Ramag 5 mg tablet number 30

Author Ольга Кияница

2017-05-11

Amount in a package 30
Product form Pills
Manufacturer Actavis
Registration certificate UA/13550/01/02
The main medicament Ramagh
morion code 277963

RAMAG instruction manual

Composition

active ingredient: ramipril; 1 tablet contains ramipril 5 mg or 10 mg;
Excipients: 
tablets 10 mg sodium bicarbonate, lactose, sodium croscarmellose, corn starch, sodium stearyl fumarate;
tablets 5 mg sodium bicarbonate, lactose, sodium croscarmellose, corn starch, sodium stearyl fumarate, pigment mixture PB24877 pink: lactose, iron oxide red (E172), iron oxide yellow (E 172).

Dosage form

pills.

Pharmacological group

ACE inhibitors (ACE). The code of automatic telephone exchange С09А А05.

Indications

Treatment of arterial hypertension.

Prevention of cardiovascular diseases: reduction of cardiovascular morbidity and mortality in patients with:

  • severe cardiovascular disease atherothrombotic genesis (history of coronary heart disease or stroke or peripheral vascular disease)
  • diabetes, have at least one cardiovascular risk factor.

Treatment of kidney disease:

  • initial glomerular diabetic nephropathy, which is indicated by the presence of microalbuminuria;
  • expressed glomerular diabetic nephropathy, which is indicated by the presence of macroproteinuria, in patients who have at least one cardiovascular risk factor;
  • expressed glomerular nondiabetic nephropathy, which is indicated by the presence of macroproteinuria ≥ 3 g / day.

Treatment of heart failure, accompanied by clinical manifestations.

Secondary prophylaxis after acute myocardial infarction: a decrease in mortality in the acute stage of myocardial infarction in patients with clinical signs of heart failure at the beginning of treatment more than 48 hours after the onset of acute myocardial infarction.

Contraindications

Hypersensitivity to the active substance or to any of the excipients included in the formulation, or to other ACE inhibitors (ACE).
Presence in the anamnesis of an angioedema (hereditary, idiopathic or earlier transferred on the background of the use of ACE inhibitors or antagonists of angiotensin II receptors).
Significant bilateral stenosis of the renal arteries or stenosis of the renal artery in the presence of a single kidney.
Ramipril should not be used in patients with arterial hypotension or hemodynamically unstable conditions.
Do not use together with preparations containing aliskiren, patients with diabetes mellitus or moderate or severe renal failure (GFR <60 ml / min).
It is necessary to avoid simultaneous use of ACE inhibitors and extracorporeal treatment methods, which result in blood contact with negatively charged surfaces, since such application can lead to severe anaphylactic reactions. Such extracorporeal treatments include dialysis or hemofiltration using certain membranes with high hydraulic permeability (eg polyacrylonitrile) and low density lipoprotein apheresis using dextran sulfate.
Pregnant women or women planning to become pregnant (see "Application for vagitismabogoduvanni gruddyu").

Dosing and Administration

The drug for oral administration.

The drug Ramagretabenduetsya take every day at the same time. The drug can be taken before, during and after meals, since eating does not affect the bioavailability of the drug. Tablets Ramag should be swallowed whole, washed down with water. They can not be chewed or crushed.

Adults.

Patients who use diuretics. At the beginning of Ramag treatment, arterial hypotension may occur, the development of which is more likely in patients who simultaneously receive diuretics. In such cases it is advisable to be cautious, since in these patients there may be a decrease in BCC and / or the number of electrolytes.

It is advisable to discontinue the use of diuretics 2-3 days before the start of Ramag treatment, if possible (see Section "Application Features").

In patients with hypertension, which can not be canceled diuretic, the preparation Ramag should be started with a dose of 1.25 mg. The function of the kidneys and the level of potassium in the blood should be carefully monitored. Further dosing Ramag should be adjusted depending on the target level of blood pressure.

Arterial hypertension.

The dose should be selected individually, depending on the characteristics of the patient's condition (see Section "Features of application") and the results of control measurements of blood pressure.

