Amprilan, 2.5mg pills, 30pcs

Composition

Active ingredient:  

ramipril – 2.5 mg/ 1 tablet.

Auxiliary substances:

sodium bicarbonate,

lactose monohydrate,

croscarmellose sodium,

pregelatinized starch,

sodium stearyl fumarate.

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 action of “liver” enzymes, is a long – acting ACE inhibitor (ACE synonyms: kininase II, dipeptidyl carboxydipeptidase I). 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 plasma and tissues with activation of the prostaglandin system and an increase in the synthesis of prostaglandins that stimulate the formation of nitric oxide (N0) in endotheliocytes, which determines its cardioprotective effect.

Angiotensin II stimulates the production of aldosterone, so taking ramipril leads to a decrease in aldosterone secretion and an increase in serum potassium.

With a decrease in the concentration of angiotensin II in blood plasma, 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 reactions (in particular, “dry” cough) is 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 manifest itself 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 taking the drug Amprilan, the antihypertensive effect may gradually increase, usually stabilizing by 3-4 weeks of regular 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 and vascular wall hypertrophy.

In patients with chronic heart failure (CHF) ramipril reduces OPSS (reduces afterload on the heart), increases the capacity of the venous bed and reduces the filling pressure of the left ventricle (LV), which, accordingly, leads to a decrease in preload on the heart. These patients experienced increased cardiac output, LV ejection fraction (LVEF), 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 reduces the incidence of myocardial infarction, stroke, and cardiovascular mortality.

In addition, ramipril reduces overall mortality rates, as well as the need for revascularization procedures, and slows the onset or progression of CHF.

In patients with heart failure with clinical manifestations that developed in the first days of acute myocardial infarction (2-9 days), the use of ramipril, initiated from the 3rd to the 10th day of acute myocardial infarction, reduced mortality (by 27%), the risk of sudden death (by 30%), the risk of progression of heart failure to severe (NYSE functional class III-IV)/resistant to therapy (by 23%), the probability 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 with normal blood pressure indicators, ramipril reduces the risk of developing nephropathy and microalbuminuria.

Pharmacokinetics

After oral use, ramipril is rapidly absorbed from the gastrointestinal tract (50-60%). 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 ramipril metabolism, 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.

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 during the day, the equilibrium 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 eliminated 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 with creatinine clearance (CC) 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 CHF, after two weeks of treatment with ramipril at 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 concentration-time curve (AUC).

In healthy elderly volunteers (65-75 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 nephropathy or non-diabetic nephropathy, preclinical and clinically expressed stages, including those with 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 total Cholesterol, reduced plasma concentrations of HDL-C, Smoking).
• Heart failure with clinical manifestations that developed within the first few days (from the 2nd to the 9th day) after acute myocardial infarction (see the section “Pharmacodynamics”).

Use during pregnancy and lactation

The drug Amprilan is contraindicated during pregnancy, as it can have an adverse effect on the fetus: impaired renal development of the fetus, decreased blood pressure of the fetus and newborns, impaired renal function, hyperkalemia, hypoplasia of the skull bones, hypoplasia of the lungs.

Therefore, before taking the drug in women of childbearing age, pregnancy should be excluded.

If a woman is planning pregnancy, then treatment with an ACE inhibitor should be discontinued.

If pregnancy occurs during treatment with Amprilan, 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 Amprilan is necessary during breastfeeding, then breast-feeding should be discontinued.

Contraindications

• Hypersensitivity to ramipril, other ACE inhibitors or any of the components of the drug (see the section “Composition”).
• Angioedema (hereditary or idiopathic, as well as after taking ACE inhibitors) in the anamnesis – the risk of rapid development of angioedema (see the section “Side effects”).
• Hemodynamically significant renal artery stenosis (bilateral or unilateral in the case of a single kidney).
• Arterial hypotension (systolic blood pressure less than 90 mm Hg) or conditions with unstable hemodynamic parameters.
• Hemodynamically significant aortic or mitral valve stenosis or hypertrophic obstructive cardiomyopathy (HOCMP).
• Primary hyperaldosteronism.
• Severe renal insufficiency (creatinine clearance less than 20 ml / min at a body surface of 1.73 m) (insufficient clinical experience).
• Nephropathy that is treated with glucocorticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), immunomodulators, and/or other cytostatic agents (there is insufficient clinical experience, see the section “Interaction with other drugs”).
• CHF in the stage of decompensation (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 hypersensitivity reactions) (see sections “Interaction with other medicinal products”, “Special instructions”).
• Low-density lipoprotein (LDL) apheresis using dextran sulfate (risk of hypersensitivity reactions) (see section “Special instructions”).
• Desensitizing therapy for hypersensitivity reactions to insect poisons, such as bees and wasps (see section “Special instructions”).
• Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal insufficiency with creatinine clearance less than 60 ml/min.
• Concomitant use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy.
• Pregnancy.
• Breast-feeding period.
• Age up to 18 years (experience in clinical use is insufficient).
• Lactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

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

• Severe heart failure (NYHA Functional Class IV).
• Unstable angina pectoris.
• Life – threatening ventricular arrhythmias.
• “Pulmonary” heart.

