Enalapril-FPO, tablets 10 mg 20 pcs

Pharmacotherapeutic group:

An angiotensin-converting enzyme (ACE) inhibitor

Pharmacodynamics:

Enalapril is an antihypertensive drug, from the group of ACE inhibitors. Enalapril is a “prodrug”: its hydrolysis produces enalaprilate, which inhibits ACE. Its mechanism of action is related to the reduction of angiotensin I and angiotensin II, the reduction of which leads to a direct reduction of aldosterone secretion. This decreases total peripheral vascular resistance, systolic and diastolic blood pressure (BP), post- and preload on myocardium.

Dilates arteries to a greater extent than veins, and there is no reflex increase in heart rate.

The hypotensive effect is more pronounced at high blood plasma renin levels than at normal or reduced levels. Decrease of BP within therapeutic limits does not affect the cerebral blood flow, the blood flow in brain vessels is maintained at a sufficient level even against the background of decreased blood pressure. It enhances coronary and renal blood flow.

Long-term use reduces hypertrophy of the left ventricular myocardium and myocytes of the resistive arterial walls, prevents the progression of heart failure and slows the development of left ventricular dilatation. Improves blood supply to ischemic myocardium. Reduces platelet aggregation.

It has some diuretic effect.

The time of onset of hypotensive effect when taken orally is 1 hour, reaches a maximum after 4-6 hours and lasts up to 24 hours. In some patients, therapy for several weeks is necessary to achieve optimal blood pressure levels. In cardiac insufficiency noticeable clinical effect is observed with long-term treatment – 6 months or more.

Pharmacokinetics:

After oral administration 60% of the drug is absorbed. Food intake does not affect the absorption of enalapril.

Enalapril is up to 50% bound to plasma proteins. Enalapril is rapidly metabolized in the liver to form the active metabolite enalaprilate, which is a more active ACE inhibitor than enalapril. The bioavailability of the drug is 40%.

The maximum concentration of enalapril in blood plasma is reached after 1 hour, of enalaprilat – 3-4 hours. Enalaprilat easily passes through the histohematic barriers, excluding the blood-brain barrier, a small amount passes through the placenta and into the breast milk.

The elimination half-life of enalaprilat is about 11 hours. Enalapril is mainly excreted by the kidneys – 60% (20% as enalapril and 40% as enalaprilat), through the intestine – 33% (6% as enalapril and 27% as enalaprilat).

It is eliminated by hemodialysis (rate 62 ml/min) and peritoneal dialysis.

Indications

– arterial hypertension;

– chronic heart failure (as part of combination therapy).

Active ingredient

Composition

1 tablet contains the active ingredient enalapril maleate 5 mg, 10 mg.

Ancillary substances:

Corn starch,

Lactose (milk sugar),

microcrystalline cellulose,

colloidal silicon dioxide (aerosil A-300),

calcium stearate.

How to take, the dosage

Prescribe orally regardless of the time of meals. Enalapril at a dose of 2.5 mg may be used to provide the dosing regimen below.

In monotherapy of arterial hypertension, the starting dose is 5 mg once daily.

If there is no clinical effect, the dose is increased by 5 mg after 1-2 weeks. After the initial dose, patients should be under medical supervision for 2 hours and an additional 1 hour until BP stabilizes. If necessary and tolerated well enough, the dose can be increased to 40 mg/day in 2 doses. After 2-3 weeks, switch to a maintenance dose of 10 to 40 mg/day, divided into 1-2 doses. In moderate arterial hypertension, the average daily dose is about 10 mg.

The maximum daily dose of the drug is 40 mg/day.

If patients are prescribed concomitantly receiving diuretics, treatment with a diuretic should be discontinued 2 to 3 days before administration of Enalapril-FPO®. If this is not possible, the starting dose of the drug should be 2.5 mg/day.

Patients with hyponatremia (serum sodium ion concentration less than 130 mmol/l) or serum creatinine concentration greater than 0.14 mmol/l have a starting dose of 2.5 mg once daily.

In renovascular hypertension, the initial dose is 2.5 to 5 mg/day. The maximum daily dose is 20 mg.