Ramag can be used in the form of monotherapy or in combination with other classes of antihypertensive drugs.

The initial dose. Treatment with Ramag should be started gradually, starting with the recommended initial dose of 2.5 mg per day.

In patients with significant activation of renin-angiotensin-after taking the initial dose, there may be a significant decrease in blood pressure. For such patients, the recommended dose is 1.25 mg, and their treatment should be started under control (see Section "Features of application").

Dose titration and maintenance dose. The dose can be doubled every 2-4 weeks until the target blood pressure level is reached; The maximum dose of Ramag is 10 mg per day. As a rule, the drug is taken 1 time per day.

Prevention of cardiovascular diseases.

The initial dose. The recommended initial dose of Ramag is 2.5 mg once a day.

Dose titration and maintenance dose. Depending on the individual tolerability of the drug, the dose should be gradually increased. It is recommended to double the dose after 1-2 weeks of treatment, and then - in 2-3 weeks - to increase it to the target maintenance dose of 10 mg once a day.

See the information above regarding the dosage of the drug for patients receiving diuretics.

Treatment of kidney disease.

In patients with diabetes and microalbuminuria.

The initial dose. The recommended initial dose of Ramag is 1.25 mg once a day.

Dose titration and maintenance dose. Depending on the individual tolerability of the drug with further treatment, the dose is increased. After 2 weeks of treatment, a single dose is recommended to double to 2.5 mg, and then to 5 mg after 2 weeks of treatment.

In patients with diabetes and at least one factor of cardiovascular risk.

The initial dose. The recommended initial dose of Ramag is 2.5 mg once a day.

Dose titration and maintenance dose. Depending on the individual tolerability of the drug with further treatment, the dose is increased. After 1-2 weeks of treatment, the daily dose of the preparation Ramag is recommended to be doubled to 5 mg, and then to 10 mg after 2-3 weeks of treatment. The target daily dose is 10 mg.

In patients with nondiabetic nephropathy, which is indicated by the presence of macroproteinuria ≥ 3 g / day.

The initial dose. The recommended initial dose of Ramag is 1.25 mg once a day.

Dose titration and maintenance dose. Depending on the individual patient's tolerability of the drug during further treatment, the dose is increased. After 2 weeks of treatment, a single dose is recommended to double to 2.5 mg, and then to 5 mg after 2 weeks of treatment.

Heart failure with clinical manifestations.

The initial dose. For patients whose condition has stabilized after treatment with diuretics, the recommended initial dose is 1.25 mg per day.

Dose titration and maintenance dose. The dose of Ramag is titrated by doubling it every 1-2 weeks until a maximum daily dose of 10 mg is reached. It is desirable to distribute the dose for 2 divided doses.

Secondary prophylaxis after acute myocardial infarction in the presence of heart failure.

The initial dose. 48 hours after the onset of myocardial infarction, patients whose condition is clinically and hemodynamically stable receive an initial dose of 2.5 mg twice a day for 3 days. If the initial dose of 2.5 mg is not tolerated well, then a dose of 1.25 mg should be applied 2 times a day for 2 days, followed by an increase to 2.5 mg and 5 mg 2 times a day. If the dose can be increased to 2.5 mg twice a day, treatment should be discontinued.

See the information above regarding the dosage of the drug for patients receiving diuretics.

Dose titration and maintenance dose. Further, the daily dose is increased by doubling it at intervals of 1-3 days until the target maintenance dose is 5 mg twice a day.

Whenever possible, the maintenance dose is divided into 2 divided doses.

If the dose can be increased to 2.5 mg twice a day, treatment should be discontinued. The experience of treating patients with severe cardiac insufficiency (IV of the NYHA classification) right after myocardial infarction is still not enough. If nevertheless it is decided to treat such patients with this drug, it is recommended to start therapy with a dose of 1.25 mg once a day and any increase should be done with extreme caution.

Special categories of patients.

