Ramipril

Ramipril – inhibitor of an angiotensin-converting enzyme (APF) of long action.

Form of release and structure

Dosage form – tablets: almost white or white color, a round ploskotsilindrichesky form, with a facet and dividing risky (in a blister strip packaging: on 10 pieces, in a cardboard pack 3 packagings; on 14 pieces, in a cardboard pack 1 or 2 packagings).

– ramiprit active ingredient of Ramipril, in 1 tablet – 2,5 mg, 5 mg or 10 mg.

Auxiliary components: lactose, cellulose microcrystallic, aerosil (silicon dioxide colloid), magnesium stearate, примогель (sodium carboxymethylstarch).

Indications to use

• Combination therapy of chronic heart failure (including with diuretics);
• Arterial hypertension;
• The heart failure which arose during the period from the second to the ninth day after an acute myocardial infarction;
• Clinically expressed and preclinical stages of a diabetic or not diabetic nephropathy (especially with the expressed proteinuria) at a combination to arterial hypertension;
• Decrease in risk of development of a stroke, myocardial infarction or cardiovascular mortality at patients with high cardiovascular risk: at the confirmed coronary heart disease (in the anamnesis with a myocardial infarction or without it), including patients after aortocoronary shunting, transdermal transluminal coronary angioplasty; at a stroke in the anamnesis, occlusal damages of peripheral arteries.

Besides, Ramipril's use is shown by a sick diabetes mellitus in the presence of not less than one accessory factor of risk: arterial hypertension, microalbuminuria, increase in plasma concentration of the general cholesterol, smoking, decrease in plasma concentration of cholesterol of lipoproteins of the high density (HS-LPVP).

Contraindications

• Chronic heart failure in a decompensation stage;
• Hypertrophic subaortic stenosis, hemodynamically significant stenosis of the mitral or aortal valve;
• Arterial hypotension (the systolic arterial pressure (AP) is below 90 mm of a mercury column) or pathology with unstable indicators of a hemodynamics;
• Hereditary or idiopathic Quincke's disease (including the anamnesis, including against the background of the previous therapy by APF inhibitors);
• Syndrome of glyukozo-galaktozny malabsorption, deficit of lactase, lactose intolerance;
• The expressed renal failure (the clearance of creatinine (CC) is less than 20 ml/min.);
• Liver failure;
• Bilateral hemodynamically significant stenosis of renal arteries (in the presence of only one kidney – unilateral);
• Hemodialysis with use of high-flowing membranes with a negatively charged surface;
• Primary hyper aldosteronism;
• Aferez of lipoproteins of low density with use of a dextran of sulfate;
• Simultaneous use of glucocorticosteroids, non-steroidal anti-inflammatory drugs, immunodepressants, cytotoxic drugs for treatment of a nephropathy;
• The accompanying hyposensibilizing therapy of reactions of hypersensitivity to poisons of bees, wasps and other insects;
• Combination therapy with antagonists of receptors of angiotensin II at a diabetic nephropathy;
• Combination to the drugs containing алискирен at patients with a renal failure (KK is less than 60 ml/min.) and a diabetes mellitus;
• Age up to 18 years;
• Period of pregnancy and breastfeeding;
• Hypersensitivity to components of drug or other APF inhibitors.

Besides, Ramipril's use is contraindicated in an acute stage of a myocardial infarction:

• Heart failure of the IV functional class on NYHA classification;
• Pulmonary heart;
• Unstable stenocardia;
• The ventricular disturbances of a heart rhythm posing hazard to life.

With care patients are recommended to appoint drug with atherosclerotic defeats of brain or coronary arteries; at the pathologies interfaced to risk of sharp decrease in the ABP with a renal failure at APF inhibition: the expressed hypertension (especially malignant arterial hypertension), chronic heart failure (especially heavy stage or at reception concerning it other hypotensive medicines), hemodynamically significant unilateral renal artery stenosis at patients with two kidneys, the previous therapy by diuretics, disturbances of water and electrolytic balance (against the background of vomiting, diarrhea, insufficient consumption of table salt and liquid, plentiful sweating); with an abnormal liver function and/or kidneys (KK is more than 20 ml/min.), a diabetes mellitus, a hyperpotassemia, a hyponatremia, general diseases of connecting fabric (including a scleroderma, a system lupus erythematosus, the accompanying therapy by the drugs (risk of oppression of a marrowy hemopoiesis, development of an agranulocytosis or neutropenia) operating on a picture of peripheral blood); at simultaneous use of antagonists of receptors of angiotensin II and/or drugs of an aliskiren at double blockade the system renin-angiotensin-aldosteronovoy (SRAA), at a state after transplantation of a kidney.

Route of administration and dosage

Pill is taken inside to or after food, swallowing entirely, washing down with water.

