Korpil - instructions for use, dose, side effects, contraindications

Capsule shell: capsule cap - dye sunset yellow [E 110] 0.032 mg, crimson dye (Ponceau 4R) [E 124] 0.032 mg, titanium dioxide 0.012 mg, gelatin 15.67 mg, purified water q.s. **

Capsule Casing - titanium dioxide 0.4759 mg, gelatin 23.5240 mg, purified water q.s. **

Inks for printing *

Capsules 5 mg

Active substance: ramipril 5 mg.

Excipients: gelatinized starch 125.5 mg.

Capsule shell: cap capsule - dye crimson (Ponso 4R) [E 124] 0.02272 mg, azorubin [E'122] dye 0.1344 mg, brilliant blue colorant [E 133] 0.0002 mg, titanium dioxide 0.1744 mg, gelatin 15.6573 mg, purified water q.s. **

Capsule Casing - titanium dioxide 0.4759, gelatin 23.5240, purified water q.s. **

Inks for printing *

Capsules 10 mg

Active substance: ramipril 10 mg.

Excipients: gelatinized starch 120 mg.

Capsule shell: cap capsule - blue patented dye [E 131] 0.0061 mg, titanium dioxide 0.2880 mg, gelatin 15.7059 mg, purified water q.s. **

Capsule casing - titanium dioxide 0,4759, gelatin 23,5240, purified water. **

Inks for printing *

* Composition of ink for printing: shellac 24-27%, dehydrated alcohol ** 23-26%, isopropyl alcohol ** 1-3%, butyl alcohol * D-3%, propylene glycol 3-7%, concentrated ammonia solution ** 1-2%, ferric oxide black oxide [E 172] 24-28%, potassium hydroxide ** 0,05-0,1%, purified water ** 15-18%.

** Removed during production.

Description:

Capsules 2.5 mg

Hard gelatin capsules number 4; the case of a capsule of white color with a black inscription "2,5", a lid of orange color with a black inscription "R". The contents of the capsule are white or almost white granular powder.

Capsules 5 mg

Hard gelatin capsules number 4; the case of a capsule of white color with a black inscription "5", a lid of a dark-burgundy color with a black inscription "R". The contents of the capsule are white or almost white granular powder.

Capsules 10 mg

Hard, gelatin capsules number 4; the case of a capsule of white color with a black inscription "10", a lid of blue color with a black inscription "R". The contents of the capsule are white or almost white granular powder.

Pharmacotherapeutic group:Angiotensin-converting enzyme (ACE) inhibitor

ATX: & nbsp

C.09.A.A ACE Inhibitors

C.09.A.A.05 Ramipril

Pharmacodynamics:

The active metabolite of ramipril, formed under the influence of "liver" enzymes - ramiprilat - is a long-acting ACE inhibitor, which is a peptidyl dipeptidase. ACE in the blood plasma and tissues catalyzes the conversion of angiotensin I into angiotensin II and the breakdown of bradykinin. Therefore, when taking ramipril, the formation of angiotensin II decreases and the accumulation of bradykinin occurs, which leads to vasodilation and a decrease in blood pressure (BP).The increased activity of kallikrein-kinin system in blood and tissues causes cardioprotective and endothelioprotective action of ramipril due to activation of the prostaglandin system and, correspondingly, an increase in the synthesis of prostaglandins stimulating the formation of nitric oxide (N0) in endotheliocytes.

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

With a decrease in the concentration of angiotensin II in the blood, its inhibiting effect on renin secretion by negative feedback is eliminated, which leads to an increase in renin activity of the blood plasma.

It is assumed that the development of some undesirable reactions (in particular, "dry" cough) is also associated with an increase in bradykinin activity.

In patients with hypertension taking ramipril leads to a decrease in blood pressure in the supine position and standing without compensatory increase in the heart rate (heart rate). Ramipril significantly reduces the overall peripheral vascular resistance (OPSS), virtually without causing changes in the renal blood flow, and the glomerular filtration rate. The hypotensive effect begins to appear after 1-2 hours after ingestion of a single dose of the drug, reaching the highest value after 3-9 hours and stored for 24 hours. At course admission, the hypotensive effect can gradually increase, usually stabilizing to 3-4_: week of regular intake 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 (the absence of the "withdrawal" syndrome).

