Enalapril-FPO, 20 mg tablets 20 pcs

Heart failure, Edema, Hypertension (high blood pressure)

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

Active ingredient

Composition

1 tablet contains:

hydrochlorothiazide 12.5 mg,

enalapril maleate 20 mg

Associates:

Lactose monohydrate 18.5 mg,

Potato starch 10 mg,

Microcrystalline cellulose 31 mg,

Povidone 2 mg,

Sodium hydrocarbonate 2 mg,

sodium carboxymethyl starch (sodium starch glycolate) 2 mg,

talk 1 mg,

magnesium stearate 1 mg.

How to take, the dosage

Appointed orally, with or after meals, the tablets are taken without chewing, with a small amount of liquid.

The adequate doses of the individual components should be determined initially. The dose should always be chosen individually for each patient. The recommended dose is 1 tablet/day. Patients should get into the habit of taking the drug regularly, at the same time, preferably in the morning.

In patients on diuretic therapy, it is recommended that treatment be discontinued or the dose of diuretics be reduced at least 3 days before treatment with the drug to prevent the development of symptomatic arterial hypotension.

Key kidney function should be investigated before starting treatment.

The duration of treatment is determined by the physician.

If the next dose of the drug is missed, it should be taken as soon as possible if there is plenty of time before the next dose. If we are a few hours away from the next dose, we need to wait and take just that dose. You should never double the dose.

In patients with renal impairment with a CK of 30-75 mL/min, the drug should only be used after prior titration of the doses of enalapril and hydrochlorothiazide separately, according to the doses in the Enalapril N combination product.

If there is no therapeutic effect, it is recommended that another drug be added or the therapy changed.

The duration of treatment is not limited.

Interaction

The use of potassium supplements, potassium-saving agents or drugs containing potassium, salt substitutes, especially in patients with renal insufficiency, may lead to a significant increase in serum potassium. Loss of potassium against the background of thiazide diuretics is usually reduced by enalapril. Serum potassium content usually remains within normal limits.

When concomitant use with lithium preparations the excretion of lithium is delayed (increase of the cardiotoxic and neurotoxic effects of lithium).

Thiazide diuretics may increase the effect of tubocurarine chloride.

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

The concomitant use of other hypotensive agents, including beta-adrenoblockers, alpha-adrenoblockers, ganglioblockers, methyldopa or slow calcium channel blockers may further decrease BP with enalapril.

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

The concomitant use of thiazide diuretics with GCS, calcitonin may lead to hypokalemia.

The concomitant use of cyclosporine with ACE inhibitors may increase the risk of hyperkalemia. Concomitant use of hydrochlorothiazide and cyclosporine may increase the risk of hyperuricemia and complicate the course of gout.

The concomitant use of NSAIDs (including selective COX-2 inhibitors) may impair the antihypertensive effect of ACE inhibitors or angiotensin II receptor antagonists. NSAIDs and ACE inhibitors have an additive effect with respect to the increase in serum potassium, which may 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 decrease the antihypertensive effect of ACE inhibitors.

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

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

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.

Single administration of colestiramine or colestipol reduces absorption of hydrochlorothiazide in the GI tract by 85% and 43%, respectively.

When ACE inhibitors and gold drugs (sodium aurothiomalate) are administered concomitantly by IV, a symptom complex has been described including facial hyperemia, nausea, vomiting and arterial hypotension.

The simultaneous use of ACE inhibitors and thiazide diuretics with trimethoprim increases the risk of hyperkalemia.

The concomitant use of ACE inhibitors and lovastatin increased the risk of hyperkalemia.

Concomitant use with ACE inhibitors may increase the hypotensive effect of tricyclic antidepressants, neuroleptics, anesthetics.

Enalapril may be used concomitantly with acetylsalicylic acid (in doses up to 300 mg/day), thrombolytics, beta-adrenoblockers and nitrates.

The doses of drugs used for gout (probenecid, sulfinpyrazone and allopurinol) may need to be adjusted because hydrochlorothiazide can increase uric acid concentration; co-administration of thiazide diuretics may lead to an increased incidence of hypersensitivity reactions to allopurinol.

Choline blockers (atropine, biperiden) may increase bioavailability of thiazide diuretics, reducing motility and rate of gastrointestinal emptying.

Thiazide diuretics delay renal excretion of cytotoxic drugs (e.g., cyclophosphamide, methotrexate) and thereby increase their myelosuppressive effects.

Hemolytic anemia may develop when hydrochlorothiazide and methyldopa are used together.

