Ramipril is a synthetic drug that has the ability to reduce performance blood pressure. This drug has the ability to reduce vascular peripheral resistance and has a cardioprotective effect. The drug can significantly reduce the likelihood of death due to myocardial infarction and minimize the risk of recurrent infarction.

Dosage form

The drug Ramipril is produced by pharmaceutical companies in the form of tablets white, flat-cylindrical shape.

Description and composition

The active substance of the drug Ramipril is ramipril.

The list of auxiliary components can be presented as follows:

• microcrystalline cellulose,
• lactose,
• colloidal silicon dioxide,
• sodium carboxymethyl starch,
• magnesium stearate.

Pharmacological group

Ramipril acts as a prodrug from which the active metabolite ramiprilat is formed in the body. The principle of antihypertensive effect is closely related to the competitive inhibition of ACE activity, which leads to a decrease in the intensity of the conversion of angiotensin I to angiotensin II, which is a powerful vasoconstrictor component. Against the background of a decrease in the concentration of angiotensin II, a secondary increase in plasma renin activity occurs due to the removal of negative feedback during the release of renin and direct inhibition of aldosterone secretion. Due to vasodilation, peripheral peripheral resistance (afterload), wedge pressure in the pulmonary capillaries (preload) and resistance in the lungs are reduced. pulmonary vessels; increases cardiac output and stress resistance.

The drug helps patients who have suffered a myocardial infarction to prevent repeated risk manifestations of a dangerous condition. The product can significantly reduce the risk sudden death from pathologies of the heart and blood vessels. The hypotensive effect after oral consumption of the composition is observed after 1 hour, the effectiveness remains for 24 hours. The maximum effect occurs 3-6 hours after taking the product. The half-life of the active component from the patient’s body is 12 hours; for patients with a history of pathologies in the liver and kidneys, this period is slightly extended.

Indications for use

The list of indications for use is as follows:

• arterial hypertension;
• chronic heart failure;
• heart failure manifested after myocardial infarction;
• diabetic nephropathy;
• stroke;
• history of coronary artery bypass grafting;
• undergone coronary angioplasty.

for adults

If there are indications for use, the composition is used as prescribed by a doctor. There is a high tolerability of the drug.

for children

Ramipril is not used in pediatric practice. The medicinal composition is contraindicated in children under 18 years of age. The effect of the active component on the children's body has not been studied.

The composition is prohibited for use during pregnancy and breastfeeding. Medicine may cause the development of serious defects. The active component is absorbed into breast milk and can provoke the manifestation of various adverse reactions in a newborn.

Contraindications

The list of contraindications to the use of the composition is presented as follows:

• severe disturbances in the functioning of the liver and kidneys;
• bilateral stenosis renal artery;
• period after kidney transplantation;
• hyperkalemia;
• aortic stenosis;
• pregnancy period;
• breastfeeding period;
• childhood and adolescence;
• hypersensitivity to ramipril.

Applications and dosages

The medicine is intended for oral administration. Initial daily dose for the patient is 1.25-2.5 mg. A similar volume is taken 2 times a day. If necessary, the dose can be increased.

for adults

The dosage of Ramipril is determined individually by the attending physician for each patient. The dose may be adjusted depending on the patient’s well-being. To prevent the body from becoming accustomed to the product, it is recommended to take the minimum effective dose. It should be remembered that patients with impaired liver and kidney function require dose adjustment.

for children

Information confirming the safety of using the product in childhood– absent. The drug is prohibited for use by children under 18 years of age.

for pregnant women and during lactation

The drug should not be used during pregnancy. It is known that active ingredient successfully overcomes the placental barrier and can influence the processes of fetal formation. Studies confirming the safety of use medicinal composition were not carried out. The drug should not be taken during breastfeeding.

Side effects

The list of adverse reactions that occur during the use of the drug includes the following:

• hypotension;
• chest pain;
• tachycardia;
• weakness;
• headache;
• sleep disorders;
• stomach ache;
• cholestatic jaundice;
• diarrhea;
• nausea and;
• proteinuria;
• alopecia;
• muscle spasms;
• decreased potency.

Interaction with other drugs

Drug interactions:

1. When used in combination with potassium-sparing diuretics, hyperkalemia may develop.
2. When used with non-steroidal anti-inflammatory drugs, the antihypertensive effectiveness may be reduced.
3. When used with loop diuretics, the hypotensive effect is enhanced.
4. Comes into contact with insulin, hypoglycemia is likely to develop.
5. When used with lithium carbonate, an increase in lithium levels in the blood serum is possible.

Special instructions

In case of liver dysfunction, patients are advised to adjust doses in accordance with creatine clearance values. Before starting treatment, a full examination is carried out; constant monitoring of this indicator is indicated.

If there is an imbalance of water balance or sodium deficiency in the body, the condition is corrected before starting therapy. Hemodialysis is not performed during therapy due to high risks anaphylactic reactions.

Overdose

The list of symptoms characteristic of an overdose includes:

• myocardial infarction;
• Quincke's edema;
• cerebrovascular accidents;
• acute hypotension, significant decrease in blood pressure;
• thromboembolic complications;
• heart rhythm failure.

Treatment consists of reducing the dosage of the drug or stopping it completely. If an overdose is manifested by symptoms of intoxication, the patient undergoes gastric lavage. Techniques symptomatic treatment are determined individually in a hospital setting.

Storage conditions

Analogues

The list of drug analogues includes the following:

• Vasolong. Indian drug, which as active substance contains ramipril. The medicine is produced in capsules and has indications and restrictions for use similar to Ramipril, causing similar unwanted effects.
• . A medicine from KRKA, which is available in tablets. It costs more than Ramipril, but by purchasing it, you can be sure of its quality. It is prescribed for treatment arterial hypertension, chronic heart failure, nephropathy, as well as for the prevention of heart attack.
• Dilaprel. A Russian drug from the Vertex company, which is produced in capsules. It differs from Ramipril in the composition of auxiliary components and price (Dilaprel is more expensive). Otherwise, both drugs are similar.
• Corpril. Indian medicine produced in capsules. The main difference from Ramipril is in the composition of the auxiliary components; this should be taken into account by patients suffering from drug intolerance. Medicines have similar indications, contraindications and adverse reactions.
• Ramigamma. A German medicine that is available in tablets and injections, which allows it to be prescribed to patients who cannot take drugs orally. It differs from Ramipril in the composition of additional components and is more expensive.
• Pyramid. The drug is available in tablets. This is a Swiss medicine from the Sandoz company, which is considered one of the best in the development and production of generics. That is why its cost is higher than Ramipril.

You can replace a prescribed drug with an analogue only after consultation with a specialist.

Price

The cost of Ramipril is on average 114 rubles. Prices range from 66 to 189 rubles.

Ramipril- ACE inhibitor, blocks the conversion of angiotensin I to angiotensin II, as a result of which (regardless of plasma renin activity) a hypotensive effect occurs (in the patient’s “lying” and “standing” position) without a compensatory increase in heart rate. Reduces aldosterone production. Reduces peripheral vascular resistance (afterload), wedge pressure in the pulmonary capillaries (preload), resistance in the pulmonary vessels; increases IOC and exercise tolerance. At long-term use promotes the reverse development of myocardial hypertrophy in patients arterial hypertension and reduces the frequency of arrhythmias during myocardial reperfusion; improves blood supply to ischemic myocardium; prevents changes in the vascular endothelium caused by a high-cholesterol diet. The cardioprotective effect is due to the effect on Pg synthesis and induction of the formation of nitric oxide (NO) in endothelial cells. Activates the kallikrein-kinin system, prevents the breakdown of bradykinin (increases its concentration), increases the synthesis of Pg. Strengthens coronary and renal blood flow. Reduces platelet aggregation. Increases tissue sensitivity to insulin, fibrinogen concentration, stimulates synthesis tissue activator profibrinolysin (plasminogen), promoting thrombolysis. The onset of the hypotensive effect is 1.5 hours after oral administration, maximum effect- after 5-9 hours, duration of action - 24 hours. There is no withdrawal syndrome. Reduces mortality in early and remote periods myocardial infarction, the frequency of recurrent infarctions and the development of heart failure. Increases the survival rate and improves the quality of life of patients with CHF. In patients with congenital and acquired heart defects, it reduces the severity of hypertension in the pulmonary circulation when taken for at least 6 months. In case of portal hypertension, it reduces blood pressure. Reduces the degree of microalbuminuria (in the initial stage) and the progression of chronic renal failure in patients with severe kidney damage due to diabetic nephropathy.

Indications for use:
Indications for use of the drug Ramipril are: arterial hypertension, malignant and refractory hypertension, vasorenal hypertension, stage II-III CHF. Diabetic nephropathy, nephropathy due to chronic diffuse diseases kidneys (preclinical and clinical stages).

Directions for use:
For arterial hypertension, the drug Ramipril taken orally, initial dose - 2.5 mg, once, in the morning, on an empty stomach or 2 times a day. In case of insufficient hypotensive effect, the dose is gradually increased every 2-3 weeks. The maximum daily dose is 10 mg, maintenance dose is 2.5-5 mg. In the absence of optimal blood pressure reduction, diuretic drugs are additionally prescribed.
CHF: initial dose - 1.25 mg/day; if necessary, increase the dose to 2.5 mg over 1-2 weeks.
When treating patients who have suffered a myocardial infarction, the initial dose is 2.5 mg 2 times a day (if tolerated poorly, take 1.25 mg during the first 2 days).
Renal failure (creatinine clearance 30-60 ml/min), age over 65 years, diabetes mellitus: initial dose - 1.25 mg, maintenance dose - 2.5 mg; maximum dose - 5 mg/day.