Have of patients with arterial hypertension.ramipril slows the development and progression of myocardial hypertrophy and vascular wall.

In patients with chronic heart failure ramipril reduces OPSS (decrease in heart afterload), 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. In these patients, when taking ramipril, there is an increase in cardiac output, ejection fraction and improvement of exercise tolerance.

With diabetic and nondiabetic nephropathy the use of ramipril slows the rate of progression of renal failure and the time of the onset of the terminal stage of renal insufficiency, and due to this,reduces the need for procedures for hemodialysis or kidney transplantation. At the initial stages of diabetic, or nondiabetic nephropathy ramipril reduces the severity of albuminuria.

In patients with a high risk of developing cardiovascular diseases as a result of or vascular lesions (diagnosed coronary heart disease, obliterans of peripheral arteries in history, stroke in the anamnesis), or diabetes mellitus with at least one an additional risk factor (microalbuminuria, arterial hypertension, an increase in total cholesterol (OX) concentrations, a decrease in the concentration of lipoprotein cholesterol high-density (HDL-C) (smoking) joining, ramipril to standard therapy significantly reduces the incidence of myocardial infarction, stroke, and mortality from cardiovascular causes. Besides, ramipril reduces general, mortality, as well as the need for revascularization procedures and slows down the occurrence or progression of chronic heart failure.

Have patients with heart failure, developed in the first days of acute myocardial infarction (2-9 days), when taking ramipril, from 3 to 10 day acute myocardial infarction, the risk of death rate (by 27%), risk of sudden death (by 30%), the risk of progression of chronic heart failure to severe (III-IV functional class by classification NUNA) resistant to therapy (by 27%), 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 from arterial hypertension, and with normal indicators HELL ramipril significantly reduces the risk of developing nephropathy and the occurrence of microalbuminuria.

Pharmacokinetics:

After oral administration ramipril quickly absorbed from the gastrointestinal tract (50% - 60%). The intake of food slows down its absorption, but does not affect the completeness of absorption. Ramipril undergoes intensive pre-systemic metabolism / activation (main in the liver by hydrolysis), which results in the formation of its only active metabolite - ramiprilat, whose activity with respect to inhibition: ACE is about 6 times higher than that of ramipril. In addition to, the result metabolism of ramipril is formed not possessing pharmacological. The activity of diketopiperazine, which is then subjected to conjugation with glucuronic acid, ramiprilate is also glucuronized and metabolized todiketopiperazine acid.

The bioavailability of ramipril after ingestion varies from 15% (for a dose of 2.5 mg) to 28% (for a dose of 5 mg). Bioaddensity of the active metabolite - ramiprilata - after taking Inside 2.5 mg and 5 mg of ramipril is approximately 45% (compared to its bioavailability after intravenous administration at the same doses). After taking ramipril inside, the maximum plasma concentrations of ramipril and ramiprilata are achieved after 1 and 2-4 hours, respectively. Decrease in plasma concentration of ramiprilata occurs in several stages: the phase of distribution and excretion with a half-life T_1/2, ramiprilata, which is about 3 hours, then the intermediate phase with T_1/2, ramiprilata, about 15 hours, and a final phase with a very low concentration of ramiprilate in the blood plasma and T_1/2, ramiprilata, which is about 4-5 days. This final phase is due to the slow release of ramiprilata from a strong bond with ACE receptors.

Despite for a prolonged final phase with a single daily ramipril intake in a dose of 2.5 mg or more, the equilibrium plasma concentration of ramiprilate is reached after approximately 4 days of treatment. With the prescription of the drug "effective" T_1/2 depending on the dose is 13-17 hours.

The association with blood plasma proteins is approximately equal to ramipril 73%, a for ramiprilate - 56%.

