More info
Active ingredients
Ramipril
Release form
Pills
Composition
Active ingredient: Ramipril (Ramipril) Active ingredient concentration (mg): 5
Pharmacological effect
An antihypertensive drug, an ACE inhibitor. The active metabolite of ramipril, ramiprilat, which is influenced by hepatic enzymes, is a long-acting ACE inhibitor, which is a peptidyl dipeptidase. ACE in plasma and tissues catalyzes the conversion of angiotensin I to angiotensin II and the breakdown of bradykinin. Therefore, when taking ramipril inside, the formation of angiotensin II decreases and there is an accumulation of bradykinin, which leads to the expansion of blood vessels and a decrease in blood pressure. An increase in the activity of the kallikrein-kinin system in the blood and tissues causes the cardioprotective and endothelioprotective effect of ramipril due to the activation of the prostaglandin system and, accordingly, an increase in the synthesis of prostaglandins that stimulate the formation of nitric oxide (NO) in endothelial cells. a decrease in the secretion of aldosterone and an increase in the serum concentrations of potassium ions. When the concentration of angiotensin II is reduced, its blood is eliminated inhibitory effect on the secretion of renin by the type of negative feedback, which leads to an increase in plasma renin activity. It is assumed that the development of some undesirable reactions (in particular dry cough) is also associated with an increase in bradykinin activity. In patients with arterial hypertension, ramipril reduces Blood pressure in the supine position and standing, without a compensatory increase in heart rate. Ramipril significantly reduces OPSS, almost without causing changes in the renal blood flow and glomerular filtration rate. The hypotensive effect begins to manifest after 1-2 hours after ingesting a single dose of the drug, reaching its highest value after 3-9 hours, and persists for 24 hours. When taking a course dose, the hypotensive effect can gradually increase, stabilizing usually by 3-4 weeks of regular use drug and then persisting for a long time. Sudden discontinuation of the drug does not lead to a rapid and significant increase in blood pressure (no withdrawal syndrome). In patients with arterial hypertension, ramipril slows down the development and progression of myocardial hypertrophy and vascular wall. In patients with chronic heart failure, ramipril reduces OPSS (decrease in heart load),increases the capacity of the venous bed and reduces the filling pressure of the left ventricle, which, respectively, leads to a decrease in the preload on the heart. In these patients, when receiving ramipril, there is an increase in cardiac output, ejection fraction and improved exercise tolerance. In diabetic and non-diabetic nephropathy, ramipril intake slows down the rate of progression of renal failure and the onset of end-stage renal failure, and thereby reduces the need for hemodialysis or transplantation procedures the kidneys. In the initial stages of diabetic or nondiabetic nephropathy, ramipril reduces albuminuria. In patients with a high risk of developing cardiovascular disease due to either vascular lesions (diagnosed with coronary artery disease, obliterating diseases of the peripheral arteries in history, stroke in history, or diabetes mellitus with no less than one additional risk factor (microalbuminuria, arterial hypertension, an increase in total cholesterol concentrations, a decrease in HDL cholesterol concentrations P, smoking) the addition of ramipril to standard therapy significantly reduces the incidence of myocardial infarction, stroke and mortality from cardiovascular causes. In addition, ramipril reduces overall mortality, as well as the need for revascularization procedures, and slows the onset or progression of chronic heart failure. In patients with heart failure that developed in the first days of acute myocardial infarction (2-9 days), while taking ramipril, starting from 3 to 10 days of acute myocardial infarction, the risk of mortality decreases (by 27%), the risk of sudden death (by 30%), the risk of progression of chronic heart failure to severe (III-IV functional class c according to NYNA) / resistant to therapy (by 27%), the probability of subsequent hospitalization due to the development of heart failure (by 26%). In the general population of patients, as well as in patients with diabetes mellitus with both arterial hypertension and normal blood pressure ramipril significantly reduces the risk of nephropathy and the occurrence of microalbuminuria.