Patients with impaired renal function. The daily dose for patients with impaired renal function depends on the creatinine clearance rate (see Section "Pharmacological properties"):

  • if creatinine clearance is ≥ 60 ml / min, there is no need to correct the initial dose (2.5 mg / day), and the maximum daily dose is 10 mg;
  • if creatinine clearance is 30-60 ml / min, there is no need to correct the initial dose (2.5 mg / day), and the maximum daily dose is 5 mg;
  • if creatinine clearance is 10-30 ml / min, the initial daily dose is 1.25 mg / day, and the maximum daily dose is 5 mg.

Patients with arterial hypertension who are on hemodialysis: when hemodialysis, ramipril is slightly excreted; the initial dose is 1.25 mg, and the maximum daily dose - 5 mg the drug should be taken a few hours after the hemodialysis session.
Patients with impaired liver function (see Section "Pharmacological properties"). Treatment with the Ramag product of patients with impaired liver function should be started under close supervision, and the maximum daily dose should be 2.5 mg.

Patients of advanced age. The initial dose should be lower, and further titration of the dose should be carried out more gradually, given the high probability of side effects, especially in very old and infirm patients. In such cases, a minimum initial dose of 1.25 mg of ramipril is prescribed.

Adverse Reactions

The safety profile of the Ramag product contains data on persistent cough and reactions caused by arterial hypotension.Serious adverse reactions include angioedema, hyperkalemia, impaired hepatic or renal function, pancreatitis, severe skin reactions, and neutropenia / agranulocytosis.

The incidence of adverse reactions is classified as follows: very often (≥ 1/10); often (from ≥ 1/100 to <1/10); infrequently (from ≥ 1/1 000 to <1/100); rarely (from ≥ 1/10 000 to <1/1 000) very rarely (<1/10 000), is unknown (can not be calculated from available data).

In each group, side effects are presented in order of decreasing severity.

Class of organs and systems
Often
Infrequently
Rarely
Rarely
Unknown
heart disorders
Myocardial ischemia, including angina pectoris or myocardial infarction, tachycardia, arrhythmia, sensation of increased heart rate, peripheral edema
On the part of the blood and lymphatic system
eosinophilia
Reduction of the number of leukocytes (including neutropenia or agranulocytosis), a decrease in the number of red blood cells, a decrease in the level of hemoglobin, a decrease in the number of platelets
Bone marrow failure, pancytopenia, hemolytic anemia
From the nervous system
Headache, dizziness
Vertigo, paresthesia, agevzia, dysgeusia
Tremor, imbalance
Cerebral ischemia, including ischemic stroke and transient ischemic attack;disorders of psychomotor functions, burning sensation, parosmia
From the side of the organs of sight
Visual impairment, including blurred vision
conjunctivitis
From the organs of hearing and balance
Hearing impairment, ringing in the ears
Respiratory, thoracic and mediastinal disorders
Unproductive irritating cough, bronchitis, sinusitis, dyspnea
Bronchospasm, including exacerbation of asthma
nasal congestion
From the gastrointestinal tract
Inflammation in the gastrointestinal tract, digestive disorders, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting
Pancreatitis (in rare cases, reported lethal effects with ACE inhibitors), increased levels of pancreatic enzymes, angioedema of the small intestine, pain in the upper abdomen, including gastritis, constipation, dry mouth
glossitis
stomatitis
From the side of the kidneys and urinary tract
Impaired renal function, including acute renal failure, increased urination, worsening of background proteinuria, increased urea levels in the blood, increased levels of creatinine in the blood
From the skin and subcutaneous tissues
Rashes, including maculopapular
Angioedema in exceptional cases - violation of airway patency due to angioedema, which can be fatal, itching, hyperhidrosis
Exfoliative dermatitis, urticaria, onycholysis
reaction photosensitive
visibility
Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, exacerbation of psoriasis, psoriatic dermatitis, pemphigoid or lichenoidal exanthema or enanthema, alopecia
From the side of the musculoskeletal system and connective tissue
Muscle spasms, myalgia
arthralgia
endocrine disorders
Syndrome of inappropriate secretion of ADH (SNSAG)
Metabolic and alimentary disorders
Increase in the level of potassium in the blood
Anorexia, decreased appetite
Decrease in the level of sodium in the blood
cardiovascular disorders
Arterial hypotension, orthostatic blood pressure lowering, syncope
tides
Stenosis of vessels, hypoperfusion, vasculitis
Raynaud phenomenon
General condition disorder
Chest pain, fatigue
pyrexia
asthenia
From the immune system
Anaphylactic and anaphylactoid reactions, an increase in the level of antinuclear antibodies
hepatobiliary system
Increased levels of hepatic enzymes and / or conjugates of bilirubin
Cholestatic jaundice, hepatic cell damage
Acute liver failure, cholestatic or cytolytic hepatitis (in very exceptional cases - with a fatal outcome)
From the side of the reproductive system and mammary glands
Transitorecternectal impotence, decreased libido
gynecomastia
From the side of the psyche
Decreased mood, anxiety, nervousness, anxiety, sleep disturbances, including drowsiness
Condition of confusion
attention violation

