Index of drugs

Treatment of hypertension. Prevention of cardiovascular diseases: reduction of morbidity and mortality from cardiovascular causes in patients with: overt cardiovascular disease with atherosclerotic atherosclerosis (ischemic heart disease, stroke or peripheral vascular disease) or at least one cardiovascular risk factor. Treatment of kidney diseases: the initial stage of diabetic glomerulopathy as determined by the occurrence of microalbuminuria; overt diabetic glomerulopathy found on the basis of proteinuria in patients with at least one cardiovascular risk factor; overt glomerulopathy with non-diabetic etiology ascertained on the basis of proteinuria ≥3 g / day. Treatment of symptomatic heart failure. Secondary prevention in patients after acute myocardial infarction: reduction of mortality in the acute phase of myocardial infarction in patients with clinical symptoms of heart failure - the drug should be included in the treatment within> 48 h after the onset of acute myocardial infarction.

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

Ramipril is converted into the active metabolite, ramipril, an ACE inhibitor (an enzyme that catalyzes the conversion of angiotensin I to vasopressor angiotensin II, as well as the breakdown of bradykinin acting vasoconstrictor). Reduction of angiotensin II production and inhibition of bradykinin degradation leads to vasodilatation. Administration of ramipril leads to a reduction in the secretion of aldosterone. In hypertensive patients, hypotension leads to hypotension in a supine and standing position without a compensatory increase in heart rate. The onset of antihypertensive effect occurs within 1-2 h after drug administration, maximum effect is observed after 3-6 h, and the effect of one drug dose is usually maintained for 24 h. 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%. C_max ramiprilat reaches 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. After repeated doses of ramipril taken once a day, 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, caused by prior use of ACE inhibitors or angiotensin II receptor antagonists). Extracorporeal therapeutic procedures leading to blood contact with surfaces with negative electric charge. Significant bilateral renal artery stenosis or artery stenosis of the only active kidney. II and III trimester of pregnancy. Do not use in patients with hypotension or hemodynamic instability. Concomitant use of aliskiren-containing products in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²).

Use with caution in patients with increased activation of the renin-angiotensin-aldosterone system due to the risk of significant decreases in blood pressure and impaired renal function (medical monitoring is necessary, including monitoring of blood pressure, especially during the initial phase of treatment or after changing the dose) - 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 with a second active kidney; with existing or possibly occurring fluid and electrolyte imbalances (including patients taking diuretics); with cirrhosis and / or ascites; undergoing major surgery or anesthetized agents that may cause hypotension (it is recommended to discontinue treatment with an ACE inhibitor one day before surgery). Electrolyte deficiency and / or hypovolaemia should be corrected before initiating therapy, however, in patients with heart failure, consideration should be given to the benefits of fluid delivery in relation to the risk of volume overload.In patients with transient or chronic heart failure after myocardial infarction and in patients who are at risk of ischemic heart or brain in severe hypotension, the initial phase of treatment with the preparation requires special medical supervision. Prior to the use of ramipril, renal function should be evaluated and monitored during treatment; Patients with impaired renal function require particularly careful monitoring. There is a risk of renal dysfunction during use, especially in patients with congestive heart failure or after kidney transplantation. The number of leukocytes should be monitored to detect possible leukopenia; more frequent controls are 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 who are taking other medicines that can change the blood picture. Use with caution in patients at risk of hyperkalemia (with renal insufficiency, age> 70 years, with uncontrolled diabetes mellitus, taking potassium salts, potassium sparing diuretics and other substances that increase potassium in the blood, as well as in dehydrated patients with acute heart failure or exacerbation chronic heart failure, metabolic acidosis) - control the level of potassium in the blood. Due to the risk of anaphylactic and anaphylactoid reactions occurring and intensifying on insect venom and other allergens, a temporary discontinuation of the ACE inhibitor against desensitization should be considered. The preparation should be discontinued in case of angioedema and ad hoc treatment should be started in a hospital setting. In differential diagnosis of abdominal pain, angioedema of the intestines should be considered. Angioedema caused by ACE inhibitors is more common in the black patients. ACE inhibitors may be less effective in lowering blood pressure in black patients. In the differential diagnosis of cough, cough induced by ACE inhibitors should be considered. The safety and efficacy of ramipril in children has not yet 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 the 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, 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 trimester of pregnancy, it is recommended an ultrasound examination of the fetus skull and kidneys; children whose mothers took the drug during pregnancy should be closely monitored for hypotension, oliguria and hyperkalemia. The drug is not recommended during breastfeeding, especially breastfeeding a newborn or premature baby.