Pharmacokinetics
Absorption, distribution and metabolism. After ingestion is rapidly absorbed from the gastrointestinal tract (50-60%). Food does not affect the completeness of absorption, but slows down absorption. Ramipril undergoes intensive presystemic metabolism / activation (mainly in the liver by hydrolysis), which results in its only active metabolite, ramiprilat, which is 6 times more active in inhibiting ACE ramipril activity. In addition, as a result of ramipril metabolism, diketopiperazine does not possess pharmacological activity, which is then conjugated with glucuronic acid, ramiprilat is also glucuronic and metabolized to diketopiperazine acid. The bioavailability of ramipril after ingestion ranges from 15% (for a dose of 2.5 mg) to 15 mg (for a dose of 2.5 mg) for a dose of 5 mg). The bioavailability of the active metabolite - ramiprilat - after oral administration of 2.5 mg and 5 mg of ramipril is approximately 45% (compared to its bioavailability after i / v administration in the same doses). Cmax of ramipril and ramiprilat is reached in blood plasma after 1 and 2-4 h, respectively. The binding of ramipril to plasma proteins is 73%, ramiprilat - 56%. InjectionThe decrease in plasma concentration of ramiprilat occurs in several stages: the initial distribution and elimination phase with T1 / 2 ramiprilat, which is approximately 3 hours, then the intermediate phase with a period T1 / 2 ramiprilat, component of approximately 15 hours and the final phase with a very low concentration of ramiprilat in the blood plasma and T1 / 2 ramiprilat of approximately 4-5 days. This final phase is associated with the slow dissociation of ramiprilat from the association with the ACE receptors. Despite the long-term final phase, taking ramipril once a day for a dose of 2.5 mg or more of Css, the concentration of ramiprilat in plasma is reached after approximately 4 days of treatment. For the course of administration of the drug T1 / 2 is 13-17 hours. After ingestion of radiolabeled ramipril (10 mg) 39% of radioactivity is excreted through the intestines and about 60% by the kidneys. After ingestion of 5 mg of ramipril in patients with bile duct drainage, almost the same amount of ramipril and its metabolites are excreted. MI and through the intestine during the first 24 hours after administration. Approximately 80-90% of metabolites in urine and bile were identified as ramiprilat and ramiprilat metabolites.Ramipril glucuronide and ramipril diketopiperazin account for approximately 10-20% of the total amount, and unmetabolized ramipril content in the urine is approximately 2%. Pharmacokinetics in special clinical situations In renal dysfunction with CC less than 60 ml / min, the elimination of ramiprilat and its metabolites by the kidneys slows down. This leads to an increase in the plasma concentration of ramiprilat, which decreases more slowly than in patients with normal renal function. When receiving ramipril in high doses (10 mg), impaired liver function slows down the systemic metabolism of ramipril to active ramiprilat and slower elimination of ramiprilat. In healthy volunteers and in patients with arterial hypertension after two weeks of ramipril treatment in a daily dose of 5 mg, there is no clinically significant accumulation of ramipril and ramiprilat. In patients with x After two weeks of ramipril treatment with a daily dose of 5 mg, a cardiac heart failure shows a 1.5–1.8-fold increase in plasma concentrations of ramiprilat and AUC. In healthy elderly volunteers (65–76 years), the pharmacokinetics of ramipril and ramiprilat are not significantly different from those in young healthy volunteers In experimental animal studies, ramipril has been shown to be excreted in breast milk.
Indications
- Arterial hypertension. - Chronic heart failure (as part of combination therapy), including developed in the first few days after acute myocardial infarction. - Diabetic nephropathy and nephropathy on the background of chronic diffuse diseases of the kidneys (chronic glomerulonephritis with severe proteinuria) - preclinical and clinically expressed stages. - In order to prevent the development of myocardial infarction, stroke or coronary death in patients with coronary artery disease, with an increased risk of cardiovascular diseases, including patients who have suffered a myocardial infarction, transcutaneous transluminal coronary angioplasty, aorto-coronary bypass.
