Ramipril-Acrihin pills 10mg, 30pcs

Composition

For 1 tablet of 10.00 mg:

Active ingredient:

ramipril – 10.00 mg.

Auxiliary substances:

lactose monohydrate (milk sugar) – 174.00 mg;

sodium bicarbonate-10.00 mg;

croscarmellose sodium-4.00 mg;

sodium stearyl fumarate-2.00 mg

Pharmacological action

Pharmacotherapy group: angiotensin converting enzyme (ACE) inhibitor ATX Code: C 09 AA 05

Pharmacological properties

Pharmacodynamics

The active metabolite of ramipril, ramiprilate, formed under the influence of “liver” enzymes, is a long – acting ACE inhibitor (ACE synonyms: kininase II, dipeptidyl carboxydipeptidase I), which is a peptidyl dipeptidase. ACE in blood plasma and tissues catalyzes the conversion of angiotensin I to angiotensin II, which has a vasoconstrictive effect, and the breakdown of bradykinin, which has a vasodilating effect.

Therefore, when taking ramipril orally, the formation of angiotensin II decreases and bradykinin accumulates, which leads to vasodilation and a decrease in blood pressure (BP). Ramipril causes an increase in the activity of the kallikrein-kinin system in 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 endotheliocytes, which determines its cardioprotective and endothelioprotective effects. Angiotensin II stimulates the production of aldosterone, so taking ramipril leads to a decrease in aldosterone secretion and an increase in the content of potassium ions in the blood serum.

With a decrease in the concentration of angiotensin II in the blood, 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 an increase in 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 (OPSS), causing virtually no changes in renal blood flow and glomerular filtration rate. The antihypertensive effect begins to develop 1-2 hours after ingestion of a single dose of the drug, reaching the highest value in 3-6 hours, and persists for 24 hours. With a course of ramipril, the antihypertensive effect may gradually increase, usually stabilizing by 3-4 weeks of regular use of the drug 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 and vascular wall hypertrophy.

In patients with chronic heart failure, ramipril reduces OPSS (reduces afterload on the heart), increases the capacity of the venous bed and reduces the filling pressure of the left ventricle, which, accordingly, leads to a decrease in preload on the heart. These patients experience increased cardiac output, ejection fraction, and improved exercise tolerance when taking ramipril. In diabetic and non-diabetic nephropathy, taking ramipril slows down the rate of progression of renal failure and the time of onset of end-stage renal failure and, therefore, 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 a high risk of developing cardiovascular diseases due to vascular lesions (diagnosed coronary heart disease, a history of peripheral artery obliterating diseases, a 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), the 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 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, initiated from 3 to 10 days of acute myocardial infarction, reduced mortality (by 27%), the risk of sudden death (by 30%), the risk of progression of heart failure to severe (NYHA functional class III-IV)/resistant to therapy (by 23%), the probability of subsequent hospitalization due to heart failure (by 26%).

In the general population of patients, as well as in patients with diabetes mellitus, both with arterial hypertension and with normal blood pressure, ramipril significantly reduces the risk of developing nephropathy and microalbuminuria.

Pharmacokinetics

After oral use, ramipril is rapidly absorbed from the gastrointestinal tract (50-60%). Simultaneous food intake slows down its absorption, but does not affect the completeness of absorption. Ramipril undergoes intensive presystemic metabolism / activation (mainly in the liver by hydrolysis), resulting in the formation of its only active metabolite, ramiprilate, whose activity with respect to ACE inhibition is approximately 6 times higher than that of ramipril. In addition, as a result of the metabolism of ramipril, diketopiperazine, which does not have pharmacological activity, is formed, which then undergoes conjugation with glucuronic acid, ramiprilate is also glucuronated and metabolized to diketopiperazic acid.

All the metabolites formed, with the exception of ramiprilate, have no pharmacological activity.

The bioavailability of ramipril after oral use ranges from 15% (for a dose of 2.5 mg) to 28% (for a dose of 5 mg). The bioavailability of the active metabolite, ramiprilate, after oral use of 2.5 mg and 5 mg of ramipril is approximately 45% (compared to its bioavailability after intravenous use at the same doses).

