Active substanceRamiprilRamipril
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  • Dosage form: & nbsppills
    Composition:

    For 1 tablet, 1.25 mg / 2.5 mg:

    Active substance: ramipril 1.25 mg / 2.50 mg

    Excipients: sodium bicarbonate, lactose monohydrate, croscarmellose sodium, pregelatinized starch, sodium stearyl fumarate, dye mixture RV 22886 yellow * (for tablets 2.5 mg)

    for 1 tablet 5 mg / 10 mg:

    Active substance: ramipril 5.00 mg / 10.00 mg

    Excipients: sodium bicarbonate, lactose monohydrate, croscarmellose sodium, pregelatinized starch, sodium stearyl fumarate, dye mixture RV 24899 pink ** (for tablets 5 mg)

    * Mixture of dyes PB 22886 yellow contains: lactose monohydrate, ferric oxide of yellow oxide (E172).

    ** A mixture of colorants PB 24899 pink contains: lactose monohydrate, iron oxide red (E172), iron oxide yellow oxide (E172).

    Description:

    Tablets 1.25 mg: oval, flat tablets white or almost white with a bevel.

    Tablets 2.5 mg: oval, flat pills of light yellow color with a bevel.

    Tablets 5 mg: oval, flat tablets of pink color with a facet, with visible impregnations.

    Tablets 10 mg: oval, flat tablets white or almost white with a bevel.

    Pharmacotherapeutic group:Angiotensin-converting enzyme (ACE) inhibitor
    ATX: & nbsp

    C.09.A.A   ACE Inhibitors

    C.09.A.A.05   Ramipril

    Pharmacodynamics:

    Ramipril is an inhibitor of long-acting angiotensin-converting enzyme (ACE). ACE catalyzes the conversion of angiotensin I into angiotensin. II: ACE is identical to kinase, an enzyme that catalyzes the breakdown of bradykinin.ACE blockade leads to a decrease in angiotensin II concentration, an increase in renin activity in blood plasma, an increase in the effect of bradykinin and an increase in aldosterone secretion, which may be the reason for an increase in the level of potassium in the blood serum. The antihypertensive and hemodynamic effects of ramipril in patients with arterial hypertension are the result of vasodilatation and a reduction in overall peripheral vascular resistance (OPSS), which in turn gradually reduces blood pressure (BP). Heart rhythm usually does not change. With prolonged therapy, left ventricular hypertrophy decreases without a negative effect on heart function. Antihypertensive effect after taking one dose of the drug inside is manifested 1-2 hours after taking ramipril inside, reaches a maximum after 3-6 hours and persists for 24 hours.

    Ramipril is effective in the treatment of chronic heart failure (CHF). In patients with signs of CHF after a previous myocardial infarction, ramipril reduces the risk of sudden death, the progression of heart failure and reduces the number of hospitalizations for worsening of the course of chronic heart failure.

    As in patients with diabetes, and without it, the drug significantly reduces the existing microalbuminuria and the risk of developing nephropathy. These effects are observed in patients with both elevated and normal BP.

    Pharmacokinetics:

    After ingestion of 50-60% ramipril quickly absorbed from the gastrointestinal tract (GIT), eating does not slow absorption. The maximum concentration in the blood serum (C max) is reached after 1 hour.

    Metabolised in the liver, with the formation of an active metabolite - ramiprilata, whose activity is 6 times higher than ramipril and inactive diketopiperazine, which is then glucuronized. Ramagrilat in the blood serum is reached 2-4 hours after ingestion, the equilibrium concentration - by the 4th day of application of the drug.

    About 73% of ramipril and 56% of ramiprilate bind to blood plasma proteins.

    Ramipril and ramiprilate is excreted mainly by the kidneys (about 60%), mainly in the form of metabolites, less than 2% of the accepted dose is excreted as unchanged ramipril.

    Ramipril is excreted in several stages. Half-life (T1/2) after applying the therapeutic dose is 13-17 hours for ramiprilata, 5.1 h for ramipril.

    Studies conducted in healthy volunteers aged 65 to 76 years showed that the pharmacokinetics of ramipril did not differ from the pharmacokinetics of young healthy volunteers.

    When, renal dysfunction, excretion of ramipril and its metabolites slows in proportion to a decrease in creatinine clearance (CK). In patients with hepatic insufficiency, metabolism of ramipril in ramiprilate can be slowed down, and the concentration of ramipril in the serum is increased.