The doctor appoints a dose on the basis of clinical indications, considering individual portability and therapeutic effect of drug.

The recommended dosing:

• Arterial hypertension: an initial dose – 2,5 mg of 1 times a day (morning) or in 2 receptions. For achievement of desirable therapeutic effect perhaps multiple increase in a dose in 2-3 weeks of treatment. A usual maintenance dose – 2,5-5 mg, maximum – 10 mg a day. At the previous therapy by diuretics them it is necessary to cancel or lower a dose not later than in 3 days prior to Ramipril's reception. An initial dose for the patients accepting diuretics, patients with insufficiency of renal function or with arterial hypertension and heart failure – 1,25 mg a day once. It is necessary to begin use under strict control of the doctor. For patients with the broken water and electrolytic balance or risk of hypotensive reaction the initial daily dose should not exceed 1,25 mg;
• Chronic heart failure: an initial dose – 1,25 mg once, if necessary a dose it is possible to double in 1-2 weeks. The daily dose should not exceed 10 mg. At a concomitant use of diuretics their dose should be lowered prior to therapy;
• The heart failure which arose within 2-9 days after an acute myocardial infarction: an initial dose – on 2,5 mg 2 times a day (in the morning and in the evening) and in two days of therapy – on 5 mg 2 times a day. A maintenance dose – 2,5-5 mg 2 times a day. At bad portability of drug (arterial hypotension) it is necessary to lower an initial dose to 1,25 mg 2 times a day, then in 2 days it can be raised to 2,5 mg, in 2 days – to 5 mg 2 times a day. The daily dose should not exceed 10 mg. At bad portability of a dose on 2,5 mg 2 times a day administration of drug should be cancelled. Because of insufficient experience of use of Ramipril for patients with the expressed heart failure of the III-IV functional class (on NYHA classification) which arose right after an acute myocardial infarction, the initial dose for this category of patients should not exceed 1,25 mg of 1 times a day. Increase in a dose has to be carried out under observation of the doctor;
• Nephropathy at chronic diffusion pathologies of kidneys, a diabetic nephropathy: an initial dose – 1,25 mg once. At good tolerance of drug the dose can be doubled every 2 week before achievement of a maintenance dose of 5 mg of 1 times a day;
• Decrease in risk of development of a stroke, myocardial infarction or cardiovascular mortality at patients with high cardiovascular risk: an initial dose – 2,5 mg once. Gradual increase in a dose is shown: in 1 week, then in 2-3 weeks – to a maintenance dose of 10 mg of 1 times a day.

The recommended mode of dosing of Ramipril for patients with a renal failure:

• KK is less than 30 ml/min.: an initial dose – 1,25 mg a day, maximum – 5 mg;
• KK of 30-60 ml/min.: an initial dose – 2,5 mg a day, maximum – 5 mg;
• KK is more than 60 ml/min.: an initial dose – 2,5 mg a day, maximum – 10 mg.

At a liver failure the initial dose should not exceed 1,25 mg, maximum – 2,5 mg once.

Initial dose for patients of advanced age – 1,25 mg a day.

Special control is required for patients 65 years, accepting diuretics, for patients with chronic heart failure are more senior at an impaired renal function and a liver. The dose is selected depending on the target objective of the ABP.

