Ramipril tablets 10mg №10×3

NameRamipril tabl. 10 mg – almost white tablets, marbling is allowed. The main active ingredient Ramipril Release form Tablets Dosage 5 mg Pharmacological properties Pharmacodynamics Mechanism of action Ramiprilat, the active metabolite of ramipril, is a long-acting angiotensin-converting enzyme (ACE) inhibitor. In plasma and tissues, ACE catalyzes the conversion of angiotensin I to angiotensin II (an active vasoconstrictor) and the breakdown of the active vasodilator bradykinin. A decrease in the formation of angiotensin II and an increase in bradykinin activity leads to vasodilation and contributes to the cardioprotective and endothelioprotective effects of ramipril. Angiotensin II stimulates the release of aldosterone, in connection with this, ramipril causes a decrease in aldosterone secretion. The overall response to ACE inhibitor monotherapy is lower in black hypertensive patients (low renin population) than in white patients. Double blockade of the renin-angiotensin-aldosterone system. Two large randomized controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes) studied the combination of an ACE inhibitor and an angiotensin II receptor antagonist (ARA). ONTARGET was a study in patients with a history of cardiovascular or cerebrovascular disease or type 2 diabetes mellitus with evidence of end organ damage.VA NEPHRON-D was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.These studies did not show significant benefit on renal and/or cardiovascular conditions and mortality, while there was an increased risk of hyperkalemia, kidney damage, hypotension compared with monotherapy.Because of similar pharmacodynamic properties, these results also apply to other ACE inhibitors and ARAs.Therefore, contraindication but the combined use of ACE inhibitors and ARA in patients with diabetic nephropathy; ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was a study designed to test the benefit of adding Aliskiren to standard therapy with ACE inhibitors or ARAs in patients with type 2 diabetes mellitus and chronic renal failure, cardiovascular disease, or their combination. The study was suspended due to an increased risk of adverse outcomes. Mortality from cardiovascular complications was numerically more frequent in the Aliskiren group than in the placebo group, adverse reactions of varying severity (hyperkalemia, kidney damage, hypotension) were more frequently observed in the Aliskiren group than in the placebo group. Pharmacodynamic action Hypotensive action Taking ramipril causes a pronounced decrease in peripheral arterial resistance. Changes in renal blood flow and glomerular filtration rate are usually not observed. Reception of ramipril causes in hypertensive patients a decrease in blood pressure in the “lying” and “standing” positions without a compensatory increase in heart rate. In most patients, a noticeable hypotensive effect occurs 1-2 hours after ingestion of a single dose. The maximum effect of a single dose is achieved 3-6 hours after ingestion. The hypotensive effect of a single dose usually lasts for 24 hours. The maximum hypotensive effect with continuous treatment with ramipril usually occurs after 3-4 weeks. It has been shown that the hypotensive effect of long-term therapy persists for 2 years. Abrupt discontinuation of ramipril does not cause a rapid and excessive rebound increase in blood pressure. Heart failure As with traditional therapy with diuretics and optional cardiac glycosides, ramipril has been shown to be effective in patients with NYHA functional class II-IV heart failure. Ramipril has favorable effects on hemodynamics (reduces the filling pressure of the left and right ventricles, reduces the total peripheral vascular resistance, increases the cardiac index), and also reduces neuroendocrine activation. Pharmacokinetics Absorption After oral administration, it is rapidly absorbed in the gastrointestinal tract: the maximum content of ramipril in the blood plasma is reached within an hour and is at least 56% of the dose taken, practically does not depend on the simultaneous intake of food. The bioavailability of the active metabolite of ramiprilat after oral administration of 2.5 mg and 5 mg of ramipril is 45%. After oral administration, the maximum plasma concentration of ramiprilat is reached after 2-4 hours. A constant plasma concentration of ramiprilat after daily administration of conventional doses of ramiprilat is reached approximately on the fourth day of treatment. Distribution Protein binding is about 73% for ramipril and about 56% for ramiprilat. Metabolism