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

After ingestion of radically labeled ramipril (10 mg), 39% of the radioactivity is excreted through the intestine and about 60% by the kidneys. After intravenous administration of ramipril, a 50-60% dose is detected in the urine in the form of ramipril and its metabolites. After intravenous administration of ramiprilat, about 70% of the dose is detected in the urine in the form ramiprilata and its metabolites, in other words, with intravenous administration of ramipril and ramiprilate, a significant portion of the dose is excreted through the intestine with bile, bypassing the kidneys (50% and 30%, respectively). After ingesting 5 mg of ramipril in patients with bile duct drainage. practically The same amounts of ramipril and its metabolites are excreted by the kidneys and through intestine within the first 24 hours after admission.

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

In animal studies, it was shown that ramipril excreted in breast milk.

In case of violations of the function, kidneys with a creatinine clearance (CC) of less than 60 ml / min, the excretion of ramiprilata 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), a violation of liver function leads to a slowing of the pre-system metabolism of ramipril to active ramiprilate and a slower elimination of ramiprilate.

In healthy volunteers and in patients with hypertension, after a two-week treatment with ramipril in a daily dose of 5 mg, there is no clinically significant accumulation of ramipril and ramiprilate.In patients with chronic heart failure after a two-week treatment with ramipril in a daily dose of 5 mg, a 1.5-1.8 fold increase in plasma concentrations of ramiprilata and an area under the pharmacokinetic curve "concentration-time" (AUC).

In healthy elderly volunteers (65-76 years old), the pharmacokinetics of ramipril and ramiprilate are not significantly different from that of young healthy volunteers.

Indications:

Essential hypertension.

Chronic heart failure (as part of combination therapy, in particular, in combination with diuretics).

Diabetic or nondiabetic nephropathy is preclinical and clinically pronounced, including those with pronounced proteinuria in particular when combined with hypertension.

Reducing the risk of developing myocardial infarction, stroke, or cardiovascular mortality in patients with high cardiovascular risk:

- in patients with confirmed ischemic heart disease, myocardial infarction in or without anamnesis, including patients undergoing percutaneous transluminal coronary angioplasty, coronary artery bypass grafting;

- in patients with a history of stroke;

- in patients with occlusive lesions of peripheral arteries;

- in patients with diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increased plasma concentrations of OX, decreased plasma concentrations of cholesterol-HDL, smoking).

Heart failure, developed during the first few days (from the 2nd to the 9th day) after an acute myocardial infarction (see the section Pharmacodynamics).

Contraindications:

Hypersensitivity to ramipril, other ACE inhibitors, or to any of the components of the drug (see section Composition).
Angioedema (hereditary or idiopathic, as well as after taking ACE inhibitors) in a history - the risk of rapid development of angioedema (see section "Side effect").
Hemodynamically significant stenosis renal arteries (bilateral or unilateral in the case of a single kidney).
Arterial hypotension (systolic blood pressure less than 90 mm Hg) or a condition with unstable parameters of hemodynamics.
Hemodynamically significant stenosis, aortic or mitral valve or hypertrophic obstructive cardiomyopathy (GOKMP).
Primary hyperaldosteronism.
Severe renal insufficiency (CC less than 20 ml / min with a body surface of 1.73 m²) (experience of clinical use is insufficient).
Hemodialysis (clinical experience is not enough).
Pregnancy.
Breastfeeding period.
Nephropathy, which is treated with glucocorticosteroids, non-steroidal anti-inflammatory drugs, immunomodulators and / or other cytotoxic agents (clinical experience is insufficient see section - "Interaction with other medicinal products").
Chronic heart failure in the stage of decompensation (the experience of clinical use is insufficient).
Age under 18 years (clinical experience is insufficient).
Hemodialysis or hemofiltration using some membranes with a negatively charged surface, such as high-flux membranes of polyacrylonitrile (developmental risk, sensitivity reactions) (see sections "Interactions with other drugs", "Special instructions").
Lysis of low-density lipoproteins using dextran sulfate (the risk of developing reactions of persistent sensitivity) (see section "Special instructions").
Hyposensitizing therapy in reactions of hypersensitivity to poisons of insects, such as bees, wasps (see section "Special instructions").

