Амприлан®

General characteristics. Structure:

Active ingredient: 1,25 mg, 2,5 mg, 5 mg or 10 mg of a ramipril.

Excipients: Natrii hydrocarbonas; lactoses monohydrate; sodium of a kroskarmelloz; starch prezhelatinizirovanny; sodium stearit fumarating; ferrous oxide yellow (E172); ferrous oxide red (E172).

The drug from group of APF inhibitors (angiotensin-converting enzyme) lowering pressure and which is used for prevention of heart diseases.

Pharmacological properties:

Pharmacodynamics. Ramipril APF inhibitor of long action. APF catalyzes transformation of angiotensin I into angiotensin II. APF is identical to a kininaza, the enzyme catalyzing disintegration of bradikinin. Blockade of APF leads to decrease in concentration of angiotensin II, increase in activity of a renin in a blood plasma, to strengthening of effect of bradikinin and increase in secretion of Aldosteronum that can be the reason of increase in level of potassium in blood serum.

Anti-hypertensive and hemodynamic effects of a ramipril at patients with arterial hypertension are result of expansion of resistive vessels and decrease in the general peripheric resistance that is gradually reduced in turn by the ABP. The cordial rhythm usually does not change. At prolonged treatment the hypertrophy of a left ventricle without negative influence on function of heart decreases. The hypotensive effect of a single dose is shown in 1–2 h after reception, reaches a maximum in 3–6 h and lasts 24 h.

Ramipril is also effective for treatment of chronic heart failure. At patients with symptoms of chronic heart failure after a myocardial infarction drug reduces risk of sudden death, progressing of heart failure in heavy/resistant insufficiency and reduces number of hospitalization concerning heart failure.

According to literary data, ramiprit considerably reduces the frequency of a myocardial infarction, stroke and cardiovascular death at patients with the increased cardiovascular risk owing to vascular diseases (such as ischemic heart disease, the had stroke or diseases of peripheral vessels) or a diabetes mellitus which have at least one accessory factor of risk (a microalbuminuria, arterial hypertension, increase in level of the general cholesterol, the LPVP low level, smoking). Drug also reduces the general mortality and the need for procedures for revascularization, slows down emergence and progressing of chronic heart failure. Both at patients with a diabetes mellitus, and without it, drug considerably reduces the available microalbuminuria and risk of development of a nephropathy. These effects are noted at patients both with raised, and with the normal ABP.

Pharmacokinetics. After intake ramiprit quickly it is soaked up from a GIT of 50-60% of drug, meal does not slow down absorption. Cmax in blood serum is reached in 1 h.

Ramipril is metabolized in a liver with formation of an active metabolite — a ramiprilat whose activity is 6 times higher, than ramiprit also inactive diketopiperazine which then glyukuronizirutsya. Cmax of a ramiprilat in blood serum is reached in 2–4 h after reception, equilibrium concentration — by 4th day of administration of drug.

About 73% of a ramipril and 56% of a ramiprilat contact proteins of a blood plasma. Ramipril and рамиприлат are brought out of an organism preferential with urine (about 60%) mainly in the form of metabolites, less than 2% of the accepted dose are removed in the form of not changed ramipril.

Ramipril is brought in several stages. T1/2 after purpose of a therapeutic dose makes 13–17 h — for a ramiprilat, 5,1 h — for a ramipril.

Researches on animals did not reveal secretion of drug with milk.

The researches conducted at healthy volunteers aged from 65 up to 76 years showed that the pharmacokinetics of a ramipril at them did not differ from pharmacokinetics at young healthy volunteers.

At a renal failure removal of a ramipril and its metabolites is slowed down in proportion to decrease in clearance of creatinine. At patients with a liver failure metabolism of a ramipril in рамиприлат can be slowed down, and concentration of a ramipril in blood serum is increased.

Indications to use:

Amprilan apply to treatment of arterial hypertension, chronic heart failure, chronic heart failure after a myocardial infarction, a diabetic and not diabetic nephropathy, and also to decrease in risk of development of a myocardial infarction, a stroke and cardiovascular mortality at patients with high risk, including patients with the confirmed coronary heart disease (with a myocardial infarction in the anamnesis or without it), the patients who transferred angioplasty, the patients who transferred coronary shunting, patients with a stroke in the anamnesis, patients with occlusal damages of peripheral arteries.