In chronic heart failure, the initial dose is 2.5 mg once and then the dose is increased by 2.5 to 5 mg every 3-4 days according to the clinical response to the maximum tolerated dose depending on the value of BP, but not more than 40 mg/day once or in 2 doses. Patients with low systolic blood pressure (less than 110 mmHg) should start therapy with a dose of 1.25 mg. The dose should be adjusted for 2-4 weeks or for shorter periods. The average maintenance dose is 5 to 20 mg/day in 1 to 2 doses.

In elderly patients a more pronounced hypotensive effect and prolonged time of action of the drug are more often observed due to decreased elimination rate of enalapril, so the recommended starting dose in elderly patients is 1.25 mg.

In chronic renal failure, cumulation occurs when filtration is less than 10 ml/min. With a creatinine clearance (CK) of 80 to 30 mL/min, the dose is usually 5 to 10 mg/day; with CK to 30 to 10 mL/min. – 2.5 – 5 mg/day, at CK less than 10 ml/min. – 1.25 – 2.5 mg/day on dialysis days only.

The duration of treatment depends on the effectiveness of therapy. If BP decreases too significantly, the dose of the drug is gradually reduced.

The drug is used both in monotherapy and in combination with other antihypertensive agents.

Interaction

Concomitant administration of enalapril with nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) may reduce the hypotensive effect of enalapril; with potassium-saving diuretics (spironolactone, triamterene, amiloride) may lead to hyperkalemia; with lithium salts – to delayed lithium excretion (plasma lithium concentration control is indicated).

In some patients with impaired renal function, and taking NSAIDs, including COX-2 inhibitors, concomitant use of ACE inhibitors may further impair renal function. These changes are reversible.

Simultaneous use with antipyretics and analgesics may decrease the effectiveness of the drug.

Enalapril weakens the effect of drugs containing theophylline.

The hypotensive effect of enalapril is increased by diuretics, beta-adrenoblockers, methyldopa, nitrates, “slow” calcium channel blockers of dihydropyridine series, hydralazine, prazosin.

Immunosuppressants, allopurinol, cytostatics increase hematotoxicity. Drugs that cause bone marrow suppression increase the risk of neutropenia and/or agranulocytosis.

The combined use of ACE inhibitors and hypoglycemic agents (insulin, hypoglycemic agents for oral administration) may increase the hypoglycemic effect of the latter with the risk of hypoglycemia. This is most often observed during the first weeks of co-administration, as well as in patients with renal insufficiency. In patients with diabetes receiving oral hypoglycemic agents and insulin, it is necessary to control blood glucose levels, especially during the first month of combined use with ACE inhibitors.

The ACE inhibitors decrease renal excretion of lithium and increase the risk of lithium intoxication. Serum lithium levels should be monitored if lithium salts need to be prescribed.

A symptomcomplex including facial redness, nausea, vomiting and arterial hypotension have been described in rare cases when gold preparations for parenteral use (sodium aurothiomalate) and ACE inhibitors (enalapril) are used together.

Special Instructions

Caution should be exercised when prescribing to patients with decreased circulating blood volume (as a result of diuretic therapy, restriction of table salt intake, hemodialysis, diarrhea and vomiting) the risk of a sudden and pronounced decrease of blood pressure after using even the initial dose of ACE inhibitor is increased.

Transient arterial hypotension is not a contraindication for continuation of treatment with the drug after stabilization of blood pressure (BP). If there is a repeated pronounced decrease in BP, the dose should be reduced or the drug should be discontinued.

The use of high-strength dialysis membranes increases the risk of anaphylactic reaction. Adjustment of the dosing regimen on days free of dialysis should be made depending on the BP level.

Before and during treatment with ACE inhibitors, periodic monitoring of BP, blood parameters (hemoglobin, potassium, creatinine, urea, activity of “liver” enzymes), urine protein is necessary.

Patients with severe chronic heart failure, coronary heart disease, and cerebrovascular disease in whom a rapid decrease of BP may result in myocardial infarction, stroke, or impaired renal function should be closely monitored.

The abrupt withdrawal of treatment does not cause “ricochet” syndrome (high blood pressure).

In newborns and infants who have had intrauterine exposure to ACE inhibitors should be closely monitored for timely detection of marked BP decreases, oliguria, hyperkalemia, and neurologic disorders that may result from decreased renal and cerebral blood flow when ACE inhibitor-induced blood pressure decreases.

In oliguria it is necessary to maintain BP and renal perfusion by administration of appropriate fluids and vasoconstrictors.

Pending investigation of parathyroid gland function should be reversed.

Alcohol increases the hypotensive effect of the drug.

At the beginning of treatment, until the end of the dosing period, one should refrain from driving and engaging in potentially hazardous activities requiring increased concentration and rapid psychomotor reactions because dizziness is possible, especially after the initial dose of ACE inhibitor in patients taking diuretics.

Before surgical procedures (including dentistry), the surgeon/anesthesiologist should be warned about the use of ACE inhibitors.

Contraindications

Hypersensitivity to enalapril and other ACE inhibitors, history of angioedema associated with treatment with ACE inhibitors and hereditary or idiopathic angioedema, pregnancy, lactation, age under 18 years (effectiveness and safety not established).

With caution, use in primary hyperaldosteronism, bilateral renal artery stenosis, artery stenosis of the single kidney, hyperkalemia, condition after renal transplantation; aortic stenosis, mitral stenosis (with hemodynamic disorders), idiopathic hypertrophic subaortic stenosis, systemic connective tissue diseases, ischemic heart disease, cerebrovascular diseases, diabetes, renal failure (proteinuria more than 1 g/day.), hepatic insufficiency, in patients on salt restricted diet or undergoing hemodialysis, in concurrent use with immunosuppressants and saluretics, in elderly patients (over 65 years old), inhibition of medullar hemopoiesis; the states accompanied with decreased volume of circulating blood (including diarrhea, vomiting).

Side effects

Enalapril-FPO® is generally well tolerated and in most cases does not cause adverse events requiring drug withdrawal.

Cardiovascular system disorders: excessive BP decrease, orthostatic collapse, rarely – chest pain, angina pectoris, myocardial infarction or stroke (usually associated with a marked decrease in blood pressure), very rarely arrhythmias (atrial brady or tachycardia, atrial fibrillation), palpitation, pulmonary artery thromboembolism, Raynaud’s syndrome.

Central nervous system disorders: dizziness, headache, weakness, insomnia, anxiety, confusion, increased fatigue, somnolence (2-3%), very rarely with high doses – nervousness, depression, paresthesia.

Sensory system disorders: vestibular system disorders, hearing and vision disorders, tinnitus.

Digestive system disorders: dry mouth, anorexia, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, abdominal pain), intestinal obstruction, pancreatitis, disorders of liver function and biliary excretion, hepatitis (hepatocellular or cholestatic), jaundice.

Respiratory system: non-productive dry cough, sore throat, hoarseness of voice, pulmonary infiltrates, interstitial pneumonitis, bronchospasm, dyspnea, rhinorrhea, pharyngitis.

Allergic reactions: Skin rash, itching, urticaria, angioneurotic edema, extremely rare dysphonia, erythema polymorphic, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus, photosensitization, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis, intestinal edema (very rare).

In laboratory parameters: hypercreatininemia, increased urea, increased activity of liver enzymes, hyperbilirubinemia, hyperkalemia, hyponatremia, hypoglycemia in diabetic patients who receive hypoglycemic agents for oral administration or insulin. In some cases decrease of hemoglobin concentration and hematocrit, increase of sedimentation rate, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia have been noted.

Urinary system disorders: impaired renal function, rarely proteinuria.

Other: alopecia, decreased libido, impotence, hot flashes.

Overdose

Symptoms: marked BP decrease up to the development of collapse, myocardial infarction, acute cerebral circulation disorder or thromboembolic complications, convulsions, stupor.

Treatment: the patient is transferred to a horizontal position with a low headboard.

In mild cases gastric lavage and oral administration of saline solution are indicated, in more severe cases – measures aimed at BP stabilization: intravenous administration of saline solution, plasma substitutes, if necessary – angiotensin II administration, hemodialysis (elimination rate of enalaprilat – 62 ml/min).

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