Renipril - instructions for use, dose, side effects, contraindications

Composition:1 tablet contains the active substance enalapril maleate - 10 or 20 mg, as well as excipients: lactose, potato starch, povidone low molecular weight, calcium stearate

Description: Ploskotsilindricheskie tablets of white color with a risk and a facet

Pharmacotherapeutic group:angiotensin-converting enzyme inhibitor (ACE)

ATX: & nbsp

C.09.A.A.02 Enalapril

Pharmacodynamics:

Renipril® - antihypertensive drug from the group of ACE inhibitors. Enalapril is a "prodrug": as a result of its hydrolysis, a enalaprilate, which inhibits ACE. The mechanism of its action is associated with a decrease in the formation of angiotensin I from angiotensin II, a decrease in its content leads to a direct decrease in the release of aldosterone. This reduces overall peripheral vascular resistance, systolic and diastolic blood pressure (BP), post-and preload on the myocardium.

Expands arteries more than veins, with a reflex increase in heart rate is not noted.

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

With prolonged use, hypertrophy of the left ventricle of the myocardium and myocytes of the walls of arteries of the resistive type decreases, prevents the progression of heart failure and slows down the development of dilatation of the left ventricle. Improves the blood supply of the ischemic myocardium. Reduces the aggregation of platelets.

Has some diuretic effect.

The time of the onset of the hypotensive effect with ingestion is 1 hour, reaches a maximum after 4-6 hours and lasts up to 24 hours. Some patients need therapy for several weeks to achieve the optimal blood pressure level. With heart failure, a noticeable clinical effect is observed with prolonged use - 6 months or more.

Pharmacokinetics:

After ingestion, 60% of the drug is absorbed. Eating does not affect the absorption of enalapril.

Enalapril binds up to 50% with blood proteins. Enalapril is rapidly metabolized in the liver to form an active metabolite of enalaprilate, which is a more active ACE inhibitor than enalapril. Bioavailability of the drug - 40%.

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

The half-life of enalaprilate is about 11 hours. enalapril mainly kidneys - 60% (20% - in the form of enalapril and 40% - in the form of enalaprilata), through the intestine - 33% (6% - in the form of enalapril and 27% - in the form of enalaprilata).

It is removed during hemodialysis (speed - 62 ml / min) and peritoneal dialysis

Indications:

arterial hypertension, with chronic heart failure (as part of a combination therapy).

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 (efficacy and safety not established).

Carefully:

Be wary of primary hyperaldosteronism, bilateral renal artery stenosis, stenosis of the artery to a solitary kidney, hyperkalemia, condition after kidney transplantation; aortic stenosis,mitral stenosis (with hemodynamic disorders), idiopathic hypertrophic subaortal stenosis, systemic connective tissue diseases, coronary heart disease, oppression of bone marrow hematopoiesis, cerebrovascular diseases, diabetes mellitus, renal failure (proteinuria more than 1 g / day), liver failure, observing a diet with restriction of salt or being on hemodialysis, while taking with immunosuppressants and saluretics, in the elderly (over 65), consisting accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting).

Dosing and Administration:

Assign inside regardless of the time of ingestion.

At monotherapy of an arterial hypertensia the initial dose - 5 mg once a day.

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

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

In the case of appointing patients who are simultaneously receiving diuretics, treatment with a diuretic should be discontinued 2-3 days before the appointment of Renipril®. If this is not possible, the initial dose of the drug should be 2.5 mg / day.

Patients with hyponatremia (concentration of sodium ions in the serum of blood less than 130 mmol / l) or serum creatinine concentration greater than 0.14 mmol / l, the initial dose - 2.5 mg once a day.

With 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 to 5 mg every 3-4 days according to the clinical response to the maximum tolerated dose, depending on the values of blood pressure, but not more than 40 mg / day. once or in 2 doses. In patients with low systolic blood pressure (less than 110 mm Hg), therapy should be started at a dose of 1.25 mg / day. The dose should be selected within 2-4 weeks or in shorter periods.The average maintenance dose is 5-20 mg / day. for 1-2 reception.

In elderly people, more pronounced hypotensive effect and lengthening of the action time of the drug are more often, which is associated with a decrease in the rate of excretion of enalapril, so the recommended starting dose for the elderly is 1.25 mg.

In chronic renal failure cumulation occurs with a decrease in filtration of less than 10 ml / min. When creatinine clearance (CC) is 80-30 ml / min, the dose is usually 5-10 mg / day, with QC up to 30-10 ml / min - 2.5-5 mg / day, with CC less than 10 ml / min - 1,25-2,5 mg / day. only during dialysis days.

The duration of treatment depends on the effectiveness of therapy. With too pronounced decrease in blood pressure, the dose of the drug is gradually reduced.

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

Side effects:

Renipril® is generally well tolerated and in most cases does not cause side effects requiring the drug to be discontinued.

From the cardiovascular system: excessive reduction of blood pressure, orthostatic collapse, rarely - chest pain, angina pectoris, myocardial infarction (usually associated with a pronounced decrease in blood pressure), rarely - arrhythmias (atrial brady or tachycardia, atrial fibrillation), palpitation, thromboembolism of the pulmonary artery branches.

From the nervous system: dizziness, headache, weakness, insomnia,anxiety, confusion, increased fatigue, drowsiness (2-3%), very rarely with high doses - nervousness, depression, paresthesia.

From the sense organs: disturbances of the vestibular apparatus, hearing and vision impairment, tinnitus.

From the digestive tract: dry mouth, anorexia, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, abdominal pain), intestinal obstruction, pancreatitis, impaired liver function and bile secretion, hepatitis, jaundice.

