Renipril

Renipril – inhibitor of the angiotensin-converting enzyme (ACE), anti-hypertensive drug.

Form of release and structure

Dosage form – tablets: ploskotsilindrichesky, white color, with a facet and risky (on 10 or 20 pieces in blister strip packagings, in a cardboard pack 1, 2 or 3 packagings).

Active agent: enalapril a maleate – 10 or 20 mg in 1 tablet.

Excipients: povidone low-molecular, potato starch, calcium stearate, lactose.

Indications to use

• Arterial hypertension;
• Chronic heart failure (as a part of a combination therapy).

Contraindications

Absolute:

• Porphyria;
• Idiopathic or hereditary hypostasis;
• The Quincke's disease in the anamnesis connected using APF inhibitors;
• Age up to 18 years;
• Period of pregnancy and lactation;
• Hypersensitivity to any component of Renipril or other APF inhibitors.

With care:

• Primary hyper aldosteronism;
• Hyperpotassemia;
• State after transplantation of a kidney;
• Bilateral stenosis of renal arteries or stenosis of an artery of the only kidney;
• Mitral (with disturbances of a hemodynamics) or an aortal stenosis;
• Idiopathic hypertrophic subaortal stenosis;
• Coronary heart disease;
• General diseases of connecting fabric;
• Diabetes mellitus;
• Oppression of a marrowy hemopoiesis;
• Liver failure;
• Renal failure (a proteinuria – more than 1 g/days);
• Cerebrovascular diseases;
• The states which are followed by decrease in volume of the circulating blood (including diarrhea and/or vomiting, carrying out a hemodialysis, therapy by diuretics, observance of a diet with restriction of consumption of table salt);
• Advanced age (65 years are more senior);
• Simultaneous use of immunodepressants or saluretics.

Route of administration and dosage

Renipril it is necessary to accept inside. Meal does not influence its efficiency.

It can be applied both as monotherapy, and in combination with other antihypertensives.

Arterial hypertension
As monodrug Renipril appoint 5 mg of 1 times a day.

Within 2 hours after reception of the first dose or until stabilization of the arterial pressure (AP) the patient has to be under observation of the doctor.

In case of lack of clinical effect within 1-2 weeks the dose is increased to 10 mg. If necessary, but on condition of good tolerance of drug, increase in a daily dose up to 40 mg in 2 receptions is possible.

2-3 weeks later pass to a maintenance therapy in a dose 10-40 mg a day into 1-2 receptions. At moderate arterial hypertension 10 mg a day there are usually enough.

The highest admissible daily dose makes 40 mg.

If Renipril is appointed to patients who already receive diuretics, they should be cancelled in 2-3 days. If there is no such opportunity, then the initial dose of enalapril has to make 2,5 mg a day.

The recommended initial dose for patients with concentration of creatinine in blood serum more than 0,14 mmol/l or a hyponatremia (concentration of ions of sodium in blood serum less than 130 mmol/l) makes 2,5 mg of 1 times a day.

At renovascular hypertensia in an initiation of treatment appoint 2,5-5 mg a day. The highest daily dose – 20 mg.

Chronic heart failure
The recommended initial dose makes 2,5 mg of 1 times a day, further each 3-4 days (depending on effect of drug) a dose gradually (on 2,5-5 mg) increase before achievement of the most tolerable and effective dose taking into account size ABP, but no more than 40 mg a day in 1-2 receptions.

At initially low systolic ABP (less than 110 mm hg) treatment begin with a daily dose 1,25 mg then within 2-4 weeks (sometimes) the doctor carries out selection of a dose to shorter time. The average maintenance dose varies ranging from 5 to 20 mg a day in 1-2 receptions.

Initial dose for elderly people – 1,25 mg.

The recommended daily doses for patients with a chronic renal failure depending on the clearance of creatinine (CC): KK of 80-30 ml/min. – 5-10 mg, KK to 30-10 ml/min. – 2,5-5 mg, KK less than 10 ml/min. – 1,25-2,5 mg only in days of dialysis.

Duration of therapy depends on efficiency of drug.

In case of too expressed decrease in the ABP Renipril's dose is gradually reduced.