Ramipril is almost completely converted to ramiprilat, diketopiperazine ester, diketopiperazine acid, and ramipril and ramiprilat glucuronides. Excretion Excretion of metabolites is carried out mainly by the kidneys. Removal of ramiprilat is carried out in several phases due to the activity of ramiprilat, saturable binding to ACE and weak dissociation with this enzyme. The terminal phase of ramiprilat elimination is long at very low plasma concentrations. With multiple doses of ramipril once a day, the “effective” half-life, important in terms of dosing, was 13-17 hours for a dosage of 5-10 mg / ml, and longer for lower dosages of 1.25-2.5 mg / ml. ml. This difference is due to the strong binding of ramiprilat to ACE. In breast milk after a single dose of ramipril and its metabolites are not detected by quantitative methods. However, with multiple doses, the effect is unknown. Patients with impaired renal function In case of impaired renal function, the excretion of ramiprilat by the kidneys is reduced, the renal clearance of ramiprilat decreases in proportion to creatinine clearance. This leads to an increase in the plasma concentration of ramiprilat, which decreases more slowly than in patients with intact kidneys. Hepatic Impaired Patients Decreased hepatic function results in slow metabolism of ramipril to ramiprilat and delayed elimination of ramiprilat; Plasma levels of ramipril are elevated in these patients. However, the maximum level of ramiprilat in patients with reduced liver function does not differ from the maximum level observed in patients with normal liver function. Indications for use Treatment of arterial hypertension: to lower blood pressure both in monotherapy and in combination with other antihypertensive agents. Prevention of cardiovascular accidents: reduction in the number of cardiovascular complications (myocardial infarction, stroke and death) in patients with: – severe atherothrombotic cardiovascular diseases (history of coronary heart disease or stroke, obliterating diseases of the arteries of the lower extremities); – diabetes mellitus and with at least one cardiovascular risk factor (see section Pharmacological properties). Secondary prevention in patients with acute myocardial infarction: reduction in the risk of death, starting from the acute phase of myocardial infarction, in patients with clinical signs of heart failure when administered 48 hours after the onset of the disease. Treatment of glomerular kidney diseases: – the initial stage of diabetic nephropathy with the presence of microalbuminuria; – overt diabetic nephropathy with the presence of macroproteinuria in patients with at least one risk factor for cardiovascular disease (see section Pharmacological properties); – obvious non-diabetic nephropathy with the presence of macroproteinuria? 3 g/day (see section Pharmacological properties). Treatment of chronic heart failure Route of administration and doses Inside. It is recommended to take Ramipril every day at the same time of the day. LS Ramipril is taken with plenty of liquid and regardless of food intake. Eating does not significantly affect the absorption of the active component of ramipril (see section Pharmacokinetics). Tablets should be swallowed whole (not chewed). Adults Patients treated with diuretics Starting the drug Ramipril may be accompanied by hypotension; this is more common in patients treated with diuretics. The lack of salts and fluids in the body is subject to preliminary correction before the start of treatment with Ramipril, diuretics should be previously limited or discontinued, no later than 2-3 days (see section Precautions). Treatment of patients who have not stopped taking diuretics should begin with the smallest single dose of 1.25 mg of ramipril. It is necessary to monitor kidney function and the content of potassium in the blood serum. The subsequent dosage of the drug Ramipril should be adjusted in accordance with the target level of blood pressure. Treatment of arterial hypertension The dosage is calculated depending on the expected therapeutic effect and the tolerability of the active substance by the patient in each case (see section Precautions). Ramipril can be used both as monotherapy and in combination with other classes of drugs for the treatment of arterial hypertension. Treatment with Ramipril should begin with an initial dose of 2.5 mg daily. In patients with a highly activated renin-angiotensin-aldesterone system, a significant decrease in blood pressure may follow the initial dose. For such patients, the recommended starting dose is 1.25 