Contraindications
Hypersensitivity to ramipril or other ACE inhibitors, angioedema in the history of therapy with ACE inhibitors, hereditary or idiopathic angioedema, bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, the condition after kidney transplantation, hemodynamically aortic orchestralosis, or an anastropic anemia or a case, or a case, or a child, you can rest with a mucus or an anesthetic infection. hyperaldosteronism, pregnancy, lactation. With caution.Severe lesions of the coronary and cerebral arteries (danger of reducing blood flow with an excessive decrease in blood pressure), unstable angina, severe ventricular arrhythmias, end-stage CHF, decompensated pulmonary heart disease, requiring the appointment of GCS and immunosuppressants (no clinical experience) - including with systemic diseases of the connective tissue, renal and / or liver failure, hyperkalemia, hyponatremia (including on the background of diuretics and a diet with restriction of Na + consumption), conditions accompanied by a decrease in BCC (including diarrhea, vomiting), the elderly age, age 18 years (safety and efficacy have not been studied).
Precautionary measures
With caution: conditions in which an excessive decrease in blood pressure is especially dangerous (with atherosclerotic lesions of the coronary and cerebral arteries); conditions accompanied by an increase in the activity of the renin-angiotensin-aldosterone system (RAAS), in which, when ACE is inhibited, there is a risk of a sharp decrease in blood pressure with deterioration of kidney function (marked arterial hypertension, especially malignant arterial hypertension; chronic heart failure, especially severe or due to which other drugs with hypotensive action; hemodynamically significant unilateral stenosis of the renal artery (if both kidneys are present); diuretic intake, impaired water and electrolyte balance as a result of inadequate intake of fluid and salt, diarrhea, vomiting, excessive sweating); dysfunction of the liver (lack of experience with the application: both strengthening and weakening of the effects of ramipril is possible; in patients with cirrhosis of the liver with ascites and edema, a significant activation of the RAAS is possible, see above. States accompanied by an increase in the activity of the RAAS); renal dysfunction (QC more than 20 ml / min with a body surface of 1.73 m2) due to the risk of hyperkalemia and leukopenia); condition after kidney transplantation; Systemic diseases of the connective tissue, incl. systemic lupus erythematosus, scleroderma, concomitant therapy with drugs that can cause changes in the pattern of peripheral blood (possibly inhibition of bone marrow hematopoiesis, the development of neutropenia or agranulocytosis); diabetes mellitus (risk of developing hyperkalemia); old age (risk of increased hypotensive action); hyperkalemia.
Use during pregnancy and lactation
Ramipril is contraindicated during pregnancy, becausecan have an adverse effect on the fetus: impaired fetal kidney development, lowering fetal and newborn blood pressure, impaired kidney function, hyperkalemia, cranial bone hypoplasia, oligohydramnios, limb contracture, cranial bones deformation, pulmonary hypoplasia. exclude pregnancy. If a woman is planning a pregnancy, the treatment with ACE inhibitors should be discontinued. If pregnancy occurs during the treatment with Tritace, follow ie, as soon as possible, stop taking it and move the patient to the treatment with other drugs, the application of which the risk to the child is naimenshim.Esli Tritace drug treatment is necessary during lactation, the breast-feeding should be discontinued.
Dosage and administration
Arterial hypertension: inside, initial dose - 2.5 mg, once, in the morning, on an empty stomach or 2 times a day. In case of insufficient hypotensive effect, the dose is gradually increased every 2-3 weeks. The maximum daily dose - 10 mg, supporting - 2.5-5 mg. In the absence of an optimal reduction in blood pressure, diuretic drugs are also prescribed. CHF: initial dose - 1.25 mg / day; if necessary, increase the dose to 2.5 mg in 1-2 weeks. When treating patients after myocardial infarction, the initial dose is 2.5 mg 2 times a day (with poor tolerance for the first 2 days take 1.25 mg each). Renal failure (CK 30-60 ml / min), age over 65 years, diabetes mellitus: initial dose - 1.25 mg, maintenance dose - 2.5 mg; The maximum dose is 5 mg / day.
