Hydrohlorotyazyd, enalapril | Enap-H tablets 25 mg + 10 mg 20 pcs.

Release form

Tablets.

Packaging

20 pcs.

Pharmacological action

ENAP-H is a combined antihypertensive drug containing enalapril maleate and hydrochlorothiazide. Enalapril maleate is an ACE inhibitor. Enalapril metabolite enalaprilat has pharmacological activity. Suppresses the formation of angiotensin II and eliminates its vasoconstrictor effect. Enap gradually reduces blood pressure, without causing an increase in heart rate and minute volume. Reduces OPSS, reduces afterload. It also reduces preload, reduces pressure in the right atrium and pulmonary circulation.

Hydrochlorothiazide is a thiazide diuretic. It disrupts the reabsorption of sodium, chlorine and water ions in the distal tubules of the nephron. It increases the excretion of potassium, magnesium, bicarbonate ions and retains calcium ions in the body. Helps reduce high blood pressure.

Enap does not affect the metabolism of glucose, lipoproteins, as well as sexual function.

Contraindications

anuria

severe renal dysfunction (KK - history of angioedema associated with the use of previous ACE inhibitors

hereditary or idiopathicangioedema

edema bilateral renal artery stenosis, single kidney artery stenosis

lactose intolerance, lactase deficiency or malabsorption of glucose / galactose

children and adolescents under 18 years of age (efficacy and safety not established)

hypersensitivity to the components of the drug Ena.

With caution, the drug should be used with severe stenosis of the aortic mouth or idiopathic hypertrophic subaortic stenosis, coronary heart disease and cerebrovascular diseases (including cerebrovascular insufficiency), because an excessive decrease in blood pressure can lead to the development of myocardial infarction and stroke, chronic heart failure, severe atherosclerosis, severe autoimmune systemic diseases of the connective tissue (including SLE, scleroderma),

Pregnancy and lactation

Enap-H is contraindicated in pregnancy, lactation

Special instructions

Arterial hypotension with all clinical consequences can occur after the first use of EnapВ®-N tablets in patients with severe heart failure and hyponatremia, severe renal failure, hypertension or left ventricular dysfunction, and especially in patients in a state of gilovolemia, as a result of diuretic therapy, a salt-free diet, diarrhea, vomiting, or hemodialysis.

In case of arterial hypotension, it is necessary to lay the patient on his back with a low headboard and, if necessary, adjust the volume of the bcc by infusion of a 0.9% sodium chloride solution.

Arterial hypotension that occurred after taking the first dose is not a contraindication for further treatment.

Caution is required in patients with coronary artery disease, severe cerebrovascular disease, aortic stenosis or idiopathic hypertrophic obstructive subaortic stenosis, which prevents outflow of blood from the left ventricle, severe atherosclerosis, in elderly patients as a result of the risk of arterial hypotension and deterioration of the blood supply to the brain, brain, .

Regular monitoring of serum concentration of electrolytes during treatment is necessary to identify possible imbalance and timely adoption of necessary measures. Determination of serum concentration of electrolytes is mandatory for patients with prolonged diarrhea, vomiting.

In patients taking EnapВ®-N, it is necessary to identify signs of imbalance in the water-electrolyte balance, such as dry mouth, thirst, weakness, drowsiness, increased irritability, myalgia and cramps (mainly calf muscles), decreased blood pressure, tachycardia, oliguria and gastrointestinal disturbances (nausea, vomiting).

The drug EnapВ®-N in patients with renal failure (CC 30-75 ml / min) should be used only after preliminary titration of doses of enalapril and hydrochlorothiazide separately, according to the doses in the combined preparation EnapВ®-N.

EnapВ®-N should be used with caution in patients with liver failure or progressive liver disease, as hydrochlorothiazide can cause hepatic coma even with minimal disturbances in the water-electrolyte balance. Several cases of acute liver failure with cholestatic jaundice have been reported, fulminant liver necrosis and death (rarely) during treatment with ACE inhibitors. In case of jaundice and increased activity of hepatic transaminases, treatment with EnapВ®-N should be stopped immediately, patients should be monitored.