mg, and the initiation of treatment should be under medical supervision (see section Precautions). The dose can be doubled at intervals of 2-4 weeks to achieve the target blood pressure level. The maximum daily dose is 10 mg. The daily dose is taken once a day. Prevention of cardiovascular accidents The recommended initial dose is 2.5 mg of Ramipril once a day. The dose is gradually increased depending on the patient’s tolerance of the active substance. It is recommended to double the dose after 1–2 weeks of treatment, and after the next 2–3 weeks, increase the maintenance dose to 10 mg Ramipril daily. See also dosing in patients previously treated with diuretics. Secondary prophylaxis in patients with acute myocardial infarction with clinical signs of heart failure After 48 hours following myocardial infarction, in clinically and hemodynamically stable patients, the recommended initial dose is 2.5 mg twice a day for three days. If the initial dose of 2.5 mg is not tolerated by the patient, 1.25 mg twice daily for 2 days should be given before increasing the dose to 2.5 mg and 5 mg twice daily. If the dose cannot be increased to 2.5 mg twice daily, treatment should be discontinued. See also dosing in patients previously treated with diuretics. The daily dose is sequentially increased, doubling it at intervals of 1-3 days until a maintenance dose of 5 mg twice a day is reached. The maintenance daily dose is recommended to be divided into 2 doses. The maximum daily dose is 10 mg. If a decision is made to treat Ramipril in patients with severe (NYHA grade IV) chronic heart failure after myocardial infarction, it is recommended to start with a dose of 1.25 mg 1 time per day. The dose should be increased with extreme caution. Treatment of kidney diseases In patients with diabetes and microalbuminuria The recommended initial dose is 1.25 mg of the drug Ramipril once a day. The dose is sequentially increased depending on the patient’s tolerance of the active substance. It is recommended to double the daily dose to 2.5 mg after 2 weeks of treatment, and then to 5 mg after the next 2 weeks. In patients with diabetes and at least one cardiovascular risk factor The recommended starting dose is 2.5 mg Ramipril once a day. The dose is sequentially increased depending on the patient’s tolerance of the active substance. It is recommended to double the daily dose to 5 mg after 2 weeks of treatment, and then to 10 mg after the next 2-3 weeks. The maximum daily dose is 10 mg. In patients with non-diabetic nephropathy with macroproteinuria? 3 g/day The recommended starting dose is 1.25 mg Ramipril once a day. The dose is sequentially increased depending on the patient’s tolerance of the active substance. It is recommended to double the daily dose to 2.5 mg after 2 weeks of treatment, and then to 5 mg after the next 2 weeks. Treatment of chronic heart failure For patients receiving diuretic therapy, the recommended initial dose is 1.25 mg Ramipril once a day. It is recommended to double the dose of Ramipril every two weeks up to a maximum daily dose of 10 mg. It is preferable to divide the daily dose into 2 doses. Special categories of patients Treatment of patients with impaired renal function The daily dose for patients with impaired renal function is prescribed taking into account creatinine clearance: if creatinine clearance ? 60 ml / min, no need to adjust the initial dose (2.5 mg daily), the maximum daily dose is 10 mg; if creatinine clearance is in the range of 30-60 ml / min, there is no need to adjust the initial dose (2.5 mg daily) , the maximum daily dose is 5 mg; if creatinine clearance is in the range of 10-30 ml / min, the initial dose is 1.25 mg daily, and the maximum daily dose is 5 mg; in patients with hypertension undergoing hemodialysis: ramipril is poorly dialyzed; the initial dose is 1.25 mg daily, and the maximum daily dose is 5 mg; the drug must be taken a few hours after hemodialysis. Patients with impaired liver function Treatment of such patients should be carried out with extreme caution and only under medical supervision. The maximum allowable daily dose in such cases is 2.5 mg of Ramipril. Elderly patients Initial doses should be lower and their administration should be more gradual due to the increased risk of adverse reactions, especially in elderly and debilitated patients. The recommended initial daily dose is 1.25 mg of Ramipril. Children Ramipril is not recommended for use in children and adolescents under 18 years of age due to insufficient relevant data on its safety and efficacy. Use during pregnancy and