After oral use of ramipril, the maximum plasma concentrations of ramipril and ramiprilate are reached in 1 and 2-4 hours, respectively. The decrease in the plasma concentration of ramiprilate occurs in several stages: a phase of distribution and elimination with a half-life (T 1/2) of ramiprilate of approximately 3 hours, then an intermediate phase with T 1/2 of ramiprilate of approximately 15 hours, and an end phase with a very low concentration of ramiprilate in blood plasma and T 1/2 of ramiprilate of approximately 4-5 days.

This final phase is due to the slow release of ramiprilate from a strong binding to ACE receptors. Despite the prolonged end-phase, with a single oral dose of 2.5 mg or more per day, the steady-state plasma concentration of ramiprilate is reached after approximately 4 days of treatment. With the course use of the drug “effective” T 1/2, depending on the dose, is 13-17 hours.

Plasma protein binding is approximately 73% for ramipril and 56% for ramiprilate.

After intravenous use, the volume of distribution of ramipril and ramiprilate is approximately 90 L and approximately 500 L, respectively.

After ingestion of radiolabeled ramipril (10 mg),39% of the radioactivity is excreted through the intestines and about 60% by the kidneys. After intravenous use of ramipril,50-60% of the dose is detected in the urine in the form of ramipril and its metabolites. After intravenous use of ramiprilate, about 70% of the dose is detected in the urine in the form of ramiprilate and its metabolites, in other words, with intravenous use of ramipril and ramiprilate, a significant part of the dose is excreted through the intestine with bile, bypassing the kidneys (50% and 30%, respectively). After oral use of 5 mg of ramipril in patients with bile duct drainage, almost identical amounts of ramipril and its metabolites are excreted by the kidneys and through the intestines within the first 24 hours after ingestion.

Approximately 80-90% of the metabolites in the urine and bile were identified as ramiprilate and ramiprilate metabolites. Ramipril glucuronide and ramipril diketopiperazine account for approximately 10-20% of the total amount, and the urinary content of unmetabolized ramipril is approximately 2%.

In animal studies, ramipril has been shown to be excreted in human milk.

In patients with impaired renal function, creatinine clearance (CC) is less than 60 ml/min. the elimination of ramiprilate and its metabolites by the kidneys slows down. This leads to an increase in the plasma concentration of ramiprilate, 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 slowdown in the presystemic metabolism of ramipril to active ramiprilate and a slower elimination of ramiprilate.

No clinically significant accumulation of ramipril and ramiprilate was observed in healthy volunteers and in patients with arterial hypertension after two weeks of treatment with ramipril at a daily dose of 5 mg.

In patients with chronic heart failure, after two weeks of treatment with ramipril in a daily dose of 5 mg, there is a 1.5-1.8 fold increase in plasma concentrations of ramiprilate and the area under the pharmacokinetic curve “concentration-time” (AUC).

In healthy elderly volunteers (65-76 years), the pharmacokinetics of ramipril and ramiprilat did not significantly differ from those in young healthy volunteers.

Indications

• Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs, for example, diuretics and slow calcium channel blockers).
• Chronic heart failure (as part of combination therapy, in particular, in combination with diuretics).
• Diabetic or non-diabetic nephropathy, preclinical and clinically expressed stages, including severe proteinuria, especially in combination 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, myocardial infarction in the anamnesis or without it, including patients undergoing percutaneous transluminal coronary angioplasty, coronary artery bypass grafting;
  • patients with a stroke history;
  • in patients with occlusive lesions of the peripheral arteries in history;
  • in patients with diabetes with at least one additional risk factor (microalbuminuria, arterial hypertension, increased plasma concentrations of OH, the decline in plasma concentrations of HDL-C, Smoking).
• Heart failure with clinical manifestations that developed during the first few days (from day 2 to day 9) after acute myocardial infarction.

Use during pregnancy and lactation

Ramipril is contraindicated during pregnancy, as it can have an adverse effect on the fetus: impaired fetal kidney development, decreased fetal and newborn blood pressure, impaired renal function, hyperkalemia, cranial hypoplasia, oligohydramnion, limb contracture, cranial deformity, lung hypoplasia. Therefore, before taking the drug in women of childbearing age, pregnancy should be excluded. If a woman is planning pregnancy, then treatment with ACE inhibitors should be discontinued. If pregnancy is confirmed during treatment with Ramipril, you should stop taking it as soon as possible and transfer the patient to other medications that will reduce the risk to the child. If treatment with Ramipril is necessary during breast-feeding, then breastfeeding should be discontinued.