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

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

Carefully:

Conditions in which excessive reduction in blood pressure is particularly dangerous (with atherosclerotic lesions of the coronary and cerebral arteries).
Conditions accompanied by increased activity of the renin-angiotensin-aldosterone system (RAAS), in which, with ACE inhibition, there is a risk of a sharp decrease in blood pressure with impaired renal function:

- severe arterial hypertension, especially malignant hypertension;

- chronic heart failure, especially severe, or about which other drugs with hypotensive action are taken;

- hemodynamically significant unilateral stenosis of the renal artery (in the presence of both kidneys);

- previous intake of diuretics;

- Violation of the water-electrolyte balance as a result of insufficient intake of liquid and table salt, diarrhea, vomiting, profuse sweating.

Dysfunction of the liver (insufficiency of the experience of application: it is possible to strengthen and weaken the effects of ramipril, in the presence of cirrhosis of the liver with ascites and edema, a significant activation of RAAS is possible, see above the states accompanied by increased activity of RAAS).
Dysfunction of the kidneys (QC more than 20 ml / min with a body surface of 1.73 m²) because of the risk of developing hyperkalemia and leukopenia.
Condition after kidney transplantation.
Systemic diseases of connective tissue, including systemic lupus erythematosus, scleroderma, concomitant therapy with drugs capable of causing changes in the picture of peripheral blood (possibly oppression of bone marrow hematopoiesis, development of neutropenia or agranulocytosis, see the section "Interaction with other drugs").
Diabetes mellitus (risk of hyperkalemia).
Elderly age (risk of increased hypotensive effect).
Hyperkalemia.

Pregnancy and lactation:

Corpril is contraindicated in pregnancy, as it may adversely affect the fetus: impairment of fetal kidney development, fetal and neonatal fetal depression, renal dysfunction, hyperkalemia, skull bones hypoplasia, oligohydramnia, limb contracture, skull bones deformation, lung hypoplasia.

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

If a woman is planning a pregnancy, then treatment with ACE inhibitorsmust be terminated.

In case of pregnancy during treatment with the drug Korpil, it should, as soon as possible, stop taking it and transfer the patient to the reception of other drugs in the application of which the risk to the child will be the least.

If treatment with the drug Korpril is necessary during the period of breastfeeding, then breastfeeding should be discontinued.

Dosing and Administration:

Inside. Capsules must be swallowed whole (not chewed), and washed down with a sufficient amount (1/2 cup) of water, regardless of food intake (ie, capsules may be taken before, during or after meals).The dose is selected depending on the therapeutic effect and tolerability of the drug to patients

Possible use of the drug ramipril in dosage form: 2.5 mg tablets with a risk (to obtain an initial dose of 1.25 mg).

Treatment with the drug Korpil usually is long, and its duration, in each case is determined by the doctor.

If not prescribed otherwise, then with normal kidney and liver function, the following dosing regimens are recommended:

With essential hypertension

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

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

With chronic heart failure

The recommended initial dose: 1.25 mg once a day (1/2, tablets with a risk). Depending on the reaction to the patient's therapy, the dose may increase. It is recommended to increase the dose at intervals of 1-2 weeks. If a daily dose of 2.5 mg or more is required, it can be taken as a single dose per day; and divide into 2 receptions.

The maximum recommended daily dose is 10 mg.

With diabetic or nondiabetic nephropathy

The recommended initial dose: 1,25-mg once a day (1/2 tablets with a risk).

The dose may increase to 5 mg once daily. At these dose states more than 5 mg once a day in controlled clinical trials have not been adequately studied.

To reduce the risk of developing myocardial infarction, stroke, or cardiovascular mortality in patients with high cardiovascular risk

The recommended initial dose: 2.5 mg once a day. Depending on the tolerability, the patient's 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 once a day.

Doses in excess of 10 mg in controlled clinical trials have not been adequately studied.

The use of the drug in patients with KK less than 0.6 ml / sec has been studied insufficiently.

With heart failure, developed during the first few days (with 2-nd to 9 th day) after acute myocardial infarction

The recommended initial dose is 5 mg per day, divided into two single doses 2.5 mg, which are taken one in the morning, and the second - in the evening. Then, depending on the patient's reaction, the dose can be increased. It is recommended that the dose at its increase is doubled with an interval of 1-3 days. Later, the total daily dose, which was initially divided into two doses, can be given only once.

The maximum recommended dose is 10 mg.