Side effects
From the side of the central nervous system: often - headache, a feeling of lightness in the head; sometimes - dizziness, agevziya (loss of taste sensitivity), dysgeusia (violation of taste sensitivity), depressed mood, anxiety, nervousness, restlessness, sleep disorders, including drowsiness; rarely - tremor, imbalance, confusion; frequency is unknown - cerebral ischemia, including ischemic stroke and transient cerebral circulation disturbance, impaired psychomotor reactions, paresthesia (burning sensation), parosmia (impaired sense of smell), impaired attention. Eyesight: sometimes visual disturbances, including blurred images; rarely - conjunctivitis. From the side of the organ of hearing: rarely - hearing loss, ringing in the ears. From the side of the respiratory system: often - dry cough (aggravated at night and when lying down),bronchitis, sinusitis, shortness of breath; sometimes bronchospasm, including worsening of asthma, nasal congestion. On the digestive system: often - inflammatory reactions in the stomach and intestines, digestive disorders, discomfort in the abdomen, dyspepsia, diarrhea, nausea, vomiting; sometimes - pancreatitis, incl. fatal (cases of pancreatitis with a fatal outcome when taking ACE inhibitors were extremely rare), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, abdominal pain, gastritis, constipation, dry oral mucosa; rarely - glossitis; frequency unknown - aphthous stomatitis (inflammatory reaction of the mucous membrane of the oral cavity). On the part of the hepatobiliary system: sometimes - increased activity of liver enzymes and concentration of conjugated bilirubin in the blood plasma; rarely - cholestatic jaundice, hepatocellular lesions; frequency unknown - acute liver failure, cholestatic or cytolytic hepatitis (death was rarely observed). urea and creatinine in the blood. From the reproductive system and mammary glands: sometimes - transient impotence due to erectile dysfunction, decreased libido; frequency is unknown: gynecomastia. From the hematopoietic system: sometimes - eosinophilia; rarely - leukopenia, including neutropenia and agranulocytosis, a decrease in the number of erythrocytes in peripheral blood, a decrease in the concentration of hemoglobin, thrombocytopenia; frequency is unknown - oppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia. From the skin and mucous membranes: often - skin rash (in particular maculopapular); sometimes - angioedema, incl. fatal (laryngeal edema can cause airway obstruction, resulting in death), pruritus, hyperhidrosis; rarely - exfoliative dermatitis, urticaria, oniholysis; very rarely - photosensitivity reactions; frequency unknown - toxic epidermal necrolysis,Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening of the course of psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (lingual) exanthema or enanthema, alopecia. For musculoskeletal system: often - muscle cramps, myalgia; sometimes - arthralgia. Disorders of metabolism, nutrition and laboratory parameters: often - an increase in the concentration of potassium in the blood; sometimes - anorexia, loss of appetite; frequency unknown - decrease in sodium concentration in the blood. From the immune system: frequency unknown - anaphylactic or anaphylactoid reactions (when ACE is inhibited, the number of anaphylactic or anaphylactoid reactions to insect poisons increases), increasing the concentration of antinuclear antibodies. Common disorders: often - chest pain, feeling tired; sometimes - fever; rarely - asthenia (weakness).
Overdose
Symptoms: excessive peripheral vasodilation with the development of a pronounced decrease in blood pressure, shock; bradycardia, water and electrolyte disorders, acute renal failure, stupor. Treatment: gastric lavage, taking adsorbents, sodium sulfate (if possible during the first 30 minutes). In the case of a pronounced decrease in blood pressure, the introduction of alpha1-adrenergic agonists (norepinephrine, dopamine) and angiotensin II (angiotensinamide) can be added to therapy for replenishing the blood volume rate and restoring electrolyte balance. In the case of bradycardia refractory to a drug treatment, it may be necessary to install a temporary artificial pacemaker. In case of overdose, it is necessary to monitor serum concentrations of creatinine and electrolytes.
