Hartil D

General characteristics. Structure:

Each tablet contains active agent of a ramipril 5 or 10 mg. Excipients: Natrii hydrocarbonas, lactoses monohydrate, starch prezhelatinizirovanny 1500, sodium of a kroskarmelloz, sodium stearit fumarating,
tablets on 5 mg also contain: ferrous oxide red, ferrous oxide yellow.
On 7 tablets in the blister. 2 or 4 blisters (on 14 or 28 tablets) in a cardboard pack together with the application instruction.

Pharmacological properties:

Ramipril inhibits the angiotensin-converting enzyme (ACE) therefore (irrespective of activity of a renin of plasma) the hypotensive effect develops (in position of the patient "lying and "standing") without compensatory increase in the heart rate (HR).
Suppression of activity of APF reduces angiotensin II level that leads, in turn, to decrease in secretion of Aldosteronum. As a result of reduction of concentration of angiotensin II, due to elimination of negative feedback, there is an increase in activity of a renin of plasma. Ramipril affects the APF circulating in blood and being in fabrics, including a vascular wall. Reduces the general peripheric vascular resistance (GPVR) or an afterload, pressure in pulmonary capillaries (preloading); increases cordial emission and increases tolerance to loading.
At prolonged use ramiprit promotes myocardium hypertrophy involution at patients with arterial hypertension.
Ramipril reduces the frequency of arrhythmias at myocardium reperfusion, improves blood supply of an ischemic myocardium.
Ramipril interferes with disintegration of bradikinin and stimulates formation of nitrogen oxide (NO) in an endothelium.
The anti-hypertensive effect begins in 1-2 hours after administration of drug inside, the maximum effect develops within 3-6 hours and remains within 24 hours. At daily use the anti-hypertensive effect increases within 3-4 weeks and remains at prolonged treatment (1-2 years). Anti-hypertensive efficiency does not depend on a sex, age and the body weight of the patient. At patients with an acute myocardial infarction ramiprit limits a zone of distribution of a necrosis, improves the forecast of life; reduces a lethality during the early and remote periods of a myocardial infarction, frequency of developing of repeated heart attacks; reduces expressiveness of displays of heart failure, slows down its progressing.
At long reception (not less than 6 months) reduces degree of pulmonary hypertensia at patients with the inborn and acquired heart diseases.
Ramipril lowers pressure in a portal vein at portal hypertensia; brakes a microalbuminuria (in initial stages) and deterioration in renal function at patients with the expressed diabetic nephropathy. At not diabetic nephropathy which is followed by a proteinuria (over 3 g/days) and a renal failure slows down further deterioration in function of kidneys, reduces a proteinuria, risk of increase in level of creatinine or development of a terminal renal failure.

Indications to use:

Arterial hypertension.
Chronic heart failure.
Chronic heart failure after an acute myocardial infarction at patients with a stable hemodynamics.
Diabetic nephropathy and chronic diffusion diseases of kidneys (not diabetic nephropathy).
Decrease in risk of development of a myocardial infarction, stroke or "coronary death" at patients with coronary heart disease, including the patients who had a myocardial infarction, chrezkozhny transluminal coronary angioplasty, aortocoronary shunting.

Route of administration and doses:

It is necessary to swallow of tablets entirely, without chewing, washing down with a large amount of liquid (about 1 glass). A pill can be taken irrespective of meal time. The dosage should be established for each patient individually taking into account therapeutic effect and portability.
Arterial hypertension: the recommended initial dose - 2,5 mg once a day (daily on 1 tablet Hartil of 2,5 mg). Depending on therapeutic effect, the dose can be raised, doubling a daily dose each 2-3 weeks. The usual maintenance dose makes 2,5-5 mg a day (1 tablet Hartil 2,5 mg or 1 tablet of 5 mg). The maximum daily dose should not exceed 10 mg.
Chronic heart failure: the recommended initial dose - 1,25 mg once a day (daily on 1 tablet of Hartil of 1,25 mg). Depending on therapeutic effect, the dose can be raised, doubling a daily dose each 2-3 weeks. In need of reception more than 2,5 mg of drug, this dose can be accepted at once or to divide into 2 receptions. The maximum daily dose should not exceed 10 mg.
Treatment after a myocardial infarction: administration of drug is recommended to be begun for 3 - 10 day after an acute myocardial infarction. The recommended initial dose, depending on a condition of the patient and time which passed after an acute myocardial infarction makes on 2,5 mg 2 times a day (2 tablets of Hartil 1,25 mg or 1 tablet of Hartil of 2,5 mg) 2 times a day. Depending on therapeutic effect, it is possible to double an initial dose to 5 mg (2 tablets of Hartil 2,5 mg or 1 tablet of Hartil of 5 mg) 2 times a day. The maximum daily dose should not exceed 10 mg. At intolerance of drug it is necessary to lower a dose.
Not diabetic or diabetic nephropathy: the recommended initial dose - 1,25 mg of 1 times a day (daily on 1 tablet of Hartil of 1,25 mg). Depending on therapeutic effect, the dose can be raised, doubling a daily dose each 2-3 weeks. In need of reception more than 2,5 mg of drug, this dose can be accepted at once or to divide into two receptions. The recommended maximum daily dose - 5 mg.
Prevention of a myocardial infarction, stroke or death from cardiovascular disturbances: the recommended initial dose - 2,5 mg once a day. Depending on portability of drug, in one week of reception the dose should be doubled in comparison with initial. This dose should be doubled after 3 weeks of reception again. The recommended maintenance dose - 10 mg once a day.
Special groups of patients
Elderly patients: use of a ramipril for the elderly patients accepting diuretics and/or with heart failure and also an abnormal liver function or kidneys, requires special attention. The dosage should be established by individual selection of doses depending on reaction to drug.
Patients with a renal failure: at a moderate renal failure (clearance of creatinine from 20 to 50 ml/min. per 1,73 sq.m of a body surface) the initial dose usually makes 1,25 mg of 1 times a day (one tablet Hartil 1,25 in days). The maximum daily dose should not exceed 5 mg.
If the clearance of creatinine is not measured, it can be calculated on blood serum creatinine level using Cockroft equation:
For men: clearance of creatinine (ml/min.) = [body weight in kg x (140 - age)/72 x creatinine of serum (mg/dl)].
For women: to increase result of calculation on the stated above equation on 0,85.
Abnormal liver functions: at abnormal liver functions equally often reduced or increased effect on administration of drug Hartil therefore at early stages of treatment patients with abnormal liver functions need careful medical observation can be observed. The maximum daily dose in such cases should not exceed 2,5 mg.
At the patients receiving diuretic therapy from - for risk of a considerable lowering of arterial pressure (ABP) it is necessary to consider the possibility of temporary cancellation or at least a dose decline of diuretics, not less than in 2-3 days (or bigger term, depending on duration of effect of diuretics) prior to administration of drug Hartil. For the patients who were earlier receiving diuretics, usually initial dose makes 1,25 mg.

Features of use:

During treatment by drug Hartil is necessary regular medical control.
After reception of the first dose, and also at increase in a dosage of diuretic and/or Hartil patients have to be during 8 h under medical observation in order to avoid development of uncontrollable hypotensive reaction, repeated measurement of the ABP is recommended.
Whenever possible it is necessary to correct dehydration, a hypovolemia, decrease in number of erythrocytes prior to administration of drug. If these disturbances have difficult character, reception of a ramipril should not be begun or continued before taking measures, the ABP preventing excessive falling and a renal failure.
Careful observation is required to patients with defeat of renal vessels (for example, clinically insignificant renal artery stenosis or hemodynamically significant stenosis of an artery of the only kidney), a renal failure, at the expressed decrease in the ABP, generally from patients with heart failure, and also after transplantation of a kidney.
The renal failure can be revealed on the increased levels of urea and creatinine of blood serum, especially if the patient accepts diuretics.
Because of decrease in synthesis of angiotensin II and secretion of Aldosteronum, in blood serum the level of sodium can decrease and raise potassium level. The hyperpotassemia meets at disturbance of functions of kidneys more often (for example, at a diabetic nephropathy) or at a concomitant use about potassium - saving diuretics.
In case of excessive decrease in the ABP of the patient it is necessary to lay and raise the lower extremities; also administration of liquid and other measures can be required.
Changes of blood are more probable at patients with an impaired renal function and an associated disease of connecting fabric (for example, a system lupus erythematosus and a scleroderma), and also in case of use of other means influencing the hemopoietic and immune systems.
Sodium level in blood serum should be checked also regularly at the patients accepting diuretics along with drug Hartil. It is also regularly necessary to check quantity of leukocytes in order to avoid development of a leukopenia. Control has to be more frequent at the beginning of therapy and at the patients belonging to any risk group.
At insufficiency of lactase, a galactosemia or a syndrome of disturbance of absorption of glucose/lactose it is necessary to consider that each tablet of drug Hartil contains the following amounts of lactose: tablets on 1,25 mg contain 79,5 mg of lactose, tablets on 2,5 mg - 158,8 mg, tablets on 5 mg - 96,47 mg, tablets on 10 mg - 193,2 mg.
Membranes with high hydraulic permeability and dextran sulfate: patients have messages on the life-threatening anaphylactoid reactions sometimes passing into shock on a hemodialysis using membranes with high hydraulic permeability (for example, from polyacrylonitrile) at simultaneous administration of APF inhibitors. Anaphylactoid reactions were also noted at the patients subjected to an aferez of lipoproteins of low density with absorption by dextran sulfate.
Experience of use of a ramipril for children, patients with a heavy renal failure (clearance of creatinine less than 20 ml/min. / 1.73 body surface sq.m) and at patients during dialysis - is limited.
Influence on driving of motor transport
In an initiation of treatment decrease in the ABP can affect ability of concentration of attention. In this case patients are recommended to refrain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions. Further extent of restriction is defined for each patient individually.

