Index of drugs

Treatment of hypertension. Prevention of cardiovascular disease: reduction of cardiovascular morbidity and mortality in patients with overt cardiovascular disease with atherosclerotic atherosclerosis (coronary disease or stroke or a history of peripheral vascular disease) or with diabetes mellitus and at least one cardiovascular disease vascular risk factor. Treatment of renal diseases: initial stage of diabetic glomerular nephropathy determined by the presence of microalbuminuria, overt diabetic glomerular nephropathy diagnosed on the basis of proteinuria in patients with at least one cardiovascular risk factor, overt non-diabetic glomerular nephropathy with macroproteinuria ≥ 3 g / day. Treatment of symptomatic heart failure. Secondary prevention after acute myocardial infarction: reduction of mortality in the acute phase of myocardial infarction in patients with clinical manifestations of heart failure; treatment should begin at least 48 hours after the onset of acute myocardial infarction.

1 tabl contains 2.5 mg, 5 mg or 10 mg ramipril. The tablets contain lactose.

Ramipril is converted into the active metabolite - ramiprilat - an ACE inhibitor (an enzyme that catalyzes the conversion of angiotensin I to angiotensin II, as well as the breakdown of bradykinin). Reduction of angiotensin II production and inhibition of bradykinin breakdown leads to vasodilatation. It also reduces the secretion of aldosterone. The onset of antihypertensive effect occurs within 1-2 h after administration, the maximum effect is observed after 3-6 h, and the effect of one dose is usually maintained for 24 h. After oral administration, ramipril is rapidly absorbed (food does not affect absorption) and achieves C_max within 1 h. The bioavailability of the active metabolite ramiprilat is 45%. Ramiprylat reaches C_max within 2-4 h after ramipril administration. Ramipril is approximately 73% bound to plasma proteins, ramipril is approximately 56% bound. Ramipril is almost completely metabolised to ramiprilat and further to other derivatives. Metabolites are mainly excreted by the kidneys. Effective T_0,5 ramiprilat is 13-17 h for doses of 5-10 mg, it is longer for smaller doses of 1.25-2.5 mg.

Hypersensitivity to ramipril, other ACE inhibitors or other components of the preparation. History of angioneurotic edema (hereditary, idiopathic or as a result of previous vasomotor edema after administration of ACE inhibitors or angiotensin II receptor antagonists). Extracorporeal procedures in which blood is exposed to surfaces with a negative electric charge. Significant bilateral renal artery stenosis or renal artery stenosis of the only active kidney. II and III trimester of pregnancy. Ramipril should not be used in patients with hypotension or haemodynamically unstable patients. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²).

Use with caution in patients with elevated renin-angiotensin-aldosterone system activity due to the risk of significant decreases in blood pressure and renal function impairment, especially if the ACE inhibitor or concomitant diuretic is given for the first time or for the first time at an increased dose (indispensable there is medical supervision, including blood pressure monitoring) - this applies to patients with severe hypertension; with decompensated congestive heart failure; hemodynamically significant impairment of inflow or outflow from the left ventricle (eg aortic or mitral valve stenosis); with unilateral renal artery stenosis and a second active kidney; with existing or potentially deficient intravascular volume or electrolytes (including patients treated with diuretics); with cirrhosis and / or ascites; undergoing major surgery or anesthetized agents that may cause hypotension. Before starting treatment, dehydration, hypovolaemia or electrolyte deficiencies should be corrected (in patients with heart failure, consideration should be given to undertaking the above actions in relation to the risk of volume overload).In addition, caution should be used in patients with transient or persistent heart failure after myocardial infarction, in patients with an increased risk of myocardial or cerebral ischaemia (the initial phase of treatment requires special medical supervision) and in elderly patients. It is recommended to discontinue treatment with ACE inhibitors the day before surgery. Before using ramipril, renal function should be evaluated and monitored during treatment, adjusting the dosage based on the results obtained, especially in the first weeks of treatment. Particularly accurate monitoring is required in patients with impaired renal function. There is a risk of renal dysfunction, especially in patients with congestive heart failure or after kidney transplantation. The likelihood of anaphylactic and anaphylactoid reactions appearing and intensifying on insect venom and other allergens increases under the influence of ACE inhibition. Temporary discontinuation of the preparation before desensitization should be considered. Caution in patients with risk of hyperkalemia (with renal insufficiency, age> 70 years, with uncontrolled diabetes mellitus, taking potassium salts, potassium sparing diuretics and other substances that increase blood potassium levels, dehydrated, with acute heart failure or metabolic acidosis) - control the concentration of potassium in the blood. It is recommended to monitor the number of white blood cells to detect possible leukopenia. More frequent monitoring is recommended in the initial phase of treatment and in patients with impaired renal function, patients with concomitant collagenosis (eg lupus erythematosus or scleroderma) and patients treated with medications that may cause changes in blood counts. In case of angioedema, the preparation should be discontinued. Intestinal angioneurotic edema has been observed in patients treated with ACE inhibitors. ACE inhibitors are more likely to cause angioneurotic edema in black patients than in non-black patients. Ramipril may be less effective in reducing blood pressure in black patients than in other breeds. The cough caused by ACE inhibitors should be taken into account in the differential diagnosis of cough. The concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalaemia and renal dysfunction (including acute renal failure) - therefore, dual blocking of the RAA system is not recommended by concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren. If the use of a dual RAA blockade is absolutely necessary, it should only be carried out under the supervision of a specialist, and the vital parameters of the patient, such as kidney function, electrolyte concentration and blood pressure should be closely monitored. In patients with diabetic nephropathy, ACE inhibitors and angiotensin II receptor antagonists should not be used concurrently. There are no data on the safety and efficacy of the preparation in patients <18 years - not recommended. Due to the lactose content, do not use the preparation in patients with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

The use of the preparation in the first trimester of pregnancy is not recommended (there is a risk of teratogenic effect). Use in the second and third trimester of pregnancy is contraindicated. Ramipril used in the second and third trimester of pregnancy is toxic to fetal development (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and newborn (renal failure, hypotension, hyperkalemia) - when exposure to the drug occurred from the second or third trimester of pregnancy Ultrasound of the skull and kidneys is recommended; newborns whose mothers took the drug during pregnancy should be closely monitored for hypotension, oliguria and hyperkalemia. The drug is not recommended during breast-feeding.

Common: pain and dizziness, dry cough with a feeling of tickling in the throat, bronchitis, paranasal sinusitis, dyspnoea, gastroenteritis, digestive disorders, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting, rash (especially spotting) follicular), muscle spasms, muscle pain, hyperkalemia, hypotension, orthostatic hypotension, syncope, chest pain, fatigue.Uncommon: myocardial ischaemia (including angina pectoris or myocardial infarction), tachycardia, arrhythmia, palpitations, peripheral edema, eosinophilia, paresthesia, loss of taste, disturbed taste, blurred vision (including blurred vision), bronchospasm (in including exacerbation of asthma symptoms), nasal mucosal edema, pancreatitis (very occasionally fatal cases), increased pancreatic enzyme activity, angioedema of the small intestine, epigastric pain, gastritis, constipation, dry mouth, renal dysfunction ( including acute renal failure), increased urine output, exacerbation of pre-existing proteinuria, increased urea and creatinine concentration in the blood, angioneurotic edema (in exceptional cases, narrowing of the airways caused by angioedema, which may result in death), pruritus, hyperhidrosis, pain st aws, anorexia, decreased appetite, hot flushes, fever, increased activity of hepatic enzymes and / or conjugated bilirubin, transient impotence, decreased libido, mood depression, anxiety, nervousness, restlessness, sleep disorders (including drowsiness). Rare: leukopenia (including neutropenia or agranulocytosis), reduced number of erythrocytes, decreased hemoglobin, decreased platelet count, tremor, balance disorders, conjunctivitis, hearing disorders, tinnitus, tongue inflammation, exfoliative dermatitis, urticaria, onycholysis, narrowing vascular, tissue hypoperfusion, vasculitis, asthenia, cholestatic jaundice, hepatocyte damage, confusion. Very rare: hypersensitivity to light. Not known: bone marrow failure, pancytopenia, haemolytic anemia, cerebral ischemia (including ischemic stroke and transient ischemic attack), impaired psychomotor ability, burning sensation, olfactory disorders, aphthous stomatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, exacerbation of psoriasis, exfoliative dermatitis, alveolar or lichenoid rash on the skin or mucous membrane, alopecia, hyponatremia, Raynaud's phenomenon, anaphylactic or anaphylactoid reactions, increased antinuclear antibody titres, acute liver failure, cholestatic or cytolytic hepatitis (extremely rarely deaths), gynecomastia, attention disorders.

