely (From the hematopoietic and lymphatic system:  – rarely: neutropenia, decreased hemoglobin and hematocrit, thrombocytopenia, leukopenia, suppression of bone marrow function;

Metabolic and nutritional disorders – infrequently: gout;

From the central nervous system:  – very often: dizziness, weakness; – often: headache, asthenia; – infrequently: insomnia, drowsiness, paresthesia, increased excitability;

From the side of the senses:  – infrequently: tinnitus.

From the cardiovascular system-often: orthostatic hypotension; – Infrequently: syncope, marked decrease in blood pressure, palpitation, tachycardia, chest pain;

Respiratory system disorders:  – often: cough; – infrequently: shortness of breath;

From the digestive system:  – often: nausea; – infrequently: diarrhea, vomiting, dyspepsia, abdominal pain, flatulence, constipation, dry mouth; – rarely: cholestatic jaundice, fulminant necrosis;

Allergic reactions:  – infrequently: Stevens-Johnson syndrome; – rarely: angioedema; – very rarely: intestinal angioedema;

From the side of the skin:  – infrequently: skin rash, itching, increased sweating, skin necrosis, alopecia;

From the genitourinary system:  – infrequently: impaired renal function, acute renal failure, impotence, decreased libido;

From the musculoskeletal system:  – often: muscle spasms; – infrequently: arthralgia;

Laboratory parameters:  – rarely: hyperglycemia, hyperuricemia, hypokalemia, hyperkalemia, hyponatremia, increased concentration of urea and creatinine in the blood serum, increased activity of “hepatic” transaminases and bilirubin;

Other services:  – a symptom complex is described, which may include fever, myalgia and arthralgia, serositis, vasculitis, increased erythrocyte sedimentation rate, leukocytosis and eosinophilia, skin rash, and a positive antinuclear antibody test.

Interaction

Serum potassium

The use of potassium supplements, potassium-sparing agents, or potassium-containing salt substitutes, especially in patients with renal insufficiency, can lead to a significant increase in serum potassium. Potassium loss in patients taking thiazide diuretics is usually reduced by enalapril. The level of potassium in the blood serum usually remains within the normal range.

Lithium

When used concomitantly with lithium preparations, lithium excretion is slowed down (increased cardiotoxic and neurotoxic effects of lithium).

Non-depolarizing muscle relaxants

Thiazide diuretics may increase the effect of tubocurarin chloride.

Narcotic analgesics/antipsychotics

Concomitant use of thiazide diuretics, narcotic analgesics, or phenothiazine derivatives may result in orthostatic hypotension.

Other antihypertensive agents

Combined with enalapril, the use of beta-blockers, alpha-blockers, ganglioblockers, methyldopa or slow calcium channel blockers may additionally reduce blood pressure.

Allopurinol, cytostatics and immunosuppressants

Concomitant use with ACE inhibitors may increase the risk of leukopenia.

Glucocorticosteroids, calcitonin

Simultaneous use of thiazide diuretics may lead to the development of hypokalemia.

Cyclosporine

Concomitant use with ACE inhibitors may increase the risk of hyperkalemia.

Nonsteroidal anti-inflammatory drugs

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective cyclookigenase-2 inhibitors) may weaken the antihypertensive effect of ACE inhibitors.

NSAIDs and ACE inhibitors have an additive effect on increasing serum potassium, which can lead to deterioration of renal function, especially in patients with impaired renal function. This effect is reversible.

NSAIDs may reduce the diuretic and antihypertensive effects of diuretics.

Antacids

Antacids may reduce the bioavailability of ACE inhibitors.

Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.

Thiazide diuretics may reduce the effect of adrenomimetics (epinephrine).

Ethanol increases the hypotensive effect of ACE inhibitors and thiazide diuretics, which can cause orthostatic hypotension.

Hypoglycemic agents for oral use and insulin

Epidemiological studies suggest that the simultaneous use of ACE inhibitors and hypoglycemic agents may lead to hypoglycemia. More often, hypoglycemia develops in the first weeks of therapy in patients with impaired renal function.Long-term and controlled clinical trials of enalapril do not confirm these data and do not limit the use of enalapril in patients with diabetes mellitus. However, such patients should be under regular medical supervision.

The use of hypoglycemic agents for oral use and insulin with thiazide diuretics may require dose adjustment.

Colestyramine and colestipol

A single dose of colestyramine or colestipol reduces the absorption of hydrochlorothiazide in the gastrointestinal tract by 85% and 43%, respectively.

Gold preparations

With the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, a symptom complex is described, including hyperemia of the facial skin, nausea, vomiting and hypotension.

How to take, course of use and dosage

Enap ® H should be taken regularly at the same time, preferably in the morning, during or after meals, without chewing, with a small amount of liquid. The recommended dose is 1 tablet per day.

In patients receiving diuretic therapy, it is recommended to discontinue treatment or reduce the dose of diuretics at least 3 days before starting treatment with Enap® H to prevent the development of symptomatic hypotension.

Renal function should be evaluated before starting treatment.

The duration of treatment is determined by the doctor.

Dosage for impaired renal function

In patients with renal insufficiency with creatinine clearance of 30-75 ml/min, Enap® H should be used only after preliminary titration of enalapril and hydrochlorothiazide doses separately, respectively, in combination with Enap® H.

Overdose

Symptoms: increased diuresis, marked decrease in blood pressure with bradycardia or other cardiac arrhythmias, convulsions, impaired consciousness (including coma), acute renal failure, impaired acid-base state and water-electrolyte balance of the blood.

Treatment: the patient is moved to a horizontal position with raised legs.