Contraindications

• Hypersensitivity to ramipril, other ACE inhibitors or any component of the drug;
• angioedema (hereditary or idiopathic, and after receiving ACE inhibitors) in history – the risk of rapid development of angioedema;
• hemodynamically significant renal artery stenosis (bilateral or unilateral in the case of a solitary kidney);
• hypotension (systolic blood pressure less than 90 mm Hg. Hg), or condition with unstable hemodynamics;
• concomitant use of drugs containing aliskiren in patients with diabetes and/or moderate or severe renal insufficiency (creatinine clearance (CC) of less than 60 ml/min/1.73 m2 body surface).
• the simultaneous use of receptor antagonists to angiotensin II in patients with diabetic nephropathy;
• hemodynamically significant stenosis of the aortic or mitral valve, or hypertrophic obstructive cardiomyopathy;
• primary aldosteronism;
• severe renal insufficiency – CC less than 20 ml/min/1.73 m2 body surface (clinical experience is insufficient);
• hemodialysis (clinical experience is insufficient);
• pregnancy/lactation;
• nephropathy, treatment of which is held by corticosteroids, nonsteroidal anti-inflammatory drugs, immunomodulators, and/or other cytotoxic drugs (clinical experience is insufficient);
• chronic heart failure in the stage of decompensation (clinical experience is insufficient);
• the age of 18 (clinical experience is insufficient);
• hemodialysis or hemofiltration using some of membranes with negatively charged surface, such as high-flow membrane of polyacrylnitrile (the risk of severe anaphylactic reactions);
• apheresis of low-density lipoproteins using the dextran sulfate (the risk of severe anaphylactic reactions);
• hyposensitization therapy for hypersensitivity reactions to poisons insects such as bees, 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 (NYHA functional class IV);
• unstable angina;
• life – threatening ventricular arrhythmias;
• “pulmonary” heart.

With caution

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

• severe hypertension, particularly malignant hypertension;
• congestive heart failure, especially heavy or accept other drugs with antihypertensive properties;
• unilateral hemodynamically significant renal artery stenosis (in the presence of both kidneys) – in these patients, even a slight increase in the concentration of creatinine in the blood serum may be a manifestation of unilateral deterioration of renal function;
• prior to the use of diuretics;
• disruption of water and electrolyte balance due to insufficient fluid intake and salt, diarrhoea, vomiting, sweating.

Impaired liver function (lack of experience with the use of ramipril: it is possible to increase or weaken the effects of ramipril; in the presence of cirrhosis of the liver with ascites and edema, significant activation of RAAS is possible). Impaired renal function (creatinine clearance greater than 20 ml / min/1.73 m2 of body surface area)due to the risk of 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 suppression of bone marrow hematopoiesis, development of neutropenia or agranulocytosis) (see the section “Interaction with other drugs”). Diabetes mellitus (risk of hyperkalemia). Advanced age (risk of increased antihypertensive effect).