Side effects

Generally Renipril is had well. In certain cases there are following side effects:

• From respiratory system: pharyngitis, unproductive dry cough, rhinorrhea, bronchospasm, intersticial pneumonitis, asthma;
• From a nervous system: increased fatigue, alarm, sleeplessness, confusion of consciousness, weakness, drowsiness, headache, dizziness; very seldom at reception of high doses – a depression, nervousness, paresthesias;
• From an urinary system: proteinuria, renal failure;
• From sense bodys: sonitus, hearing disorder and sight, disturbance of a vestibular mechanism;
• From cardiovascular system: excessive lowering of arterial pressure, orthostatic collapse; seldom – stenocardia, a retrosternal pain, a myocardial infarction; extremely seldom – a thromboembolism of branches of a pulmonary artery, a cardiopalmus, arrhythmias (atrial fibrillation, atrial bradycardia or tachycardia);
• From a digestive tract: dispepsichesky frustration (a diarrhea/lock, nausea, vomiting, pains in a stomach), anorexia, dryness in a mouth, jaundice, intestinal impassability, an abnormal liver function and a zhelchevydeleniya, pancreatitis, hepatitis;
• From laboratory indicators: hyperpotassemia, hyperbilirubinemia, hyponatremia, increase in content of urea, giperkreatininemiya, increase in activity of liver enzymes; in rare instances – an eosinophilia, a neutropenia, thrombocytopenia, increase in SOE, decrease in a hematocrit; patients with autoimmune diseases have an agranulocytosis;
• Allergic reactions: urticaria, itch, skin rash, Quincke's disease; extremely seldom – a pempigus, a serositis, stomatitis, a photosensitization, a glossitis, a miositis, a vasculitis, arthritis, an arthralgia, a polymorphic erythema, a dysphonia, exfoliative dermatitis, a toxic epidermal necrolysis, Stephen-Johnson's syndrome;
• Others: inflows, decrease in a libido, alopecia.

Special instructions

Tranzitorny arterial hypotension is not a contraindication for therapy continuation the Reniprily ambassador of stabilization of the ABP. However in case of the repeated expressed lowering of arterial pressure it is necessary to reduce a dose or to cancel drug.

At use of high-permeability dialysis membranes the risk of development of anaphylactic reaction increases. Dose adjustment in days, free from dialysis, it is necessary to carry out, based on the ABP level.

Careful observation is required to patients with coronary heart disease, diseases of vessels of a brain and heavy heart failure since at them sharp decrease in the ABP can lead to a renal failure, a stroke or a myocardial infarction.

Before purpose of drug and during its use it is necessary to control periodically the ABP, protein level in blood, and also concentration of urea, potassium, hemoglobin, creatinine, activity of liver enzymes.

At the expressed autoimmune diseases (for example, a scleroderma or a system lupus erythematosus) against the background of Renipril's reception the risk of development of a neutropenia or agranulocytosis increases.

The sharp termination of therapy does not lead to a withdrawal (sharp increase in arterial pressure).

Alcohol strengthens hypotensive effect of drug therefore it is necessary to refuse the use of alcoholic drinks.

At a renal failure removal of an active metabolite of enalapril can decrease that is fraught with increase in its concentration in a blood plasma. Reduction of a dose of Renipril can be required by such patients.

Newborns and babies, whose mothers accepted drug during pregnancy, there have to be under careful medical observation for early detection of neurologic frustration, hyperpotassemias, oligurias, the expressed decrease in the ABP – frustration, possible owing to reduction of a brain and renal blood-groove at decrease in the ABP called by APF inhibitor.

At an oliguria it is necessary to support the ABP and renal perfusion, the corresponding liquids and vasoconstrictors for this purpose enter.

Renipril it is necessary to cancel in need of a research of functions of epithelial bodies.

The dose decline can be required by patients with a stenosis of renal arteries (a renal artery) since they increased risk of increase in content of creatinine and urea in blood serum therefore within the first several weeks of treatment it is necessary to control function of kidneys.

Patients should warn the doctor and/or the anesthesiologist about administration of drug in need of surgical intervention, including dental.

With caution Renipril it is necessary to take at chronic heart failure in case of simultaneous use of diuretics and/or cardiac glycosides.

Due to the probability of development of dizziness, especially after the first dose at the patients receiving diuretics in an initiation of treatment and during titration of a dose it is necessary to refrain from driving and performance of potentially dangerous works requiring the speed of reactions and/or special attention.

Medicinal interaction

• Non-steroidal anti-inflammatory drugs, estrogen: the hypotensive effect decreases;
• Kaliysberegayushchy diuretics (Triamterenum, Spironolactonum, amiloride): the risk of development of a hyperpotassemia increases;
• Lithium salts: lithium removal is slowed down (it is necessary to control concentration of lithium in a blood plasma);
• The drugs causing oppression of marrow: the risk of development of a neutropenia and/or agranulocytosis increases;
• Febrifugal and anesthetics: efficiency of enalapril decreases;
• Theophylline: its effect decreases;
• Ethanol, beta adrenoblockers, blockers of slow calcium channels, means for the general anesthesia, nitrates, diuretics, Prazozinum, гидралазин, Methyldopum: hypotensive effect of enalapril amplifies;
• Immunodepressants, cytostatics, Allopyrinolum: the gematotoksichnost amplifies.

Terms and storage conditions

To store at a temperature up to 25 °C in the place, unavailable to children.

Period of validity – 4 years.