With caution

• 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 activity of the renin-angiotensin-aldosterone system (RAAS), in which ACE inhibition is associated with a risk of a sharp decrease in blood pressure with impaired renal function:
• severe hypertension, especially malignant hypertension;
• CHF, particularly serious or for which you taken other drugs with antihypertensive properties;
• unilateral hemodynamically significant renal artery stenosis (in the presence of both kidneys);
• 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 both increase and weaken the effects of ramipril; in the presence of cirrhosis of the liver with ascites and edema, significant activation of RAAS is possible, see above “Conditions accompanied by increased RAAS activity”).
• Impaired renal function (creatinine clearance greater than 20 ml / min at a body surface of 1.73 m2)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).
• Elderly patients (risk of increased antihypertensive effect).
• Hyperkalemia.
• Concomitant use of Amprilan with drugs containing aliskiren or ARA II (with double blockade of the 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”).

Side effects

Classification of the incidence of side effects recommended by the World Health Organization (WHO):

• very common > 1/10>
• common > 1/100 to >< 1/10
• uncommon > 1/1000 to >< 1/100
• rare > 1/10000 to >< 1/1000
• very rare < 1/10000
• frequency unknown – cannot be estimated based on available data.

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, vertigo (a feeling of “lightness” in the head);

infrequent: vertigo, paresthesia, ageusia (loss of taste sensitivity), dysgeusia (violation of taste sensitivity); rare: tremor, impaired balance; frequency unknown: cerebral ischemia, including ischemic stroke and transient ischemic stroke, impaired psychomotor reactions (reduction reaction), a burning sensation, parosmia (violation of the perception of odors).

Visual impairment:

infrequently: visual disturbances, including blurred images; rarely: conjunctivitis.

Hearing disorders:

rare: hearing loss, ringing in the ears.

Mental disorders:

infrequently: depressed mood, anxiety, nervousness, motor restlessness, sleep disturbance, including drowsiness; rarely: confusion; frequency unknown: attention disorder.

Respiratory, thoracic and mediastinal 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 digestive system:

often: inflammatory reactions in the stomach and intestines, digestive disorders, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting; infrequently: fatal pancreatitis (cases of pancreatitis with a fatal outcome when taking ACE inhibitors were extremely rare), increased activity of pancreatic enzymes in blood plasma, angioedema of the small intestine, upper abdominal pain, including 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).

Kidney and urinary tract disorders:

infrequently: impaired renal function, including the development of acute renal failure, increased urinary excretion, increased pre-existing proteinuria, increased plasma urea and creatinine concentrations.

Genital and breast disorders:

infrequently: transient impotence due to erectile dysfunction, decreased libido; frequency unknown: gynecomastia.

Blood and lymphatic system disorders:

infrequently: eosinophilia; rarely: leukopenia, including non-atropenia and agranulocytosis, decreased peripheral red blood cell count, decreased hemoglobin, thrombocytopenia; frequency unknown: inhibition of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.

Skin and subcutaneous tissue disorders:

common: skin rash, particularly maculopapular; infrequent: angioedema, including those 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, aggravation of the course of psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (lichen-like) exanthema or enanthema, alopecia.

Musculoskeletal and connective tissue disorders:

common: muscle cramps, myalgia; uncommon: arthralgia.

Endocrine system disorders:

frequency unknown: syndrome of inadequate antidiuretic hormone secretion (ADH SNA).

Metabolic and nutritional disorders:

often: increased blood plasma potassium; infrequently: anorexia, decreased appetite; frequency unknown: decreased blood sodium content.

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.

General disorders and disorders at the injection site:

often: chest pain, increased fatigue; infrequently: fever; rarely: asthenia (weakness).

Interaction

Vasopressor sympathomimetics (epinephrine, norepinephrine) may reduce the hypotensive effect of ramipril. With the simultaneous use of these drugs, the level of blood pressure should be carefully monitored.

ACE inhibitors enhance the inhibitory effect of ethanol on the central nervous system.