Side effects

The undesirable effects listed below are listed according to the following gradations in their frequency: very common (> 10%); common (>> 1%, >>< 10%); infrequently (> 0,1%, < 10%); infrequently (>< 1%); rarely (> 0.01%,0.1%); very rarely (< 1%); rarely (>Cardiac disorders: infrequently – myocardial ischemia, including the development of an angina attack or myocardial infarction, tachycardia, arrhythmias (appearance or increase), palpitations, peripheral edema. Vascular disorders: often-excessive decrease in blood pressure, violation of orthostatic regulation of vascular tone (orthostatic hypotension), syncopal states; infrequently – “hot flashes” of blood to the skin of the face; rarely – occurrence or increase of circulatory disorders against the background of stenosing vascular lesions, vasculitis; frequency unknown-Raynaud’s syndrome. Nervous system disorders: often-headache, dizziness (a feeling of “lightness” in the head); infrequently-vertigo, paresthesia, ageusia (loss of taste sensitivity), dysgeusia (impaired taste sensitivity); rarely-tremor, balance disorders; frequency unknown – cerebral ischemia, including ischemic stroke and transient cerebrovascular accident, psychomotor reactions, burning sensation, parosmia (impaired perception of odors). Visual disorders: infrequently-visual disorders, including blurred vision; rarely-conjunctivitis. Hearing disorders: rarely – hearing disorders, tinnitus. Mental disorders: infrequently-depression, anxiety, nervousness, motor restlessness, sleep disorders, including drowsiness; rarely-confusion; frequency unknown-attention disorders. Respiratory system disorders: often – ” dry “cough (worse at night and in the “lying” position), bronchitis, sinusitis, shortness of breath; infrequently – bronchospasm, including worsening of the course of bronchial asthma, nasal congestion. Disorders of the gastrointestinal tract: often-inflammatory reactions in the stomach and intestines, digestive disorders, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting; infrequently-fatal pancreatitis, includingincreased activity of pancreatic enzymes in blood plasma, intestinal angioedema, upper abdominal pain, including those associated with gastritis, constipation, dryness of the oral mucosa; rarely – glossitis; frequency unknown – aphthous stomatitis (inflammatory reaction of the oral mucosa). Liver and biliary tract disorders: infrequently-increased activity of “liver” enzymes and the concentration of conjugated bilirubin in blood plasma; rarely-cholestatic jaundice, hepatocellular lesions; frequency unknown-acute liver failure, cholestatic or cytolytic hepatitis (fatal outcome was extremely rare). Renal and urinary tract disorders: infrequently-impaired renal function, including the development of acute renal failure, increased urinary excretion, increased pre-existing proteinuria, increased blood urea and creatinine concentrations. Disorders of the reproductive system and mammary glands: infrequently-transient impotence due to erectile dysfunction, decreased libido; frequency unknown-gynecomastia. Disorders of the blood 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 the concentration of hemoglobin, thrombocytopenia; frequency unknown – inhibition of bone marrow hematopoiesis, pancytopenia, hemolytic anemia. Disorders of the skin and subcutaneous tissues: often – skin rash, in particular, maculopapular; infrequently – angioedema, including with a fatal outcome (laryngeal edema can cause airway obstruction, leading to death), pruritus, hyperhidrosis (increased sweating); rarely – exfoliative dermatitis, urticaria, onycholysis; very rarely – photosensitization reactions; frequency unknown – toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, psoriasis aggravation, psoriasis-like dermatitis, pemphigoid or lichenoid (lichen-like) exanthema or enanthema, alopecia. Musculoskeletal and connective tissue disorders: often-muscle cramps, myalgia; infrequently-arthralgia. Endocrine system disorders: frequency unknown-syndrome of inadequate secretion of antidiuretic hormone. Metabolic and nutritional disorders: often-an increase in the concentration of potassium in the blood; infrequently – anorexia, decreased appetite; frequency unknown-a decrease in the concentration of sodium in the blood. Immune system disorders: frequency unknown – anaphylactic or anaphylactoid reactions (with ACE inhibition, the number of anaphylactic or anaphylactoid reactions to insect poisons increases), an increase in the titer of antinuclear antibodies. Common disorders: often-chest pain, feeling tired; infrequently-fever; rarely-asthenia (weakness).

Interaction

Contraindicated combinations

The use of some high-flow membranes with a negatively charged surface (for example, polyacrylonitrile membranes) during hemodialysis or hemofiltration; the use of dextran sulfate for low-density lipoprotein apheresis.

Risk of developing severe anaphylactoid reactions. If the patient needs these procedures, then other types of membranes should be used (in the case of plasmapheresis and hemofiltration) or the patient should be transferred to antihypertensive drugs of other groups.

Simultaneous 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 insufficiency with creatinine clearance

Concomitant use of Ramipril and angiotensin II receptor antagonists (ARA II)

Concomitant 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”).

Not recommended combinations

With potassium salts, potassium-sparing diuretics (for example, amiloride, triamterene, spironolactone, eplerenone), other drugs that can increase the content of potassium in the blood serum (including ARA II, tacrolimus, cyclosporine, trimethoprim, sulfamethoxazole, which are part of cotrimoxazole (a combined antibacterial agent containing sulfamethoxazole and trimethoprim)).