In mild cases, gastric lavage and ingestion of activated carbon are indicated, in more serious cases-measures aimed at stabilizing blood pressure-intravenous use of plasma substitutes, infusion of 0.9% sodium chloride solution.

The patient should be monitored for blood pressure, heart rate, respiratory rate, serum concentration of urea, creatinine, electrolytes and diuresis, if necessary – intravenous angiotensin II, hemodialysis (enalaprilate elimination rate-62 ml / min).

Special instructions

Arterial hypotension

Hypotension with all clinical consequences may occur after the first use of Enap ® H tablets in patients with severe CHF and hyponatremia, severe renal insufficiency or left ventricular dysfunction, and, in particular, in patients with hypovolemia, as a result of diuretic therapy, a salt-free diet, diarrhea, vomiting or hemodialysis.

In case of hypotension, the patient should be placed on his back with a low headboard and, if necessary, adjust the volume of BCC by infusion of 0.9% sodium chloride solution. Hypotension that occurs after the first dose is not a contraindication for further treatment.

Caution should be exercised in patients with ischemic heart disease, severe cerebrovascular diseases, aortic stenosis or idiopathic hypertrophic obstructive subaortic stenosis that interferes with the outflow of blood from the left ventricle, severe atherosclerosis, in elderly patients as a result of the risk of hypotension and impaired blood supply to the heart, brain and kidneys.

Violations of the water-electrolyte balance

It is necessary to regularly monitor the serum concentration of electrolytes during treatment to identify possible imbalances and timely take the necessary measures. Determination of serum electrolyte concentrations is mandatory for patients with prolonged diarrhea and vomiting.

In patients taking Enap® H, it is necessary to detect signs of impaired water-electrolyte balance, such as dry mouth, thirst, weakness, drowsiness, increased excitability, myalgia and convulsions (mainly of the calf muscles), decreased blood pressure, tachycardia, oliguria and gastrointestinal disorders (nausea, vomiting).

Impaired renal function

Enap ® H in patients with renal insufficiency (creatinine clearance 30-75 ml / min) should be used only after preliminary titration of enalapril and hydrochlorothiazide doses separately, respectively, to the doses in the combined Enap® H preparation.

Impaired liver function

Enap ® H should be used with caution in patients with hepatic insufficiency or progressive liver diseases, since hydrochlorothiazide can cause hepatic coma even with minimal violations of the water-electrolyte balance. Several cases of acute hepatic insufficiency with cholestatic jaundice, fulminant liver necrosis, and death (rare) have been reported during treatment with ACE inhibitors. If jaundice occurs and the activity of “hepatic” transaminases increases, treatment with Enap® H should be stopped immediately and patients should be monitored.

Metabolic and endocrine effects

Caution should be exercised in all patients treated with hypoglycemic agents for oral use or insulin, as hydrochlorothiazide may weaken, and enalapril may increase their effect.

Thiazide diuretics can reduce the excretion of calcium by the kidneys and cause a slight and transient increase in serum calcium.

Severe hypercalyshemia may be a sign of latent hyperparathyroidism. Thiazide diuretics should be discontinued prior to parathyroid function testing.

During treatment with thiazide diuretics, serum cholesterol and triglyceride concentrations may increase. Thiazide diuretic therapy may worsen hyperuricemia and/or exacerbate the course of gout in some patients. However, enalapril increases the excretion of uric acid by the kidneys, thereby counteracting the hyperuricemic effect of hydrochlorothiazide.

Allergic reactionsand/Angioedema

If angioedema of the face occurs, it is usually sufficient to cancel therapy and prescribe antihistamines to the patient.

Angioedema of the tongue, pharynx, or larynx can be fatal. In case of angioedema of the tongue, pharynx or larynx, which can lead to airway obstruction, it is necessary to immediately introduce epinephrine (0.3-0.5 ml of epinephrine (epinephrine) solution subcutaneously in a ratio of 1:1000) and maintain airway patency (intubation or tracheostomy).

Among black patients receiving ACE inhibitor therapy, the incidence of angioedema is higher than among patients of other races.

Patients with a history of angioedema that is not associated with ACE inhibitors have an increased risk of developing angioedema when taking any ACE inhibitor.

Hypersensitivity reactions may occur in patients taking thiazide diuretics, both in the presence and in the absence of a history of allergic reactions. Worsening of the course of systemic lupus erythematosus has been reported.

Due to the increased risk of anaphylactic reactions, Enap® H should not be prescribed to patients undergoing hemodialysis using high-flow polyacrylonitrile membranes (AN69®), undergoing low-density lipoprotein apheresis with dextran sulfate and immediately before the procedure of desensitization to wasp or bee venom.

Surgical procedures/ General anesthesia

Before surgery (including dentistry), it is necessary to warn the anesthesiologist about the use of ACE inhibitors. During surgery or general anesthesia using agents that cause hypotension, ACE inhibitors can block the formation of angiotensin II in response to the compensatory release of renin. If a marked decrease in blood pressure occurs due to such a mechanism, it can be corrected by increasing the volume of circulating blood.

Cough

Coughing has been reported with ACE inhibitors. The cough is dry and prolonged, which disappears after discontinuation of ACE inhibitors. In the differential diagnosis of cough, it is necessary to take into account the cough caused by the use of ACE inhibitors.

Influence on the ability to drive a vehicle and other mechanical means:

At the beginning of treatment with Enap® H, a marked decrease in blood pressure, dizziness and drowsiness may occur, which may reduce the ability to drive vehicles, engage in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions. Therefore, at the beginning of treatment, it is not recommended to drive vehicles and engage in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

 In a dark place, at a temperature not exceeding 25 °C.

Shelf life

5 years

Active ingredient

Hydrochlorothiazide, Enalapril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension, Heart Failure