Lithium preparations: with simultaneous use of lithium preparations and ACE inhibitors, cases of reversible increase in the concentration of lithium in the blood serum have been reported. Concomitant use with thiazide diuretics may increase the concentration of lithium and the risk of its toxic effect against the background of taking an ACE inhibitor. NSAIDs

: combination of ACE inhibitors with NSAIDs (non-selective COX-1 and COX-2 inhibitors from the NSAID group, for example, acetylsalicylic acid in doses that have an anti-inflammatory effect): the hypotensive effect of ACE inhibitors decreases; the risk of impaired renal function increases, up to the development of acute renal failure; the serum potassium content increases in patients with pre-existing renal dysfunction.

Tricyclic antidepressants, antipsychotics (neuroleptics): they enhance the hypotensive effect and increase the risk of orthostatic hypotension (additive effect).

GCS, tetracosactide: reduction of the hypotensive effect (fluid retention).

Potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone) and potassium preparations: the combined use of ramipril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing salt substitutes is not recommended.

Care should be taken and regular monitoring of the potassium content in the blood plasma and ECG parameters should be carried out.

Hypoglycemic agents for oral use (sulfonylurea derivatives) and insulin: the use of ACE inhibitors may increase the hypoglycemic effect of oral hypoglycemic agents and insulin in patients with diabetes mellitus; when they are used together, glucose tolerance may increase, which may require dose adjustment of oral hypoglycemic agents and insulin.

Allopurinol, cytostatic drugs, immunosuppressants, corticosteroids (for systemic use) and procainamide: concomitant use of these drugs with ACE inhibitors may increase the risk of leukopenia.

General anesthesia products: ACE inhibitors may enhance the antihypertensive effect of some general anaesthetics.

Gold preparations: when prescribing ACE inhibitors, including ramipril, to patients receiving gold (sodium aurothiomalate) intravenously, nitrate-like reactions (nausea, vomiting, a marked decrease in blood pressure, hyperemia of the facial skin) were noted.

How to take, course of use and dosage

The tablet should be taken orally regardless of the time of the meal (that is, tablets can be taken both before, during or after a meal) and washed down with a sufficient amount (1/2 cup) of water. Do not chew or crush the tablets before taking them.

The dose is selected depending on the therapeutic effect and tolerability of the drug by the patient.

Treatment with Amprilan is usually long-term, and its duration is determined by the doctor on a case-by-case basis.

Unless otherwise prescribed, the following dosage regimens are recommended for normal renal and hepatic function.

With arterial hypertension

Usually, the initial dose is 2.5 mg once a day in the morning. If taking Amprilan® at this dose for 3 weeks or more fails to normalize blood pressure, the dose can be increased to 5 mg per day. If the 5 mg dose is not effective enough, it can be doubled again after 2 to 3 weeks to the maximum recommended daily dose of -10 mg.

As an alternative to increasing the dose to 10 mg per day with insufficient antihypertensive effectiveness of a daily dose of 5 mg, it is possible to add other antihypertensive agents, in particular, diuretics or slow calcium channel blockers.

With CHF

The recommended starting dose 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 used either once a day or divided into two doses.

The maximum recommended daily dose is 10 mg.

For diabetic or non-diabetic nephropathy

The recommended starting dose is 1.25 mg once a day.

The dose can be increased to 5 mg once a day. In these conditions, doses above 5 mg once a day 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 starting dose is 2.5 mg once a day.

Depending on the patient’s tolerance to Amprilan, the dose may 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. The use of a dose exceeding 10 mg per day has not been sufficiently studied in controlled clinical trials.

The use of the drug in patients with creatinine clearance less than 0.6 ml / sec has not been sufficiently studied.

In case of 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 of 2.5 mg, which are taken one 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 take 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. Further, the total daily dose, which was initially divided into two doses, can be used 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 such patients decide to start treatment with Amprilan, 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 Amprilan in selected groups of patients

Patients with impaired renal function

For creatinine clearance from 50 to 20 ml / min per 1.73 m of body surface area, the initial daily dose is usually 1.25 mg. The maximum allowable daily dose is 5 mg.

Patients with incompletely 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 / day.

Patients with previous diuretic therapy

If possible, discontinue diuretics 2-3 days (depending on the duration of action of diuretics) before starting treatment with Amprilan®, or at least reduce the dose of diuretics taken. Treatment of such patients should begin with the lowest dose, equal to 1.25 mg of Amprilan®, taken once a day, in the morning.

After taking the first dose and each time after increasing the dose of Amprilan 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 reaction of blood pressure to taking the drug Amprilan can either increase (due to slowing down the elimination of ramiprilate), or weaken (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: marked decrease in blood pressure, bradycardia, shock, impaired water-electrolyte balance, acute renal failure, stupor.