Side effects:
From the cardiovascular system: decreased blood pressure, orthostatic collapse, tachycardia, arrhythmias, angina pectoris, myocardial infarction.
From the outside genitourinary system: development or strengthening of chronic renal failure, proteinuria, decreased libido and potency.
From the outside nervous system: cerebral ischemia, stroke, dizziness, headache, weakness, drowsiness, paresthesia; when used in high doses- insomnia, anxiety, depression, confusion.
From the senses: vestibular disorders, disturbances of taste, smell, hearing and vision, tinnitus.
From the outside digestive system: nausea, vomiting, diarrhea or constipation, intestinal obstruction, pancreatitis, hepatitis, cholestatic jaundice, impaired liver function with the development of acute liver failure, pain in the epigastric region, dry mouth, thirst, decreased appetite, stomatitis, glossitis.
From the respiratory system: “dry” cough, bronchospasm, shortness of breath, rhinorrhea.
Allergic reactions: skin rash, itching, urticaria, photosensitivity; angioedema of the face, extremities, lips, tongue, glottis and/or larynx, exfoliative dermatitis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), pemphigus (pemphigus), serositis, vasculitis, myositis, myalgia, arthralgia, arthritis, eosinophilia.
From the hematopoietic organs: anemia, decreased Hb and hematocrit, neutropenia, thrombocytopenia, agranulocytosis, pancytopenia, hemolytic anemia.
Other: convulsions, alopecia, hyperthermia.
Laboratory indicators: hypercreatininemia, hyperammonemia, increased activity of “liver” transaminases, hyperbilirubinemia, hyperkalemia, hyponatremia, the appearance of antinuclear antibodies.
Effect on the fetus: impaired development of the fetal kidneys, decreased blood pressure in the fetus and newborns, impaired renal function, hyperkalemia, cranial hypoplasia, oligohydramnios, limb contracture, cranial deformation, pulmonary hypoplasia.

Contraindications:
Contraindications to the use of the drug Ramipril are: hypersensitivity to ramipril or other ACE inhibitors, history of angioedema during therapy ACE inhibitors, hereditary or idiopathic angioedema, bilateral renal artery stenosis, stenosis of the artery of a solitary kidney, condition after kidney transplantation, hemodynamically significant aortic or mitral stenosis, HOCM, primary hyperaldosteronism, pregnancy, lactation period. With caution. Severe damage to the coronary and cerebral arteries (danger of decreased blood flow due to excessive decrease in blood pressure), unstable angina, severe ventricular arrhythmias, end-stage CHF, decompensated “pulmonary” heart, diseases requiring the use of corticosteroids and immunosuppressants (lack of clinical experience) - incl. for systemic diseases connective tissue, renal and/or liver failure, hyperkalemia, hyponatremia (including against the background of diuretics and a diet with limited Na+ intake), conditions accompanied by a decrease in blood volume (including diarrhea, vomiting), elderly age, age 18 years (safety and effectiveness of use have not been studied).

Pregnancy:
Ramipril Contraindicated for use during pregnancy and lactation (breastfeeding).

Interaction with other drugs:
With the simultaneous use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium supplements, salt substitutes and dietary supplements containing potassium, hyperkalemia may develop (especially in patients with impaired renal function), because ACE inhibitors reduce the content of aldosterone, which leads to potassium retention in the body while limiting the excretion of potassium or its additional intake into the body.
When used simultaneously with NSAIDs, the hypotensive effect of ramipril may be reduced and renal function may be impaired.
When used simultaneously with loop or thiazide diuretics, the antihypertensive effect is enhanced. Severe arterial hypotension, especially after taking the first dose of a diuretic, appears to occur due to hypovolemia, which leads to a transient increase in the hypotensive effect of ramipril. There is a risk of developing hypokalemia. The risk of kidney dysfunction increases.
When used simultaneously with drugs that have a hypotensive effect, the hypotensive effect may be enhanced.
When used simultaneously with immunosuppressants, cystostatics, allopurinol, procainamide, the risk of developing leukopenia may increase.
When used simultaneously with insulin, hypoglycemic agents, sulfonylurea derivatives, and metformin, hypoglycemia may develop.
When used simultaneously with allopurinol, cystostatics, immunosuppressants, procainamide, the risk of developing leukopenia may increase.
When used simultaneously with lithium carbonate, it is possible to increase the concentration of lithium in the blood serum.

Overdose:
Symptoms of drug overdose Ramipril: acute arterial hypotension, cerebrovascular accident, angioedema, myocardial infarction, thromboembolic complications.
Treatment: dose reduction or complete withdrawal of the drug; gastric lavage, transferring the patient to a horizontal position, taking measures to increase blood volume (administration of isotonic sodium chloride solution, transfusion of other blood substitute fluids), symptomatic therapy: epinephrine (s.c. or i.v.), hydrocortisone (i.v.), antihistamines.

Storage conditions:
List B: In a dry place, protected from light, at a temperature not exceeding 25 °C.

Release form:
Ramipril - tablets of 0.0025 and 0.005 g in a package of 28 pieces.

Additionally:
After taking the first dose, as well as when increasing the dosage of the diuretic and/or ramipril, patients should be under medical supervision for 8 hours to avoid the development of an uncontrolled hypotensive reaction. In patients with CHF, taking the drug can lead to the development of severe arterial hypotension, which in some cases is accompanied by oliguria or azotemia and rarely by the development of acute renal failure. The lower limit of systolic blood pressure for therapy in early dates myocardial infarction is considered to be 100 mm Hg. Patients with malignant arterial hypertension or concomitant decompensated CHF should begin treatment in a hospital setting. Before starting and during therapy with ACE inhibitors, it is necessary to count the total number of leukocytes and determine leukocyte formula(up to 1 time per month in the first 3-6 months of treatment in patients with an increased risk of neutropenia - with impaired renal function, systemic connective tissue diseases or those receiving high doses, as well as at the first signs of infection). If neutropenia is confirmed (the number of neutrophils is less than 2 thousand/μl), therapy with ACE inhibitors should be discontinued. Before and during treatment, it is necessary to monitor blood pressure, kidney function (creatinine, urea), K+ and other electrolytes in plasma, Hb, and the activity of “liver” enzymes in the blood. Caution must be exercised when prescribing the drug to patients on a low-salt or salt-free diet ( increased risk development of arterial hypotension). In patients with reduced blood volume (as a result of diuretic therapy), with limited salt intake, during dialysis, with diarrhea and vomiting, symptomatic hypotension may develop. Transient hypotension is not a contraindication for continuing treatment after stabilization of blood pressure. In case reoccurrence severe hypotension, the dose should be reduced or the drug discontinued. The use of AN69 dialysis membranes in combination with ACE inhibitors is not recommended (due to the possibility of developing anaphylactoid reactions in patients). If the history shows indications of the development angioedema, not associated with taking ACE inhibitors, then such patients still have an increased risk of developing it when taking it. Safety and efficacy in pediatric practice: Close monitoring for hypotension, oliguria and hyperkalemia is recommended for neonates exposed in utero to ACE inhibitors. With oliguria, it is necessary to maintain blood pressure and renal perfusion by administering appropriate fluids and vasoconstrictor drugs. In newborns and infants there is a risk of oliguria and neurological disorders, possibly due to a decrease in renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors (received during pregnancy and after childbirth); Lower initial doses and close monitoring are recommended. Care should be taken when performing physical exercise or hot weather due to the risk of dehydration and hypotension due to decreased fluid volume. It is not recommended to consume ethanol. Before surgery (including dentistry), the surgeon/anesthesiologist must be warned about the use of ACE inhibitors. During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretic drugs)

After oral administration, ramipril is rapidly absorbed from gastrointestinal tract (50-60%). Eating slows down its absorption, but does not affect the completeness of absorption. Ramipril undergoes extensive first-pass metabolism/activation (mainly in the liver by hydrolysis), resulting in the formation of its only active metabolite, ramiprilat, whose ACE inhibitory activity is approximately 6 times greater than that of ramipril. In addition, as a result of the metabolism of ramipril, diketopiperazine, which does not have pharmacological activity, is formed, which is then conjugated with glucuronic acid. Ramiprilat is metabolized to diketopiperazic acid and glucuronidated. The bioavailability of ramipril after oral administration ranges from 15% (for a dose of 2.5 mg) to 28% (for a dose of 5 mg). The bioavailability of the active metabolite, ramiprilat, after oral administration of 2.5 mg and 5 mg of ramipril is approximately 45% (compared to its bioavailability after intravenous administration in the same doses). After taking ramipril orally, the maximum plasma concentrations (Cmax) of ramipril and ramiprilat in the blood plasma are reached after 1 and 2-4 hours, respectively. The decrease in plasma concentration of ramiprilat occurs in several stages: a distribution and elimination phase with a half-life (T?2) of ramiprilat of approximately 3 hours, then an intermediate phase with a T?2 of ramiprilat of approximately 15 hours, and a final phase with a very low concentration ramiprilat in blood plasma and T?, ramiprilat, which is approximately 4-5 days. This final phase is due to the slow release of ramiprilat from its strong binding to ACE receptors. Despite the long final phase with a single oral dose of ramipril during the day at a dose of 2.5 mg or more, the equilibrium plasma concentration of ramiprilat is achieved after approximately 4 days of treatment. When prescribing the drug in a course, “effective” T? depending on the dose, it is 13-17 hours. Plasma protein binding is approximately 73% for ramipril, and 56% for ramiprilat. Following intravenous (IV) administration, the volume of distribution of ramipril and ramiprilat is approximately 90 L and 500 L, respectively. After ingestion of radiolabeled ramipril (10 mg), 39% of the radioactivity is excreted by the intestines and about 60% by the kidneys. After intravenous administration of ramipril, 50-60% of the dose is found in the urine in the form of ramipril and its metabolites. After intravenous administration of ramiprilat, about 70% of the dose is found in the urine in the form of ramiprilat and its metabolites, i.e. with intravenous administration of ramipril and ramiprilat, a significant part of the dose is excreted through the intestines with bile, bypassing the kidneys (50% and 30%, respectively). After oral administration of 5 mg ramipril in patients with drainage bile ducts Almost equal amounts of ramipril and its metabolites are excreted by the kidneys and intestines during the first 24 hours after administration. Approximately 80-90% of the metabolites in urine and bile were identified as ramiprilat and ramiprilat metabolites. Ramipril glucuronide and ramipril diketopiperazine account for approximately 10-20% of the total amount, and the content of unmetabolized ramipril in urine is approximately 2%. Animal studies have shown that ramipril is excreted in the milk of lactating mice and rats, however, with repeated use in a dose of 10 mg, ramipril and its metabolites create low concentrations in milk. In case of impaired renal function with creatinine clearance (CC) less than 60 ml/min, the excretion of ramiprilat and its metabolites by the kidneys slows down. This leads to an increase in plasma concentrations of ramiprilat, which decreases more slowly than in patients with normal renal function. When taking ramipril in high doses (10 mg), impaired liver function leads to a slower first-pass metabolism of ramipril to active ramiprilat and a slower elimination of ramiprilat. In healthy volunteers and patients with arterial hypertension, after 2 weeks of treatment with ramipril at a daily dose of 5 mg, no clinically significant accumulation of ramipril and ramiprilat was observed. In patients with chronic heart failure, after 2 weeks of treatment with ramipril at a daily dose of 5 mg, a 1.5-1.8-fold increase in plasma concentrations of ramiprilat and the area under the pharmacokinetic concentration-time curve AUC was observed. In healthy elderly volunteers (65-76 years), the pharmacokinetics of ramipril and ramiprilat do not differ significantly from those in young healthy volunteers.