lactation It is not recommended to take drugs Ramipril in the first trimester of pregnancy (see section Precautions). This drug is contraindicated in the second and third trimesters of pregnancy (see section Contraindications). There are no conclusive epidemiological data on the risk of teratogenicity due to the use of ACE inhibitors during the first trimester of pregnancy; however, a small risk cannot be ruled out. If the patient is planning pregnancy, treatment with ACE inhibitors should be discontinued and replaced with another antihypertensive drug with a safer pregnancy profile. Therapy with ACE / ARA inhibitors in the second and third trimesters of pregnancy can cause fetotoxicity (decreased renal function, oligohydramnios, severe skull hypoplasia) and neonatal intoxication (renal failure, hypotension, hyperkalemia). Patients who have had cases of taking ACE inhibitors since the second trimester of pregnancy are advised to check the function of the kidneys and skull using ultrasound. Newborns whose mothers have taken ACE inhibitors should be evaluated for hypotension, oliguria, and hypokalemia (see Contraindications and Precautions). Since it is not known for certain whether ramipril passes into human milk and causes undesirable effects in breastfed children, the use of Ramipril during breastfeeding is contraindicated. It is recommended to choose an alternative treatment that has a better safety profile during breastfeeding. Precautions Special categories of patients Pregnancy ACE inhibitors such as ramipril or angiotensin II receptor antagonists (ARAs) should not be used during pregnancy. If the patient is planning a pregnancy, then before continuing therapy with ACE inhibitors / ARA, it is necessary to select another treatment for hypertension with a more reliable safety profile for pregnancy. If pregnancy is detected during treatment with ACE / ARA inhibitors, you should immediately stop taking the medication and start therapy with drugs from other classes (see sections Contraindications and Adverse reactions). Patients at risk of hypotension: Patients with increased activity of the renin-angiotensin-aldosterone system Patients with increased activity of the renin-angiotensin-aldosterone system are at risk of a sharp drop in blood pressure and deterioration of renal function during ACE inhibition, especially at the beginning of treatment or when the dose of ACE inhibitors is first increased or co-administered diuretics. Possible manifestations of increased activity of the renin-angiotensin-aldosterone system must be taken into account, carrying out constant medical supervision, including monitoring of blood pressure, in cases, for example: patients with severe hypertension; patients with decompensated congestive heart failure; patients with clinically significant hemodynamic disorders (inflow or outflow ) in the left ventricle (eg, aortic stenosis, mitral stenosis); patients with unilateral renal artery stenosis with a second functional kidney; patients with electrolyte and/or fluid deficiency (including patients previously treated with diuretics); patients with cirrhosis of the liver and / or ascites; patients undergoing major surgery or during anesthesia with agents that cause hypotension. Before starting treatment, it is recommended to correct dehydration, hypovolemia, or electrolyte deficiency (in patients with heart failure, such corrective actions should be evaluated taking into account the risk of exceeding the volume). Transient or permanent heart failure after myocardial infarction; patients at risk of cardiac or cerebral ischemia due to acute hypotension. The initial stages of treatment require special medical supervision. Dual blockade of the renin-angiotensin-aldosterone system is associated with an increased risk of hypotension, hyperkalemia, and renal dysfunction (including acute renal failure) compared with monotherapy. Dual RAAS blockade with ACE inhibitors, ARBs, or Aliskiren cannot be recommended for any patient, especially those with diabetic nephropathy. In some cases, when the combined use of ACE inhibitors and ARA is absolutely indicated, careful supervision of a specialist and mandatory monitoring of kidney function, water and electrolyte balance, and blood pressure are necessary. This refers to the use of candesartan or valsartan as add-on therapy to ACE inhibitors in patients with chronic heart failure. Conducting a double blockade of the RAAS under the close supervision of a specialist and mandatory monitoring of kidney function, water and electrolyte balance and blood pressure is possible in patients