From the respiratory system: unproductive dry cough, interstitial pneumonitis, bronchospasm, dyspnea, rhinorrhea, pharyngitis.

Allergic reactions: skin rash, itching, urticaria, angioedema, extremely rare - dysphonia, polymorphic erythema, exfoliative dermatitis, Stephen-Johnson syndrome, toxic epidermal necrolysis, pemphigus, photosensitivity, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis.

From the laboratory indicators: hyperkreatininemia, increased urea levels, increased activity of "hepatic" enzymes, hyperbilirubinemia, hyperkalemia, hyponatremia.In some cases, reduced hematocrit, increased ESR, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia.

From the urinary system: impaired renal function, proteinuria. Other: alopecia, decreased libido, hot flashes.

Overdose:

Symptoms: marked decrease in blood pressure up to the development of collapse, myocardial infarction, acute disturbance of cerebral circulation or thromboembolic complications, convulsions, stupor.

Treatment: the patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage and ingestion of saline are shown, in more severe cases - measures aimed at stabilizing blood pressure: intravenous injection of physiological solution, plasma substitutes, if necessary - the introduction of angiotensin II, hemodialysis (the rate of excretion of enalaprilat is on average 62 ml / min ).

Interaction:

With the simultaneous administration of Renipril® with non-steroidal anti-inflammatory drugs (NSAIDs), estrogen may reduce hypotensive effect; with potassium-sparing diuretics (spironolactone, triamterene, amiloride) can lead to hyperkalemia; with lithium salts - to slow down the excretion of lithium (shown control of the concentration of lithium in blood plasma).

Simultaneous administration with antipyretic and analgesic agents may decrease the effectiveness of enalapril.

Enalapril weakens the effect of drugs containing theophylline.

The hypotensive effect of enalapril is enhanced by diuretics, beta-blockers, methyldopa, nitrates, blockers of "slow" calcium channels, hydralazine, prazozin, medicines for general anesthesia, ethanol.

Immunosuppressants, allopurinol, cytotoxic drugs increase hematotoxicity. Drugs that cause bone marrow depression, increase the risk of developing neutropenia and / or agranulocytosis.

Special instructions:

Caution should be exercised when prescribing Renipril® to patients with reduced circulating blood volume (due to diuretic therapy, limiting intake of salt, hemodialysis, diarrhea, and vomiting), the risk of a sudden and severe decrease in blood pressure after applying even an initial dose of an ACE inhibitor is increased.Transient arterial hypotension is not a contraindication for continuing treatment with the drug after BP stabilization. In the case of a re-expressed decrease in blood pressure should reduce the dose or cancel the drug.

The use of high permeability dialysis membranes increases the risk of developing an anaphylactic reaction. Correction of the dosing regimen on days free from dialysis should be performed depending on the level of blood pressure.

Before and during treatment with ACE inhibitors, periodic monitoring of blood pressure, blood counts (concentration of hemoglobin, potassium, creatinine, urea, activity of "liver" enzymes) and protein in the urine is necessary.

It should be carefully monitored for patients with severe heart failure, coronary heart disease and cerebrovascular disease, in which a sharp decrease in blood pressure can lead to myocardial infarction, stroke, or renal dysfunction.

Sudden abolition of treatment does not lead to the syndrome of "withdrawal" (a sharp rise in blood pressure).

For newborns and infants who have been exposed to intrauterine exposure to inhibitors ACE, it is recommended to carefully monitor for the timely detection of a marked decrease in blood pressure, oliguria,hyperkalemia and neurological disorders, possibly due to a decrease in renal and cerebral blood flow with a decrease in blood pressure caused by ACE inhibitors. In oliguria it is necessary to maintain BP and renal perfusion by introducing appropriate fluids and vasoconstrictors.

Before the study of parathyroid gland functions, the drug should be discontinued. Alcohol enhances the hypotensive effect of the drug.

Before surgery (including dentistry), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors.

In the presence of renal failure, it is possible to reduce the excretion of the active metabolite, leading to an increase in its concentration in the blood plasma. Such patients may require the administration of smaller doses of the drug.

In patients with hypertension and unilateral or bilateral stenosis of the renal arteries, an increase in urea and creatinine in the blood serum is possible.

These patients need to monitor kidney function during the first few weeks of therapy. You may need to reduce the dosage of the drug.

Consideration should be given to the relationship between risk and potential benefit in appointing Renipril® to patients with coronary and cerebrovascular insufficiency due to the risk of increased ischemia in cases of excessive arterial hypotension.

The drug should be administered with caution to patients with diabetes because of the risk of developing hyperkalemia.

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

In patients with severe autoimmune diseases, for example, systemic lupus erythematosus or scleroderma, the risk of developing neutropenia or agranulocytosis in patients receiving Renipril® is increased.

Caution is advised when prescribing Renipril® for the therapy of chronic heart failure in patients receiving cardiac glycosides and / or diuretics.

Effect on the ability to drive transp. cf. and fur:

At the beginning of treatment, before the end of the dose selection period, it is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions,as dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretics.

Form release / dosage:

Tablets of 10 and 20 mg.

Packaging:

For 10 or 20 tablets in a planar cell pack. For 1, 2 or 3 contour packagings together with instructions for use in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life: 4 years. Do not use after the expiry of the period indicated on the package

Terms of leave from pharmacies:On prescription

Registration number:P N000084 / 01

Date of registration:28.06.2010

The owner of the registration certificate:PHARMSTANDART-FORESTRY, OJSC PHARMSTANDART-FORESTRY, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-FORESTRY, OJSC Russia

Information update date: & nbsp21.10.2015

Illustrated instructions

Instructions

Renipril® (Renipril®)