Special conditions

Before starting treatment with Ramepress®, hyponatremia and hypovolemia must be corrected. In patients who have previously taken diuretics, it is necessary to discontinue them or at least reduce their dose 2-3 days before starting ramipril (in this case, the condition of patients with chronic heart failure should be carefully monitored, due to the possibility of decompensation in them with an increase in BCC). After taking the first dose of the drug, as well as when increasing its dose and/or the dose of diuretics (especially loop diuretics), it is necessary to ensure careful medical monitoring of the patient for at least 8 hours so that appropriate measures can be taken in a timely manner in case of an excessive decrease in blood pressure. If Ramepress® is used for the first time or at a high dose in patients with increased RAAS activity, their blood pressure should be carefully monitored, especially at the beginning of treatment, because these patients have an increased risk of excessive reduction in blood pressure (see section "Precautions"). The simultaneous use of ramipril with aliskiren-containing drugs or angiotensin II receptor antagonists (with double blockade of the RAAS) has an increased risk of a pronounced decrease in blood pressure, the development of hyperkalemia and deterioration of renal function compared with monotherapy. For malignant arterial hypertension and heart failure, especially in acute stage myocardial infarction, treatment with Ramepress® should only be started in a hospital setting. In patients with chronic heart failure, taking the drug can lead to the development of a pronounced decrease in blood pressure, which in some cases is accompanied by oliguria or azotemia and rarely by the development of acute renal failure. Caution should be exercised when treating elderly patients, because they may be particularly sensitive to ACE inhibitors; in the initial phase of treatment, it is recommended to monitor renal function indicators (see also section “Method of administration and dosage”). In patients for whom a decrease in blood pressure may pose a certain risk (for example, in patients with atherosclerotic narrowing of the coronary or cerebral arteries), treatment should begin under strict medical supervision. Caution should be exercised during physical activity and/or hot weather due to the risk of increased sweating and dehydration with the development of arterial hypotension due to a decrease in blood volume and a decrease in sodium content in the blood. It is not recommended to drink alcohol during treatment with Ramepress®. Transient arterial hypotension is not a contraindication for continuing treatment after stabilization of blood pressure. If severe arterial hypotension reoccurs, the dose should be reduced or the drug discontinued. Cases of angioedema of the face, extremities, lips, tongue, pharynx or larynx have been observed in patients treated with ACE inhibitors. If swelling occurs in the face (lips, eyelids) or tongue, or difficulty swallowing or breathing, the patient should immediately stop taking Ramepress®. Angioedema, localized in the area of ​​the tongue, pharynx or larynx (possible symptoms: difficulty swallowing or breathing), can be life-threatening and requires urgent measures to relieve it: subcutaneous administration of 0.3-0.5 mg or intravenous drip of 0.1 mg of epinephrine (adrenaline) (under the control of blood pressure, heart rate and ECG) followed by the use of corticosteroids (iv, intramuscular, or orally); IV administration is also recommended antihistamines(antagonists of Hi- and Hg-histamine receptors), and in case of insufficiency of Ci-esterase enzyme inactivators, you can consider the need to administer Ci-esterase enzyme inhibitors in addition to epinephrine. The patient should be hospitalized and monitored until symptoms are completely relieved, but not less than 24 hours. In patients receiving ACE inhibitors, cases of intestinal angioedema, which was manifested by abdominal pain with or without nausea and vomiting, were observed; in some cases, angioedema of the face was simultaneously observed. This condition was diagnosed during computed tomography or ultrasound examination abdominal cavity or during surgery. If a patient develops the above-described symptoms during treatment with ACE inhibitors, the patient should differential diagnosis consider the possibility of developing intestinal angioedema in them. Treatment aimed at desensitization to insect venom (bees, wasps) and simultaneous administration of ACE inhibitors can initiate anaphylactic and anaphylactoid reactions (for example, decreased blood pressure, shortness of breath, vomiting, allergic reactions). skin reactions), which can sometimes be life-threatening. During treatment with ACE inhibitors, hypersensitivity reactions to insect venom (for example, bees, wasps) develop faster and are more severe. If desensitization to insect venom is necessary, the ACE inhibitor should be temporarily replaced with an appropriate drug of a different class. When using ACE inhibitors, life-threatening, rapidly developing anaphylactoid reactions have been described, sometimes up to the development of shock during hemodialysis or plasma filtration using certain; high-flow membranes (for example, polyacrylonitrile membranes) (see also membrane manufacturer's instructions). The combined use of Ramepress® and these types of membranes (for example, for urgent hemodialysis or hemofiltration) should be avoided. IN in this case it is preferable to use other membranes or avoid taking ACE inhibitors. Similar reactions were observed with LDL apheresis using dextrin sulfate. Therefore, this method should not be used in patients receiving ACE inhibitors. In patients with impaired liver function, the response to treatment with Ramepress® may be either enhanced or weakened. In addition, in patients with severe liver cirrhosis with edema and/or ascites, significant activation of the RAAS is possible, so special care should be taken when treating these patients (see also section "Dosage and Administration"). Before surgery (including dental surgery), it is necessary to warn the surgeon/anesthesiologist about the use of ACE inhibitors. It is recommended to closely monitor neonates exposed in utero to ACE inhibitors for hypotension, oliguria, and hyperkalemia. In oliguria, it is necessary to maintain blood pressure and renal perfusion by administering appropriate fluids and vasoconstrictors. These neonates are at risk of developing oliguria and neurological disorders, possibly due to decreased renal and cerebral blood flow due to the decrease in blood pressure caused by ACE inhibitors. Monitoring laboratory parameters before and during treatment with Ramepress® (up to 1 time per month in the first 3-6 months of treatment) Monitoring renal function (determining serum creatinine concentrations) When treating with ACE inhibitors in the first weeks of treatment and subsequently, it is recommended to monitor renal function . Particularly careful monitoring is required in patients with acute and chronic heart failure, impaired renal function, after kidney transplantation, patients with renovascular diseases, including patients with hemodynamically significant unilateral renal artery stenosis in the presence of two kidneys (in such patients, even a slight increase in serum creatinine concentration may be indicator of decreased kidney function). Monitoring electrolyte concentrations Regular monitoring of serum potassium levels is recommended. Particularly careful monitoring of potassium levels in the blood serum is required for patients with impaired renal function, significant disturbances in water and electrolyte balance, and chronic heart failure. Monitoring hematological parameters (cat (hemoglobin rate, number of leukocytes, erythrocytes, platelets, leukocyte formula) It is recommended to monitor indicators general analysis blood to detect possible leukopenia. More regular monitoring is recommended at the beginning of treatment and in patients with impaired renal function, as well as in patients with connective tissue diseases or in patients simultaneously receiving other drugs that can change the peripheral blood picture (see section "Interaction with other drugs") . White blood cell control is essential for early detection leukopenia, which is especially important in patients with an increased risk of its development, as well as at the first signs of infection. If neutropenia is detected (the number of neutrophils is less than 2000/μl), discontinuation of treatment with ACE inhibitors is required. If symptoms due to leukopenia appear (for example, fever, increased lymph nodes, tonsillitis), urgent monitoring of the peripheral blood picture is necessary. If signs of bleeding appear (tiny petechiae, red-brown rashes on the skin and mucous membranes), monitoring of platelets in the peripheral blood is also necessary. Determination of the activity of “liver” enzymes, the concentration of bilirubin in the blood If jaundice appears or a significant increase in the activity of “liver” enzymes, treatment with Ramepress® should be stopped and medical supervision of the patient should be provided. Effect on the ability to drive vehicles and other mechanisms During the period of treatment with Ramepress®, it is necessary to refrain from engaging in potentially hazardous activities, including driving vehicles, requiring increased concentration and speed of psychomotor reactions, because while taking it, dizziness, decreased speed of psychomotor reactions, and attention may occur, especially after taking the first dose.

Compound

• One 2.5 mg tablet contains:
• active substance: ramipril in terms of 100% substance - 2.5 mg;
• excipients: lactose monohydrate - 165.4 mg; sodium bicarbonate -0.6 mg; microcrystalline cellulose - 20 mg; hypromellose - 1 mg; arginine - 0.3 mg; croscarmellose sodium - 4 mg; colloidal silicon dioxide - 2 mg; methylated silicon dioxide (colloidal hydrophobic silicon dioxide) - 2 mg; sodium stearyl fumarate - 2 mg; iron oxide yellow dye - 0.2 mg.

