Index of drugs

Treatment of hypertension. Prevention of cardiovascular disease: reduction of morbidity and mortality from cardiovascular causes in patients with overt cardiovascular disease with atherosclerotic disease (ischemic heart disease or stroke or peripheral vascular disease) or with at least one cardiovascular factor risk. Treatment of kidney disease: the initial stage of diabetic glomerular nephropathy determined by the presence of microalbuminuria; overt diabetic nephropathy ascertained on the basis of proteinuria in patients with at least one cardiovascular risk factor; overt glomerular nephropathy with non-diabetic etiology based on 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 (from the third day after the infarction).

1 tabl contains 2.5 mg, 5 mg or 10 mg ramipril.

Ramipril is converted in the liver to ramiprilat, which is an inhibitor of the angiotensin-converting enzyme - an enzyme that catalyzes the conversion of angiotensin I to angiotensin II in tissues and tissues, and the degradation of bradykinin, which causes vasodilatation. Ramipril also reduces the secretion of aldosterone. In hypertensive patients, ramipril causes lowering of blood pressure in supine and standing position without compensatory increase of cardiac function. It reduces the peripheral vascular resistance. The onset of antihypertensive activity occurs in most patients about 1-2 hours after drug administration. The maximum effect after a given dose usually occurs after 3-4 weeks. In patients with heart failure ramipril, ramipril has been shown to have a beneficial effect on haemodynamics in the heart (reduced left and right ventricular filling pressure, decreased total peripheral vascular resistance, increased minute capacity and a better cardiac index). ). It also reduces neuroendocrine activation. After oral administration, ramipril is rapidly absorbed from the gastrointestinal tract (food does not affect absorption). The bioavailability of ramiprilat after oral administration of 2.5 mg and 5 mg ramipril is 45%. The binding of ramipril to plasma proteins is 73% and ramiprilat is approximately 56%. Ramipril is almost completely hydrolyzed to ramiprilat. Metabolites are mainly excreted by the kidneys. After multiple 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. In patients with renal insufficiency, renal excretion of ramiprilat decreases.

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. Patients with hypotonia and haemodynamically unstable patients. II and III trimester of pregnancy. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²).

In patients with increased activation of the renin-angiotensin-aldosterone system, there is an increased 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 and after the first dose increase (these patients require medical supervision including monitoring blood pressure): patients with severe hypertension, with decompensated congestive heart failure, hemodynamically significant impairment of inflow or outflow from the left ventricle (e.g.stenosis of aortic or mitral valve), unilateral renal artery stenosis with second active kidney, cirrhosis and / or ascites, patients with or with dehydration or hyponatremia (including patients treated with diuretics) and patients undergoing major surgery or anesthesia agents that can cause hypotension. It is recommended to correct dehydration, hypovolaemia or sodium deficiency before starting treatment (in patients with heart failure, consideration should be given to undertaking the above measures taking into account the risk of volume overload). Caution in other patients at increased risk of hypotension: patients with transient or permanent heart failure after myocardial infarction, increased risk of myocardial ischemia or brain in case of acute hypotension (initial phase of treatment requires special medical supervision) and in elderly patients. Angiotensin converting enzyme inhibitors should be discontinued the day before surgery. Particularly cautiously used in patients with impaired renal function. Due to the risk of anaphylactic and anaphylactoid reactions appearing and intensifying on insect venom and other allergens, one should consider temporary discontinuation of the preparation before desensitization. Caution in patients at increased risk of hyperkalemia: patients with renal failure, poorly controlled diabetes, taking potassium salts, potassium-containing diuretics and other substances that increase blood potassium levels, patients with dehydration, patients> 70 years and patients with acute heart failure , acute exacerbation of chronic heart failure or metabolic acidosis - these patients should be regularly monitored for potassium in the blood. 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. 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. The safety and efficacy of ramipril in children have not been established, and no precise recommendations have been made regarding the dosage regimen.