    Indications:
    • Arterial hypertension;
    • Chronic heart failure (as part of combination therapy), incl. developed on 2-9 days after myocardial infarction;
    • Diabetic nephropathy and nephropathy in the background of chronic diffuse kidney diseases (preclinical and clinical stages), incl. chronic glomerulonephritis with severe proteinuria;
    • reduction in the risk of myocardial infarction, stroke, and cardiovascular mortality in patients with high cardiovascular risk, including patients with confirmed coronary heart disease (with or without myocardial infarction), patients undergoing percutaneous transluminal coronary angioplasty,coronary bypass, with a history of stroke and patients with occlusive lesions of peripheral arteries.
    Contraindications:

    Hypersensitivity to ramipril and any other component of the drug or other ACE inhibitors, angioedema in the anamnesis (hereditary, idiopathic or angioedema due to the administration of ACE inhibitors (in the anamnesis)); hemodynamically significant bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, condition after kidney transplantation, hemodialysis, renal failure (CC less than 20 ml / min), hemodynamically significant aortic and / or mitral stenosis (risk of excessive BP reduction with subsequent renal dysfunction) , hypertrophic obstructive cardiomyopathy (GOKMK), chronic heart failure in the stage of decompensation, severe arterial hypotension (blood pressure less than 90 mm Hg), or unstable hemodynamics, primary (efficacy and safety have not been established), galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome, nephropathy, hypertension,treatment of which is carried out by glucocorticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), immunomodulators and / or cytostatics.

    Carefully:

    Tsevere lesions, coronary and cerebral arteries (risk reduction of blood flow in the excessive decrease in blood pressure), malignant hypertension, unstable angina, aortic and / or mitral stenosis, severe ventricular arrhythmias, heart failure (IV functional class classification NYHA), decompensated "pulmonary heart", renal and / or hepatic insufficiency, gaperkaliemiya, hyponatremia (including background diuretics and diet with restriction of salt intake), a condition associated with decreased blood volume (CBV), including diarrhea, vomiting; systemic connective tissue disease, diabetes, depression of bone marrow blood circulation, elderly, hemodialysis using vysokoprotochnyh polyacrylonitrile membranes - the risk of anaphylactoid reactions; before the procedure for the apheresis of low-density lipoprotein (LDL), the simultaneous conduct of desensitizing therapy with allergens (for example,venom of Hymenoptera).

    Pregnancy and lactation:

    The preparation Amprilan® is contraindicated for use during pregnancy, tk. it can have an adverse effect on the fetus (renal dysfunction, hyperkalemia, hypoplasia of the skull bones, hypoplasia of the lungs, etc.). Therefore, before beginning the use of Amprilan® in women of childbearing age, pregnancy should be excluded.

    When diagnosing pregnancy, the drug Amprilan® should be discontinued as soon as possible. If you need to use Amprilan® during lactation, breastfeeding should be discontinued.

    Dosing and Administration:

    Inside, entirely, without chewing, squeezed enough liquid, regardless of food intake.

    The dose is selected depending on the therapeutic effect and the tolerance of the drug to the patient.

    The treatment with Amprilan® is long, its duration in each case is determined by the doctor.

    Arterial hypertension: the recommended initial dose of Amprilan® is 2.5 mg once a day. Depending on the patient's reaction, the dose can be doubled with a 1-2 week interval.Usually, the maintenance dose is 2.5-5 mg per day, the maximum daily dose is 10 mg.

    Patients taking diuretics should cancel or reduce their dose at least 3 days before the start of Amprilan®.

    Chronic heart failure: the recommended initial dose of Amprilan® is 1.25 mg once a day. Depending on the therapeutic effect, the dose can be doubled with an interval of 1-2 weeks.

    The maximum daily dose is -10 mg.

    In patients receiving large doses of diuretics, the dose of diuretics must be reduced before starting therapy with Amprilan®.

    Heart failure (developed for several days (from 2 to 9 days) after acute myocardial infarction.

    The recommended initial dose is 5 mg per day, divided into 2 single doses of 2.5 mg (1 tablet), one of which is taken in the morning, and the second in the evening. If the patient does not tolerate the initial dose (there is an excessive decrease in blood pressure), it should be reduced to 1.25 mg twice a day. Then, depending on the patient's reaction, the dose can be doubled again (2, 5 mg) at intervals of 1-3 days.Later, the daily dose, which was initially divided into two, can be given only once.