Ramipril indications for use

• Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs);
• chronic heart failure (as part of combination therapy, in particular, in combination with diuretics);
• diabetic or non-diabetic nephropathy, preclinical and clinically pronounced stages, incl. with severe proteinuria, especially when combined with arterial hypertension;
• reducing the risk of myocardial infarction, stroke or cardiovascular mortality in patients at high cardiovascular risk:
• -in patients with confirmed coronary disease heart disease (CHD), with or without a history of myocardial infarction, including patients who have undergone percutaneous transluminal coronary angioplasty, coronary artery bypass grafting;
• - in patients with a history of stroke;
• - in patients with a history of occlusive lesions of peripheral arteries;
• -in patients with diabetes mellitus with at least one additional factor risk (microalbuminuria, arterial hypertension, increased plasma concentrations of TC, decreased plasma concentrations of HDL-C, smoking);
• heart failure with clinical manifestations, which developed during the first few days (2-9 days) after acute heart attack myocardium (see section “Pharmacodynamics”).

Ramipril contraindications

• Hypersensitivity to ramipril, other ACE inhibitors, or to any of the components of the drug (see section "Composition");
• angioedema (hereditary or idiopathic, as well as after taking ACE inhibitors in history) - the risk of rapid development of angioedema (see section " Side effect»);
• hemodynamically significant stenosis of the renal arteries (bilateral or unilateral in the case of a solitary kidney);
• arterial hypotension (systolic blood pressure less than 90 mm Hg) or conditions with unstable hemodynamic parameters;
• hemodynamically significant stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy;
• primary hyperaldosteronism;
• severe renal failure (creatinine clearance less than 20 ml/min/1.73 m2) (experience of clinical use is insufficient).
• hemodialysis (experience of clinical use is insufficient);
• pregnancy;
• breastfeeding period;
• nephropathy, which is treated with glucocorticosteroids (GCS), non-steroidal

Ramipril dosage

• 2.5 mg

Ramipril side effects

• The undesirable effects listed below are given in accordance with the following gradations of the frequency of their occurrence: very often (? 10%); often (? 1%, Cardiac disorders -, infrequently - myocardial ischemia, including the development of an attack of angina or myocardial infarction, tachycardia, arrhythmias (appearance or intensification), palpitations, peripheral edema.
• Vascular disorders: often - excessive decrease in blood pressure, impaired orthostatic regulation vascular tone(orthostatic hypotension), syncope; infrequently - “flushes” of blood to the skin of the face; rarely - the occurrence or intensification of circulatory disorders against the background of stenotic vascular lesions, vasculitis; frequency unknown - Raynaud's syndrome.
• Nervous system disorders: often - headache, dizziness (feeling of “lightness” in the head); uncommon - vertigo, paresthesia, ageusia (loss of taste sensitivity), dysgeusia (impaired taste sensitivity); rarely - tremor, imbalance; frequency unknown - cerebral ischemia, including ischemic stroke and transient cerebrovascular accident, impaired psychomotor reactions, burning sensation, parosmia (impaired odor perception). Visual disturbances: uncommon - visual disturbances, including vagueness visual perception; rarely - conjunctivitis.
• Hearing disorders - rarely - hearing impairment, ringing in the ears.
• Mental disorders -, infrequently - depression, anxiety, nervousness, motor restlessness, sleep disorders, including drowsiness; rarely - confusion; frequency unknown - impaired attention.
• Disorders of the respiratory system: often - “dry” cough (worsening at night and when lying down), bronchitis, sinusitis, shortness of breath; infrequently - bronchospasm, including worsening of the course bronchial asthma, nasal congestion.
• Gastrointestinal disorders: often - inflammatory reactions in the stomach and intestines, digestive disorders, discomfort in the abdominal area, dyspepsia, diarrhea, nausea, vomiting; uncommon - fatal pancreatitis, incl. and with a fatal outcome (cases of pancreatitis with a fatal outcome when taking ACE inhibitors were observed extremely rarely), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, pain in the upper abdomen, incl. associated with gastritis, constipation, dry oral mucosa; rarely - glossitis; frequency unknown - aphthous stomatitis (inflammatory reaction of the oral mucosa).
• Disorders of the liver and biliary tract, infrequently - increased activity of liver enzymes and the concentration of conjugated bilirubin in the blood plasma; rarely - cholestatic jaundice, hepatocellular lesions; frequency unknown - acute liver failure, cholestatic or cytolytic hepatitis (death was extremely rare).
• Renal and urinary tract disorders: uncommon - renal dysfunction, including the development of acute renal failure, increased urine output, increased pre-existing proteinuria, increased concentrations of urea and creatinine in the blood.
• Violations by reproductive system and mammary glands: infrequently - transient impotence due to erectile dysfunction, decreased libido; frequency unknown - gynecomastia.
• Blood disorders and lymphatic system: infrequently - eosinophilia; rarely - leukopenia, including neutropenia and agranulocytosis, a decrease in the number of red blood cells in the peripheral blood, a decrease in hemoglobin concentration, thrombocytopenia; frequency unknown - suppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.
• Violations by skin and subcutaneous tissues, often - skin rash, in particular maculopapular; infrequently - angioedema, incl. and with a fatal outcome (swelling of the larynx can cause airway obstruction, leading to fatal outcome), itchy skin, hyperhidrosis ( increased sweating); rarely exfoliative dermatitis, urticaria, onycholysis; very rarely - photosensitivity reactions; frequency unknown - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (lichenoid) exanthema or enanthema, alopecia.
• Disorders of the musculoskeletal system and connective tissue: often - muscle cramps, myalgia; infrequently - arthralgia.
• Violations by endocrine system: frequency unknown - syndrome of inappropriate secretion of antidiuretic hormone.
• Metabolic and nutritional disorders: often - increased potassium concentration in the blood; infrequently - anorexia, loss of appetite; frequency unknown - decreased sodium concentration in the blood.
• Immune system disorders: frequency unknown - anaphylactic or anaphylactoid reactions (with ACE inhibition, the number of anaphylactic or anaphylactoid reactions to insect venoms increases), increased titer of antinuclear antibodies.
• General disorders: often - chest pain, feeling tired; infrequently - increased body temperature; rarely - asthenia (weakness).

Drug interactions

Contraindicated combinations Use of certain high-flow membranes with a negatively charged surface (for example, polyacrylonitrile membranes) when performing hemodialysis or hemofiltration; the use of dextran sulfate during LDL apheresis is a risk of developing severe anaphylactic reactions. Concomitant use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and/or impaired renal function (GFR less than 60 ml/min). With vildagliptin - in patients taking both ACE inhibitors and vildagliptin, an increase in the incidence of angioedema was observed. With mTOR inhibitors (eg, temsirolimus) - an increased incidence of angioedema has been observed in patients taking both ACE inhibitors and mTOR inhibitors. Not recommended combinations With potassium salts, potassium-sparing diuretics (for example, amiloride, triamterene, spironolactone, eplerenone (spironolactone derivative)) - a more pronounced increase in the concentration of potassium in the blood serum is possible (with simultaneous use, regular monitoring of the concentration of potassium in the blood serum is required). Combinations that should be used with caution With antihypertensive drugs (for example, diuretics) and other drugs that can lower blood pressure (nitrates, tricyclic antidepressants, general and local anesthetics, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin) - potentiation of the hypotensive effect; regarding combination with diuretics, see also sections “Method of administration and dosage”, “Side effects”, “Special instructions”; when combined with diuretics, the sodium content in the blood serum should be monitored. With sleeping pills, narcotics and painkillers, a more pronounced decrease in blood pressure is possible. With vasopressor sympathomimetics (epinephrine, isoproterenol, dobutamine, dopamine) - a decrease in the hypotensive effect of ramipril, especially careful monitoring of blood pressure is required. With allopurinol, procainamide, cytostatics, immunosuppressants, corticosteroids (glucocorticosteroids and mineralocorticosteroids) and other drugs that can affect hematological parameters - combined use increases the risk of developing hematological reactions (see section "Special instructions"), With lithium salts - increased serum concentration lithium and increased cardio- and neurotoxic effects of lithium. Therefore, serum lithium concentrations should be monitored. With hypoglycemic agents for oral administration (sulfonylurea derivatives, biguanides), insulin - due to a decrease in insulin resistance under the influence of ACE inhibitors, it is possible to enhance the hypoglycemic effect of these drugs, up to the development of hypoglycemia. Particularly close monitoring of blood glucose concentrations is recommended at the beginning of joint use these drugs with ACE inhibitors. Combinations that should be taken into account With NSAIDs (indomethacin, acetylsalicylic acid) - the effect of ramipril may be weakened, the risk of renal dysfunction and increased potassium levels in the blood serum may be increased. With heparin, it is possible to increase the potassium content in the blood serum. With sodium chloride - weakening of the hypotensive effect of ramipril or less effective treatment symptoms of chronic heart failure. With ethanol - increased vasodilation. Ramipril may increase the effects of ethanol on the body. With estrogens - weakening of the hypotensive effect of ramipril (fluid retention). Desensitization therapy for hypersensitivity to insect venoms - ACE inhibitors, including ramipril, increase the likelihood of developing severe anaphylactic or anaphylactoid reactions to insect venoms. It is believed that this effect may occur with other allergens.

Overdose

Symptoms: excessive peripheral vasodilation with the development of a pronounced decrease in blood pressure, shock; bradycardia, water and electrolyte disturbances, acute renal failure, stupor. Treatment: gastric lavage, administration of adsorbents (if possible within the first 30 minutes). In the case of a pronounced decrease in blood pressure, therapy to replenish blood volume and restore water and electrolyte balance may additionally be prescribed?? - adrenergic agonists (norepinephrine), dopamine and angiotensinamide. In case of refractory drug treatment bradycardia may require temporary artificial driver rhythm. In case of overdose, it is necessary to monitor serum concentrations of creatinine and electrolytes.

Storage conditions

• store in a dry place
• store at room temperature 15-25 degrees
• keep away from children
• store in a place protected from light

Information provided

Suffering from high blood pressure, I tried many medications, some good ones that kept my blood pressure normal and some that didn’t help, both expensive and cheap.

The main thing is that medicines have become unaffordable over time.

My husband and I are elderly people, so we take a lot of medications, but we are desperately short of money. Every time I go to the pharmacy, I realize that each time I need more and more money for medications.

At one time, blood pressure pills did not help me, I was taking Ramipril at that time, it felt like I was between heaven and earth, my upper pressure reached one hundred and seventy millimeters of mercury.