Common: increased potassium in the blood, headache, dizziness, hypotension, orthostatic hypotension, syncope, unproductive irritant cough, bronchitis, paranasal sinusitis, dyspnoea, gastrointestinal mucositis, digestive disorders, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting, rash (especially maculopapular), muscle cramps, muscle pain, chest pain, fatigue. Uncommon: eosinophilia, anorexia, decreased appetite, mood depression, anxiety disorders, nervousness, anxiety (especially motor), sleep disorders (including drowsiness), dizziness, paresthesias,loss of taste, disturbed taste, blurred vision (including blurred vision), myocardial ischemia (including angina pectoris or myocardial infarction), tachycardia, arrhythmia, palpitations, peripheral edema, hot flushes, bronchospasm (including exacerbation) symptoms of asthma), nasal mucosal edema, pancreatitis (occasionally fatal cases), increased pancreatic enzyme activity, angioneurotic edema of the small intestine, epigastric pain (including gastritis), constipation, dry mouth, increased activity of enzymes hepatic and / or conjugated bilirubin, angioneurotic edema (in exceptional cases, narrowing of the airways caused by angioedema may result in death), pruritus, excessive sweating, joint pain, impaired renal function (including severe renal failure), polyuria, worsening of previous existing white in the blood, elevated blood creatinine, transient impotence, decreased libido, fever. Rare: reduced number of white blood cells (including neutropenia or agranulocytosis), reduced number of erythrocytes, decreased hemoglobin, decreased platelet count, disturbed consciousness, tremor, balance disorders, conjunctivitis, impaired hearing, tinnitus, vasoconstriction, hypoperfusion, inflammation vasculitis, cholangitis, cholestatic jaundice, hepatocyte damage, exfoliative dermatitis, urticaria, onycholysis, asthenia. Very rare: hypersensitivity to light. Not known: marrow aplasia, pancytopenia, haemolytic anemia, anaphylactic or anaphylactic reactions, elevated antinuclear antibodies, decreased sodium in the blood, attention deficits, central nervous system ischemia (including ischemic stroke and transient ischemic attack), psychomotor disorder, feeling burning, olfactory disorders, Raynaud's phenomenon, aphthous stomatitis, severe hepatic failure, cholestatic or cytolytic hepatitis (extremely rarely fatal), toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, exacerbation of psoriasis, psoriasis-like inflammation skin, bullous rash or lichenoid on the skin or mucous membranes, hair loss, gynecomastia.

Orally. Adults.Hypertension. Individually depending on the patient's profile 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 overemphasized after the initial dose; in this group of patients the initial dose is 1.25 mg and the treatment should be started under the supervision of a physician. The dose may be doubled in the period from 2 to 4 weeks to achieve the target blood pressure. The maximum dose is 10 mg / day. The drug is usually given 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 depending on the patient's tolerance. It is recommended to double the dose after 1-2 weeks of treatment, and after the Next 2-3 weeks increase to the target maintenance dose of 10 mg once a day.Treatment of kidney disease in diabetic patients with microalbuminuria. The starting dose is 1.25 mg once a day. The dose should be gradually increased. It is recommended to double the dose to 2.5 mg once daily after the second week of treatment, and then to 5 mg after the next 2 weeks.Treatment of kidney disease in diabetic patients with at least one cardiovascular risk factor. The starting dose is 2.5 mg once a day. The dose should be increased gradually depending on the patient's tolerance. It is recommended to double the dose to 5 mg once a day after 1-2 weeks of treatment, and then to 10 mg after the next 2-3 weeks. The target dose is 10 mg / day.Nephropathy for non-diabetic etiology based on proteinuria ≥ 3 g / day. The starting dose is 1.25 mg once a day. The dose should be gradually increased. It is recommended to double the dose to 2.5 mg once daily after the second week of treatment, and then to 5 mg after the next 2 weeks.Symptomatic heart failure. For stable patients whose condition has been stabilized with a diuretic, 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 / day. It is preferred to administer the preparation in two divided doses.Secondary prophylaxis after acute myocardial infarction with heart failure. In a patient clinically and haemodynamically stable after 48 hours from an acute myocardial infarction, the starting dose is 2.5 mg 2 times a day for 3 days. If the initial 2.5 mg dose is poorly 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 to 3 days until the target dose of 5 mg 2 times a day. Whenever possible, the maintenance dose should be administered in 2 divided 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 (care should be taken when increasing doses).Special groups of patients. Patients treated with diuretics may experience hypotension after switching to ramipril. If possible, diuretics should be discontinued 2-3 days before treatment with ramipril. In patients with hypertension who are undergoing diuretics, ramipril should be started with a 1.25 mg dose. 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 renal impairment, the daily dose should be determined on the basis of creatinine clearance (CCr) - CCr ≥ 60 ml / min: initial dose unchanged, maximal daily dose 10 mg; CCr 30-60 ml / min: initial dose unchanged, maximum daily dose 5 mg; CCr 10-30 ml / min: initial dose 1.25 mg / day, maximum daily dose of 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 less, and increasing doses more gradually, the initial dose of 1.25 mg should be considered.Way of giving. Tablets may be taken before, during or after a meal, and should be given with liquids at the same time of the day. The tablets should not be crushed or chewed.