Application of the drug ramipril in certain groups of patients

Patients with impaired renal function

With SC from 50 to 20 ml / min at 1.73 m² the initial daily dose is usually 1.25 mg (1/2 tablet with a risk). The maximum permissible daily dose is 5 mg.

Patients with prior diuretic therapy It is necessary, if possible, to cancel diuretics for 2-3 days (depending on the duration of the action of diuretics) before starting treatment with Korpril 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 ramipril (1/2 tablet with a risk), taken once a day in the morning. After taking the first dose and every 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.

Patients of advanced age (over 65 years).

The initial dose is reduced to 1.25 mg / day (1/2 tablet with a risk).

Patients with hepatic impairment

The response of blood pressure to taking Korpril can both increase (by slowing down the removal of ramiprilate) and decrease (by slowing the conversion of low-active ramipril to active ramiprilate). Therefore, at the beginning of treatment, careful medical supervision is required. The maximum allowable daily dose is 2.5 mg.

Side effects:

The undesirable effects listed below are given in accordance with the following gradations of their occurrence frequency:

very often: (> 10%);

often: (>1%-<10%);

infrequently: (> 0.1% - <1%);

rarely: (0.01% - 0.1%);

very rarely: (<0.01%, including individual messages);

the frequency is unknown: according to the available data, it is not possible to establish the frequency of occurrence.

Heart Disease

Infrequent: myocardial ischemia, including the development of an attack of angina or myocardial infarction, tachycardia, arrhythmia (appearance or gain), palpitations, peripheral edema.

Vascular disorders

Often: excessive decrease in blood pressure, violation of orthostatic regulation of vascular tone (orthostatic hypotension), syncopal conditions.

Infrequently: the "tides" of blood to the skin of the face.

Rarely: the occurrence or intensification of circulatory disorders against the background of stenosing vascular lesions, vasculitis.

The frequency is unknown: Raynaud's syndrome.

Disorders from the central nervous system

Often: headache, a feeling of "lightness" in the head

Infrequent: dizziness, agevia (loss of taste sensitivity), dysgeusia (a violation of taste sensitivity).

Rarely: tremor, imbalance.

The frequency is unknown: cerebral ischemia, including ischemic stroke and transient impairment of cerebral circulation, impaired psychomotor reactions, paresthesia (burning sensation), parosmia (impaired perception of odors).

Disturbances on the part of the organ of sight

Infrequent: visual disturbances, including blurred image.

Rarely: conjunctivitis.

Hearing disorders

Rarely: hearing impairment, ringing in the ears.

Disorders from the psyche

Infrequent: depressed mood, anxiety, nervousness, motor anxiety, sleep disturbances, including drowsiness.

Rarely: confusion.

The frequency is unknown: attention violation.

Disturbances from the respiratory system

Often: "dry" cough (worse at night and lying down), bronchitis, sinusitis, dyspnea.

Infrequently: bronchospasm, including weighting of the course of bronchial asthma, nasal congestion.

Disturbances from the digestive tract

Often: inflammatory reactions in the stomach and intestines, digestive disorders, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting.

Infrequently: pancreatitis, including fatal cases (cases of pancreatitis with fatal outcome with the intake of ACE inhibitors were very rare), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, abdominal pain, gastritis, constipation, dryness of the mucosa oral cavity.

Rarely: glossitis.

The frequency is unknown: aphthous stomatitis (inflammatory reaction of the oral mucosa).

Disorders from the hepatobiliary system

Infrequently: increased activity of "hepatic" enzymes and concentration of conjugated bilirubin in blood plasma

Rarely: cholestatic jaundice, hepatocellular lesions.

The frequency is unknown: acute liver failure, cholestatic or cytolytic hepatitis (lethal outcome was observed extremely rarely).

Disorders from the kidneys and urinary tract

Infrequent: renal dysfunction, including acute renal failure, increased urine output, increased pre-existing proteinuria, increased urea and creatinine levels in the blood.

Disorders from the reproductive system and mammary glands

Infrequently: transient impotence due to erectile dysfunction, decreased libido.

The frequency is unknown: gynecomastia.

Violations of the blood and lymphatic system

Infrequently: eosinophilia.