Overdose

Symptoms of intoxication. Overdose can cause excessive expansion of peripheral vessels (with severe arterial hypotension, shock), bradycardia, electrolyte imbalance and kidney failure.

Treatment of intoxication. Primary detoxification, for example by means of a promyshlashulunka, application of adsorbents, sodium sulfate (if possible, during the first 30 minutes).

In the case of arterial hypotension, in addition to measures aimed at restoring fluid volume and salt balance, agonists α 1 adrenoreceptors (eg norepinephrine, dopamine) or angiotensin II (angiotensinamide) should be used, which is usually only in separate research laboratories.

Ramiprilate, an active metabolite of ramipril, is poorly excreted from the systemic blood flow by hemodialysis.

Use during pregnancy and lactation

Pregnancy.

The drug is contraindicated for pregnant women or women planning pregnancy. If during pregnancy the pregnancy is confirmed, its use should be immediately stopped and, if necessary, replaced with another drug approved for use in pregnant women.

The period of breastfeeding.

Studies in animals have shown that ramipril enters breast milk. As it is not known, ramipril enters breast milk, the use of Ramagu during breastfeeding is contraindicated.

Children

The drug is contraindicated for use in children.

Special security measures

Ramipril should be used under the constant supervision of a doctor.

In patients who were treated with ACE inhibitors, there were cases of angioedema of the face, limbs, lips, tongue, glottis or pharynx. Urgent treatment of angioedema, which poses a threat to life, provides for the immediate administration of epinephrine (subcutaneously or slowly intravenously) in parallel with ECG monitoring and blood pressure.Recommended hospitalization, supervision of the patient for at least 12-24 hours. The patient can be discharged only after the symptoms have completely disappeared.

In patients who were treated with ACE inhibitors, cases of angioedema of the intestine were observed. These patients complained of abdominal pain (with or without nausea or vomiting); in some cases also there was an angioedema of the face. Symptoms of angioedema edema disappeared after discontinuation of the ACE inhibitor.

There is sufficient experience with the appropriate therapeutic Ramagu children, patients with severe renal impairment (creatinine clearance less than 20 mL / min per 1.73 m 2 of body surface area), and patients who are on dialysis.

Application features

Patients with increased activity of the renin-angiotenzinovoisistemy.

In the treatment of patients with renin- angiotensin sistemipidvischena should take extra care. Such patients are at risk of sudden and significant reduction in blood pressure and worsening of renal function due to ACE inhibition, especially when an ACE inhibitor or a diuretic Related assigned the first time or for the first time at a higher dose. In early drug preparation or with increasing doses careful control of blood pressure should be as long as there is a possibility of a sharp decline.