    The maximum daily dose is 10 mg. If a patient does not tolerate a dose increase to 2.5 mg twice a day, then the drug should be discontinued.

    Diabetic nephropathy and nephropathy in the background of chronic diffuse kidney diseases: the recommended initial dose of Amprilan® is 1.25 mg once a day. Depending on the patient's tolerability of ramipril, the dose of the drug may increase in the future: it is recommended to double the dose every 2 weeks to a maintenance dose of 5 mg once a day.

    Reducing the risk of myocardial infarction, stroke and cardiovascular mortality: recommended initial dose of the drug

    Amprilan® is 2.5 mg once a day, which then gradually increases depending on the tolerability of the drug: it is recommended to double the dose after 1 week of therapy, and then after another 2-3 weeks - until reaching the target maintenance dose of 10 mg once a day .

    Use of Amprilan® in selected patient groups

    Impaired renal function:

    In patients with QC more than 30 ml / min dose adjustment is not required.

    For patients with KK less than 30 ml / min - the initial daily dose of 1.25 mg, and the maximum daily dose of 5 mg.

    Dysfunction of the liver:

    The initial dose is 1.25 mg once a day.

    The maximum dose is 2.5 mg once a day.

    Careful observation of elderly patients (over 65 years of age) taking diuretics is necessary. The dose of Amprilan® should be selected depending on the level of blood pressure.

    Side effects:

    Classification of the incidence of adverse events (WHO):

    very often> 1/10

    often from> 1/100 to <1/10

    infrequently from> 1/1000 to <1/100

    rarely from> 1/10000 to <1/1000

    very rarely from <1/10000, including individual messages.

    From the cardiovascular system:

    -often: marked decrease in blood pressure (in, at the beginning of therapy, with increasing dose or adherence to diuretic therapy), orthostatic hypotension, syncopal conditions;

    -secondly: peripheral edema, palpitation, angina pectoris, arrhythmia;

    -very rare: myocardial ischemia, myocardial infarction, increased circulatory disorders against the background of stenosing vascular lesions, Raynaud's syndrome, vasculitis, tachycardia, "tides" of blood to the skin of the face;

    From the nervous system:

    -frequently: headache, weakness;

    -secondly: increased fatigue, nervousness, depression, tremor, imbalance, confusion, anxiety, dizziness, motor anxiety, sleep disorders;

    -very rare: paresthesia, impaired perception of odors (parosmia), transient ischemic attacks, ischemic stroke, cerebral ischemia, impaired concentration;

    From the genitourinary system:

    - Transient impotence, decreased libido, impaired renal function up to acute renal failure, increased urine output, increased pre-existing proteinuria, increased urea and creatinine concentrations;

    -very rare: gynecomastia;

    From the respiratory system:

    -frequently: "dry" non-productive cough, worse at night and in the "lying" position; more frequent in women and non-smoking patients, sinusitis, bronchitis, dyspnea;

    - rarely: nasal congestion, pharyngitis, bronchospasm, including aggravation of the course of bronchial asthma;

    From the skin:

    -frequently: maculopapulletic skin rash;

    - often: itchy skin, excessive sweating (against the background of a decrease in blood pressure);

    -very rarely maculopapular rash and erythema, pemphigus, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, worsening of psoriasis flow psoriazoformnye, pemfigoidnye and lichenoid lesions of the skin and mucous membranes, alopecia;

    -very rare: urticaria, onycholysis, exfoliative dermatitis, photosensitivity;

    From the digestive system:

    -Frequently: inflammation of the mucosa of the gastrointestinal tract, indigestion, abdominal discomfort, dyspepsia, nausea, diarrhea, vomiting;

    -rare: increased activity "liver" enzyme, increasing the concentration of bilirubin, cholestatic jaundice, acute liver failure, cholestatic hepatitis, hepatocellular lesion, dryness of the oral mucosa, stomach pain, gastritis, constipation; pancreatitis, including with lethal outcome (pancreatitis cases fatal taking ACE inhibitors rarely observed), intestinal angioedema, decreased appetite, anorexia;

    -very rare: glossitis; aphthous stomatitis;

    From the musculoskeletal system:

    -Often: myalgia, muscle cramps;

    -only: arthralgia;

    From the sense organs:

    - Often: visual disorders, including blurred vision, conjunctivitis, hearing impairment, impaired sense of smell and taste (eg, metallic taste, partial or temporary loss of taste sensations);

    Allergic reactions:

    - Very rarely: angioedema with involvement of the mucous membrane of the lips, eyes, tongue, larynx and pharynx, anaphylactic or anaphylactoid reactions (poison of insects), an increase in the concentration of antinuclear bodies;

    Laboratory indicators:

    -secondly: hyperkalemia, moderate (sometimes pronounced) hypogemoglobinemia or neutropenia, erythropenia and thrombocytopenia, increased activity of pancreatic enzymes;

    Very rarely: hyponatremia, proteinuria (although ACE inhibitors usually decrease previous proteinuria) or an increase in diuresis (in conjunction with worsening of the heart), agranulocytosis, pancytopenia, bone marrow depression, hemolytic anemia;

    Other:

    -perhaps: hyperthermia;

    -very rare: fever.

    Overdose:

    Symptoms: marked decrease in blood pressure, bradycardia, shock, disturbance of water electrolyte balance, acute renal failure, stupor.

    Treatment: in mild cases of overdose - gastric lavage, intake of adsorbents and sodium picosulphate (preferably within 30 minutes after ingestion). With a marked decrease in blood pressure - iv injection of catecholamines, alpha 1-adrenergic agonists (norepinephrine, dopamine), angiotensin II (angiotensinamide), the patient should be placed on the back with a low headboard, if necessary, the BCC can be replenished by infusing 0.9% sodium chloride solution; at a bradycardia - the statement of the temporary artificial driver of a rhythm is possible.

    It is necessary to carefully monitor blood pressure, kidney function and potassium in the blood serum.The effectiveness of hemodialysis is not established.

    Interaction:

    Vasopressornye sympathomimetics (epinephrine, norepinephrine) can reduce the hypotensive effect of ramipril. With the simultaneous use of these drugs, you should carefully monitor the blood pressure level. ACE inhibitors increase the inhibitory effect of ethanol on the central nervous system (CNS).

    Lithium preparations:

    while simultaneous use of lithium drugs and ACE inhibitors, cases of a reversible increase in the concentration of lithium in serum were recorded.Simultaneous use with thiazide diuretics can increase the concentration of lithium and the risk of its toxic effect against the background of an ACE inhibitor.

    Nonsteroidal anti-inflammatory drugs (HPVP)

    The combination of ACE inhibitors with NSAIDs (nonselective inhibitors of cyclooxygenase-2 (COX-2) from the NSAID group, for example, acetyl-isicyl acid in doses exerting anti-inflammatory effect of COX-2); - hypotensive effect of ACE inhibitors is reduced;

    -the risk of impaired renal function is increased, up to the development of acute renal failure

    -increases the potassium content in blood serum in patients with pre-existing renal dysfunction.

    Tricyclic antidepressants. antipsychotic drugs (antipsychotics):

    -increase the hypotensive effect and increase the risk of developing orthostatic hypotension (additive effect).

    Glucocorticosteroids. tetracosactide:

    -reduction of hypotensive effect (fluid retention).

    Potassium-sparing diuretics (spironolactone. triamterene. amiloride. eplerenone) and potassium preparations:

    Joint use of ramipril and potassium-sparing diuretics, as well as preparations of potassium and potassium-containing substitutes for edible salt is not recommended.

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

    Hypoglycemic agents for oral administration (derivatives of sulfonylureas ") and insulin:

    -Application of ACE inhibitors can enhance the hypoglycemic effect of hypoglycemic agents for ingestion and insulin in patients with diabetes mellitus; when they are used together, there may be an increase in glucose tolerance, which may require correction of doses of hypoglycemic agents for ingestion and insulin.

    Allopurinol. cytostatic. immunosuppressants, glucocorticosteroids (with systemic application) and procainamide:

    - simultaneous use of these drugs with ACE inhibitors may increase the risk of developing leukopenia.

    Means for general anesthesia: andACE inhibitors can enhance the antihypertensive effect of certain agents for general anesthesia.

    Preparations of gold: at the appointment of ACE inhibitors, including ramipril, patients receiving a drug of gold (sodium aurothiomalate) IV, nitrate-like reactions were noted (nausea, vomiting, marked decrease in blood pressure, hyperemia of the facial skin).

    Special instructions:

    At the beginning of treatment it is necessary to evaluate the function of the kidneys. Kidney function in patients with impaired renal function, with heart failure, bilateral stenosis of the renal arteries or stenosis of the single kidney artery, as well as in patients after kidney transplantation, should be carefully monitored.