The preparation is not recommended in the first trimester of pregnancy and is contraindicated in the second and third trimester of pregnancy. Treatment with ACE inhibitors during the second and third trimesters of pregnancy leads to toxic effects on the human fetus (decreased renal function, oligohydramnios, delayed ossification of the bone of the skull cover) and the newborn (renal failure, hypotension, hyperkalemia). If exposure to ACE inhibitors occurs from the beginning of the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Newborns of mothers taking ACE inhibitors should be observed towards hypotension. Ramipril is not recommended during breast-feeding.

Common (≥1 / 100, <1/10): pain and dizziness, irritant cough, bronchitis, paranasal sinusitis, dyspnoea, gastrointestinal mucositis, digestive disorders, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting, rash (especially maculopapular), muscle cramps, myalgia, hyperkalemia, hypotension, orthostatic hypotension, fainting, chest pain, fatigue. Uncommon (≥1 / 1000, <1/100): myocardial ischaemia (including angina pectoris or myocardial infarction), tachycardia, arrhythmias, palpitations, peripheral edema, eosinophilia, paresthesia, lack or disorder of taste, dysfunction vision (including blurred vision), bronchospasm (including exacerbation of asthma symptoms), nasal mucosal edema, pancreatic disorders (occasionally deaths), elevated pancreatic enzymes, angioedema of the small intestine, epigastric pain, gastritis, constipation,dryness of the oral mucosa, impaired renal function (including acute renal failure), polyuria, exacerbation of pre-existing proteinuria, elevated urea nitrogen and creatinine concentration in the blood, angioedema (in exceptional cases, deaths), pruritus, excessive sweating, painful joints, anorexia, decreased appetite, hot flushes, fever, increased transaminase and / or conjugated bilirubin, transient impotence, decreased libido, depressed mood, anxiety disorders, nervousness, anxiety (especially motor), sleep disorders (including drowsiness). Rare (≥1 / 10,000, <1/1000): leukopenia (including neutropenia or agranulocytosis), decreased erythrocyte count, decreased hemoglobin, decreased platelet count, tremor, disturbed balance, conjunctivitis, hearing impairment, tinnitus, inflammation of the tongue, exfoliative dermatitis, urticaria, separation of the nail from the placenta, vasoconstriction, hypoperfusion, vasculitis, asthenia, cholestatic jaundice, hepatocyte damage, disturbance of consciousness. Very rare (<1 / 10,000): hypersensitivity to light. In addition, bone marrow aplasia, pancytopenia, haemolytic anemia, ischemia o.u.n. (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, psoriasis-like dermatitis, bullous rash or lichen on the skin or mucous membrane, hair loss, hyponatraemia, Raynaud's phenomenon, anaphylactic and anaphylactoid reactions, elevated antinuclear antibodies, acute liver failure, cholestatic or cytolytic hepatitis (very rarely deaths), gynecomastia, attention deficit. There is a risk of renal dysfunction, especially in patients with congestive heart failure or after kidney transplantation.

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 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 may be doubled in the period from 2 to 4 weeks to achieve the target blood pressure. 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.Common diabetic nephropathy based on 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 glomerular nephropathy with non-diabetic etiology ascertained on the basis of proteinuria ≥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. For stable patients whose condition has been stabilized with a diuretic, the recommended starting dose is 1.25 mg once a day. Doubling should be done every 1-2 weeks, up to a maximum dose of 10 mg. It is preferred to administer the product in 2 doses.Secondary prevention 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 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 made to treat patients in this group, a starting dose of 1.25 mg once a day is recommended.
If possible, diuretics should be discontinued 2-3 days before treatment with ramipril. In patients with hypertension who are undergoing diuretics, ramipril should be initiated at a dose of 1.25 mg. 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 without changes (2.5 mg / day), the maximum daily dose of 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 less, and increasing doses more gradually, the initial dose of 1.25 mg should be considered.
The tablets can be taken with or without food, and they should be given with the liquids at the same time of the day. The tablets should not be crushed or chewed.