Side effects

• Cardiovascular system: often – orthostatic hypotension, faints (syncopal states), strong decrease in the ABP; infrequently – peripheral hypostases, heartbeat, rushes of blood to face skin, myocardium ischemia (including development or strengthening of arrhythmia, development of a myocardial infarction or an attack of stenocardia, tachycardia); seldom – a vasculitis, strengthening or emergence of disturbances of peripheric circulation; frequency is unknown – Reynaud's syndrome;
• Respiratory system: often – sinusitis, bronchitis, short wind, the dry cough (amplifying in a prone position and at night); infrequently – a nose congestion, a bronchospasm, weighting of a clinical course of bronchial asthma;
• Nervous system: often – feeling of ease in the head, a headache; infrequently – an ageusia, dizziness, a dysgeusia; seldom – balance disturbance, a tremor; frequency is unknown – disturbance of psychomotor reactions, brain ischemia, disturbance of cerebral circulation (passing), an ischemic stroke, paresthesias, a parosmiya;
• Alimentary system: often – discomfort in a stomach, nausea, vomiting, inflammatory reactions in a stomach and intestines, dyspepsia, diarrhea, digestive disturbances; infrequently – abdominal pains, pancreatitis (in rare instances with a lethal outcome), an intestinal Quincke's disease, a xerostomia, increase in activity in a blood plasma of enzymes of a pancreas, gastritis, a lock; seldom – a glossitis; frequency is unknown – aphthous stomatitis;
• Mental disturbances: infrequently – alarm, drowsiness, the suppressed mood, nervousness, sleep disorders, motive concern; seldom – confusion of consciousness; frequency is unknown – disorders of attention;
• Acoustic organ: seldom – a ring in ears, a hearing disorder;
• Organ of sight: infrequently – an image vagueness, a vision disorder; seldom – conjunctivitis;
• Gepatobiliarny system: infrequently – increase in contents in a blood plasma of the conjugated bilirubin, increase in activity of liver enzymes; seldom – hepatocellular defeats, cholestatic jaundice; frequency is unknown – an acute liver failure, cytolytic or cholestatic hepatitis (it is extremely rare with a lethal outcome);
• Urinary system: infrequently – functional disorder of kidneys, development of an acute renal failure, increase in a diuresis, strengthening of the proteinuria which was (earlier existing) increase in content of creatinine and urea in blood;
• Lymphatic system and system of blood: infrequently – an eosinophilia; seldom – a neutropenia, a leukopenia, an agranulocytosis, decrease in maintenance of erythrocytes in peripheral blood, decrease in level of concentration of hemoglobin, a leukocytosis, thrombocytopenia; frequency is unknown – a pancytopenia, hemolitic anemia, oppression of a marrowy hemopoiesis;
• Mammary glands and reproductive system: infrequently – passing impotence, decrease in a libido; frequency is unknown – a gynecomastia;
• Musculoskeletal system: often – a mialgiya, muscular spasms; infrequently – an arthralgia;
• Dermatological reactions: often – skin rash, infrequently – a hyperhidrosis, a skin itch, a Quincke's disease (including with a lethal outcome); seldom – онихолизис, urticaria, exfoliative dermatitis; very seldom – a photosensitization; frequency is unknown – a multiformny erythema, a toxic epidermal necrolysis, a pempigus, Stephens-Johnson's syndrome, psoriazopodobny dermatitis, weighting of a course of psoriasis, an alopecia, a lichenoid or pemfigoidny dieback or an enantema;
• Immune system: frequency is unknown – anaphylactoid or anaphylactic reactions (including on poisons of insects), increase in maintenance of antinuclear antibodies;
• Metabolism, laboratory indicators, food: often – increase in level of potassium in blood serum; infrequently – a loss of appetite, anorexia; frequency is unknown – decrease in level of sodium in blood;
• General disturbances: often – feeling of fatigue, a stethalgia; infrequently – fervescence; seldom – an adynamy.

Special instructions

Purpose of drug should be made after careful assessment of function of kidneys of the patient. Treatment needs to be accompanied with control of function of kidneys, especially at patients with defeat of renal vessels.

Prior to the beginning of and during Ramipril's use regular control of the ABP, function of kidneys (urea, creatinine), the level of content of potassium and other electrolytes, hemoglobin, activity of liver enzymes is required.

Reception of the first and each increase in a dose have to be carried out under observation of the doctor, it will allow to avoid development of uncontrollable hypotension and other undesirable effects.

Patients with malignant arterial hypertension are recommended to begin treatment in stationary conditions.

In case of increase in level of concentration of creatinine and urea in blood serum at patients with an impaired renal function it is necessary to lower a dose or to cancel drug as development of a hyperpotassemia is possible.

At considerable activity of liver enzymes or emergence of jaundice Ramipril's use should be cancelled.

When developing tranzitorny arterial hypotension administration of drug should be stopped temporarily, after stabilization of the ABP treatment can be continued, repetition of the expressed hypotension is the basis for reduction of a dose or drug withdrawal.

At planned surgery, including dental, the patient has to inform the surgeon and the anesthesiologist on treatment ramiprily not to allow sharp decrease in the ABP means for the general anesthesia. Reception of tablets is recommended to be stopped in 12 hours prior to operation.

During treatment it is regularly necessary to control the level of leukocytes of blood for early detection of possible development of an agranulocytosis or a neutropenia.

The risk of development of a hyperpotassemia in patients with arterial hypertension increases at chronic heart failure, purpose of drugs of potassium, a concomitant use of amiloride, Spironolactonum, Triamterenum (kaliysberegayushchy diuretics).

At emergence in the patient of abdominal pains with nausea and vomiting when carrying out the differential diagnosis it is necessary to consider the possibility of development of an intestinal Quincke's disease.

In case of performing the desensibilizing therapy at stings of poisonous insects APF inhibitors need to be replaced with antihypertensives from other groups.

Emergence of dry cough during treatment can be connected with administration of drug.

Patients are recommended to avoid exercise stresses and influence of high temperatures of air.

During Ramipril's reception patients cannot manage vehicles and mechanisms.

Medicinal interaction

At Ramipril's appointment the doctor has to warn the patient about need of preliminary consultation before simultaneous use of any medicines.

Terms and storage conditions

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

Period of validity – 2 years.