The attending physician prescribed me a more expensive medicine, and my blood pressure returned to normal.

Then I decided to try folk remedies to clean blood vessels, I used a teaspoon of flaxseed oil on an empty stomach and cloves (three pieces per glass of water), brewed and drank on an empty stomach, the result exceeded all my expectations. I'll repeat it again in the fall.

After that, I again switched to the cheap domestic drug Ramipril, taking the smallest dose of 2.5 mg. and I’m not in poverty.

"Ramipril" is produced by Northern Star, they come different dosages, I usually buy a five and divide it into two parts; if necessary, I take a whole tablet.

I take Ramipril tablets on an empty stomach and wash them down with water - a single dose.

For greater effect, the tablets can be taken with a diuretic, but not at the moment All I need is Ramipril tablets, I’ve been feeling great for many months now, I measure my blood pressure several times a week.

The cost of thirty tablets is one hundred twenty-six rubles.

I think (in my own way) personal experience), that Ramipril tablets can be taken to regulate blood pressure, but under strict control, and then each organism is strictly individual, what is good for someone may be bad for another, and hypertension is not something to joke about.

I also tried Lisinopril from a Belarusian manufacturer (I went on a visit and forgot the pills), they have the same effect on me, the composition is the same.

It is very important to choose your drug that is right for you, I think that it’s not even a matter of price, sometimes a more expensive drug does a worse job than a cheaper one.

Today I choose Ramipril, some of my friends also chose this domestic drug.

Be healthy everyone!

Video review

All(5)

Catad_pgroup ACE inhibitors

Ramipril - official instructions by application

Registration number:

LP-004927

Trade name of the drug:

Ramipril

International nonproprietary name:

ramipril

Dosage form:

pills

Composition per 1 tablet 2.50 mg:

Active ingredient: ramipril – 2.50 mg.
Excipients: lactose monohydrate (milk sugar) – 92.00 mg; sodium bicarbonate – 2.50 mg; croscarmellose sodium – 2.00 mg; sodium stearyl fumarate – 1.00 mg.

Composition per 1 tablet 5.00 mg:

Active ingredient: ramipril – 5.00 mg.
Excipients: lactose monohydrate (milk sugar) – 87.00 mg; sodium bicarbonate – 5.00 mg; croscarmellose sodium – 2.00 mg; sodium stearyl fumarate – 1.00 mg.

Composition per 1 tablet 10.00 mg:

Active ingredient: ramipril – 10.00 mg.
Excipients: lactose monohydrate (milk sugar) – 174.00 mg; sodium bicarbonate – 10.00 mg; croscarmellose sodium – 4.00 mg; sodium stearyl fumarate – 2.00 mg.

Description:

tablets with a dosage of 2.5 mg are round, biconvex tablets of white or almost white color with a score.
Tablets with a dosage of 5 mg and 10 mg are round, flat-cylindrical tablets of white or almost white color with a chamfer and a score.

Pharmacotherapeutic group:

angiotensin converting enzyme (ACE) inhibitor

ATX Code:

Pharmacological properties

Pharmacodynamics
Formed under the influence of “liver” enzymes, the active metabolite of ramipril, ramiprilat, is a long-acting ACE inhibitor (ACE synonyms: kininase II, dipeptidylcarboxydipeptidase I), which is a peptidyl dipeptidase. ACE in blood plasma and tissues catalyzes the conversion of angiotensin I to angiotensin II, which has a vasoconstrictor effect, and the breakdown of bradykinin, which has a vasodilator effect.
Therefore, when ramipril is taken orally, the formation of angiotensin II decreases and bradykinin accumulates, which leads to vasodilation and a decrease in blood pressure (BP). Ramipril-induced increase in the activity of the kallikrein-kinin system in the blood and tissues with activation of the prostaglandin system and an increase in the synthesis of prostaglandins that stimulate the formation of nitric oxide in endothelial cells determines its cardioprotective and endothelial-protective effects. Angiotensin II stimulates the production of aldosterone, so taking ramipril leads to a decrease in the secretion of aldosterone and an increase in the content of potassium ions in the blood serum.
When the concentration of angiotensin II in the blood decreases, its inhibitory effect on renin secretion by the type of negative feedback is eliminated, which leads to an increase in plasma renin activity.
It is assumed that the development of some adverse events(in particular dry cough) is also associated with increased bradykinin activity.
In patients with arterial hypertension, taking ramipril leads to a decrease in blood pressure in the “lying” and “standing” positions, without a compensatory increase in heart rate (HR). Ramipril significantly reduces total peripheral vascular resistance (TPVR), causing virtually no changes in renal blood flow and glomerular filtration rate. The antihypertensive effect begins to develop 1-2 hours after oral administration of a single dose of the drug, reaching highest value after 3-6 hours, and persists for 24 hours. With a course of ramipril, the antihypertensive effect can gradually increase, usually stabilizing by 3-4 weeks of regular drug use and then persisting for a long time. Sudden discontinuation of the drug does not lead to a rapid and significant increase in blood pressure (no withdrawal syndrome),
In patients with arterial hypertension, ramipril slows down the development and progression of myocardial hypertrophy and vascular wall.
In patients with chronic heart failure, ramipril reduces peripheral vascular resistance (reduces afterload on the heart), increases venous capacity and reduces left ventricular filling pressure, which, accordingly, leads to a decrease in preload on the heart. In these patients, when taking ramipril, there is an increase in cardiac output, ejection fraction and improved exercise tolerance. In diabetic and non-diabetic nephropathy, taking ramipril slows the rate of progression of renal failure and the time of onset terminal stage renal failure and, due to this, reduces the need for hemodialysis or kidney transplantation. In the initial stages of diabetic or non-diabetic nephropathy, ramipril reduces the incidence of albuminuria. In patients with high risk development cardiovascular diseases due to vascular lesions (diagnosed coronary heart disease, obliterating diseases history of peripheral arteries, history of stroke) or diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increased total cholesterol (TC), decreased high-density lipoprotein cholesterol (HDL-C), smoking) addition of ramipril to standard therapy significantly reduces the incidence of myocardial infarction, stroke and mortality from cardiovascular diseases. In addition, ramipril reduces overall mortality rates, as well as the need for revascularization procedures and slows down the onset or progression of chronic heart failure.
In patients with heart failure and clinical manifestations that developed in the first days of acute myocardial infarction (2-9 days), the use of ramipril, started from 3 to 10 days of acute myocardial infarction, reduced mortality (by 27%), the risk of sudden death (by 30 %), risk of progression of heart failure to severe (III-IV functional class according to the NYHA classification)/refractory to therapy (by 23%), the likelihood of subsequent hospitalization due to the development of heart failure (by 26%).
In the general population of patients, as well as in patients with diabetes mellitus, both with arterial hypertension and normal indicators Blood pressure, ramipril significantly reduces the risk of developing nephropathy and microalbuminuria.

Pharmacokinetics
After oral administration, ramipril is rapidly absorbed from the gastrointestinal tract (50-60%). Simultaneous use food slows down its absorption, but does not affect the completeness of absorption. Ramipril undergoes extensive first-pass metabolism/activation (mainly in the liver by hydrolysis), resulting in the formation of its only active metabolite, ramiprilat, whose ACE inhibitory activity is approximately 6 times greater than that of ramipril. In addition, as a result of the metabolism of ramipril, diketopiperazine, which does not have pharmacological activity, is formed, which is then conjugated with glucuronic acid; ramiprilat is also glucuronidated and metabolized to diketopiperazine acid.
All metabolites formed, with the exception of ramiprilat, pharmacological activity don't have.
The bioavailability of ramipril after oral administration ranges from 15% (for a dose of 2.5 mg) to 28% (for a dose of 5 mg). The bioavailability of the active metabolite, ramiprilat, after oral administration of 2.5 mg and 5 mg of ramipril is approximately 45% (compared to its bioavailability after intravenous administration in the same doses).
After oral administration of ramipril, maximum plasma concentrations of ramipril and ramiprilat are achieved after 1 and 2-4 hours, respectively. The decrease in plasma concentration of ramiprilat occurs in several stages: a distribution and elimination phase with a half-life (T 1/2) of ramiprilat of approximately 3 hours, then an intermediate phase with a T 1/2 of ramiprilat of approximately 15 hours, and a final phase with a very low the concentration of ramiprilat in the blood plasma and T 1/2 of ramiprilat, which is approximately 4-5 days. This final phase is due to the slow release of ramiprilat from its strong binding to ACE receptors. Despite the long final phase, with a single oral dose of ramipril during the day at a dose of 2.5 mg or more, the equilibrium plasma concentration of ramiprilat is achieved after approximately 4 days of treatment. With a course of use of the drug, the “effective” T1/2, depending on the dose, is 13-17 hours.
The binding to plasma proteins is approximately 73% for ramipril and 56% for ramiprilat.
Following intravenous administration, the volume of distribution of ramipril and ramiprilat is approximately 90 L and approximately 500 L, respectively.
After oral administration of radiolabeled ramipril (10 mg), 39% of the radioactivity is excreted through the intestines and about 60% through the kidneys. After intravenous administration of ramipril, 50-60% of the dose is found in the urine in the form of ramipril and its metabolites. After intravenous administration of ramiprilat, about 70% of the dose is found in the urine in the form of ramiprilat and its metabolites, in other words, when intravenous administration ramipril and ramiprilat, a significant part of the dose is excreted through the intestines with bile, bypassing the kidneys (50% and 30%, respectively). After oral administration of 5 mg of ramipril in patients with bile duct drainage, almost equal amounts of ramipril and its metabolites are excreted by the kidneys and intestines during the first 24 hours after administration.
Approximately 80-90% of the metabolites in urine and bile were identified as ramiprilat and ramiprilat metabolites. Ramipril glucuronide and ramipril diketopiperazine account for approximately 10-20% of the total amount, and the content of unmetabolized ramipril in urine is approximately 2%.
In animal studies, ramipril has been shown to be excreted into human milk.
In case of impaired renal function with creatinine clearance (CC) less than 60 ml/min. excretion of ramiprilat and its metabolites by the kidneys slows down. This leads to an increase in plasma concentrations of ramiprilat, which decreases more slowly than in patients with normal renal function.
When taking ramipril in high doses (10 mg), impaired liver function leads to a slower first-pass metabolism of ramipril to active ramiprilat and a slower elimination of ramiprilat.
In healthy volunteers and patients with arterial hypertension, after two weeks of treatment with ramipril at a daily dose of 5 mg, no clinically significant accumulation of ramipril and ramiprilat is observed. In patients with chronic heart failure, after two weeks of treatment with ramipril at a daily dose of 5 mg, a 1.5-1.8 fold increase in plasma concentrations of ramiprilat and the area under the pharmacokinetic concentration-time curve (AUC) is observed.
In healthy elderly volunteers (65-76 years), the pharmacokinetics of ramipril and ramiprilat do not differ significantly from those in young healthy volunteers.

Indications for use

• Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs, for example, diuretics and slow blockers calcium channels).
• Chronic heart failure (as part of combination therapy, in particular in combination with diuretics).
• Diabetic or non-diabetic nephropathy, preclinical and clinically pronounced stages, including with severe proteinuria, especially when combined with arterial hypertension.
• Reducing the risk of myocardial infarction, stroke, or cardiovascular mortality in patients at high cardiovascular risk:
  • in patients with confirmed coronary heart disease, a history of myocardial infarction or without it, including patients who have undergone percutaneous transluminal coronary angioplasty, coronary artery bypass grafting;
  • in patients with a history of stroke;
  • in patients with a history of occlusive lesions of peripheral arteries;
  • in patients with diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increased plasma concentrations of TC, decreased plasma concentrations of HDL-C, smoking).
• Heart failure with clinical manifestations that developed during the first few days (from the 2nd to the 9th day) after acute myocardial infarction.

Contraindications

• Hypersensitivity to ramipril, other ACE inhibitors or any other component of the drug;
• history of angioedema (hereditary or idiopathic, as well as after taking ACE inhibitors) - risk of rapid development of angioedema;
• hemodynamically significant stenosis of the renal arteries (bilateral or unilateral in the case of a solitary kidney);
• arterial hypotension (systolic blood pressure less than 90 mm Hg) or conditions with unstable hemodynamic parameters;
• simultaneous use of drugs containing aliskiren in patients with diabetes mellitus and/or moderate and severe renal failure (creatinine clearance (CC) less than 60 ml/min/1.73 m² body surface area).
• simultaneous use with angiotensin II receptor antagonists in patients with diabetic nephropathy;
• hemodynamically significant stenosis of the aortic or mitral valve, or hypertrophic obstructive cardiomyopathy;
• primary hyperaldosteronism;
• severe renal failure - CC less than 20 ml/min/1.73 m² body surface area (experience of clinical use is insufficient);
• hemodialysis (experience of clinical use is insufficient);
• pregnancy/breastfeeding period;
• nephropathy, which is treated with glucocorticosteroids, non-steroidal anti-inflammatory drugs, immunomodulators and/or other cytotoxic drugs (experience of clinical use is insufficient);
• chronic heart failure in the stage of decompensation (experience of clinical use is insufficient);
• age under 18 years (experience of clinical use is insufficient);
• hemodialysis or hemofiltration using certain membranes with a negatively charged surface, such as high-flow polyacrylonitrile membranes (risk of severe anaphylactic reactions);
• apheresis of low-density lipoproteins using dextran sulfate (risk of severe anaphylactic reactions);
• hyposensitizing therapy for hypersensitivity reactions to insect venoms, such as bees and wasps.
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose).

Additional contraindications when using the drug in the acute stage of myocardial infarction:

• chronic heart failure (functional class IV according to the NYHA classification);
• unstable angina;
• life-threatening ventricular arrhythmias;
• "pulmonary" heart.

With caution

Concomitant use of Ramipril with drugs containing aliskiren or angiotensin II receptor antagonists (with dual blockade of the renin-angiotensin-aldosterone system (RAAS) there is an increased risk of a sharp decrease in blood pressure, the development of hyperkalemia and deterioration of renal function compared with monotherapy) (see . section "Special instructions").
Conditions in which an excessive decrease in blood pressure is especially dangerous (with atherosclerotic lesions of the coronary and cerebral arteries).
Conditions accompanied by an increase in the activity of the RAAS, in which, with ACE inhibition, there is a risk of a sharp decrease in blood pressure with deterioration of renal function:

• severe arterial hypertension, especially malignant arterial hypertension;
• chronic heart failure, especially severe or for which others are being taken medicines with antihypertensive effect;
• hemodynamically significant unilateral renal artery stenosis (in the presence of both kidneys) - in such patients, even a slight increase in serum creatinine concentration may be a manifestation of unilateral deterioration in renal function;
• previous use of diuretics;
• disturbances in water and electrolyte balance as a result of insufficient fluid intake and table salt, diarrhea, vomiting, profuse sweating.

Liver dysfunction (lack of experience with use: it is possible to either enhance or weaken the effects of ramipril; in patients with cirrhosis of the liver with ascites and edema, significant activation of the RAAS is possible).
Impaired renal function (creatinine clearance more than 20 ml/min/1.73 m² body surface area) due to the risk of developing hyperkalemia and leukopenia.
Condition after kidney transplantation.
Systemic connective tissue diseases, including systemic lupus erythematosus, scleroderma, concomitant therapy with drugs that can cause changes in the peripheral blood picture (possible inhibition of bone marrow hematopoiesis, development of neutropenia or agranulocytosis) (see section “Interaction with other drugs”).
Diabetes mellitus(risk of developing hyperkalemia).
Old age(risk of increased antihypertensive effect).
Hyperkalemia.

Use during pregnancy and breastfeeding

Ramipril is contraindicated during pregnancy, as it may have adverse effects on the fetus: impaired development of the fetal kidneys, decreased blood pressure in the fetus and newborns, impaired renal function, hyperkalemia, hypoplasia of the skull bones, oligohydramnios, contracture of the limbs, deformation of the skull bones, pulmonary hypoplasia.
Therefore, before starting to take the drug in women childbearing age pregnancy should be excluded.
If a woman is planning a pregnancy, treatment with ACE inhibitors should be discontinued.
If the fact of pregnancy is confirmed during treatment with Ramipril, you should stop taking it as soon as possible and transfer the patient to take other drugs, the use of which will have the least risk for the child.
If treatment with Ramipril is necessary during breastfeeding, then breast-feeding must be stopped.

Directions for use and doses

The tablets should be taken regardless of the time of meal (that is, the tablets can be taken before, during or after meals) and washed down sufficient quantity(1/2 cup) water. Do not chew or crush the tablets before taking.
The dose is selected depending on therapeutic effect and patient tolerance of the drug. Treatment is usually long-term, and its duration in each case is determined by the doctor.
Unless otherwise prescribed, then normal function kidneys and liver, the dosage regimens presented below are recommended.
For arterial hypertension
Usually the initial dose is 2.5 mg 1 time per day in the morning. If, when taking the drug at this dose for 3 weeks or more, it is not possible to normalize blood pressure, then the dose can be increased to 5 mg of ramipril per day. If the dose of 5 mg is insufficiently effective, after 2-3 weeks it can be further doubled to the maximum recommended daily dose of 10 mg per day.
As an alternative to increasing the dose to 10 mg per day if the antihypertensive effectiveness of the daily dose of 5 mg is insufficient, it is possible to add other antihypertensive drugs to the treatment, in particular, diuretics or blockers of “slow” calcium channels.
For chronic heart failure
The recommended starting dose is 1.25 mg (1/2 tablet of 2.5 mg) once a day. Depending on the patient's response to therapy, the dose may be increased. It is recommended to double the dose at intervals of 1-2 weeks. If a daily dose of 2.5 mg or higher is required, it can be given either once a day or divided into 2 doses.
The maximum recommended daily dose is 10 mg.
For diabetic or non-diabetic nephropathy
The recommended starting dose is 1.25 mg 1 time per day (1/2 tablet of 2.5 mg). The dose can be increased to 5 mg 1 time per day. For these conditions, doses above 5 mg once daily have not been sufficiently studied in controlled clinical studies.
To reduce the risk of myocardial infarction, stroke, or cardiovascular mortality in patients at high cardiovascular risk
The recommended starting dose is 2.5 mg once a day. Depending on the patient's tolerance to the drug, the dose can be gradually increased. It is recommended to double the dose after 1 week of treatment, and over the next 3 weeks of treatment, increase it to the usual maintenance dose of 10 mg once daily.
Doses greater than 10 mg have not been sufficiently studied in controlled clinical studies. The use of the drug in patients with CC less than 0.6 ml/sec has not been sufficiently studied.
For heart failure with clinical manifestations that developed during the first few days (from the 2nd to the 9th day) after acute myocardial infarction
The recommended starting dose is 5 mg per day, divided into two single doses 2.5 mg, which are taken one in the morning and the other in the evening. If the patient does not tolerate this initial dose (an excessive decrease in blood pressure is observed), then he is recommended to take 1.25 mg (1/2 tablet of 2.5 mg) 2 times a day for two days.
Then, depending on the patient's response, the dose may be increased. It is recommended that the dose be doubled at intervals of 1-3 days when increasing it. Later, the total daily dose, which was initially divided into two doses, can be given once. The maximum recommended dose is 10 mg.
Currently, the experience of treating patients with severe chronic heart failure (III-IV functional class according to the NYHA classification), which arose immediately after acute myocardial infarction, is insufficient. If the decision is made to treat such patients with Ramipril, it is recommended that treatment begin with the lowest possible dose of 1.25 mg (1/2 tablet of 2.5 mg) once daily, and special care should be taken with each increase. doses.
Use of the drug Ramipril in certain groups of patients
Patients with impaired renal function
With CC from 50 to 20 ml/min, the initial daily dose is usually 1.25 mg (1/2 tablet of 2.5 mg). The maximum permissible daily dose is 5 mg.
Patients with incompletely corrected loss of fluid and electrolytes, patients with severe arterial hypertension, as well as patients for whom an excessive decrease in blood pressure poses a certain risk (for example, with severe atherosclerotic lesions of the coronary and cerebral arteries)
The initial dose is reduced to 1.25 mg/day (1/2 tablet of 2.5 mg).
Patients with previous diuretic therapy
If possible, it is necessary to discontinue diuretics 2-3 days (depending on the duration of action of the diuretics) before starting treatment with Ramipril, or at least reduce the dose of diuretics taken. Treatment of such patients should begin with the lowest dose of 1.25 mg ramipril (1/2 tablet of 2.5 mg), taken once a day, in the morning. After taking the first dose and whenever the dose of ramipril and/or diuretics, especially loop diuretics, is increased, patients should be under medical supervision for at least 8 hours to avoid an uncontrolled hypotensive reaction.
Elderly patients (over 65 years old)
The initial dose is reduced to 1.25 mg per day (1/2 tablet of 2.5 mg).
Patients with liver dysfunction
The blood pressure response to taking the drug Ramipril can either increase (due to slowing down the excretion of ramiprilat) or weaken (due to slowing down the conversion of low-active ramipril to active ramiprilat). Therefore, careful medical supervision is required at the beginning of treatment. The maximum permissible daily dose is 2.5 mg.