It is possible to increase the content of potassium in the blood serum, sometimes significantly pronounced (with simultaneous use, careful monitoring of the content 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 reduce blood pressure (nitrates, tricyclic antidepressants, general and local anesthesia, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin) – potentiation of the antihypertensive effect; when combined with diuretics, the serum sodium content should be regularly monitored.

With sleeping pills, narcotic drugs, and painkillers – a more pronounced decrease in blood pressure is possible.

With vasopressor sympathomimetics (epinephrine (epinephrine), isoproterenol, dobutamine, dopamine) – reducing the antihypertensive effect of Ramipril, especially 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 developing hematological reactions.

With lithium salts-an increase in the serum concentration of lithium and an increase in the cardio – and neurotoxic effects of lithium. Therefore, the lithium content in the blood serum should be monitored.

With hypoglycemic agents (for example, insulins, hypoglycemic agents for oral use (sulfonylureas, biguanides)) – due to the decrease in insulin resistance under the influence of ACE inhibitors, it is possible to increase the hypoglycemic effect of these drugs, up to the development of hypoglycemia. Especially careful monitoring of blood glucose concentrations is recommended at the beginning of their combined use with ACE inhibitors.

With dipeptidyl peptidase type IV (DPP-IV) inhibitors (gliptins), for example, sitagliptin, saxagliptin, vildagliptin, linagliptin-in patients taking ACE inhibitors and gliptins simultaneously, an increase in the incidence of angioedema was observed.

With racecadotril (an enkephalinase inhibitor used to treat acute diarrhea) – increased risk of angioedema.

With estramustine – increased risk of angioedema.

With mTOR inhibitors( mammalian Target of Rapamycin-the target of rapamycin in mammalian cells), for example, temsirolimus, sirolimus, everolimus-in patients taking both ACE inhibitors and mTOR inhibitors, an increase in the incidence of angioedema was observed.

Combinations to take into account

With nonsteroidal anti-inflammatory drugs (Indometacin, acetylsalicylic acid (more than 3 g / day)) – it is possible to weaken the effect of ramipril, increase the risk of impaired renal function and increase the content of potassium in the blood serum.

With heparin – it is possible to increase the content of potassium in the blood serum.

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 effect of ethanol on the body.

With estrogens-weakening of the antihypertensive effect of ramipril (fluid retention).

Desensitizing therapy for hypersensitivity to insect poisons-ACE inhibitors, including Ramipril, increase the likelihood of developing severe anaphylactic or anaphylactoid reactions to insect poisons. It is assumed that this effect may also occur with the use of other allergens.

How to take, course of use and dosage

The drug Ramipril-Akrikhin is taken orally, swallowed whole (without chewing) and washed down with a sufficient amount (1/2 cup) of water, regardless of food intake (i. e. tablets can be taken both before, during or after meals). With arterial hypertension. Usually, the initial dose of Ramipril-Akrikhin is 2.5 mg once a day in the morning. The dose may be increased to 5 mg ramipril per day. The maximum recommended daily dose is 10 mg per day. As an alternative to increasing the dose to 10 mg per day, if the therapeutic effectiveness of the daily dose of 5 mg is insufficient, it is possible to add other antihypertensive agents to the treatment, in particular, diuretics or slow calcium channel blockers (BMCC). In case of chronic heart failure. The recommended initial dose of Ramipril-Akrikhin is 1.25 mg once a day. Depending on the patient’s response to the therapy, the dose may increase. 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 taken 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 initial dose of Ramipril-Akrikhin is 1.25 mg once a day. The dose can be increased to 5 mg once a day. In these conditions, doses greater than 5 mg once daily have not been sufficiently studied in controlled clinical trials. To reduce the risk of myocardial infarction, stroke, or cardiovascular mortality in patients at high cardiovascular risk. The recommended initial dose of Ramipril-Akrikhin 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 during the next 3 weeks of treatment – increase it to the usual maintenance dose of 10 mg 1 time per day. Doses exceeding 10 mg have not been sufficiently studied in controlled clinical trials. The use of Ramipril-Akrikhin in patients with creatinine clearance less than 0.6 ml / s has not been sufficiently studied. In case of heart failure that developed during the first few days (2-9 days) after acute myocardial infarction. The recommended initial dose of Ramipril-Akrikhin is 5 mg per day, divided into 2 single doses of 2.5 mg, one of which is taken in the morning and the second in the evening. If the patient does not tolerate this initial dose (there is an excessive decrease in blood pressure), then he is recommended to give 1.25 mg 2 times a day for two days. Then, depending on the patient’s response, the dose can be increased. It is recommended that the dose should be doubled at intervals of 1-3 days if increased. 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 heart failure (NYHA functional Class III-IV) that occurred immediately after acute myocardial infarction is insufficient. If these patients decide to start treatment with Ramipril-Akrihine, it is recommended that treatment should start with the lowest possible dose – 1.25 mg once a day, and special care should be taken with each dose increase. Use of Ramipril-Acriquine in selected groups of patientspatients with impaired renal function. For creatinine clearance from 50 to 20 ml / min/1.73 m2, the initial daily dose is usually 1.25 mg. The maximum allowable daily dose is 5 mg. Patients with incomplete corrected fluid and electrolyte loss, 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 damage to the coronary and cerebral arteries). The initial dose is reduced to 1.25 mg per day. Patients with previous diuretic therapy. If possible, discontinue diuretics 2-3 days in advance (depending on the duration of action of diuretics) before starting treatment with Ramipril-Acriquine, or at least reduce the dose of diuretics taken. Treatment of such patients should begin with the lowest dose of 1.25 mg ramipril, taken once a day, in the morning. After taking the first dose and each time after increasing the dose of ramipril and / or loop diuretics, patients should be under medical supervision for at least 8 hours to avoid an uncontrolled hypotensive reaction. Elderly patients (over 65 years of age). The initial dose is reduced to 1.25 mg per day. Patients with impaired liver function. The blood pressure response to Ramipril-Acriquine may either increase (due to slowing down the elimination of ramiprilate) or decrease (due to slowing down the conversion of low-level ramipril to active ramiprilate). Therefore, careful medical supervision is required at the beginning of treatment. The maximum allowable daily dose is 2.5 mg.

Overdose

Symptoms: excessive peripheral vasodilation with the development of a pronounced decrease in blood pressure, shock; bradycardia, water and electrolyte disorders, acute renal failure, stupor. Treatment: gastric lavage, intake of adsorbents, sodium sulfate (if possible during the first 30 minutes). In the case of a marked decrease in blood pressure, the use of alpha-1-adrenergic agonists (norepinephrine, dopamine) and angiotensin II agonists (angiotensinamide) can be added to therapy to replenish the volume of circulating blood and restore water-electrolyte balance disorders. If bradycardia is refractory to medical treatment, it may be necessary to install a temporary pacemaker. In case of overdose, serum creatinine concentrations and electrolyte levels should be monitored. Hemodialysis is indicated in cases of renal failure.

Special instructions

Before starting treatment with Ramipril, hyponatremia and hypovolemia should be eliminated. In patients who have previously taken diuretics, they should be discontinued or at least their dose reduced 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 with an increase in the volume of circulating blood).

After taking the first dose of the drug, as well as when increasing its dose and/or the dose of diuretics (especially “loop”), it is necessary to ensure careful medical supervision of the patient for at least 8 hours in order to take timely appropriate measures 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, then their blood pressure should be carefully monitored, especially at the beginning of treatment, since these patients have an increased risk of excessive blood pressure reduction (see the section “With caution”).

In patients with 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 – the development of acute renal failure.

Caution should be exercised in the treatment of elderly patients, as they may be particularly sensitive to ACE inhibitors, and it is recommended to monitor renal function indicators in the initial phase of treatment (see also the section “Dosage and use”).

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 exercise and / or hot weather because of the risk of increased sweating and dehydration with the development of hypotension, due to a decrease in the volume of circulating blood and a decrease in the content of sodium in the blood.

During treatment with Ramipril, it is not recommended to consume alcohol (ethanol).

A temporary excessive decrease in blood pressure is not a contraindication for continuing treatment after blood pressure stabilization. In case of repeated development of a pronounced decrease in blood pressure, the dose should be reduced or the drug should be discontinued.

Concomitant 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 excessive lowering of blood pressure, 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 insufficiency with creatinine clearance 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.

Angioedema of the face, extremities, lips, tongue, pharynx, or larynx has been reported in patients treated with ACE inhibitors. If there is swelling in the face (lips, eyelids) or tongue, or difficulty swallowing or breathing, the patient should immediately stop taking the drug. Angioedema localized in the tongue, pharynx or larynx (possible symptoms: swallowing or breathing disorders) can be life-threatening and requires urgent measures to stop it: subcutaneous use of 0.3-0.5 mg or intravenous drip of 0.1 mg of epinephrine (epinephrine) (under the control of blood pressure, heart rate and ECG), followed by the use of glucocorticosteroids (IV, iv or inside); intravenous use of antihistamines (H1 antagonists) is also recommended. and H2-histamine receptors), and in case of insufficient inactivators of the C1-esterase enzyme, the need to introduce inhibitors of the C1-esterase enzyme in addition to epinephrine (epinephrine) may be considered.

The patient should be hospitalized and monitored until symptoms are completely relieved, but not less than 24 hours. In patients treated with ACE inhibitors, cases of intestinal angioedema were observed, which was manifested by abdominal pain with or without nausea and vomiting; in some cases, angioedema of the face was also observed simultaneously. If a patient develops the above symptoms during treatment with ACE inhibitors, the possibility of developing intestinal angioedema should also be considered during the differential diagnosis.

Treatment aimed at desensitization to insect venom (such as bees, wasps) and simultaneous use of ACE inhibitors can initiate anaphylactic and anaphylactoid reactions (for example, decreased blood pressure, shortness of breath, vomiting, allergic skin reactions), which can sometimes be life-threatening. Against the background of treatment with ACE inhibitors, hypersensitivity reactions to the venom of insects (such as bees, wasps) develop faster and are more severe. If desensitization to insect venom is necessary, then the ACE inhibitor should be temporarily replaced with an appropriate drug of another group.

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 the instructions of membrane manufacturers). It is necessary to avoid the combined use of Ramipril and the use of this type of membrane, for example, for urgent hemodialysis or hemofiltration. In this case, it is preferable to use other types of membranes or exclude the use of ACE inhibitors. Similar reactions were observed in low-density lipoprotein apheresis with 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 cirrhosis of the liver with edema and / or ascites, significant activation of the RAAS is possible, so special care should be taken when treating these patients (see also the section “Dosage and use”). Before surgery (including dental surgery), the surgeon/anesthesiologist should be warned about taking ACE inhibitors.

It is recommended that newborns who have been exposed to ACE inhibitors in utero should be closely monitored for hypotension, oliguria, and hyperkalemia.

With oliguria, it is necessary to maintain blood pressure and renal perfusion by introducing appropriate fluids and vasoconstrictors. These newborns are at risk of developing oliguria and neurological disorders, possibly due to reduced renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors.

Monitoring of laboratory parameters before and during treatment with Ramipril up to 1 time per month in the first 3-6 months of treatment.

Monitoring of renal function (determination of serum creatinine concentrations)

During treatment with ACE inhibitors, monitoring of renal function is recommended during the first weeks of treatment and thereafter. Especially 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 with two kidneys (in such patients, even a slight increase in serum creatinine concentration can be an indicator of decreased renal function).

Monitoring of the electrolyte content

Regular monitoring of serum potassium and sodium levels is recommended. Especially careful monitoring of the potassium content in the blood serum is required in patients with impaired renal function, significant violations of the water-electrolyte balance, and chronic heart failure.

Monitoring of hematological parameters (hemoglobin, number of white blood cells, red blood cells, platelets, leukocyte formula)

It is recommended to monitor the indicators of a general blood test 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 receiving other medications that can change the peripheral blood picture at the same time (see the section “Interaction with other medications”). Monitoring the number of white blood cells is necessary for early detection of leukopenia, which is especially important in patients with an increased risk of developing it, 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. In case of signs of bleeding (small petechiae, red-brown rashes on the skin and mucous membranes), it is also necessary to monitor the number of platelets in the peripheral blood.

Determination of the activity of “liver” enzymes, bilirubin concentration in the blood

If jaundice or a significant increase in the activity of “liver” enzymes occurs, treatment with the drug should be discontinued and the patient should be monitored by a doctor.

Influence on the ability to drive vehicles and mechanisms

During treatment, caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions (dizziness may occur, especially after the initial dose of an ACE inhibitor in patients taking diuretics).

Storage conditions

In a dark place at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date.

Active ingredient

Ramipril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets