Рамилонг

General characteristics. Structure:

Pharmacological properties:

Pharmacodynamics. Ramipril is lipophilic pro-medicine and after absorption is metabolized in a liver to a ramiprilat. The active metabolite, рамиприлат, is inhibitor of the angiotensin-converting enzyme (ACE) of long action. In a blood plasma and fabrics this enzyme catalyzes transition of angiotensin I to angiotensin II (active vasoconstrictive agent) and splitting of an active vazodilatator of bradikinin. Reduction of formation of angiotensin II and increase in activity of bradikinin leads to vasodilatation and makes the contribution to cardioprotective and endotelioprotektivny action of a ramipril. Angiotensin II stimulates release of Aldosteronum, in this regard ramiprit causes decrease in secretion of Aldosteronum.

Reception of a ramipril leads to considerable reduction of peripheric resistance, in general without causing changes in a renal blood-groove and glomerular filtration rate. Reception of a ramipril causes a lowering of arterial pressure (ABP) both in a prone position, and in a standing position without compensatory increase in heart rate. The anti-hypertensive effect is observed in 1-2 hours after intake of a single dose of drug. The hypotensive effect remains within 24 hours. The maximum hypotensive action of Ramilonga develops usually by 3-4 week of constant administration of drug and is supported within 2 years. The sudden termination of administration of drug does not lead to bystry and significant increase in the ABP. Administration of drug reduces mortality (including sudden death), the risk of development of the expressed heart failure, reduces number of hospitalization of patients with clinical signs of chronic heart failure after an acute myocardial infarction. At patients with the diabetic and not diabetic clinically expressed nephropathy drug reduces the speed of progressing of a renal failure, and at a preclinical stage of a diabetic and not diabetic nephropathy ramiprit reduces an albuminuria.

Drug favorably influences carbohydrate metabolism and a lipidic profile, has the expressed bradikininovy effects, causes decrease in the expressed hypertrophy of a myocardium and a vascular wall.

Pharmacokinetics. After intake it is soaked up in digestive tract (50-60%). Food does not influence extent of absorption, but slows down absorption. Being pro-medicine, ramiprit is exposed to intensive presistemny metabolism (mainly in a liver by hydrolysis) as a result of which its only active metabolite – рамиприлат is formed. Except formation of this active metabolite, at a glyukuronirovaniye of a ramipril and a ramiprilat inactive metabolites are formed: ramiprit diketopiperazine and рамиприлат diketopiperazine. Ramiprilat approximately by 6 times inhibits APF more actively, than ramiprit. Bioavailability for a ramipril after intake of 2,5-5 mg of 15-28%; for a ramiprilat of 45%.

The maximum concentration ramiprit and the ramiprilata is reached in a blood plasma in 1 and 3 hours, respectively. After administration of drug daily, single during the day in a dose of 5 mg steady concentration of a ramiprilat in a blood plasma is reached by 4th day. At course purpose of the drug T1/2 makes 13-17 hours. Communication with proteins of a blood plasma makes for a ramipril 73%, and for a ramiprilat – 56%.

At intake about 60% of drug are removed with urine and about 40% with bile, and less than 2% are removed in an invariable look.

At renal failures removal of a ramipril and its metabolites is slowed down in proportion to decrease in the clearance of creatinine (CC). It leads to increase in plasma concentration of a ramiprilat and their slower decrease in comparison with patients with normal function of kidneys. At the patients having liver diseases transformation of a ramipril in рамиприлат is slowed down, concentration of a ramipril in a blood plasma can increase by 3 times, at the same time the maximum concentration in a blood plasma of a ramiprilat does not change. At heart failure increase in concentration of a ramiprilat by 1,5-1,8 times is noted. At elderly people the drug pharmacokinetics significantly does not change. In researches on animals it was shown that ramiprit gets into maternal milk.

Indications to use:

- arterial hypertension;
- chronic heart failure (as a part of a combination therapy), including, developed during the first several days after an acute myocardial infarction;
- a diabetic nephropathy and a nephropathy against the background of chronic diffusion diseases of kidneys (a chronic glomerulonephritis with the expressed proteinuria) – the preclinical and clinically expressed stages;
- decrease in risk of development of a myocardial infarction, stroke or "coronary death" at patients with coronary heart disease, with the increased risk of cardiovascular diseases, including the patients who had a myocardial infarction, chrezkozhny transluminal coronary angioplasty, aortocoronary shunting.

Route of administration and doses:

Perhaps excessive lowering of arterial pressure in an initiation of treatment Ramilongom, especially, at patients with the low content of salts and liquids in an organism (for example, vomiting, a diarrhea, treatment by diuretics), heart failure (especially, after an acute myocardial infarction) or heavy hypertensia.

Shortage of salts and liquid in an organism is subject to a preliminary correcting prior to treatment by drug - diuretics should be limited or cancelled previously, not later than 2-3 days.

At malignant hypertensia and in case of heart failure, in particular, after an acute myocardial infarction, treatment by Ramilong should be begun in stationary conditions.