Side effect

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often (≥1/10), often (≥1/100), infrequently (≥1/1000, <1/100), rarely (≥1/10000, <1/1000), very rarely (<1/10000, включая единичные случаи), frequency unknown(insufficient data to estimate the frequency of development).
Blood and lymphatic system disorders
Uncommon: eosinophilia.
Rarely: leukopenia, including neutropenia and agranulocytosis, decreased number of red blood cells in peripheral blood, decreased hemoglobin, thrombocytopenia, lymphadenopathy.
Frequency unknown: suppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.
Immune system disorders
Frequency unknown: anaphylactic or anaphylactoid reactions (with ACE inhibition, the severity of anaphylactic or anaphylactoid reactions to insect venoms increases), increased titer of antinuclear antibodies.
Endocrine system disorders
Frequency unknown: syndrome of inappropriate antidiuretic hormone secretion.
Metabolic and nutritional disorders
Common: increased potassium levels in the blood.
Uncommon: anorexia, decreased appetite.
Frequency unknown: decreased sodium levels in the blood.
Mental disorders
Uncommon: depressed mood, anxiety, nervousness, restlessness, sleep disturbances, including drowsiness.
Rarely: confusion.
Frequency unknown: impaired attention.
Nervous system disorders
Common: headache, dizziness (feeling of “lightness” in the head).
Uncommon: vertigo, paresthesia, ageusia (loss of taste sensitivity), dysgeusia (impaired taste sensitivity).
Rarely: tremor, imbalance.
Frequency unknown: cerebral ischemia, including ischemic stroke and transient cerebrovascular accident, impaired psychomotor reactions (decreased response), parosmia (impaired odor perception), paresthesia.
Visual disorders
Uncommon: visual disturbances, including blurred images.
Rarely: conjunctivitis.
Hearing and labyrinth disorders
Rarely: hearing impairment, tinnitus.
Heart disorders
Uncommon: myocardial ischemia, including the development of an attack of angina or myocardial infarction, tachycardia, cardiac arrhythmias (appearance or intensification), palpitations, peripheral edema.
Vascular disorders
Often: excessive decrease in blood pressure, impaired orthostatic regulation of vascular tone (orthostatic hypotension), syncope.
Uncommon: flushes of blood to the facial skin.
Rarely: the occurrence or intensification of circulatory disorders against the background of stenotic vascular lesions, vasculitis.
Frequency unknown: Raynaud's syndrome.
Respiratory, thoracic and mediastinal disorders
Common: dry cough (worsening at night and when lying down), bronchitis, sinusitis, shortness of breath.
Uncommon: bronchospasm, including worsening of bronchial asthma, nasal congestion.
Gastrointestinal disorders
Often: inflammatory reactions in the stomach and intestines, digestive disorders, discomfort in the abdominal area, dyspepsia, diarrhea, nausea, vomiting.
Uncommon: pancreatitis, including fatal ones (cases of fatal pancreatitis when taking ACE inhibitors were extremely rare), increased activity of pancreatic enzymes in the blood plasma, angioedema of the small intestine, pain in the upper abdomen, including associated with gastritis, constipation, dry oral mucosa.
Rarely: glossitis.
Frequency unknown: aphthous stomatitis (inflammatory reactions of the oral mucosa).
Disorders of the liver and biliary tract
Uncommon: increased activity of liver enzymes and the concentration of conjugated bilirubin in the blood plasma.
Rarely: cholestatic jaundice, hepatocellular lesions.
Frequency unknown: acute liver failure, cholestatic or cytolytic hepatitis (extremely fatal).
Skin and subcutaneous tissue disorders
Common: skin rash, particularly maculopapular rash.
Uncommon: angioedema, including death (swelling of the larynx can cause airway obstruction, leading to death), itching, hyperhidrosis (increased sweating).
Rarely: exfoliative dermatitis, urticaria, onycholysis.
Very rare: photosensitivity reactions.
Frequency unknown: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening of psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (lichenoid) exanthema or enanthema, alopecia.
Musculoskeletal and connective tissue disorders
Common: muscle cramps, myalgia.
Uncommon: arthralgia.
Renal and urinary tract disorders
Uncommon: renal dysfunction, including the development of acute renal failure, increased urine output, increased pre-existing proteinuria, increased concentrations of urea and creatinine in the blood.
Disorders of the genital organs and breast
Uncommon: erectile dysfunction with transient impotence, decreased libido.
Frequency unknown: gynecomastia.
General and administration site disorders
Common: chest pain, increased fatigue.
Uncommon: increased body temperature.
Rarely: asthenia (weakness).

Overdose

Symptoms: excessive peripheral vasodilation with the development of a pronounced decrease in blood pressure, shock; bradycardia, fluid and electrolyte disturbances, acute renal failure, stupor.
Treatment: gastric lavage, taking adsorbents, sodium sulfate (if possible within the first 30 minutes). In the case of a pronounced decrease in blood pressure, the administration of alpha 1-adrenergic agonists (norepinephrine, dopamine) and angiotensin II agonists (angiotensinamide) can be added to therapy to replenish circulating blood volume and restore water-electrolyte imbalances. In case of bradycardia refractory to drug treatment, installation of a temporary pacemaker may be required. In case of overdose, it is necessary to monitor serum creatinine concentrations and electrolyte levels.
Hemodialysis is indicated in cases of renal failure.

Interaction with other drugs

Contraindicated combinations
The use of certain high-flow membranes with a negatively charged surface (for example, polyacrylonitrile membranes) when performing hemodialysis or hemofiltration; use of dextran sulfate in low-density lipoprotein apheresis.
Risk of developing severe anaphylactoid reactions. If the patient requires these procedures, then other types of membranes should be used (in the case of plasmapheresis and hemofiltration) or the patient should be switched to taking antihypertensive drugs of other groups.
Concomitant use of Ramipril and drugs containing aliskiren
Concomitant use of Ramipril and drugs containing aliskiren in patients with diabetes mellitus or moderate or severe renal failure with creatinine clearance<60 мл/мин противопоказано и не рекомендуется у других пациентов (см. разделы «Противопоказания», «С осторожностью», «Особые указания»).
Concomitant use of Ramipril and angiotensin II receptor antagonists (ARA II)
The simultaneous use of the drug and ARA II in patients with diabetic nephropathy is contraindicated and is not recommended in other patients (see sections “Contraindications”, “With caution”, “Special instructions”).

Combinations not recommended
With potassium salts, potassium-sparing diuretics (for example, amiloride, triamterene, spironolactone, eplerenone), other drugs that can increase the level of potassium in the blood serum (including ARA II, tacrolimus, cyclosporine, trimethoprim, sulfamethoxazole, included in cotrimoxazole (combined antibacterial agent , containing sulfamethoxazole and trimethoprim)).
An increase in potassium levels in the blood serum is possible, sometimes significantly (with simultaneous use, careful monitoring of potassium levels in the blood serum is required).

Combinations to use with caution
With antihypertensive drugs (for example, diuretics) and other drugs that can lower blood pressure (nitrates, tricyclic antidepressants, general and local anesthesia, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin)– potentiation of the antihypertensive effect; when combined with diuretics, serum sodium levels should be regularly monitored.
With sleeping pills, narcotics and painkillers– a more pronounced decrease in blood pressure is possible.
With vasopressor sympathomimetics (epinephrine (adrenaline), isoproterenol, dobutamine, dopamine)– reduction of the antihypertensive effect of the drug Ramipril; particularly careful monitoring of blood pressure is recommended.
With allopurinol, procainamide, cytostatics, immunosuppressants, corticosteroids (glucocorticosteroids and mineralocorticosteroids) and other drugs that may affect hematological parameters– combined use increases the risk of hematological reactions.
With lithium salts– increased serum lithium concentration and increased cardio- and neurotoxic effects of lithium. Therefore, the lithium content in the blood serum should be monitored.
With hypoglycemic agents (for example, insulins, oral hypoglycemic agents (sulfonylureas, biguanides))– due to a decrease in insulin resistance under the influence of ACE inhibitors, the hypoglycemic effect of these drugs may be enhanced, up to the development of hypoglycemia. Particularly careful monitoring of blood glucose concentrations is recommended when starting their combined use with ACE inhibitors.
With dipeptidyl peptidase type IV (DPP-IV) inhibitors (gliptins), for example, sitagliptin, saxagliptin, vildagliptin, linagliptin - an increased incidence of angioedema was observed in patients taking both ACE inhibitors and gliptins.
With racecadotril(an enkephalinase inhibitor used to treat acute diarrhea) – increases the risk of developing angioedema.
With estramustine– increased risk of developing angioedema.
With mTOR inhibitors (mammalian Target of Rapamycin- target of rapamycin in mammalian cells), for example, temsirolimus, sirolimus, everolimus - an increase in the incidence of angioedema was observed in patients taking both ACE inhibitors and mTOR inhibitors.