Hypokalemia or hypomagnesemia caused by thiazide diuretics may contribute to rhythm disturbances when taking cardiac glycosides.

In hypovolemia caused by thiazide diuretics, there is an increased risk of acute renal failure when high doses of iodine-containing contrast agents are administered.

Concomitant intravenous administration of amphotericin B, as well as administration of GCS, corticotropin or laxatives and hydrochlorothiazide, may exacerbate water-electrolyte imbalances, especially hypokalemia.

Simultaneous use with carbamazepine may lead to symptomatic hyponatremia.

Hydrochlorothiazide should be used with caution with drugs that may cause ventricular tachycardia of the “pirouette” type, such as some antiarrhythmic drugs, neuroleptics.

The simultaneous use of thiazide diuretics with drugs containing calcium salts may develop hypercalcemia.

Special Instructions

Arterial hypotension with all clinical consequences may occur after the first administration of Enalapril-N in patients with severe CHF and hyponatremia, severe renal failure or left ventricular dysfunction and, in particular, in patients with hypovolemia due to diuretic therapy, salt-free diet, diarrhea, vomiting or hemodialysis.

In case of arterial hypotension, the patient should be placed on his back with a low headboard and, if necessary, the volume of the blood circulation 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.

Cautions are required in patients with CHD, marked cerebrovascular disease, aortic stenosis or idiopathic hypertrophic obstructive subaortic stenosis impeding blood flow from the left ventricle, marked atherosclerosis, in elderly patients due to risk of arterial hypotension and worsening of blood supply to heart, brain and kidneys.

The serum electrolyte concentrations should be monitored regularly during treatment to detect possible imbalances and take timely, appropriate measures. Determination of serum electrolyte concentrations is mandatory in patients with prolonged diarrhea, vomiting.

In patients taking Enalapril N the signs of electrolyte and water imbalances, such as oral dryness, thirst, weakness, somnolence, hyperexcitability, myalgia and cramps (primarily of the calf muscles), decreased blood pressure, tachycardia, oliguria, and gastrointestinal disturbances (nausea, vomiting) should be identified.

Enalapril N 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 the Enalapril N combination drug.

Enalapril N should be used with caution in patients with hepatic impairment or advanced liver disease because hydrochlorothiazide may cause hepatic coma even with minimal electrolyte-water imbalances. Several cases of acute hepatic failure with cholestatic jaundice, fulminant liver necrosis and death have been reported (rarely) during treatment with ACE inhibitors. If jaundice and increased hepatic transaminase activity occur, treatment with Enalapril N should be discontinued immediately and patients should be monitored.

Caution is necessary in all patients receiving treatment with oral hypoglycemic agents or insulin, because hydrochlorothiazide may weaken and enalapril may potentiate their effects.

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

Developed hypercalcemia may be a sign of occult hyperparathyroidism. Thiazide diuretics must be discontinued before parathyroid function testing.

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

The 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, thereby counteracting the hyperuricemic effect of hydrochlorothiazide.

In case 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 could lead to airway obstruction, epinephrine (0.3-0.5 ml of epinephrine (adrenaline) solution p/k at a ratio of 1:1000) should be given immediately and airway patency maintained (intubation or tracheostomy).

The incidence of angioedema is higher among non-Hispanic patients 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.

Because of the increased risk of anaphylactic reactions, Enalapril H should not be used in patients on hemodialysis with high flow polyacrylonitrile membranes (AN 69®) undergoing LDL apheresis with dextran sulfate and immediately prior to desensitization with moth venom allergen.

Before surgical procedures (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 marked decrease in BP develops, explained by such a mechanism, it can be corrected by increasing the RBC.

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

The drug may cause a positive result in antidoping tests.

Impact on driving and operating machinery

At the beginning of treatment with Enalapril N, a marked decrease in BP, dizziness and somnolence may occur, which may impair the ability to drive vehicles, 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 dangerous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

– hypersensitivity to drug components or sulfonamide derivatives;

– anuria;

– marked renal dysfunction (CK< 30 ml/min);

– history of angioedema associated with previous use of ACE inhibitors and sulfonamide derivatives;

– hereditary or idiopathic angioedema;

– lactose intolerance, lactase deficiency, or glucose/galactose malabsorption;

– pregnancy;

– lactation (breastfeeding) period;

– childhood and adolescence under 18 years of age (efficacy and safety not established).