If do not appoint differently, then in case of patients with normal renal and hepatic function use the following recommendations about dosing.

For decrease in risk of development of a myocardial infarction, a stroke or death from cardiovascular diseases at patients with the increased cardiovascular risk:

The recommended initial dose – on 2,5 mg of a ramipril (½ tablets of 5 mg), once a day. Depending on portability, the dose is gradually increased. In a week it is recommended to double a dose, and in 3 weeks to bring it to the usual maintenance dose equal to 10 mg of a ramipril.

Heart failure of easy and average severity (NYHA II and III) after acute (2-9 - day) a myocardial infarction:

At this indication installation of a dose of Ramilonga can be carried out only in stationary conditions at patients with a stable hemodynamics.

Patients with the accompanying anti-hypertensive therapy are subjected to very careful monitoring in order to avoid falling of arterial pressure. Usually, an initial dose – on 2,5 mg of a ramipril, in the morning and in the evening (a daily dose - 5 mg of a ramipril).

The dose can be increased depending on a condition of the patient. It is possible to double it each 1-2 days to the maximum daily dose: on 5 mg ramiprit in the morning and in the evening (i.e. the daily dose of-10 mg ramiprit).

Arterial hypertension. Usually, the initial dose – 2,5 mg ramiprit in the morning. This dose is also a maintenance dose. If at such dosage within 3 weeks and it is not possible to normalize pressure any more, then it is possible to increase a dose to 5 mg of a ramipril a day. The maximum dose – 10 mg of a ramipril a day.

If the hypotensive effect of a daily dose of 5 mg of a ramipril is insufficient, it is necessary to weigh a possibility of additional use, for example, of diuretics or calcic antagonists. Thanks to it it is possible to increase hypotensive effect of a ramipril.

Doses for patients with disturbance of renal function (the clearance of creatinine <60 ml/min.), is more senior than 65 years, and also with the accompanying diabetes mellitus:

The initial dose – 1,25 mg ramiprit in the morning. The maintenance dose makes, usually, 2,5 mg of a ramipril a day. The maximum daily dose should not exceed 5 mg of a ramipril.

Рамилонг accept inside, washing down with enough liquid and it is not dependent on meal.

After an acute myocardial infarction patients with heart failure have to start reception of the daily dose specified for them, having divided it into 2 receptions (in the morning and in the evening). In other cases all daily dose can be accepted at one time, in the morning.

At the acute myocardial infarction which was complicated by development of heart failure, treatment by Ramilong should be begun not earlier than for the 2nd day after a heart attack, but no later than the 10th day. Drug is recommended to accept not less than 15 months.

To accept Ramilong along with diuretics, and also at the heart failure broken by renal and hepatic function follows only under observation of the doctor. The dose of Ramilonga is established by the doctor by individual selection depending on the target objective of the ABP and reaction of the patient to treatment.

Features of use:

Use of Ramilonga is contraindicated at pregnancy and during breastfeeding. Pregnancy. You need to tell surely your doctor if you suspect that you became pregnant (or could become pregnant). The doctor will recommend to you to stop administration of drug before pregnancy or at once as soon as you learned about pregnancy approach, and will appoint to you other medicine. This medicine is not recommended to be accepted on early durations of gestation and it is contraindicated at duration of gestation more than 3 months as can cause serious violations in the child if more than 3 months are accepted by the pregnant woman on term.

Feeding by a breast. Tell your doctor if you nurse or you are going to begin feeding with a breast. This medicine is not recommended to the nursing women and your doctor can recommend you other treatment if you plan to continue feeding and, in particular, if your child newborn or was born premature.

Precautionary measures. Treatment by Ramilong usually is long, its duration in each case is defined by the doctor. It also demands regular medical control, in particular, from patients with the broken function of a liver and kidneys.

At emergence of signs of disturbance of the immunity caused by a leukopenia (for example, fevers, a hyperadenosis, tonsillitis), and also at emergence of signs of bleeding (the smallest petechias, a red-brown enanthesis and mucous) it is necessary to see your attending physician immediately.

During treatment it is necessary to abstain from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions since dizziness, especially after an initial dose of APF inhibitor at the patients accepting diuretic means is possible.

It is necessary to be careful when performing physical exercises or hot weather because of risk of dehydration and arterial hypotension, owing to reduction of volume of liquid. It is not recommended to use ethanol. Before surgical intervention (including stomatology) it is necessary to warn the surgeon/anaesthesiologist about use of APF inhibitors. When developing hypostases, for example in a face (lips, eyelids) of either language, or disturbance of swallowing or breath it is necessary to stop administration of drug immediately. A Quincke's disease in the field of language, drinks, or throats (possible symptoms: disturbance of swallowing or breath) can threaten life and result in need of rendering acute management.

Side effects:

From an urinary system: increase in level of urea in blood serum, a giperkreatininemiya (especially at co-administration of diuretics), a renal failure, a renal failure; seldom - a hyper proteinuria, strengthening of the existing proteinuria, increase in amount of the emitted urine.

