Index of drugs

Treatment of hypertension. Prevention of cardiovascular disease: reduction of cardiovascular morbidity and mortality in patients with overt atherosclerotic cardiovascular disease (ischemic heart disease or history of stroke or peripheral vascular disease) or with diabetes and at least one risk factor for systemic diseases cardiovascular. Treatment of kidney disease: the beginning of diabetic glomerular nephropathy characterized by microalbuminuria; overt diabetic glomerular nephropathy, characterized by macroproteinuria in patients with at least one risk factor for cardiovascular disease; overt glomerular nephropathy, non-diabetic, characterized by proteinuria ≥ 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 symptoms of heart failure - the preparation should be included in the treatment within> 48 h after the onset of acute myocardial infarction (from day 3 after myocardial infarction).

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

Ramipril is converted into the active metabolite, ramipril, 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 degradation lead to vasodilatation. Ramiprillat reduces the secretion of aldosterone. After oral administration, ramipril is rapidly absorbed (food does not affect absorption), reaching 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, about 56% ramipril. Metabolites are mainly excreted by the kidneys. After repeated doses of ramipril taken once a day, 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 components of the preparation or other ACE inhibitors. History of angioneurotic edema (hereditary, idiopathic or resulting from prior therapy with an ACE inhibitor or angiotensin II receptor antagonist). Therapies based on extracorporeal circulation, in which blood is exposed to contact with negatively charged surfaces. Significant bilateral renal artery stenosis or one-sided stenosis in the only kidney. II and III trimester of pregnancy. Do not use in patients with hypotension or hemodynamic instability. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²).

Patients at special risk of hypotension (initial phase of treatment requires special supervision): patients with transient or persistent heart failure after myocardial infarction, patients at risk of ischemic heart or brain in case of acute hypotension and patients with strong activation of the renin system angiotensin-aldosterone system. In patients with markedly elevated activity of the renin-angiotensin-aldosterone system, there is a risk of a sudden and significant reduction in blood pressure and deterioration of renal function following the inhibition of angiotensin-converting enzyme. Especially if the ACE inhibitor or concomitant diuretic is given for the first time or when the dose is first increased. The following patients should be expected to undergo significant activation of the renin-angiotensin-aldosterone system and should be monitored, including blood pressure monitoring: patients with severe hypertension, uncompensated congestive heart failure, haemodynamically significant disturbances of inflow and outflow of blood from the left ventricle ( e.g. mitral or aortic valve stenosis), unilateral renal artery stenosis with the second active kidney, cirrhosis and / or ascites, patients who have or may be deficient in fluids or salts (including patients treated with diuretics), undergoing major surgery surgery or during anesthesia with agents that cause hypotension. It is recommended to correct dehydration, hypovolaemia or salt shortage before starting treatment (in patients with heart failure, the benefits of fluid administration should be carefully weighed against the risk of conduction). Use with caution in elderly patients.It is recommended to discontinue the use of ACE inhibitors, if possible, one day before surgery. You should check your kidney function and adjust your dose before and during your treatment, especially during the first weeks of treatment. Patients with impaired renal function require particularly close supervision. There is a risk of impaired renal function, especially in patients with congestive heart failure or kidney transplantation. In case of angioedema, the preparation should be discontinued and immediate treatment should be initiated. Intestinal angioedema was also observed. In the case of ACE inhibition, the likelihood of anaphylactic and anaphylactoid reactions to insect venom and other allergens increases. Temporary discontinuation of the drug should be considered before desensitization. Use with caution in patients at risk of hyperkalaemia: patients with renal failure, elderly (> 70 years old), uncontrolled diabetes, taking potassium salts, potassium sparing diuretics and other active substances that increase plasma potassium levels or with conditions such as dehydration , acute heart failure, metabolic acidosis. The white blood cell count should be monitored to detect any leucopenia occurring. Control should be more frequent in the initial phase of treatment and in patients with impaired renal function, with co-existing vascular collagenosis (eg lupus erythematosus and scleroderma) and when concomitant use of other drugs that may cause changes in the blood picture. ACE inhibitors are more likely to cause angioneurotic edema in black patients than in other breeds. Ramipril may be less effective in lowering blood pressure in black patients than in non-black patients. As part of the differential diagnosis of cough, the possibility of cough caused by an ACE inhibitor should be considered. The safety, efficacy and dosage of ramipril in children have not been established. 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. Due to the lactose content of 2.5 mg and 5 mg tablets, they should not be given to patients with hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

The preparation is not recommended during the first trimester of pregnancy (there is a risk of teratogenic effects). The drug is contraindicated in the second and third trimester of pregnancy. Treatment with ACE inhibitors during the second and third trimester of pregnancy leads to toxic effects on the human fetus (decreased renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, hypotension, hyperkalemia). If there is exposure to ACE inhibitors from the beginning of the second trimester of pregnancy, it is recommended to perform ultrasound examination of the skull and renal function. Infants of mothers receiving ACE inhibitors should be carefully monitored for hypotension. The drug is not recommended during breast-feeding.