Interaction with other drugs
Contraindicated combinations Using certain high-flow membranes with a negatively charged surface (for example, polyacrylonitrile membranes) when performing hemodialysis or hemofiltration and using dextran sulfate when apheresis of low-density lipoproteins increases the risk of developing severe anaphylactic reactions. , spironolactone) perhaps a more pronounced increase in the concentration of potassium in serum e blood (while the application requires careful control of the concentration of potassium in blood serum) .Kombinatsii to be applied with ostorozhnostyuS antihypertensives (especially diuretics) and other drugs that lower blood pressure (nitrates,tricyclic antidepressants) potentiation of the hypotensive effect is noted; when combined with diuretics, serum sodium should be monitored. With hypnotics, narcotics and anesthetics, a more pronounced decrease in BP. With vasopressor sympathomimetics (epinephrine), a decrease in the hypotensive effect of ramipril is noted, careful control of AD is required. , systemic corticosteroids and other means that may affect hematological parameters, increases the risk of leukopenia. With lithium salts There is an increase in serum lithium concentration and an increase in the cardio-and neurotoxic effect of lithium. With oral hypoglycemic agents (sulfonylurea derivatives, biguanides) and insulin: due to a decrease in insulin resistance under the influence of ramipril, the hypoglycemic effect of these drugs can be increased up to the development of hypoglycemia. which should be taken into account with NSAIDs (indomethacin, acetylsalicylic acid) may weaken the effect of ramipril, increase the risk of drug sheniya renal function and increase in serum potassium concentration krovi.S heparin may increase the concentration of potassium in serum krovi.S sodium chloride may weaken the hypotensive action of ramipril and less effective treatment of the symptoms of chronic heart ethanol nedostatochnosti.S noted increased vasodilation. Ramipril may increase the adverse effect of ethanol on the body. With estrogen, a weakening of the hypotensive effect of ramipril (fluid retention) is noted. When desensitizing therapy is used, if you are hypersensitive to insect poisons, ACE inhibitors, including ramipril, increase the likelihood of severe anaphylactic or anaphylactoid reactions of insects.
special instructions
Before starting treatment with Tritace it is necessary to eliminate hyponatremia and hypovolemia. In patients who have previously taken diuretics, it is necessary to cancel them, or at least reduce their dose 2-3 days before starting taking the drug Tritace (in this case, the condition of patients with chronic heart failure should be carefully monitored,due to the possibility of decompensation in them due to an increase in the BCC). After taking the first dose of the drug, as well as increasing its dose and / or diuretic dose (especially loop), it is necessary to ensure close medical observation of the patient for at least 8 hours timely take appropriate measures in case of excessive decrease in blood pressure. If Tritace is used for the first time or in a high dose in patients with increased RAAS activity, then they should be carefully monitored for blood pressure, especially at the beginning of treatment, so as in these patients there is an increased risk of excessive reduction in blood pressure. In malignant hypertension and heart failure, especially in the acute stage of myocardial infarction, treatment with Tritace should be started only in a hospital setting. In patients with chronic heart failure, taking the drug can lead to the development of pronounced decrease in blood pressure, which in some cases is accompanied by oliguria or azotemia and rarely the development of acute renal failure. Care should be taken when treating Research Institute of elderly patients, since they may be particularly sensitive to ACE inhibitors; in the initial phase of treatment, it is recommended to monitor renal function indicators. In patients for whom a decrease in blood pressure may present a certain risk (for example, in patients with atherosclerotic narrowing of the coronary or cerebral arteries), treatment should begin under strict medical supervision. Caution should be exercised during physical exertion and / or hot weather due to the risk of sweating and dehydration with the development of arterial hypotension, due to the mind nsheniya bcc and reducing the sodium concentration in krovi.Vo Tritace time of treatment is not recommended to use alcohol.