From cardiovascular system: seldom - the expressed decrease in the ABP, postural hypotension, ischemia of a myocardium or vessels of a brain, a myocardial infarction, arrhythmia, a syncope, an ischemic stroke, passing ischemia of vessels of a brain, tachycardia, peripheral hypostases (in ankle joints).

Allergic reactions: Quincke's disease of the person, lips, century, language, glottis and/or throat, reddening of integuments, feeling of heat, conjunctivitis, itch, urticaria, makulo-papular dieback and enantema, mnogoformny exudative erythema (including Stephens-Johnson's syndrome), pemphigus (pempigus), serositis, exacerbation of psoriasis, toxic epidermal necrolysis (Lyell's disease), onycholysis, increase in a caption of antinuclear antibodies, eosinophilia, vasculitis, mialgiya, arthralgia, arthritis.

Dermatological reactions: photosensitization; sometimes - an alopecia.

From a respiratory organs: often - dry (without phlegm), reflex cough which amplifies at night when the patient is in horizontal position most often arises at women and at non-smoking patients. In certain cases APF inhibitor replacement helps. Nevertheless, the proceeding cough can force patients to stop to accept APF inhibitors absolutely. Development of catarral rhinitis, sinusitis, bronchitis, a bronchospasm and диспноэ is possible.

From the alimentary system: nausea, pain in epigastric area, increase in activity of enzymes of a liver and pancreas, bilirubin; seldom - an inflammation of a mucous membrane of a GIT, intestinal impassability, an abnormal liver function, with possible development of an acute liver failure; very seldom - cholestatic jaundice, digestive disturbances, vomiting, diarrhea, a lock and loss of appetite, taste change ("metal" smack), decrease in flavoring feelings and sometimes even taste loss, dryness in a mouth, stomatitis, a glossitis, pancreatitis.

From bodies of a hemopoiesis: seldom - reduction of number of erythrocytes, decrease in level of hemoglobin from a lung to considerable, thrombocytopenia and a leukopenia; sometimes - a neutropenia, an agranulocytosis, a pancytopenia, hemolitic anemia.

From TsNS: balance disturbance, headache, nervousness, tremor, sleep disorder, weakness, confusion of consciousness, depression, feeling of concern, paresthesia, muscular spasms.

From sense bodys: vestibular disturbances, disturbance of taste, sense of smell, hearing and sight, sonitus.

Others: decrease in an erection and sexual desire, fever, development of a syndrome of Reynaud; seldom - a hyperpotassemia, a hyponatremia.

Interaction with other medicines:

- potassium salts, kaliysberegayushchy diuretics (for example, amiloride, Triamterenum, Spironolactonum) - simultaneous use leads to a hyperpotassemia (control of potassium in blood serum is necessary);
- anti-hypertensive means (in particular, diuretics) and other drugs, the reducing ABP - the concomitant use leads to strengthening of action of a ramipril;
somnolent, narcotic and anesthetics - can cause sharp decrease in the ABP;
- angiotonic sympathomimetic drugs (Epinephrinum) and estrogen can cause weakening of action of a ramipril;
- Allopyrinolum, procaineamide, cytostatic means, immunodepressants – risk of development of a leukopenia at simultaneous use with ramiprily;
lithium - increase in concentration of serumal lithium and as a result strengthening kardio-and neurotic effect of lithium;
- peroral hypoglycemic means (sulphonylurea derivatives, guanyl guanidines), insulin - strengthening of a hypoglycemia;
- non-steroidal anti-inflammatory drugs (indometacin, acetylsalicylic acid) - weakening of action of a ramipril is possible;
- heparin - possible increase in potassium concentration in blood serum;
- table salt - weakening of action of a ramipril;
- alcohol - strengthening of hypotensive effect of a ramipril.

Contraindications:

Рамилонг it is contraindicated in the following cases:

- hypersensitivity to active ingredient to a ramipril, other APF inhibitors and other components of drug;
- patients at whom according to anamnestic data the Quincke's disease (risk of bystry development of a Quincke's disease (see the section "Side effect"), including, against the background of reception of APF inhibitors was observed earlier;
- the expressed renal failure (KK less than 20 ml/min. at a body surface of 1,73 sq.m);
- hemodialysis;
- a renal artery stenosis (bilateral, in case of one kidney unilateral);
state after renal transplantation;
- hemodynamically significant stenosis of the aortal or mitral valve or hypertrophic subaortic stenosis;
primary aldosteronism;
- pregnancy (is subject to identification prior to treatment, in case of purpose of drug contraception is necessary);
- breastfeeding (it is necessary to stop);
- age up to 18 years (efficiency and safety are not established).

Overdose:

Symptoms: the expressed decrease in the ABP, shock, the expressed bradycardia, disturbances of water and electrolytic balance, an acute renal failure, a stupor.

Treatment: to accept absorbent carbon and to ask immediately for emergency medical service.

Storage conditions:

In the place protected from moisture and light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

10 or 15 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil.

On three blister strip packagings on 10 tablets together with the application instruction in a pack from a cardboard; on two blister strip packagings on 15 tablets together with the application instruction in a pack from a cardboard.