Rarely: leukopenia, including neutropenia, and agranulocytosis, a decrease in the number of erythrocytes in peripheral blood, a decrease in hemoglobin, thrombocytopenia.

The frequency is unknown: oppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.

Disturbances from the skin and mucous membranes

Often: skin rash, in particular maculopapular.

Infrequently: angioedema, including fatal. Outflow (laryngeal edema^-can cause airway obstruction leading to death), skin itching, hyperhidrosis (increased sweating).

Rarely: exfoliative dermatitis, urticaria, onycholysis.

Very rarely: photosensitization reactions.

The frequency is unknown: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, psoriatic psoriasis, psoriasis dermatitis, pemphigoid or lichenoid, (lichen) exanthema or enanthema, alopecia.

Disorders from the musculoskeletal system and connective tissue

Often: muscle cramps, myalgia.

Infrequently: arthralgia.

Disorders from the metabolism, nutrition and laboratory indicators

Often: increased potassium in the blood.

Infrequent: anorexia, decreased appetite.

Unknown frequency: decrease in the concentration of sodium in the blood.

Immune system disorders

The frequency is unknown: anaphylactic or anaphylactoid reactions (with the inhibition of ACE, the amount of anaphylactic or anaphylactoid reactions to insect venoms increases),increase in the concentration of antinuclear antibodies.

Common violations

Often: chest pain, fatigue.

Infrequent: increased body temperature.

Rarely: asthenia (weakness).

Overdose:

Symptoms: excessive peripheral vasodilation with the development of pronounced decrease in blood pressure, shock; bradycardia, water-electrolyte disorders, acute renal failure, stupor.

Treatment: washing the stomach, taking adsorbents, sodium sulfate (if possible for the first 30 minutes). In the case of a marked decrease in blood pressure, the introduction of alpha-adrenergic agonists may be added to therapy for replenishing the volume of circulating blood and restoring the electrolyte balance (norepinephrine, dopamine). In the case of refractory to medical treatment of bradycardias, it may be necessary to install a temporary artificial pacemaker. In case of an overdose, it is necessary to monitor serum concentrations of creatinine and electrolytes.

Interaction:

Contraindicated combinations

Use of some high-permeability membranes with a negatively charged surface (for example: polyacrylonitrile membranes) during hemodialysis or hemophilia; use of dextran sulfate in the apheresis of low density lipoproteins

Risk of development of severe anaphylactic reactions.

Not recommended combinations

FROM potassium salts, potassium-sparing diuretics (for example, amteridom, triamterene, spironolactone)

A more pronounced increase in the serum potassium content is possible. simultaneous application requires regular monitoring of potassium concentration in blood serum).

Combinations that should be used with caution

With antihypertensive drugs (especially diuretics) and other drugs that reduce blood pressure (nitrates, tricyclic antidepressants)

Potentiation of hypotensive effect; when combined with diuretics should monitor the sodium content in the blood serum.

With sleeping pills, narcotic and anesthetics

Perhaps a more pronounced decrease in blood pressure.

With vasopressor sympathomimetics (epinephrine)

Reducing the hypotensive effect of ramipril, careful monitoring of blood pressure is required.

With allopurinol, procainamide, cytostatics, immunosuppressants) with systemic glucocorticosteroids and other agents that can affect hematological parameters

Joint application increases the risk of developing of leukopenia.

With lithium salts

An increase in serum lithium concentration and an increase in the cardio- and neurotoxic effect of lithium

FROM hypoglycemic agents for admission inwards (derivatives of sulfonylurea, biguanides), insulin

In connection with a decrease in insulin resistance under the influence of ramipril, it is possible to increase the hypoglycemic effect of these drugs right up to the development of hypoglycemia.

Combinations that should be taken into account

With non-steroidal anti-inflammatory drugs (indomethacin, acetylsalicylic acid)

It is possible to weaken the action of ramipril; increased risk of impaired renal function and increased serum potassium levels.

With heparin

It is possible to increase the potassium content in the blood serum.

With sodium chloride

Weakening of the hypotensive effect of ramipril and less effective treatment of symptoms of chronic heart failure.

With ethanol

Increased symptoms of vasodilation. Ramipril can enhance the adverse effects of ethanol on the body.

