Renipril, tablets 20 mg 30 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 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 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 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 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

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 reduce the hypotensive effect; with potassium-saving diuretics (spironolactone, triamterene, amiloride) may lead to hyperkalemia; with lithium salts – to delay lithium excretion (control of plasma lithium concentration is indicated.)

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

Enalapril weakens the effect of drugs containing theophylline.

Enalapril hypotensive effect is increased by diuretics, beta-adrenoblockers, methyldopa, nitrates, slow calcium channel blockers, hydralazine, prazosin, drugs for general anesthesia, ethanol.

Immunosuppressants, allopurinol, cytostatics increase hematotoxicity. Drugs that cause 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 sudden and pronounced BP decrease 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 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, periodic monitoring of BP, blood parameters (hemoglobin, potassium, creatinine, urea, activity of “hepatic” enzymes), urine protein is necessary.

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

The abrupt withdrawal of treatment does not result in “withdrawal” syndrome (a rapid 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 impairment that may result from decreased 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 dose adjustment period is completed, 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 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 risk/benefit ratio of administration of Renipril® to patients with coronary and cerebrovascular insufficiency should be considered due to the risk of increased ischemia with excessive arterial hypotension.

The drug should be prescribed with caution in patients with diabetes due to the risk of hyperkalemia.

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

Patients with severe 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.

Synopsis

Contraindications

Hypersensitivity to enalapril and other ACE inhibitors, hereditary or idiopathic edema, history of angioedema associated with treatment with ACE inhibitors, porphyria, 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, coronary heart disease, suppression of medullary hematopoiesis, cerebrovascular disease, diabetes, renal failure (proteinuria – more than 1 g/day), hepatic insufficiency, in patients on a salt restricted diet or undergoing hemodialysis, when concomitant administration with immunosuppressants and saluretics, in elderly patients (over 65 years old), conditions accompanied by decreased volume of circulating blood (including diarrhea, vomiting).

Side effects

Renipril® is generally well tolerated and in most cases does not cause side effects requiring withdrawal of the drug.

Cardiovascular side effects: excessive decrease in BP, orthostatic collapse, rarely – chest pain, angina pectoris, myocardial infarction (usually associated with a pronounced decrease in BP), extremely rare – arrhythmias (atrial brady or tachycardia, atrial fibrillation), palpitation, pulmonary artery branch thromboembolism.

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

Sensory organs: disorders of the vestibular system, hearing and vision disorders, tinnitus.

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

In the respiratory system: non-productive dry cough, 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.

In laboratory parameters: hypercreatininemia, increased urea, increased activity of liver enzymes, hyperbilirubinemia, hyperkalemia, hyponatremia. In some cases decrease of hematocrit, increase of sedimentation rate, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia are noted.

Since the urinary system: renal dysfunction, proteinuria.

Others:alopecia, decreased libido, 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 intake 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 averages 62 ml/min).

Similarities