Increased activity of the renin-angiotensin system can be expected, in particular:

  • in patients with severe, osoblivozloyakisnoyu, gipertenzieyu.U initial phase of treatment requires special medical supervision;
  • in heart failure patients, especially those with severe or so, which was treated with other drugs that can lower blood pressure. In the case of severe heart failure in the initial phase of treatment requires special medical control;
  • patients with hemodynamically significant difficulties inflow or outflow of blood from the left ventricle (eg by aortic stenosis or mitral valve stenosis or hypertrophic cardiomyopathy). In the initial phase of treatment requires special medical control;
  • in patients with hemodynamically significant stenosis of the renal artery. In the initial phase of treatment requires special medical supervision. It may be necessary to stop the initiation of treatment with diuretics;
  • patients who previously received diuretiki.Yakschopripinennya or receiving a reduced dose of the diuretic is not possible, in the initial phase of treatment requires special medical control;
  • in patients in whom there is or may develop a lack of fluid or salt (as a result of inadequate fluid intake or salt, or, for example, due to diarrhea, vomiting or excessive sweating in cases where the lack of compensation fluid and salt is not enough).

In general, it is recommended correction of dehydration, hypovolemia, or a lack of salt before treatment (but for patients with heart failure, such corrective measures should be carefully evaluated in terms of the risk of volume overload). If clinically significant conditions Ramagom treatment can begin or continue only if at the same time take appropriate measures to prevent an excessive reduction in blood pressure and deterioration of renal function.

Patients with liver disease.

In patients with impaired liver function effect of ramipril treatment may be either increased or decreased. Moreover, in patients with severe liver cirrhosis with edema and / or ascites activity of the renin-angiotensin system may be significantly increased, so during the treatment of such patients need to take special care.

Patients with a significant decrease in blood pressure.

Patients for which a significant reduction in blood pressure is of particular risk (e.g. in patients with a hemodynamically significant stenosis of coronary arteries or vessels that supply blood to the brain), in the initial phase of treatment requires special medical supervision.

Elderly patients.

Elderly patients response to ACE inhibitors may be more pronounced. At the beginning of treatment is recommended to evaluate their kidney function.

Monitoring of renal function.

It is recommended to monitor renal function, especially in the first weeks of treatment with an ACE inhibitor. Particularly careful monitoring is necessary in patients with:

  • heart failure,
  • renovascular disease, including patients with hemodynamically significant unilateral renal artery stenosis. In the latter group of patients, even a slight increase in creatinine level in the blood serum may be indicative of unilateral renal impairment
  • worsening renal function
  • transplanted kidney.

Monitoring electrolytes balance.

It is recommended to carry out regular monitoring of the concentration of potassium in the blood serum. More frequently check the level of potassium in the serum of patients required with reduced kidney function.

Hematological monitoring.

It is recommended to monitor the number of white blood cells for timely detection of the possible leukopenia. More frequent monitoring is recommended at the beginning of the treatment of patients with renal impairment, with concomitant collagen disease (eg lupus erythematosus or scleroderma) or those treated by other drugs that can cause changes in the blood picture.

Racial differences.

ACE inhibitors are more likely to cause angioedema in patients blacks than in other races. Like other ACE inhibitors, ramipril hypotensive effect may be less severe in blacks compared to patients with other races. This may be due to the fact that patients blacks with hypertension is more common in hypertension with low renin activity.

Cough.

In applying the ACE inhibitors were reported occurrence of cough. Characteristically, the cough unproductive, long and disappears after discontinuation of therapy. In the differential diagnosis of cough should be remembered at possibility of cough due to the use of ACE inhibitors.

The ability to influence the reaction rate when driving vehicles or other mechanisms

Some side effects (e.g. certain symptoms of lowering blood pressure, in particular nausea, dizziness) may impair attention and psychomotor speed reactions in the patient.

The interaction with other drugs and other types of interactions

Contraindicated combination.

Methods extracorporeal therapies that result in contact of blood with negatively charged surfaces, such as dialysis or hemofiltration using certain membranes with high flux intensity (e.g. polyacrylonitrile membranes) and LDL-apheresis using a dextrin sulphate.

Nerekomendovanikombinatsii.

potassium salt, kaliyzberigayuchidiuretiky: should expect an increase in the concentration of potassium in the blood serum. During simultaneous treatment with ramipril potassium-sparing diuretics (e.g. spironolactone), or potassium salts requires careful monitoring of serum potassium concentration.

Use with caution.