with chronic heart failure with intolerance to aldosterone antagonists (spironolactone), who have persistent symptoms of chronic heart failure, despite other adequate therapy. Elderly patients See section Dosage and Administration Surgery It is recommended to stop treatment with ACE inhibitors (including ramipril), if possible, the day before surgery. Monitoring of renal function Renal function is subject to control before the appointment of drugs Ramipril. Monitoring of renal function is recommended, in particular, in the first weeks of treatment, especially in patients with renal insufficiency (see section Dosage and administration). Possible risk of impaired renal function, especially in patients with congestive heart failure or after kidney transplantation. Angioedema Cases of angioedema have been reported in patients treated with ACE inhibitors, including ramipril (see section Adverse Reactions). If angioedema occurs during treatment, Ramipril should be discontinued immediately. Emergency treatment must be started immediately. The patient should be observed for at least 12-24 hours and discharged only after the disappearance of all symptoms. A case of angioedema of the intestine has been reported in patients treated with ACE inhibitors, including the drug Ramipril (see section Adverse reactions). Patients had abdominal pain (sometimes accompanied by nausea and vomiting). Anaphylactic reactions during desensitization The likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom is increased with ACE inhibitors. It is assumed that a similar effect may also occur when interacting with other allergens. Prior to the start of desensitization, the possibility of temporarily stopping the use of Ramipril should be considered. Hyperkalemia Hyperkalemia has been observed in some patients treated with ACE inhibitors, including the drug Ramipril. Patients at risk of developing hyperkalemia include patients with renal insufficiency; aged > 70 years; uncontrolled diabetes mellitus; using potassium salts, potassium-sparing diuretics or other substances that increase the content of potassium in the plasma; also conditions such as dehydration, acute cardiac decompensation, metabolic acidosis. During simultaneous treatment with these drugs, strict monitoring of serum potassium concentration is necessary (see section Interaction with other medicinal products and other forms of interaction). Hyponatremia In some patients treated with ramipril, a syndrome of inappropriate secretion of antidiuretic hormone (SNS ADH) was observed, leading to hyponatremia. Regular monitoring of serum sodium is recommended in elderly patients and other patients at increased risk of hyponatremia. Neutropenia/agranulocytosis Neutropenia/agranulocytosis, as well as thrombocytopenia and anemia, are rare, and bone marrow depression has also been reported. It is recommended to monitor the number of leukocytes to prevent possible leukopenia. More detailed monitoring is recommended at the initial stages of treatment and in patients with impaired renal function with concomitant collagenosis (lupus erythematosus or scleroderma) treated with other drugs that may affect the blood picture (see section Interaction with other drugs and other forms interactions and adverse reactions). Ethnic differences The risk of angioedema when taking ACE inhibitors is more likely in black patients than in white patients. The overall response to ACE inhibitor monotherapy is lower in black (Afro-Caribbean) patients with hypertension (low renin population) than in white patients. Cough Cough has been reported during treatment with ACE inhibitors. The cough is unproductive, persistent and disappears after discontinuation of therapy. When making a differential diagnosis of cough in a patient, the possibility of its association with the use of ACE inhibitors should be taken into account. The 5 mg tablets contain the excipient Ponceau 4R (E 124), which may cause allergic reactions. Interactions with other drugs Contraindicated combinations Extracorporeal treatments that involve blood contact with negatively charged surfaces, such as dialysis or hemofiltration with high flow membranes (eg, polyacrylonitrile) and low-density lipoprotein (LDL) apheresis with dextran sulfate, should not be used during treatment with Ramipril, as this may lead to anaphylactoid reactions (see section Contraindications). If such treatment is needed, other types of filtration membranes and other (non-ACE inhibitor) classes of antihypertensive agents are used. Precautions in use Potassium salts, heparin, potassium-sparing