Side effects:

From warmly vascular system: decrease in the ABP, orthostatic hypotension, tachycardia, is rare – the arrhythmia, strengthening of disturbance of blood circulation of bodies caused by narrowing of blood vessels. At excessive decrease in the ABP, generally at patients with coronary heart disease and clinically significant vasoconstriction of a brain, myocardium ischemia (stenocardia or a myocardial infarction) and brain ischemia can develop (it is possible with dynamic disturbance of cerebral circulation or a stroke).
From urinogenital system: development or strengthening of a renal failure, strengthening of the existing proteinuria, reduction of volume of urine (at the beginning of administration of drug), decrease in a libido.
From the central nervous system: dizziness, headache, weakness, drowsiness, paresthesias, nervous irritability, concern, tremor, muscular spasm, disturbances of mood; when using in high doses - sleeplessness, uneasiness, a depression, confusion of consciousness, faints.
From sense bodys: vestibular disturbances, taste disturbances (for example, metal taste), sense of smell, hearing and sight, sonitus.
From the alimentary system: nausea, vomiting, diarrhea or a lock, pain in epigastric area, dryness in a mouth, thirst, a loss of appetite, stomatitis, hypersensitivity or an inflammation of a mucous membrane of cheeks, pancreatitis, it is rare - hepatitis, cholestatic jaundice, an abnormal liver function with development of an acute liver failure.
From respiratory system: Sukhoi cough, a bronchospasm (at patients with a hyperexcitability of a tussive reflex), an asthma, a rhinorrhea, rhinitis, sinusitis, bronchitis.
Allergic reactions: skin rash, itch, small tortoiseshell, conjunctivitis, photosensitization; seldom - a Quincke's disease of the person, extremities, lips, language, a throat or throat, exfoliative dermatitis, a multiformny exudative erythema (including Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease), a pemphigus (pempigus), a serositis, an onycholysis, a vasculitis, a miositis, a mialgiya, an arthralgia, arthritis, an eosinophilia.
From bodies of a hemopoiesis: anemia, decrease in concentration of hemoglobin and hematocrit, thrombocytopenia, leykotsitopeniya, neutropenia, agranulocytosis, pancytopenia, hemolitic anemia. There can be a decrease in number of erythrocytes. Marrow depression.
Others: spasms, alopecia, hyperthermia, sweating.
Laboratory indicators: a giperkreatininemiya, increase in level of an urea nitrogen, increase in activity of "hepatic" transaminases, a hyperbilirubinemia, a hyperpotassemia, a hyponatremia, it is extremely rare - increase in a caption of an antinuclear factor.
Influence on a fruit: disturbance of development of kidneys of a fruit, decrease in the ABP of a fruit and newborns, renal failure, hyperpotassemia, skull hypoplasia, олигогидрамнион, contracture of extremities, deformation of a skull, hypoplasia of lungs.