Antihypertensive drugs (e.g. diuretics), and other drugs can lower blood pressure (e.g. nitrates, tricyclic antidepressants, anesthetics) should be expected to enhance the antihypertensive effect of ramipril. Recommended regularly monitor serum sodium concentration in patients treated with concurrent diuretic treatment.

Vasoconstrictor sympathomimetic. Can weaken the effect of lowering blood tiskuRamagu. It is recommended to carefully monitor your blood pressure.

Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other drugs which may cause changes in hemogram, may increase the likelihood of hematological reactions while the use of ramipril.

lithium salt. Excretion of lithium by the action of ACE inhibitors can be reduced. Such a reduction can lead to increased concentration of lithium in blood serum and increased lithium toxicity. It is therefore necessary to control the concentration of lithium.

Antidiabetic agents (e.g. insulin and sulfonylurea derivatives).

ACE inhibitors mozhutzbilshuvaty effect of insulin. In some cases this may lead to hypoglycemic reactions in patients receiving simultaneously antidiabetics. At the beginning of treatment is recommended particularly careful monitoring of blood glucose levels.

Food.

Food does not significantly alter the absorption of ramipril.

Take into account.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and acetylsalicylic acid. May weaken the effect of lowering blood pressure under the influence of ramipril. Also, simultaneous treatment with ACE inhibitors and NSAIDs can cause deterioration of renal function and potassium levels in the serum.

Heparin. May increase the concentration of potassium in the blood serum.

Alcohol. Increases vasodilatation. Ramag may increase the effects of alcohol.

Salt. Increased intake of salt can attenuate Ramagu hypotensive effect.

Method specific desensitization. As a consequence of inhibiting ACE increasing the likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom. It is believed that such an effect can also be observed for other allergens.

Pharmacological properties

Ramiprilat, the active metabolite of ramipril, inhibits the enzyme dipeptidilkarboksipeptidazu I (synonyms: ACE; kininaza II). In plasma and tissues this enzyme catalyzes the conversion of angiotensin I into the active vasoconstrictor substance (vasoconstrictor) angiotensin II, as well as degradation of the active vazodilatatorabradikininu. Reducing the formation of angiotensin II and bradykinin inhibiting decay leads to vasodilation.

Since angiotensin II also stimulates the release of aldosterone, resulting in action ramiprilata aldosterone secretion decreases. Increased activity of bradykinin, obviously, leads and endotelioprotektorny cardioprotective effects observed during experiments on animals. To date, it not established how this affects the development of certain undesirable effects (eg hacking cough).

ACE inhibitors are effective for the patients with hypertension who have renin plasma concentration is low. The average effect of ACE inhibitor monotherapy in patients blacks (usually in patients with hypertension and low renin concentration) was lower compared to the corresponding figure among other races.

Pharmacodynamics.

Ramipril causes a marked reduction in peripheral arterial resistance. In general plazmotik kidney and glomerular filtration rate does not change significantly.

Introduction of ramipril to patients with hypertension leads to lower blood pressure in supine and standing, without a compensatory increase in heart rate.

In most patients, the antihypertensive effect after oral administration of a single dose appears in 1-2 hours. The maximal effect of a single dose is usually achieved after 3-6 hours and typically lasts 24 hours.

The maximum antihypertensive effect of long-term treatment with ramipril generally occurs within 3-4 weeks. It was revealed that long-term treatment, it is stored for 2 years.

Upon abrupt cessation of administration of ramipril is no rapid and significant increase in blood pressure.

Patients with non-diabetic or diabetic nephropathy explicit ramipril reduces the rate of progression of renal failure and end-stage renal failure, therefore there is a need for dialysis or kidney transplantation. In patients who are non-diabetic or diabetic nephropathy, the initial ramipril reduces the excretion of albumin.

These studies have shown that ramipril with high statistical significance decreases the incidence of myocardial infarction, stroke or cardiovascular death. Furthermore, ramipril reduces the overall mortality and the need for revascularization, and delays the onset and progression of congestive heart failure. Ramipril reduces the risk of nephropathy in the overall group of patients, and among patients with diabetes. Ramipril also significantly reduces the incidence of microalbuminuria. Such effects have been observed in patients with both hypertension and with normotension.