diuretics and other substances that increase the concentration of potassium in the plasma (for example, ARA, trimethoprim, tacrolimus, cyclosporine, spironolactone): a more pronounced increase in the concentration of potassium in the blood serum (hyperkalemia). During concomitant treatment with these drugs, strict monitoring of serum potassium levels is necessary; antihypertensive agents (diuretics) and other substances that can lower blood pressure (eg, nitrates, tricyclic antidepressants, anesthetics, alcohol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin , terazosin): increased hypotensive effect of drugs Ramipril. The potential risk of hypotension should be excluded (see section Dosage and administration); vasopressive sympathomimetics and other substances (for example, isoproterenol, dobutamine, dopamine, adrenaline): the hypotensive effect of Ramipril may be weakened, careful monitoring of blood pressure is recommended; allopurinol, procainamide, cytostatics, immunosuppressants, systemic corticosteroids and other drugs that affect the blood picture: increased likelihood of hematological reactions (see section Precautions); lithium salts: ACE inhibitors can cause an increase in serum lithium concentrations, resulting in increased cardiotoxicity and lithium neurotoxicity ( regular monitoring of serum lithium levels is required); antidiabetic agents, including insulin: hypoglycemic reactions may occur. It is recommended to carry out especially careful monitoring of blood glucose levels; non-steroidal anti-inflammatory drugs, painkillers and acetylsalicylic acid: it is possible to weaken the hypotensive effect of drugs Ramipril; possible increased risk of impaired renal function and an increase in serum potassium concentration; “mTOR (mammalian Target of Rapamycin) – inhibitors (estramustine, everolimus, sirolimus) or vildagliptin: with simultaneous use, an increase in the incidence of angioedema may occur. Contraindications Hypersensitivity to the active substance ramipril and other components of the drug or other ACE inhibitors; patients who, according to the anamnestic data, have previously experienced angioedema (hereditary, idiopathic or due to the use of ACE inhibitors); extracorporeal treatments, during which blood comes into contact with negatively charged surfaces (see. section Interaction with other medicinal products and other forms of interaction); established renal artery stenosis (bilateral, in the case of one kidney – unilateral); pregnancy and lactation (see sections Precautions, Pregnancy and feeding breastfeeding); in combination with drugs containing Aliskiren, in patients with diabetes mellitus or with moderate / severe renal insufficiency (GFR < 60 ml / min / 1.73 m2). age up to 18 years (efficacy and safety have not been established). Ramipril should not be administered to patients with low blood pressure or hemodynamically unstable condition. Composition 10 mg tablet contains - active ingredient: ramipril - 10 mg; excipients: starch 1500 (corn starch partially pregelatinized), hydroxypropyl methylcellulose, sodium stearyl fumarate, monocrystalline cellulose. Overdose Symptoms of intoxication Symptoms associated with an overdose of ACE inhibitors may include: increased peripheral vasodilation (accompanied by hypotension, shock), bradycardia, electrolyte imbalance, renal failure. Patients should be monitored closely and treatment should be determined by the nature and timing of the drug and the type and severity of symptoms. In addition to general measures aimed at removing ramipril from the body (for example, gastric lavage, administration of adsorbents) and measures to restore hemodynamic stability, the use of alpha1 adrenergic agonists or angiotensin II may be required. Ramiprilat, the active metabolite of ramipril, is almost never dialyzed. Side effects During therapy with ramipril, side effects such as persistent dry cough and hypotensive reactions may occur. Serious adverse reactions include angioedema, hyperkalemia, deterioration of kidney and liver function, pancreatitis, some skin reactions, and neutropenia/agranulocytosis. The frequency of occurrence of adverse reactions is determined as follows: very frequent (> 1/10), frequent (> 1/100, <1/10), infrequent (> 1/1000, <1/100), rare (> 1/10000, <1/1000), very rare (<1/10000) and unknown (cannot be estimated from available data). Storage conditions In a place protected from light and moisture, at a temperature not exceeding 25 ° C. Keep out of the reach of children. Buy Ramipril tablets 10mg No. 10x3 Price for Ramipril tablets 10mg No. 10x3