Caution is necessary in all patients receiving treatment with hypoglycemic agents for oral administration or insulin, since hydrochlorothiazide can weaken, and enalapril enhance their effect.

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

Severe hypercalcemia may be a sign of latent hyperparathyroidism. Before conducting a study of the function of the parathyroid glands, thiazide diuretics must be canceled.

During treatment with thiazide diuretics, serum cholesterol and triglyceride concentrations may increase.

Thiazide diuretic therapy in some patients may exacerbate hyperuricemia and / or exacerbate the course of gout. However, enalapril enhances the excretion of uric acid by the kidneys, thereby counteracting the hyperuricemic effect of hydrochlorothiazide.

In the event of angioedema of the face, discontinuation of therapy and the appointment of antihistamines are usually sufficient.

Angioedema of the tongue, pharynx, or larynx may be fatal. With angioedema of the tongue, pharynx or larynx, which can lead to obstruction of the respiratory tract, it is necessary to immediately inject epinephrine (0.3-0.5 ml of a solution of epinephrine (adrenaline) sc in a ratio of 1: 1000) and maintain airway (intubation or tracheostomy).

Among patients of the Negroid race receiving therapy with an ACE inhibitor, the incidence of angioedema is higher than among patients of a different race.

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

In patients taking thiazide diuretics, hypersensitivity reactions can develop both in the presence and in the absence of a history of allergic reactions. A deterioration in the course of systemic lupus erythematosus has been reported.

Due to the increased risk of anaphylactic reactions, the drug EnapВ®-N should not be prescribed to patients hemodialysis using high-flow polyacrylonitrile membranes (AN 69В®) undergoing apheresis of low-density lipoproteins with dextransulfate and immediately before the desensitization procedure for aspen or bee venom.

Before surgery (including dentistry), an anesthetist should be warned about the use of ACE inhibitors.

During surgery or during general anesthesia using hypotensive medications, ACE inhibitors can block the formation of angiotensin II in response to compensatory release of renin. If a marked decrease in blood pressure develops, which is explained by a similar mechanism, it can be corrected by an increase in bcc.

Cough was observed with ACE inhibitors. Cough dry, long, which disappears after you stop taking ACE inhibitors. With a differential diagnosis of cough, cough caused by the use of ACE inhibitors should be considered.

Influence on the ability to drive vehicles and control mechanisms

At the beginning of treatment with EnapВ®-N, a marked decrease in blood pressure, dizziness and drowsiness may occur, which may reduce the ability to drive vehicles and engage in other potentially dangerous activities that require an increased concentration of attention and the 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 an increased concentration of attention and speed of psychomotor reactions.

Composition

1 tablet: - enalapril maleate 10 mg

- hydrochlorothiazide 25 mg

Excipients: sodium bicarbonate, dye quinoline yellow (E104), lactose monohydrate, calcium hydrogen phosphate anhydrous, corn starch, talc, magnesium stearate.

Dosage and administration of

Take the drug Enap®-N regularly at the same time, preferably in the morning, during or after a meal, without chewing, washed down with a small amount of liquid.

Recommended dose - 1 tablet / day.

In patients undergoing diuretic therapy, it is recommended to cancel treatment or reduce the dose of diuretics at least 3 days before the start of treatment with Enap®-N to prevent the development of symptomatic hypotension. Before starting treatment, kidney function should be examined.

The duration of treatment is determined by the doctor individually.

In patients with renal failure with CC of 30-75 ml / min, Enap®-N should be used only after preliminary titration of doses of enalapril and hydrochlorothiazide separately, corresponding to the doses in the combined preparation of Enap®-N.

Side effects

Classification of the incidence of side effects WHO: very often (> 1/10), often (> 1/100 and 1/1000 and 1/10 000 and From the hematopoietic system: rarely - neutropenia, decreased hemoglobin and hematocrit, thrombocytopenia, leukopenia, inhibition of bone marrow function.

Metabolism: infrequently - gout.