With estrogens

Weakening of the hypotensive effect of ramipril (fluid retention).

Desensitizing therapy with hypersensitivity to insect venoms

ACE inhibitors, including ramipril, increase the likelihood of developing severe anaphylactic or anaphylactoid reactions to insect venoms.

Special instructions:

Before starting treatment with the drug Korpil it is necessary to eliminate hyponatremia and hypovolemia. In patients who have been taking diuretics, it is necessary to cancel them, or at least reduce their dose 2-3 days before the start of the drug, Korpil (in this case, carefully monitor the condition of patients with chronic heart failure, due to the possibility of developing them decompensation due to increased volume of circulating blood).

After taking the first dose of the drug, as well as increasing its dose and / or dose of diuretics (especially "loop"), it is necessary to ensure careful medical supervision of the patient for at least 8 hours to promptly take appropriate measures in case of excessive blood pressure lowering.

If the drug is used for the first time or in high dose in patients with increased activity of RAAS, they should carefully monitor blood pressure, especially at the beginning of treatment, as these patients have an increased risk of excessive blood pressure lowering (see below).(See the Precautions section.)

With malignant arterial hypertension and heart failure in particular in the acute stage of myocardial infarction, drug treatment. Korpril should be started only in a hospital.

In patients with chronic heart failure, taking the drug may lead to a marked 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, since they may be particularly sensitive to ACE inhibitors, it is recommended to monitor the initial phase of treatment. indicators of kidney function (see also section "Dosing and Administration").

In patients for whom a reduction 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.

Care should be taken with physical activity and / or hot weather because of the risk of increased sweating and dehydration with the development of arterial hypotension, due to a decrease in the volume of circulating blood and a decrease in the concentration of sodiumin blood.

During treatment with the drug, it is not recommended to drink alcohol.

Transient arterial hypotension is not a contraindication for continuing treatment after stabilizing blood pressure. In the case of repeated occurrence of severe arterial hypotension, the dose should be reduced or the drug should be withdrawn.

Patients treated with ACE inhibitors experienced cases of angioedema of the face, extremities, lips, tongue, pharynx or larynx. If there is swelling in the face (lips / eyelids) or tongue, or a violation of swallowing or breathing - the patient should immediately stop taking the drug. Angioedema, localized in the area of the tongue, pharynx / or larynx (possible symptoms: violation of swallowing or breathing) can be life threatening and requires urgent measures for its reduction: subcutaneous injection of 0.3-0.5 mg or intravenous drip injection of 0.1 mg epinephrine (adrenaline) (under the control of blood pressure, heart rate and ECG) following the use of glucocorticosteroids (iv / m / or inside), it is also recommended intravenous administration of antihistamines (antagonists H₁ and H₂-gistaminovyh receptors), and in case of insufficiency of enzyme inactivators C1-esterase can consider the need to introduce in addition to epinephrine enzyme inhibitors C1-esterase. The patient should be hospitalized and monitored until the symptoms come to a complete relief, but not less than 24 hours.

In patients receiving ACE inhibitors, there were cases of intestinal angioedema, which manifested itself with abdominal pain with or without nausea and vomiting; in some cases, angioedema has also been observed. When a patient appears on the background of treatment with ACE inhibitors of the above-described symptoms, the differential diagnosis should also consider the possibility of developing an intestinal angioedema.

Treatment aimed at desensitization to insect venom (bees, wasps) and simultaneous administration of ACE inhibitors can initiate anaphylactic and anaphylactoid reactions (eg, lowering blood pressure, dyspnea, vomiting, allergic skin reactions), which can sometimes be life threatening.Against the background of treatment with ACE inhibitors, hypersensitivity reactions to insect venom (eg, bees, wasps) develop more rapidly and take more severe course. If desensitization to insect venom is required, the ACE inhibitor should be temporarily replaced by a corresponding drug of another class.