Route of administration and doses:

Inside, irrespective of meal, washing down with enough liquid. At arterial hypertension the recommended initial dose of Amprilan makes 2,5 mg of 1 times a day. Depending on reaction of the patient the dose can double with a 1-2 weeks interval. Usually maintenance dose makes 2,5–5 mg/days, the maximum daily dose — 10 mg/days.

The patients accepting diuretics need to cancel or reduce their dose at least in 3 days prior to Amprilan's appointment.

At patients with arterial hypertension at whom diuretics were not cancelled or at patients with arterial hypertension and a heart or renal failure the initial daily dose makes 1,25 mg in 1 reception. Treatment should be begun under strict control of the doctor.

At chronic heart failure the recommended initial dose of drug Amprilan makes 1,25 mg/days in 1 reception. Depending on the therapeutic answer of the patient the dose can double with a 2 weeks interval. The maximum daily dose — 10 mg.

At the patients receiving diuretics in high doses before therapy by drug the dose of diuretics should be reduced.

Treatment of heart failure after a myocardial infarction can be begun only in the conditions of a hospital between 3 and 10 days after a myocardial infarction. The initial dose makes 2,5 mg 2 times a day (in the morning and in the evening), in 2 days the dose is raised to 5 mg by 2 times a day (in the morning and in the evening). The maintenance dose of Amprilan makes 2,5–5 mg 2 times a day. Drug is accepted in the morning and in the evening.

At development of arterial hypotension the initial dose is reduced to 1,25 mg by 2 times a day. In 2 days the dose can be increased to 2,5 mg 2 times again a day, in 2 days the dose can be raised to 5 mg 2 times a day (in the morning and in the evening).

The maximum daily dose — 10 mg. If the patient badly transfers increase in a dose to 2,5 mg 2 times to days, then treatment by Amprilan should be stopped.

At a diabetic and not diabetic nephropathy the recommended initial dose of drug Amprilan makes 1,25 or 2,5 mg of 1 times a day. Depending on portability the patient of a ramipril the drug dose increases further: it is recommended to double a dose in each 2 weeks to supporting — 5 mg of 1 times a day.

For decrease in risk of development of a myocardial infarction, a stroke and cardiovascular death: the recommended initial dose of drug Amprilan makes 2,5 mg of 1 times a day. The drug dose is gradually increased afterwards, depending on portability of drug Amprilan: it is recommended to double a dose in 1–2 weeks of therapy, and then in 2–3 weeks — before achievement of a target maintenance dose in 10 mg of 1 times a day.

Renal failure: patients with clearance of creatinine have more than 0,5 ml / with (30 ml/min.) changes of a dose it is not required.

For patients with clearance of creatinine less than 0,5 ml / with (30 ml/min.) the initial daily dose of 1,25 mg, and the maximum daily dose — 5 mg is recommended.

Liver failure: the initial recommended dose — 1,25 mg once a day and the maximum daily dose — 2,5 mg.

Careful observation of the patients of advanced age (is more senior 65 years) accepting diuretics and of patients with heart failure and the broken renal and hepatic function is necessary. Amprilan's dose should be selected depending on the target objective of the ABP.

Features of use:

Amprilan it is necessary to apply with care at treatment of patients with heavy damages of coronary and cerebral arteries (danger of decrease in a blood-groove at excessive falling of the ABP), at unstable stenocardia, with heavy ventricular disturbances of a rhythm, at chronic heart failure of the IV stage, with dekompensirovanny "pulmonary heart", at a renal and/or liver failure, a hyperpotassemia, a hyponatremia (including against the background of diuretics and a diet with salt consumption restriction), at the states which are followed by decrease in OTsK (including diarrhea, vomiting), at general diseases of connecting fabric, a diabetes mellitus, oppression of a marrowy hemopoiesis, at elderly people.

In an initiation of treatment it is necessary to estimate renal function. It is necessary to control carefully function of kidneys during treatment amprilany, especially at patients with the weakened function of kidneys, with defeat of renal vessels (for example clinically insignificant stenosis of renal arteries or hemodynamically significant stenosis of an artery of the only kidney); heart failure.

The risk of hypersensitivity and allergopodobny (anaphylactoid) reactions increases at the patients who are at the same time accepting APF inhibitors and undergoing procedures of a hemodialysis with use of dialysis membranes of AN69. Similar reactions were revealed at LPNP afereza with the help a sulfate dextran therefore at treatment by APF inhibitors it is necessary to avoid use of this method.