Interaction with other medicines:

Allopyrinolum, corticosteroids, procaineamide, cytostatics and other substances causing blood changes: increase in risk of disturbances from system of a hemopoiesis.
Antidiabetic drugs (insulin or derivative sulfourea): excessive decrease in level of sugar of blood. This phenomenon can be connected with the fact that APF inhibitors can increase sensitivity of fabrics to insulin.
Anti-hypertensive means (for example, diuretics) or other means possessing anti-hypertensive action (for example, nitrates, tricyclic antidepressants and anesthetics): strengthening of anti-hypertensive effect is possible.
Salts of potassium and kaliysberegayushchy diuretics, heparin: the concomitant use with ramiprily because of risk of development a hyperpotassemia is not recommended.
Lithium salts: increase in level of lithium in blood serum increases risk kardio-and nephrotoxicity.
Non-steroidal anti-inflammatory drugs and salt (sodium): decrease in efficiency of APF inhibitors.
Membranes with high hydraulic permeability and dextran sulfate: patients have messages on the life-threatening anaphylactoid reactions sometimes passing into shock on a hemodialysis using membranes with high hydraulic permeability (for example, from polyacrylonitrile) at simultaneous administration of APF inhibitors. Anaphylactoid reactions were also noted at the patients subjected to an aferez of lipoproteins of low density with absorption by dextran sulfate.
At the desensibilizing therapy which is carried out for decrease in allergic reaction to stings of insects (for example, bees and wasps) during reception of APF inhibitors: there can be a heavy, life-threatening anaphylactoid reaction (falling of arterial pressure, breath disturbance, vomiting, skin reactions). Therefore APF inhibitors cannot be given to the patients receiving the desensibilizing therapy.
Alcohol: ramiprit can strengthen effect of alcohol.

Contraindications:

Hypersensitivity to a ramipril or any other component of drug.
Quincke's disease in the anamnesis, including connected with the previous therapy by APF inhibitors.
Hemodynamically significant bilateral stenosis of renal arteries and stenosis of an artery of the only kidney.
Arterial hypotension or unstable hemodynamics.
Pregnancy and period of a lactation.
Primary hyper aldosteronism.
Renal failure (the clearance of creatinine is lower than 20 ml/min.)
With care
Hemodynamically significant aortal or mitral stenosis (risk of excessive decrease in the ABP with the subsequent renal failure); heavy primary malignant arterial hypertension; severe damages of coronary and cerebral arteries (danger of decrease in a blood-groove at excessive decrease in the ABP), unstable stenocardia, heavy ventricular disturbances of a rhythm, HSN end-stage, dekompensirovanny "pulmonary" heart, diseases demanding purpose of glucocorticosteroids and immunodepressants (lack of clinical experience) - including at general diseases of connecting fabric, a heavy renal and/or liver failure, a hyperpotassemia, a hyponatremia (including against the background of diuretics and a diet with restriction of consumption of Na+), the initial or expressed manifestations of deficit of liquid and electrolytes; the states which are followed by decrease in volume of the circulating blood (including diarrhea, vomiting), a diabetes mellitus, oppression of a marrowy hemopoiesis, a state after renal transplantation, advanced age, age up to 18 years (efficiency and safety are not established).
There is only a limited experience of use of a ramipril for the patients who are on dialysis.

Overdose:

Symptoms: the expressed decrease in the ABP, bradycardia, shock, disturbance of water and electrolytic balance, an acute renal failure.
Treatment: in case of easy overdose - a gastric lavage, administration of adsorbents and sodium sulfate (it is desirable within 30 minutes after reception).
At acute overdose: control and support of zhiznennovazhny functions in the conditions of intensive care unit; at decrease in the ABP - introduction of catecholamines and angiotensin II. To lay the patient on a back with sublime position of legs, to enter additional amounts of liquid and sodium.
It is unknown whether the artificial diuresis, haemo filtering and correction pH of urine accelerate removal of a ramipril. It should be considered by consideration of a possibility of a hemodialysis and haemo filtering (see also section "Contraindications").

Storage conditions:

At a temperature below 25 °C, in the place, unavailable to children.

Period of validity
Tablets 1,25 mg:18 months.
Tablets of 2,5 mg, 5 mg and 10 mg: 2 years.
Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, 2,5 mg + 12,5 mg, 5 mg + 25 mg. According to 14 tab. in the blister from PVC / ПХТФЭ / aluminum foil. 2 blisters are packed into a cardboard pack.