With the use of ACE inhibitors, life-threatening, rapidly developing anaphylactoid reactions have been described, sometimes up to the development of shock during exercise. hemodialysis or plasma filtration using certain high-flow membranes (for example, polyacrylonitrile membranes), (see also manufacturers' instructions, membranes). It is necessary to avoid joint use of the drug Korpil and such membranes, for example, for urgent hemodialysis or hemofiltration. In this case, it is preferable to use other membranes or to exclude the use of ACE inhibitors. Similar reactions were observed in the apheresis of low-density lipoproteins using dextran sulfate. Therefore, this method should not be used in patients receiving ACE inhibitors.

In patients with impaired hepatic function, the response to treatment with Korpil may be either increased or decreased.In addition, in patients with cirrhosis of the liver with edema and / or ascites, significant activation of RAAS is possible, therefore, special care must be taken in the treatment of these patients (see also "Dosage and Administration").

Before surgery (including dental surgery), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors.

It is recommended to closely monitor newborns who have been exposed to the intrauterine effect of ACE inhibitors for the detection of arterial hypotension, oliguria and hyperkalemia. In oliguria it is necessary to maintain blood pressure and renal perfusion by introducing appropriate fluids and vasoconstrictors .. In neonates, there is a risk of oliguria and neurological disorders, possibly due to a decrease in renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors.

Control of laboratory parameters before and during treatment with the drug Korpil (up to 1 time per month in the first 3-6 months of treatment)

Control of kidney function (determination of serum creatinine concentrations)

In the treatment of ACE inhibitors in the first weeks of treatment of willows.later, it is recommended to monitor kidney function. Particularly careful monitoring is required for patients with acute and chronic heart failure, renal dysfunction, kidney transplantation, patients with renovascular disease, including patients with hemodynamically significant unilateral renal artery stenosis in the presence of two kidneys (in such patients, even a slight increase in serum creatinine concentration may be an index of decreased renal function).

Controlling the concentration of electrolytes

Regular monitoring of the potassium concentration in the blood serum is recommended. Especially regular monitoring of potassium concentration in blood serum is required for patients with impaired renal function, significant violations of water-electrolyte balance, chronic heart failure.

Control of hematological parameters (hemoglobin, leukocytes, erythrocytes, platelets, leukocyte formula)

It is recommended to monitor the parameters of the general blood test, to identify possible leukopenia. More regular monitoring is recommended at the beginning of treatment and in patients with impaired renal function,as well as in patients with connective tissue diseases or in patients receiving concomitantly other drugs capable of altering the pattern of peripheral blood (see section "Interaction with Other Drugs"). Controlling the number of leukocytes is necessary for the early detection of leukopenia, which is especially important in patients with an increased risk of developing it, and also at the first signs of infection. If neutropenia is detected (the number of neutrophils is less than 2000 / μL), treatment with ACE inhibitors should be discontinued.

When symptoms appear due to leukopenia (eg, fever, enlargement of lymph nodes, tonsillitis), urgent monitoring of the picture of peripheral blood is needed. In case of signs of bleeding (the smallest petechiae, red-brown rashes on the skin and mucous membranes), it is also necessary to control the number of platelets in the peripheral blood.

Determination of the activity of "liver" enzymes, the concentration of bilirubin in the blood

When jaundice or significant increase in the activity of "liver" enzymes, treatment with Korpil should be stopped and medical supervision of the patient should be provided.

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

During the period of treatment with the drug, Korpril should refrain from engaging in potentially dangerous activities, including driving, requiring increased concentration of attention and speed of psychomotor reactions. on the background of its reception, there may be dizziness, decreased speed of psychomotor reactions, attention, especially after taking the first dose.

Form release / dosage:

Capsules 2.5 mg, 5 mg or 10 mg.

Packaging:

14 capsules in a strip of aluminum foil laminated with low density polyethylene. 1 or 2 strips together with instructions for use in a cardboard bundle.

10 capsules in a strip of aluminum foil laminated with low density polyethylene. 1, 2 or 3 strips together with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use at the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001316

Date of registration:01.12.2011

Expiration Date:01.12.2016

Date of cancellation:2017-04-19

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Representation: & nbspSAN PHARMACEUTICAL INDUSTRIES LTD. SAN PHARMACEUTICAL INDUSTRIES LTD. India

Information update date: & nbsp04.02.2018

Illustrated instructions

Instructions

Korpril® (Corpril®)