During treatment by Amprilan at patients with the broken renal function, especially at simultaneous treatment by diuretics, the level of urea and creatinine in blood serum can increase. In this case treatment should be continued by smaller doses of Amprilan or to cancel drug. At patients with the broken renal function the risk of emergence of a hyperpotassemia increases.

At patients with the broken hepatic function owing to decrease of the activity of hepatic esterases metabolism of a ramipril and formation of an active metabolite can be slowed down. In this regard treatment of such patients should be begun only under strict medical observation.

It is necessary to be careful at Amprilan's appointment to the patients who are on a low-salt or electrolyte-deficient diet (the increased risk of development of arterial hypotension). At patients with reduced OTsK (as a result of therapy by diuretics), when carrying out dialysis, at diarrhea and vomiting development of symptomatic hypotension is possible.

Tranzitorny arterial hypotension is not a contraindication for continuation of treatment after stabilization of the ABP. In case of repeated developing of the expressed hypotension it is necessary to reduce a dose or to cancel drug.

At the patients who are exposed to extensive surgical interventions or receiving other means causing arterial hypotension during the general anesthesia, Amprilan can cause blockade of formation of angiotensin II owing to compensatory release of a renin. If the doctor connects development of arterial hypotension with the mechanism mentioned above, arterial hypotension can be corrected by increase in volume of a blood plasma.

In rare instances during treatment APF inhibitors observe an agranulocytosis, an erythrocytopenia, thrombocytopenia, a haemoglobinaemia or oppression of marrow. At the beginning and during treatment it is necessary to control quantity of white blood cells for identification of a possible neutropenia / agranulocytosis. More frequent control is recommended at patients with a renal failure, with diseases of connecting fabric (for example a system lupus erythematosus or a scleroderma) and at the patients who are at the same time accepting the HP exerting impact on a hemopoiesis (see. "Interaction"). Calculation of uniform elements of blood has to be carried out also at emergence of clinical signs of a neutropenia/agranulocytosis and the raised bleeding.

At patients with arterial hypertension at treatment by Amprilan increase in level of potassium in blood serum is seldom noted. The risk of a hyperpotassemia increases at chronic heart failure, simultaneous treatment by kaliysberegayushchy diuretics (Spironolactonum, amiloride, Triamterenum) and purpose of drugs of potassium.

When using APF inhibitors during the desensibilizing therapy to aspen or to apitoxin there can be anaphylactoid reactions (for example arterial hypotension, an asthma, vomiting, skin rash) which can be life-threatening.

Hypersensitivity reactions can arise at stings of insects (for example bees or wasps). In need of performing the desensibilizing treatment by bee or aspen poison it is necessary to cancel APF inhibitors and to continue treatment by suitable drugs from other groups.

Before therapy ramiprily it is necessary to exclude pregnancy existence. Ramipril is not recommended to the women planning pregnancy. If treatment ramiprily is absolutely necessary, it is necessary to prevent pregnancy approach. If pregnancy occurs during treatment, drug has to be immediately cancelled and replaced to other HP.

During treatment by Amprilan it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions (dizziness, especially after an initial dose of APF inhibitor at the patients accepting diuretic HP is possible). Patients are recommended to refrain from driving and work with mechanisms until the response to treatment is clear.

Side effects:

From cardiovascular system: decrease in the ABP, orthostatic hypotension, an orthostatic collapse, tachycardia, is rare — arrhythmia, stenocardia, a myocardial infarction.

From urinogenital system: development or strengthening of symptoms of a renal failure, proteinuria, reduction of volume of urine, decrease in a libido.

From TsNS: brain ischemia, a stroke, dizziness, a headache, weakness, drowsiness, paresthesias, nervous irritability, concern, a tremor, a muscular spasm, disturbances of mood, at use in high doses — sleeplessness, uneasiness, a depression, confusion of consciousness, a syncope.

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, intestinal impassability, pancreatitis, hepatitis, cholestatic jaundice, an abnormal liver function with development of a liver failure, dryness in a mouth, thirst, a loss of appetite, stomatitis, a glossitis.

From respiratory system: Sukhoi cough, bronchospasm, asthma, rhinorrhea, rhinitis, sinusitis, bronchitis.