Combinations to Consider
With nonsteroidal anti-inflammatory drugs (indomethacin, acetylsalicylic acid (more than 3 g/day))– the effect of ramipril may be weakened, the risk of renal dysfunction and an increase in potassium levels in the blood serum may be increased.
With heparin– an increase in potassium levels in the blood serum is possible.
With sodium chloride– weakening of the antihypertensive effect of the drug and less effective treatment of symptoms of chronic heart failure.
With ethanol– increased symptoms of vasodilation. The drug may increase the effects of ethanol on the body.
With estrogens– weakening of the antihypertensive effect of ramipril (fluid retention).
Desensitization therapy for hypersensitivity to insect venoms– ACE inhibitors, including the drug Ramipril, increase the likelihood of developing severe anaphylactic or anaphylactoid reactions to insect venoms. It is assumed that this effect may also occur with other allergens.

Special instructions

Before starting treatment with Ramipril, it is necessary to eliminate hyponatremia and hypovolemia. In patients who have previously taken diuretics, it is necessary to discontinue them or at least reduce their dose 2-3 days before starting Ramipril (in this case, the condition of patients with chronic heart failure should be carefully monitored, due to the possibility of developing decompensation with an increase in circulating blood volume).
After taking the first dose of the drug, as well as when increasing its dose and/or the dose of diuretics (especially loop diuretics), it is necessary to ensure careful medical monitoring of the patient for at least 8 hours so that appropriate measures can be taken in a timely manner in case of an excessive decrease in blood pressure.
If Ramipril is used for the first time or at a high dose in patients with increased RAAS activity, their blood pressure should be carefully monitored, especially at the beginning of treatment, since these patients have an increased risk of an excessive decrease in blood pressure (see section “With caution”).
In case of malignant arterial hypertension and heart failure, especially in the acute stage of myocardial infarction, treatment with Ramipril should be started only in a hospital setting.
In patients with chronic heart failure, taking the drug can lead to the development of a pronounced decrease in blood pressure, which in some cases is accompanied by oliguria or azotemia and rarely by the development of acute renal failure.
Caution should be exercised when treating elderly patients, as they may be particularly sensitive to ACE inhibitors; in the initial phase of treatment, it is recommended to monitor renal function (see also section "Dosage and Administration").
In patients for whom a decrease in blood pressure may pose a certain risk (for example, in patients with atherosclerotic narrowing of the coronary or cerebral arteries), treatment should begin under strict medical supervision.
Caution should be exercised during physical activity and/or hot weather due to the risk of increased sweating and dehydration with the development of arterial hypotension due to a decrease in circulating blood volume and a decrease in sodium levels in the blood.
During treatment with Ramipril, it is not recommended to drink alcohol (ethanol).
A transient excessive decrease in blood pressure is not a contraindication for continuing treatment after stabilization of blood pressure. In case of repeated development of a pronounced decrease in blood pressure, the dose should be reduced or the drug discontinued.
The simultaneous use of Ramipril with drugs containing aliskiren or with ARA II, leading to double blockade of the RAAS, is not recommended due to the risk of an excessive decrease in blood pressure, the development of hyperkalemia and deterioration of renal function compared to monotherapy. Concomitant use of Ramipril with drugs containing aliskiren in patients with diabetes mellitus and/or moderate to severe renal failure with creatinine clearance<60 мл/мин противопоказано (см. разделы «Противопоказания», «Взаимодействие с другими лекарственными средствами»).
Concomitant use with ARA II in patients with diabetic nephropathy is contraindicated (see sections “Contraindications”, “Interaction with other drugs”) and is not recommended in other patients.
Cases of angioedema of the face, extremities, lips, tongue, pharynx or larynx have been observed in patients treated with ACE inhibitors. If swelling occurs in the face (lips, eyelids) or tongue, or difficulty swallowing or breathing, the patient should immediately stop taking the drug. Angioedema, localized in the area of ​​the tongue, pharynx or larynx (possible symptoms: difficulty swallowing or breathing), can be life-threatening and requires urgent measures to relieve it: subcutaneous administration of 0.3-0.5 mg or intravenous drip of 0.1 mg of epinephrine (adrenaline) (under the control of blood pressure, heart rate and ECG) followed by the use of glucocorticosteroids (iv, intramuscular or orally); Intravenous administration of antihistamines (H1 and H2-histamine receptor antagonists) is also recommended, and in case of insufficiency of C1-esterase enzyme inactivators, the need to administer C1-esterase enzyme inhibitors in addition to epinephrine (adrenaline) can be considered. The patient should be hospitalized and monitored until symptoms are completely relieved, but not less than 24 hours.
Cases of intestinal angioedema, manifested by abdominal pain with or without nausea and vomiting, have been observed in patients receiving ACE inhibitors; in some cases, angioedema of the face was simultaneously observed. If a patient develops the symptoms described above during treatment with ACE inhibitors, the possibility of developing intestinal angioedema should be considered when making a differential diagnosis.
Treatment aimed at desensitization to insect venom (such as bees, wasps) and concomitant use of ACE inhibitors can initiate anaphylactic and anaphylactoid reactions (eg, decreased blood pressure, shortness of breath, vomiting, allergic skin reactions), which can sometimes be life-threatening. During treatment with ACE inhibitors, hypersensitivity reactions to insect venom (such as bees, wasps) develop faster and are more severe. If desensitization to insect venom is necessary, the ACE inhibitor should be temporarily replaced with a corresponding drug from another group.
Life-threatening, rapidly developing anaphylactoid reactions, sometimes leading to shock, have been described with the use of ACE inhibitors during hemodialysis or plasma filtration using certain high-flux membranes (for example, polyacrylonitrile membranes) (see also membrane manufacturer's instructions). The combined use of Ramipril and the use of this type of membrane, for example, for emergency hemodialysis or hemofiltration, should be avoided. In this case, it is preferable to use other types of membranes or avoid taking ACE inhibitors. Similar reactions were observed with low-density lipoprotein apheresis using dextran sulfate. Therefore, this method should not be used in patients receiving ACE inhibitors.
In patients with impaired liver function, the response to treatment with Ramipril may be either enhanced or weakened. In addition, in patients with severe liver cirrhosis with edema and/or ascites, significant activation of the RAAS is possible, so special care should be taken when treating these patients (see also section "Dosage and Administration").
Before surgery (including dental surgery), it is necessary to warn the surgeon/anesthesiologist about taking ACE inhibitors.
It is recommended to closely monitor neonates exposed in utero to ACE inhibitors for hypotension, oliguria, and hyperkalemia. In oliguria, it is necessary to maintain blood pressure and renal perfusion by administering appropriate fluids and vasoconstrictors. These neonates are at risk of developing oliguria and neurological disorders, possibly due to decreased renal and cerebral blood flow due to the decrease in blood pressure caused by ACE inhibitors.
Monitoring laboratory parameters before and during treatment with Ramipril up to 1 time per month in the first 3-6 months of treatment.
Monitoring kidney function (determining serum creatinine concentrations)
When treating with ACE inhibitors, it is recommended to monitor renal function in the first weeks of treatment and subsequently. Particularly careful monitoring is required in patients with acute and chronic heart failure, impaired renal function, after kidney transplantation, patients with renovascular diseases, including patients with hemodynamically significant unilateral renal artery stenosis in the presence of two kidneys (in such patients, even a slight increase in serum creatinine concentration may be indicator of decreased kidney function).
Electrolyte control
Regular monitoring of serum potassium and sodium levels is recommended. Particularly careful monitoring of potassium levels in the blood serum is required for patients with impaired renal function, significant disturbances in water and electrolyte balance, and chronic heart failure.
Monitoring of hematological parameters (hemoglobin, number of leukocytes, erythrocytes, platelets, leukocyte formula)
It is recommended to monitor the general blood test to identify possible leukopenia. More regular monitoring is recommended at the beginning of treatment and in patients with impaired renal function, as well as in patients with connective tissue diseases or in patients simultaneously receiving other drugs that can change the peripheral blood picture (see section "Interactions with other drugs") . Monitoring the number of leukocytes is necessary for the early detection of leukopenia, which is especially important in patients with an increased risk of its development, as well as at the first signs of infection. If neutropenia is detected (the number of neutrophils is less than 2000/μl), discontinuation of treatment with ACE inhibitors is required.
If symptoms due to leukopenia appear (for example, fever, enlarged lymph nodes, tonsillitis), urgent monitoring of the peripheral blood picture is necessary. If signs of bleeding appear (tiny petechiae, red-brown rashes on the skin and mucous membranes), monitoring the number of platelets in the peripheral blood is also necessary.
Determination of the activity of “liver” enzymes, the concentration of bilirubin in the blood
If jaundice or a significant increase in the activity of “liver” enzymes appears, treatment with the drug should be stopped and medical supervision of the patient should be provided.

Impact on the ability to drive vehicles and machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretic drugs).

Release form

Tablets 2.5 mg, 5.0 mg, 10.0 mg.
7, 10, 14, 25, 28 or 30 tablets in a blister pack made of polyvinyl chloride film and printed varnished aluminum foil.
10, 20, 30, 40, 50 or 100 tablets in jars made of polyethylene terephthalate for medicines or polypropylene for medicines, sealed with high-density polyethylene caps with first-opening control, or polypropylene caps with a “push-turn” system or caps from low-density polyethylene with first opening control.
One can or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 blister packs along with instructions for use are placed in a cardboard package (pack).

Storage conditions

In a place protected from light at a temperature not exceeding 25°C.
Keep out of the reach of children.

Best before date

3 years. Do not use after expiration date.

Vacation conditions

Available with prescription

Manufacturer:

Ozon LLC
Legal address: 445351, Russia, Samara region, Zhigulevsk, st. Pesochnaya, 11.
Address of production, including for correspondence and receipt of claims:
Russia, Samara region, Zhigulevsk, st. Gidrostroiteley, 6.