    Liver failure

    In rare cases, with the use of ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant hepatic necrosis develops, sometimes fatal. When jaundice or a significant increase in the activity of "hepatic" transaminases with the use of 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 develops rarely. The risk of developing arterial hypotension is increased in the following patients:

    • patients with severe chronic heart failure: treatment is started with the lowest possible dose of Amprilan® (1.25 mg);
    • patients taking diuretics: if possible, it is necessary to cancel the diuretic in advance or reduce its dose; treatment is started with a minimal dose of Amprilan® (1.25 mg);
    • patients who may develop hypovolemia due to insufficient intake of fluids, diarrhea, vomiting, or excessive sweating in conditions of inadequate compensation for salt and fluid loss. It is usually recommended to correct the BCC before treatment, but if these conditions become clinically significant, Amprilan® treatment can be initiated and / or continued with a minimum dose (1.25 mg) and under medical supervision.

    Aortic stenosis / mitral stenosis / GOKMP

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

    Neutropenia / agranulopytosis

    In patients taking ACE inhibitors, there may be cases of development of neutropenia / agranulocytosis, thrombocytopenia and anemia. In patients with normal, renal function in the absence of other complications of neutropenia. Develops seldom and passes independently after withdrawal-ACE inhibitors.

    Ramipril should be used with great care in patients with connective tissue diseases and simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially with existing impairments of kidney function. These patients can develop severe infections that are not amenable to intensive antibiotic therapy. In the case of ramipril, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that if any signs of an infectious disease (sore throat, fever) appear, you should immediately consult a doctor.

    Hypeokalemia

    It can develop during treatment with ACE inhibitors, including ramipril. Risk factors for hyperkalemia are renal failure, elderly age, diabetes mellitus, some concomitant conditions (decreased BCC, acute heart failure in decompensation, metabolic acidosis), simultaneous intake of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as preparations of potassium or potassium-containing substitutes for edible salt and the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin). Hyperkalemia can lead to serious heart rhythm disturbances, sometimes with a fatal outcome.

    Potassium-sparing diuretics and potassium preparations

    Joint use of Amprilan® and potassium-sparing diuretics, as well as potassium and potassium-containing substitutes for edible salt is not recommended.

    Surgical procedures / General anesthesia

    The use of ACE inhibitors in patients undergoing surgery with the use of general anesthesia can lead to a marked decrease in blood pressure, especially with the use of general anesthetics, which have an antihypertensive effect.

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

    Cough

    Against the background of therapy with an ACE inhibitor, dry cough may occur, which disappears after the withdrawal of this group. When dry cough should be remembered. on the possible association of this symptom with the use of an ACE inhibitor.

    Anaphylactoid reactions during desensitization procedures

    There are separate reports on the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the poison of Hymenoptera insects (bees, wasps).ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The appointment of an ACE inhibitor should be avoided for patients receiving immunotherapy with venom of Hymenoptera. Nevertheless, the development of anaphylactoid reactions can be avoided by the temporary withdrawal of the ACE inhibitor at least 24 hours before the desensitization procedure begins.

    Anaphylactoid reactions during apheresis of LDL

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

    Hemodialysis

    In patients receiving ACE inhibitors, hemodialysis using high-flow membranes (for example, AN69®) Anaphylactoid reactions were noted. Therefore, it is desirable to use a different type of membrane or to use an antihypertensive drug of another pharmacotherapeutic group.

    Effect on the ability to drive transp. cf. and fur:

    During the treatment period, care must be taken during occupations with potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions, possible dizziness, drowsiness, confusion, and other side effects.

    Form release / dosage:

    Tablets, 1.25 mg, 2.5 mg, 5 mg, 10 mg.

    Packaging:

    7 or 10 tablets per blister.

    -2, 4, 8, 12 or 14 blisters (7 tablets each) together with instructions for use in a cardboard package;

    -3, 6, or 9 blisters (10 tablets each) together with instructions for use in a cardboard pack.

    Storage conditions:

    At a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    Tablets 1.25 mg: 2 of the year

    Tablets 2.5 mg, 5 mg and 10 mg: 3 years.

    Do not use the drug after the expiration date

    Terms of leave from pharmacies:On prescription
    Registration number:LS-001621
    Date of registration:23.12.2010 / 29.03.2017
    Expiration Date:Unlimited
    The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO
    Manufacturer: & nbsp
    Information update date: & nbsp24.08.2017
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