Treatment: in mild cases of overdose-gastric lavage, use of adsorbents and sodium picosulfate (preferably within 30 minutes after oral use).

With a pronounced decrease in blood pressure — iv use of catecholamines, alpha-1-adrenergic agonists (norepinephrine, dopamine), angiotensin II (angiotensinamide), the patient should be laid on his back on a surface with a low headboard, if necessary, the BCC can be replenished by infusion of 0.9% sodium chloride solution; with bradycardia, a temporary artificial pacemaker can be set.

Blood pressure, kidney function, and serum potassium should be carefully monitored. The effectiveness of hemodialysis has not been established.

Special instructions

Renal function should be evaluated at the beginning of treatment. Renal function should be carefully monitored in patients with impaired renal function, heart failure, bilateral renal artery stenosis or stenosis of the artery of a single kidney, as well as in patients after kidney transplantation.

Liver failure

In rare cases, against the background of the use of ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant liver necrosis develops, sometimes with a fatal outcome. If jaundice occurs or there is a significant increase in hepatic transaminase activity while taking ACE inhibitors, the use of Amprilan® should be discontinued.

In patients with uncomplicated arterial hypertension after taking the first dose of the drug, symptomatic arterial hypotension rarely develops. The risk of hypotension is increased in the following patients::

• Patients with severe CHF: treatment is initiated with the lowest possible dose of Amprilan® (1.25 mg).
• Taking diuretics: if possible, it is necessary to cancel the diuretic in advance or reduce its dose; treatment begins with a minimum dose of Amprilan® (1.25 mg).
• Patients at risk of developing hypovolemia due to insufficient fluid intake, diarrhea, vomiting, or excessive sweating in conditions of insufficient compensation for salt and fluid loss. It is usually recommended to adjust the BCC before starting treatment, but if these conditions become clinically significant, treatment with Amprilan® can be initiated and / or continued with a minimum dose (1.25 mg) and under medical supervision.

Aortic stenosis/mitral stenosis/HOCMP

ACE inhibitors should be used with caution in patients with left ventricular exit tract obstruction and aortic and / or mitral stenosis.

Neutropenia/agranulocytosis

Patients taking ACE inhibitors may develop neutropenia/agranulocytosis, thrombocytopenia, and anemia. In patients with normal renal function in the absence of other complications, neutropenia rarely develops and resolves independently after the withdrawal of ACE inhibitors.

Ramipril should be used with great caution in patients with connective tissue diseases and simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially in patients with existing renal dysfunction. These patients may develop severe infections that do not respond to intensive antibiotic therapy. If ramipril is used, it is recommended to periodically monitor the number of white blood cells in the blood. The patient should be warned that if there are any signs of an infectious disease (sore throat, fever), it is necessary to immediately consult a doctor.

Hyperkalemia

It may develop during treatment with ACE inhibitors, including ramipril. Risk factors for hyperkalemia include renal failure, advanced age, diabetes mellitus, certain concomitant conditions (decreased BCC, acute heart failure in the decompensation stage, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing salt substitutes, and the use of other drugs that increase the potassium content in blood plasma (for example, heparin). Hyperkalemia can lead to serious cardiac arrhythmias, sometimes fatal.

Potassium-sparing diuretics and potassium supplements

The combined use of Amprilan® and potassium-sparing diuretics, as well as potassium preparations and potassium-containing salt substitutes, is not recommended.

Surgical interventions/general anesthesia

The use of ACE inhibitors in patients undergoing surgery with general anesthesia may lead to a pronounced decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect.

It is recommended to stop taking ACE inhibitors, including ramipril,12 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors.

Cough

Against the background of therapy with an ACE inhibitor, a dry cough may occur, which disappears after the withdrawal of drugs of this group. If a dry cough occurs, you should be aware of the possible association of this symptom with taking an ACE inhibitor.

Anaphylactoid reactions during desensitization procedures

There are isolated reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenopteran venom (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions, undergoing desensitization procedures. Avoid prescribing an ACE inhibitor to patients receiving hymenopteran venom immunotherapy. However, the development of anaphylactoid reactions can be avoided by temporarily stopping the ACE inhibitor at least 24 hours before the start of the desensitization procedure.

Anaphylactoid reactions during LDL apheresis

In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flow membranes.

Hemodialysis

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flow membranes (for example, AN69®). Therefore, it is advisable to use a different type of membrane or use a hypotensive drug of a different pharmacotherapeutic group.

Influence on the ability to drive a car or perform work that requires increased speed of physical and mental reactions

During treatment, caution should be exercised when engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions, as dizziness, drowsiness, confusion and other side effects are possible.

Form of production

Pills.

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Ramipril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets