Renipril, tablets 20 mg 20 pcs

Pharmacotherapeutic group: angiotensin-converting enzyme inhibitor.

ATX code C09AA02

Pharmacological properties

Renipril^® is an antihypertensive drug from the ACE inhibitor group. 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 plasma renin levels than at normal or reduced levels. Decrease of BP within therapeutic limits has no effect on the cerebral blood flow, the blood flow in the brain vessels is maintained at a sufficient level even against the background of reduced blood pressure. It enhances coronary and renal blood flow.

Long-term use reduces hypertrophy of the left ventricular myocardium and myocytes of the walls of the resistive arteries, 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 heart failure, a noticeable clinical effect is observed with long-term use – 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 blood proteins. Enalapril is rapidly metabolized in the liver to form the active metabolite enalaprilat, 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 – after 3-4 hours. Enalaprilat easily passes through 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 h. Elimination of enalapril is mainly 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,

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

Active ingredient

Composition

1 tablet contains enalapril maleate 20 mg.

How to take, the dosage

Prescribe orally regardless of the time of meals.

In monotherapy of arterial hypertension, the initial 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 10-40 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 prescribed to patients concomitantly receiving diuretics, treatment with a diuretic must be discontinued 2 to 3 days before administration of Renipril®. If this is not possible, the initial dose of the drug should be 2.5 mg/day.

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

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

In chronic heart failure, the initial dose is 2.5 mg once, then the dose is increased by 2.5-5 mg every 3-4 days according to the clinical response to the maximum tolerated dose depending on BP values, 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/day. Dose adjustment should be carried out during 2-4 weeks or in shorter periods. The average maintenance dose is 5-20 mg/day in 1-2 doses.

The elderly are more likely to have a more pronounced hypotensive effect and prolonged time of action of the drug due to decreased elimination rate of enalapril, so the recommended starting dose for the elderly is 1.25 mg.

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

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

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

Interaction

Concomitant administration of Renipril® with nonsteroidal anti-inflammatory drugs (NSAIDs), estrogens may decrease the hypotensive effect; with potassium-saving diuretics (spironolactone, triamterene, amiloride) may lead to hyperkalemia; with lithium salts – slowed excretion of lithium (monitoring of lithium concentration in blood plasma is indicated).

Simultaneous use with antipyretics and pain medications may decrease the effectiveness of enalapril.
Enalapril weakens the effect of drugs containing theophylline.

Enalapril hypotensive effects are enhanced by – diuretics, beta-adrenoblockers, methyldopa, nitrates, slow calcium channel blockers, hydralazine, prazosin, drugs for general anesthesia, ethanol.

Immunosuppressants, allopurinol and cytostatics increase hematotoxicity.

The drugs causing bone marrow suppression increase the risk of neutropenia and/or agranulocytosis.

Special Instructions

Caution should be exercised when prescribing Renipril® 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 BP decrease after administration of even the initial dose of ACE inhibitor is increased. Transient hypotension is not a contraindication for continuation of treatment with the drug after BP stabilization. In case of repeated pronounced BP decrease, the dose should be reduced or the drug should be discontinued.

The use of highly permeable 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, BP, blood parameters (hemoglobin, potassium, creatinine, urea, liver enzymes activity), urine protein should be monitored.

Patients with severe heart failure, coronary heart disease, and cerebrovascular disease in whom a sharp decrease in BP may lead to myocardial infarction, stroke, or impaired renal function should be closely monitored.
Sudden treatment withdrawal does not lead to “withdrawal” syndrome (a sharp rise in BP).

In newborns and infants who have had intrauterine exposure to ACE inhibitors should be closely monitored for the timely detection of marked BP decline, oliguria, hyperkalemia, and neurologic disorders that may result from reduced renal and cerebral blood flow with ACE inhibitor-induced BP decline. In oliguria, it is necessary to maintain BP and renal perfusion by administration of appropriate fluids and vasoconstrictors.

The drug should be discontinued before parathyroid function study.

Alcohol increases the hypotensive effect of the drug.

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

Warn the surgeon/anesthesiologist about the use of ACE inhibitors before surgical procedures (including dentistry).

In the presence of renal insufficiency, excretion of the active metabolite may be reduced, resulting in increased plasma concentrations. These patients may require prescribing lower doses of the drug.

In patients with arterial hypertension and unilateral or bilateral renal artery stenosis, serum urea and creatinine may increase.

In such patients, renal function should be monitored during the first few weeks of therapy. Dose reduction of the drug may be necessary.

The relation of risk and potential benefit should be considered when prescribing Renipril® to patients with coronary and cerebrovascular insufficiency because of danger of increasing ischemia in case of excessive arterial hypotension.
The drug should be used with caution in patients with diabetes due to risk of hyperkalemia.

Patients with a history of angioedema may have an increased risk of angioedema with Renipril® treatment.

Patients with significant autoimmune diseases, such as systemic lupus erythematosus or scleroderma, have an increased risk of developing neutropenia or agranulocytosis while taking Renipril®.

We recommend caution when prescribing Renipril® for therapy of chronic heart failure in patients treated with cardiac glycosides and/or diuretics.

Contraindications

Hypersensitivity, children under 18 years of age.

Side effects

Dizziness, headache, weakness, increased fatigue, dry cough, orthostatic hypotension, palpitations, heart pain, nausea.

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 infusion of saline solution, plasma substitutes, angiotensin II administration, hemodialysis if necessary (elimination rate of enalaprilat – 62 ml/min).

Pregnancy use

It is contraindicated during pregnancy. Women who are breastfeeding should stop breastfeeding.

Similarities