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

Heart failure, Hypertension (high blood pressure), Edema

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

Active ingredient

Composition

On 1 tablet:

The active ingredients:

Hydrochlorothiazide 25.00 mg

Enalapril maleate 10.00 mg

Associates:

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, E104 0.06 mg

How to take, the dosage

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

In patients on therapy with diuretics, it is recommended to discontinue the treatment or decrease the dose of diuretics at least 3 days prior to treatment with Enap® N to prevent development of symptomatic arterial hypotension.

Renal function should be investigated before starting treatment.

The duration of treatment is determined by the physician.

Dose in impaired renal function

. In patients with renal impairment with a CKR of 30-75 ml/min, Enap® H should be used only after prior titration of doses of enalapril and hydrochlorothiazide separately, according to doses in Enap® H combination therapy.

Interaction

Serum potassium

The use of potassium supplements, potassium-saving agents, or preparations containing potassium salt substitutes, especially in patients with renal insufficiency, may result in a significant increase in serum potassium. Potassium loss on thiazide diuretics is usually reduced by enalapril. Serum potassium content usually remains within normal limits.

Lithium

In concomitant use with lithium preparations – slowing of lithium excretion (increase of cardiotoxic and neurotoxic effects of lithium).

Non-depolarizing myorelaxants

Thiazide diuretics may increase the effect of tubocurarine chloride.

Narcotic analgesics/neuroleptics

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

Other antihypertensive agents

The co-administration of beta-adrenoblockers, alpha-adrenoblockers, ganglion blockers, methyldopa or slow calcium channel blockers with enalapril may further decrease BP.

Allopurinol, cytostatics and immunosuppressants

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

Glucocorticosteroids, calcitonin

Concomitant use of thiazide diuretics may lead to hypokalemia.

Cyclosporine

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

Non-steroidal anti-inflammatory drugs

The concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) (including selective cyclo-oxygenase-2 inhibitors) may weaken the antihypertensive effect of ACE inhibitors.

NSAIDs and ACE inhibitors have an additive effect on the increase of serum potassium that may lead to worsening of renal function, especially in patients with impaired renal function. This effect is reversible.

NSAIDs may decrease the diuretic and antihypertensive effects of diuretics.

Antacids

Antacids may decrease the bioavailability of ACE inhibitors.

Sympathomimetics may decrease the antihypertensive effect of ACE inhibitors.

Tiazide diuretics may decrease the effect of adrenomimetics (epinephrine).

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

Hypoglycemic oral agents and insulin

Epidemiological studies suggest that 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. Nevertheless, such patients should be under regular medical supervision.

The use of oral hypoglycemic agents and insulin with thiazide diuretics may require adjustment of their doses.

Colestiramine and colestipol

A single dose of colestiramine or colestipol reduces gastrointestinal absorption of hydrochlorothiazide by 85% and 43%, respectively.

Gold preparations

. When ACE inhibitors and gold preparations (sodium aurothiomalate) are administered simultaneously intravenously, a symptomcomplex including facial skin hyperemia, nausea, vomiting, and arterial hypotension has been described.

Special Instructions

Arterial Hypotension

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

In case of arterial hypotension, the patient should be laid on the back with a low headboard and, if necessary, the volume of the circulatory blood pressure should be corrected by infusion of 0.9% sodium chloride solution. Arterial hypotension occurring after the first dose is not a contraindication for further treatment.

. Caution is required in patients with coronary heart disease, marked cerebrovascular disease, aortic stenosis or idiopathic hypertrophic obstructive subaortic stenosis preventing blood outflow from the left ventricle, marked atherosclerosis, in elderly patients due to risk of arterial hypotension and worsening of blood supply to the heart, brain and kidneys.

Disorders of water-electrolyte balance

He needs regular monitoring of serum electrolyte concentrations during treatment to detect possible imbalance and take appropriate measures in time. Determination of serum electrolyte concentrations is mandatory for patients with prolonged diarrhea, vomiting.

. In patients taking Enap® N it is necessary to detect signs of electrolyte-water imbalance such as dry mouth, thirst, weakness, somnolence, increased excitability, myalgia and cramps (mainly calf muscle), decreased blood pressure, tachycardia, oliguria and gastrointestinal disorders (nausea, vomiting).

Kidney function impairment

Enap® H in patients with renal impairment (CK 30-75 ml/min) should be used only after prior titration of doses of enalapril and hydrochlorothiazide separately, according to the doses in Enap® H combination therapy.

Hepatic dysfunction

Enap® H should be used with caution in patients with hepatic impairment or advanced liver disease because hydrochlorothiazide may cause hepatic coma even with minimal impairment of the water-electrolyte balance. Several cases of acute hepatic failure with cholestatic jaundice, fulminant liver necrosis, and death have been reported (rarely) during treatment with ACE inhibitors. In case of jaundice and increased “hepatic” transaminase activity, treatment with Enap® N should be immediately discontinued and patients should be under observation.

Metabolic and endocrine effects

. Caution is necessary in all patients treated with oral hypoglycemic agents or insulin, as hydrochlorothiazide may attenuate and enalapril may potentiate their effects.

Thiazide diuretics may decrease renal calcium excretion and cause a slight and transient increase in serum calcium.

The marked hypercalcemia may be a sign of occult hyperparathyroidism. Thiazide diuretics must be discontinued before parathyroid function study.

The treatment with thiazide diuretics may increase cholesterol and triglyceride concentrations in blood serum.
Therapy with thiazide diuretics in some patients may aggravate hyperuricemia and/or aggravate the course of gout. However, enalapril increases uric acid excretion by the kidneys, thus counteracting the hyperuricemic effect of hydrochlorothiazide.

Allergic reactions/Angioneurotic edema

In the event of angioedema of the face, withdrawal of therapy and administration of antihistamines to the patient is usually sufficient.

The angioedema of the tongue, pharynx, or larynx can be fatal. If angioedema of the tongue, pharynx, or larynx can lead to airway obstruction, epinephrine (0.3-0.5 ml of epinephrine (adrenaline) solution subcutaneously at a ratio of 1:1000) should be given immediately and airway patency maintained (intubation or tracheostomy).

The incidence of angioedema is higher among patients of the Negro race receiving ACE inhibitor therapy than among patients of other racial backgrounds.

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 may develop with or without a history of allergic reactions. Worsening of the course of systemic lupus erythematosus has been reported.

Due to increased risk of anaphylactic reactions Enap® H should not be used in patients on hemodialysis with high flow polyacrylonitrile membranes (AN69®) undergoing low density lipoprotein apheresis with dextransulfate and immediately before the procedure of desensitization to wasp or bee venom.

Surgical interventions/general anesthesia

Pre-surgery (including dentistry), the anesthesiologist should be warned about the use of ACE inhibitors.
During surgical interventions or general anesthesia with agents causing arterial hypotension, ACE inhibitors may block angiotensin II formation in response to compensatory renin release. If a pronounced decrease in BP develops due to this mechanism, it can be corrected by increasing circulating blood volume.

Cough

Cough has been noted when using ACE inhibitors. Cough is dry and prolonged, which disappears after discontinuation of ACE inhibitors. In the differential diagnosis of cough, cough caused by use of ACE inhibitors must also be considered.

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

At the beginning of treatment with Enap® N there may be a marked decrease of BP, dizziness and somnolence which may impair the ability to drive vehicles and to engage in other potentially dangerous activities requiring increased concentration and rapid psychomotor reactions. Therefore, at the beginning of treatment, it is not recommended to drive vehicles and engage in other potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

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

Side effects

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

Metabolic and nutritional disorders
– infrequent: Gout;

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

On the senses:
– infrequently: tinnitus;

Cardiovascular system disorders
– often: orthostatic hypotension;
– infrequently: fainting, marked decrease in BP, palpitations, tachycardia, chest pain;

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

Digestive system disorders:
– frequently: 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;

Skin disorders:
– infrequent: skin rash, itching, increased sweating, skin necrosis, alopecia;

Urinary system disorders:
– infrequent: impaired renal function, acute renal failure, impotence, decreased libido;

Musculoskeletal system disorders:
– often: muscle cramps;
– infrequently: arthralgia;

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

Other:
– A symptom complex has been described that may include fever, myalgia and arthralgia, serositis, vasculitis, increased erythrocyte sedimentation rate, leukocytosis and eosinophilia, skin rash, positive antinuclear antibody test.

Overdose

Symptoms: increased diuresis, marked BP decrease with bradycardia or other cardiac rhythm disorders, convulsions, consciousness disorders (including coma), acute renal failure, disorders of acid-base balance and water-electrolyte balance of blood.

Treatment: the patient is transferred to the horizontal position with elevated legs.

In mild cases gastric lavage and oral intake of activated charcoal are indicated, in more serious cases – measures aimed at BP stabilization – intravenous administration of plasma substitutes, infusion of 0.9% sodium chloride solution.

The patient’s blood pressure, heart rate, respiratory rate, serum concentrations of urea, creatinine, electrolytes, and urine output should be controlled, and if necessary – intravenous angiotensin II administration, hemodialysis (enalaprilat excretion rate – 62 ml/min).

Similarities