Orally. Adults.Hypertension. Individually depending on the patient's clinical characteristics and blood pressure control. The drug can be used alone or in combination with antihypertensive drugs from other groups. The starting dose is 2.5 mg a day. In the group of patients with strong activation of the renin-angiotensin-aldosterone system, the blood pressure may be overtaxed after the initial dose. In this group of patients the initial dose is 1.25 mg and treatment should be started under medical supervision. The dose can be doubled at an interval of 2-4 weeks to reach your blood pressure target. The maximum dose is 10 mg a day. The drug is usually dosed once a day.Prevention of diseases of the cardiovascular system. The starting dose is 2.5 mg once a day. The dose should be increased gradually: it is recommended to double the dose after 1-2 weeks of treatment, and after 2-3 weeks, increase to the target maintenance dose of 10 mg once a day.The initial stage of diabetic glomerular nephropathy determined by the presence of microalbuminuria. The starting dose is 1.25 mg once a day. The dose should be increased gradually: it is recommended to double the dose to 2.5 mg once a day for 2 weeks and then to 5 mg for a further 2 weeks.Non-clinical diabetic glomerular nephropathy ascertained on the basis of proteinuria in patients with at least one cardiovascular risk factor. The starting dose is 2.5 times a day. The dose should be increased gradually: it is recommended to double the dose to 5 mg once a day for 1-2 weeks, and then to 10 mg for the Next 2-3 weeks. The target dose is 10 mg.Public non-diabetic glomerular nephropathy with macroproteinuria ≥3 g / day. The starting dose is 1.25 mg once a day. The dose should be increased gradually: it is recommended to double the dose to 2.5 mg once a day for 2 weeks and then to 5 mg for a further 2 weeks.Symptomatic heart failure. In stable patients treated with diuretics, the recommended starting dose is 1.25 mg once a day.Dose titration should be carried out every 1-2 weeks, up to a maximum dose of 10 mg. It is recommended to administer the preparation twice a day.Secondary prevention after acute myocardial infarction with heart failure. In a patient clinically and haemodynamically stable after 48 hours from myocardial infarction, the starting dose is 2.5 mg 2 times a day for 3 days. If the initial 2.5 mg dose is not tolerated, 1.25 mg twice daily for 2 days should be used prior to increasing the dose to 2.5 mg, followed by 5 mg 2 times daily. If the dose can not be increased to 2.5 mg 2 times daily, treatment should be discontinued. The daily dose should be doubly doubled at intervals of 1-3 days until a maintenance dose of 5 mg 2 times a day is achieved. Whenever possible, the maintenance dose should be administered in 2 doses. There is insufficient data on the management of patients with severe (NYHA IV) heart failure immediately after the heart attack, if a decision is taken to treat patients in this group, starting with a 1.25 mg dose once a day is recommended and special care should be taken when increasing the dose.Special groups of patients. If possible, the diuretic should be discontinued 2-3 days before beginning treatment with ramipril. In patients with hypertension who have not been discontinued, ramipril should be initiated at a dose of 1.25 mg. Renal function and potassium levels should be monitored. The further dosage of the preparation should be determined depending on the blood pressure target. In patients with impaired renal function, the daily dose should be determined on the basis of creatinine clearance: creatinine clearance ≥60 ml / min initial dose unchanged (2.5 mg / day), maximum daily dose 10 mg; creatinine clearance 30-60 ml / min initial dose unchanged (2.5 mg / day), maximum daily dose 5 mg; creatinine clearance 10-30 ml / min initial dose 1.25 mg / day, maximum daily dose 5 mg; in hemodialyzed hypertensive patients, the initial dose is 1.25 mg / day and the maximum daily dose of 5 mg, the drug should be administered several hours after hemodialysis. In patients with hepatic impairment, treatment should be started under strict medical supervision and the maximum daily dose is 2.5 mg. In elderly patients, starting doses should be smaller and slower, the initial dose of 1.25 mg should be considered. The tablets can be taken with or without food, with liquid. It is recommended to take tablets at the same time of the day.