CNS: very often - dizziness, weakness often - headache, asthenia infrequently - insomnia, drowsiness, paresthesia, increased arousal bridge, tinnitus

From the cardiovascular system: often - orthostatic hypotension infrequently - fainting, marked decrease in blood pressure, sensation of palpitations, tachycardia, chest pain.

From the respiratory system: 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.

Dermatological reactions: infrequently - skin rash, itching, sweating, skin necrosis, alopecia.

From the genitourinary system: infrequently - impaired renal function, acute renal failure.

From the reproductive system: infrequently - impotence, decreased libido.

From the musculoskeletal system: often - muscle cramps infrequently - arthralgia.

On the part of laboratory parameters: rarely - hyperglycemia, hyperuricemia, hypokalemia, hyperkalemia, hyponatremia, an increase in the concentration of urea and creatinine in the blood serum, an increase in the activity of hepatic transaminases and bilirubin.

Others: a symptom complex has been described that may include fever, myalgia and arthralgia, serositis, vasculitis, increased ESR, leukocytosis and eosinophilia, skin rash, a positive test for antinuclear antibodies.

Drug Interactions

The use of potassium supplements, potassium-sparing agents or potassium-containing preparations, salt substitutes, especially in patients with renal failure, can lead to a significant increase in serum potassium.

Potassium loss with thiazide diuretics is usually reduced by enalapril. Serum potassium usually remains within the normal range.

With simultaneous use with lithium preparations, lithium excretion is slowed down (increased cardiotoxic and neurotoxic effects of lithium).

Thiazide diuretics may enhance the effect of tubocurarine chloride.

The simultaneous use of thiazide diuretics, opioid analgesics or phenothiazine derivatives can lead to orthostatic hypotension.

Together with enalapril, the use of beta-blockers, alpha-blockers, ganglion blockers, methyldopa or slow calcium channel blockers can further reduce blood pressure.

Concomitant use of allopurinol, cytostatics, and immunosuppressants with ACE inhibitors may increase the risk of developing leukopenia.

Concomitant use of thiazide diuretics with corticosteroids, calcitonin can lead to the development of hypokalemia.

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

The simultaneous use of NSAIDs (including selective COX-2 inhibitors) can weaken the antihypertensive effect of ACE inhibitors. NSAIDs and ACE inhibitors have an additive effect on increasing serum potassium levels, which can lead to impaired renal function, especially in patients with impaired renal function. This effect is reversible. NSAIDs may reduce the diuretic and antihypertensive effects of diuretics.

Antacids may decrease the bioavailability of ACE inhibitors.

Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.

Thiazide diuretics may reduce the effects of adrenergic agonists (epinephrine).

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

Epidemiological studies suggest that the simultaneous use of ACE inhibitors and hypoglycemic agents can lead to hypoglycemia. More often hypoglycemia develops in the first weeks of therapy in patients with impaired renal function. Long-term and controlled clinical studies 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 administration and insulin with thiazide diuretics may require dose adjustment.

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

With the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) iv, a symptom complex has been described, including facial flushing, nausea, vomiting, and arterial hypotension.

overdose

Symptoms: increased diuresis, severe BP with bradycardia or other cardiac arrhythmias, convulsions, impaired consciousness (including coma), acute renal failure, impaired KSH and water-electrolyte balance.

Treatment: the patient is transferred to a horizontal position with his legs raised. In mild cases, gastric lavage and intake of activated charcoal are indicated, in more serious cases, measures aimed at stabilizing blood pressure - in / into the introduction of plasma substitutes, infusion of 0.9% sodium chloride solution.

Patient should monitor blood pressure, heart rate, respiratory rate, serum concentration of urea, creatinine, electrolytes and diuresis, if necessary - in / in the introduction of angiotensin II, hemodialysis (excretion rate of enalaprilat - 62 ml / min).

Storage conditions

Store in a humidified place at a temperature not exceeding 25 РC.

Active ingredient

Hydrochlorothiazide, enalapril

lekarstvennaja tablet form



KRKA d.d. Novo mesto AO, Slovenia