Common: pain and dizziness; dry, irritating cough, bronchitis, sinusitis, dyspnea; gastroenteritis, digestive disorders, abdominal pain, dyspepsia, diarrhea, nausea, vomiting; rash (especially maculopapular), muscle spasms, muscle pain; hyperkalemia; hypotension, decrease in orthostatic pressure, fainting, chest pain, fatigue. Uncommon: ischemic heart disease (including angina pectoris or myocardial infarction), tachycardia, arrhythmias, palpitations, edema of peripheral tissues; eosinophilia; paresthesia, loss of taste, distortion of taste sensation; visual impairment (including blurred vision); bronchospasm (including severity of asthma), rhinitis; pancreatitis (very rare cases of deaths), increase in pancreatic enzymes, angioedema of the intestines,pain in the upper abdomen (including gastritis), constipation, dry mouth; impaired renal function (including acute renal failure), increased urine output, worsening of pre-existing proteinuria, increased blood urea, increased serum creatinine; angioedema (very rare cases of death due to airway obstruction caused by angioneurotic edema), pruritus, profuse sweating; arthralgia; anorexia, decreased appetite; sudden redness of the skin; fever; increase in liver enzymes and / or serum bilirubin; transient impotence, lowering of libido; mood depression, anxiety, nervousness, movement excitability, sleep disorders (including insomnia). Rare: decrease in the number of white blood cells (including neutropenia or agranulocytosis), decrease in the number of red blood cells, decrease in hemoglobin, thrombocytopenia; tremor, balance disorders, conjunctivitis; impaired hearing, tinnitus; tongue inflammation; exfoliative dermatitis, urticaria, separation of nails from the matrix; vasoconstriction, hypoperfusion, vasculitis; asthenia; cholestatic jaundice, hepatocellular damage; state of entanglement. Very rare: hypersensitivity to light. Not known: bone marrow suppression, pancytopenia, haemolytic anemia; anemia of the brain (including ischemic stroke and transient ischemic episode), impaired psychomotor performance, burning sensation, olfactory dysfunction; aphthous stomatitis; toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, exacerbation of psoriasis, hair loss, psoriatic-like lesions, pemphymat-like or lichen-like rash on the skin or mucous membranes, alopecia; hyponatremia; Raynaud's syndrome; anaphylactic or anaphylactoid reactions, the presence of anti-nuclear antibodies; acute hepatic failure, cholestatic or cytolytic hepatitis (very rare cases of death); gynecomastia; concentration disorders. The nature and severity of adverse events in children (from 2 to 16 years) are similar to adult patients, with the incidence of the following side effects being higher in children: often - tachycardia, nasal congestion and runny nose, conjunctivitis, uncommon - tremors, hives. The general safety profile of ramipril in pediatric patients is not significantly different from the safety profile observed among adults.

Orally. Adults.Hypertension. Individually depending on the patient's characteristics and blood pressure. The drug can be used alone or in combination with antihypertensive drugs from other groups. The starting dose is 2.5 mg a day. The dose should be increased gradually. 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 cardiovascular diseases. 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.Patients with diabetes and 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.Patients with diabetes and at least one risk factor for cardiovascular disease. 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 per day.Patients with non-diabetic glomerular nephropathy and macroproteinuria ≥ 3 g per 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. For stable patients treated with diuretics, the recommended starting dose is 1.25 mg daily. 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 2 times daily for 2 days should be given, followed by a dose increase to 2.5 mg and 5 mg twice 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 treatment of patients with severe (NYHA IV) heart failure immediately after the heart attack, if a decision is taken to treat patients in this group, it is recommended to start treatment with a dose of 1.25 mg once a day, taking particular care when increasing the dose.Special groups of patients. In patients treated with diuretics, if possible, the diuretic should be discontinued 2-3 days prior to 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. Later, the dosage of the drug should be adjusted to the target blood pressure. 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, the starting doses should be smaller and slower, especially in very old and weak patients; the initial dose of 1.25 mg should be considered. The tablets should be taken at the same time of the day, regardless of meals, with liquid. The tablets can not be chewed and chewed.