Allergic reactions: skin rash, itch, small tortoiseshell, conjunctivitis, photosensitization; Quincke's disease of the person, extremities, lips, language, throat and/or throat, exfoliative dermatitis, multiformny exudative erythema (including Stephens-Johnson's syndrome), toxic epidermal necrolysis (scalded skin syndrome), pemphigus, serositis, onycholysis, vasculitis, miositis, mialgiya, arthralgia, arthritis, eosinophilia.

Others: spasms, an alopecia, a hyperthermia, the increased sweating.
Laboratory indicators: giperkreatininemiya, increase in level of an urea nitrogen, increase in activity of hepatic transaminases, hyperbilirubinemia, hyperpotassemia, hyponatremia, emergence of antinuclear antibodies.

Influence on a fruit: dysfunction of a fruit, decrease in the ABP of a fruit and newborns, renal failure, hyperpotassemia, hypoplasia of bones of a skull, олигогидрамнион, contracture of extremities, deformation of bones of a skull, hypoplasia of lungs.

Interaction with other medicines:

Ramipril strengthens the oppressing effect of ethanol on TsNS. Reception of salt with food can reduce hypotensive effect of a ramipril.

Simultaneous use of a ramipril and other means, the reducing ABP, (for example diuretics, nitrates, tricyclic antidepressants, anesthetics), leads to strengthening of hypotensive effect of a ramipril.

Co-administration of a ramipril and drugs of potassium or kaliysberegayushchy diuretics can become the hyperpotassemia reason.

Angiotonic sympathomimetics (for example adrenaline, noradrenaline) can reduce hypotensive effect of a ramipril. In this regard at simultaneous treatment it is necessary to control the ABP level carefully.

Co-administration of a ramipril and Allopyrinolum, immunodepressants, corticosteroids, procaineamide, tsitostatik increases probability of changes of a peripheral picture of blood.

Co-administration of a ramipril and drugs of lithium leads to decrease in excretion of lithium, it is necessary to control concentration of lithium in blood serum (risk of emergence of toxic effects).

APF inhibitors can strengthen effect of hypoglycemic means (for example insulin or derivatives of sulphonylurea) that in some cases can become the hypoglycemia reason. In this regard sugar level in blood has to be controlled carefully, especially at the beginning of combined use.

Simultaneous use of a ramipril and NPVS (for example acetylsalicylic acid and indometacin) can weaken hypotensive effect of a ramipril. In addition simultaneous use can cause a hyperpotassemia and increase risk of a renal failure.

Simultaneous use of heparin and ramipril can become the hyperpotassemia reason.

Anaphylactic and anaphylactoid reactions to poison of stinging insects (it is possible also to other allergens) are more expressed during treatment by APF inhibitors.

Contraindications:

Hypersensitivity to a ramipril and any other component of drug or other APF inhibitors.

Drug should not be used at patients with a Quincke's disease in the anamnesis, including APF inhibitors, hemodynamically significant bilateral stenosis of renal arteries, a stenosis of an artery of the only kidney connected with the previous therapy, after transplantation of kidneys, at patients on a hemodialysis, at a renal failure (creatinine Cl <20 ml/min.), at patients with hemodynamically significant aortal or mitral stenosis (risk of excessive decrease in the ABP with the subsequent renal failure), with a hypertrophic subaortic stenosis, primary hyper aldosteronism, at pregnancy, in the period of a lactation, aged up to 18 years (efficiency and safety are not established).

Overdose:

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

Treatment: in mild cases of overdose — a gastric lavage, administration of adsorbents and sodium of sulfate (it is desirable within 30 min. after reception). At the expressed decrease in the ABP — in/in introduction of catecholamines, angiotensin II, the patient has to be laid on a back with a low headboard, in need of OTsK can be filled by infusion of 0,9% of solution of sodium chloride; at bradycardia — use of a pacemaker.

It is necessary to control carefully the ABP, function of kidneys and potassium concentration in blood serum. Efficiency of a hemodialysis for elimination of intoxication is not established.

Storage conditions:

To store at a temperature no more than 25 °C. To store in    the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of 1,25 mg; 2,5 mg; 5 mg; 10 mg. On 10 tablets in the blister. The blister on 10 tablets: 3 blisters in a cardboard pack together with the application instruction.