The drug should be used with caution in the following conditions: bilateral renal artery stenosis, artery stenosis of the single kidney;

pronounced aortic and mitral stenosis or hypertrophic obstructive cardiomyopathy;

IBS and cerebrovascular disease (including

IBS and cerebrovascular disease (including cerebrovascular insufficiency), because excessive lowering of BP can lead to myocardial infarction and stroke;

Chronic heart failure; Severe atherosclerosis;

Severe autoimmune systemic connective tissue disease (including systemic lupus erythematosus).scleroderma);

inhibition of medullary hematopoiesis;

diabetes, because Thiazide diuretics can decrease glucose tolerance;

Hyperkalemia; conditions after renal transplantation; impaired liver function and/or renal function (CK 30-75 ml/min);

conditions accompanied by decreased RBC (as a result of diuretic therapy, with restriction of table salt intake, diarrhea, and vomiting);

primary hyperaldosteronism;

Elderly age.

Side effects

WHO side effect frequency classification: very frequently (>1/10), frequently (>1/100 and < 1/10), infrequently (>1/1000 and < 1/100), rarely (>1/10 000 and < 1/1000), very rarely (< 1/10 000), frequency unknown.

Hematopoietic system: infrequent – anemia; rare – neutropenia, decreased hemoglobin and hematocrit, thrombocytopenia, leukopenia, agranulocytosis, suppressed bone marrow function, suppressed bone marrow function, pancytopenia, leukopenia, lymphadenopathy, autoimmune diseases.

Endocrine system disorders: frequency is unknown – syndrome of impaired ADH secretion.

Nervous system disorders: common – headache, depression, fainting; infrequent – confusion, drowsiness, insomnia, nervousness, paresthesia, dizziness; rarely – sleep disorders, paresis (due to hypokalemia).

An organ of vision: very common – visual disturbances; frequency unknown – xanthopsia.

The cardiovascular system: often – marked decrease in BP (including orthostatic hypotension), chest pain, arrhythmias, tachycardia, angina pectoris; infrequent – myocardial infarction or stroke, palpitations; rarely – Raynaud’s syndrome; frequency unknown – necrotizing angiitis (vasculitis, cutaneous vasculitis).

Respiratory system: very common – cough; common – shortness of breath; infrequent – rhinorrhea, sore throat, hoarseness, bronchospasm; rare – pulmonary infiltrates, rhinitis, allergic alveolitis/eosinophilic pneumonia, respiratory distress syndrome (including pneumonitis and pulmonary edema).

Digestive system disorders: very common – nausea; common – diarrhea, abdominal pain, taste disorders; infrequent – intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, anorexia, stomach irritation, dry oral mucosa, peptic ulcer; rarely – stomatitis, aphthous ulcers, glossitis, liver failure, hepatitis (hepatocellular or hemolytic), cholestasis, fulminant liver necrosis; very rarely – intestinal angioedema.

Skin and subcutaneous tissue: common – skin rash, angioedema of the face, extremities, lips, tongue, vocal cleft, larynx; infrequent – increased sweating, skin itching, urticaria, alopecia; rare – erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, vesicles, erythroderma, lupus-like skin reactions, exacerbation of systemic lupus erythematosus.

Muscular system disorders: frequently – muscle cramps; infrequently – arthralgia.

Arenal system disorders: infrequent – renal dysfunction, acute renal failure, proteinuria; rarely – oliguria, interstitial nephritis.

With the reproductive system: infrequent – decreased potency, rarely – gynecomastia.

Others: very common – asthenia; common – fatigue; infrequent – muscle cramps, tinnitus, general malaise, fever; frequency unknown (for hydrochlorothiazide) – fever, weakness.

Laboratory tests: frequently – hyperkalemia, hypercreatininemia; infrequently – hyperuricemia, hyponatremia; rarely – increased liver transaminases activity, hyperbilirubinemia.

When using ACE inhibitors, a symptom complex has been described that includes fever, serositis, vasculitis, myalgia, myositis, arthralgia, arthritis, a positive antinuclear antibody test, increased CSF, eosinophilia, leukocytosis, exanthema, photosensitivity reaction or other dermatological disorders.

In concomitant administration of ACE inhibitors and intravenous administration of sodium aurothiomalate, a symptom complex including facial hyperemia, nausea, vomiting, and arterial hypotension has been described.

Overdose

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

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 infusion of plasma substitutes, infusion of 0.9% sodium chloride solution. The patient’s blood pressure, heart rate, respiration rate, serum concentrations of urea, creatinine, electrolytes and urine output should be controlled, and if necessary – intravenous angiotensin II injection, hemodialysis (enalaprilat excretion rate – 62 ml/min).

Similarities