Pharmacokinetics.

In the first pass liver metabolism occurs prodrugs (ramipril), in which is formed the only active metabolite ramiprilat (by hydrolysis, it takes place mainly in the liver). Besides such activation to form ramiprilat, ramiprilglyukuronizuetsya and converted into ramiprildiketopiperazin (ether). Ramiprilat also glyukuronizuetsya and converted into ramiprilatdiketopiperazin ( acid).

As a result of this activation / metabolizatsiiprolikiv about 20% is bioavailable peroralnoramiprilu received.

Biodostupnistramiprilatu after oral administration of 2.5 and 5 mg of ramipril is approximately 45% compared to its availability after administration of the same doses.

After taking 10 mg of ramipril labeled with a radioactive isotope, approximately 40% of the total radioactive isotope with feces and about 60% of the urine. After ingesting 5 mg of ramipril, patients with a drainage of the bile ducts with urine and zhovchjukskretuvalas approximately the same amount of ramipril and its metabolites in the first 24 hours.

Approximately 80-90% of metabolites in urine and bile are in ramiprilate or metabolites of ramiprilate.Ramipriluglucoronide and ramipril-diketopiperazine constitute about 10-20% of the total, and non-meta- lyzed by-about 2%.

There is evidence that ramipril enters the breast milk of animals.

Ramipril is rapidly absorbed after oral administration. As was determined by measuring the amount of the radioactive isotope in urine, it reflects only one of the ways of elimination, the absorption of ramipril is at least 56%. The introduction of ramipril together with a meal did not have a significant effect on absorption.

The maximum plasma concentration of ramipril is reached after 1:00 after oral administration. The period of drinking and drinking is approximately 1:00. The maximum concentration of ramiprilate in the blood plasma is observed between 2 and 4:00 after oral administration of ramipril.

The decrease in the concentration of ramiprilate in plasma occurs in several phases. The half-period of the initial phase of distribution and elimination is about 3:00. After this, a transition phase occurs (with a half-life of about 15 hours), and then the final phase, during which the plasma concentrations of ramiprilate are very low, with a half-life of about 4-5 days.

The presence of the final phase is due to the slow dissociation of ramiprilate from the near, but saturated bond with ACE.

Despite the long final phase of withdrawal, after a single dose of ramipril at a dose of 2.5 mg or more, the steady state - when plasma concentrations of ramiprilat remain constant - is reached after 4 days. After taking multiple doses, the effective half-life, depending on the dose, is 13-17 hours.

The invitro study showed that the inhibiting constant of prilatum was 7 pmol / L, and the time of pyrolysation with prilatu with ACE was 10.7 hours, which indicates a high activity.

The binding of ramipril and ramiprilate to plasma proteins is about 73% and 56%, respectively.

In healthy people aged 65 to 76 years, the kinetics of ramipril and ramiprilate is similar to that of young healthy individuals.

If the renal function is impaired, the excretion of ramiprilata by the kidneys decreases, the renal clearance of ramiprilat decreases in proportion to the creatinine clearance. This leads to an increase in plasma concentrations of ramiprilate, which decreases significantly more slowly than in individuals with normal renal function.

With the introduction of high doses (10 mg) with a violation of liver function, the conversion of ramipril to ramipril occurs later, the plasma concentrations of ramipril increase and the removal of ramiprilate slows down.

Just as in healthy volunteers and patients with hypertension, after oral administration of 5 mg ramipril once a day for 2 weeks in patients with congestive heart failure, significant accumulation of ramipril and ramiprilate was not observed.

Basic physical and chemical properties

tablets 5 mg tablets without shell, flat, capsule-like, pink, with a notch on one side and side walls, marked R3;
tablets 10 mg tablets without shell, flat, capsule-like, from white to almost white, with a notch on one side and side walls marked R4.

Shelf life

2 years.

Storage conditions

Store in the original packaging at a temperature not higher than 25 ° C. Keep out of the reach of children.

Packaging

10 tablets in a blister, 3 blisters in a cardboard box.

Category of leave

On prescription.


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