Tritace - instructions for use, doses, side effects, contraindications

White or almost white oblong tablets with a separation risk on both sides, "neck" on the sides in the risk area and engraving "HMO / HMO" on one side.

Pharmacotherapeutic group:inhibitor of angiotensin-converting enzyme (ACE).

ATX: & nbsp

C.09.A.A ACE Inhibitors

C.09.A.A.05 Ramipril

Pharmacodynamics:

Formed under the influence of "liver" enzymes, the active metabolite of ramipril - ramiprilat - is a long-acting ACE inhibitor (synonyms ACE: kininase II, dipeptidylcarboxydipeptidase I). ACE in the blood plasma and tissues catalyzes the conversion of angiotensin I to angiotensin II, which has a decongestant effect, and decay Bradykinin, which has a vasodilating effect. 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 ramipril-induced increase in the activity of the kallikrein kinin system in blood and tissues with activation of the prostaglandin system and an increase in the synthesis of prostaglandins stimulating the formation of nitric oxide (N0) in endothelial cells, causes its cardioprotective and endothelioprotective effect. Angiotensin II stimulates the production of aldosterone, therefore, taking ramipril leads to a decrease in the secretion of aldosterone and an increase in the concentrations of potassium ions in the blood serum.

With a decrease in the concentration of angiotensin II in the blood, its inhibitory effect on renin secretion by type of some undesirable reactions (in particular "dry" cough) is associated with an increase in bradykinin activity. In patients with hypertension taking ramipril leads to a decrease in blood pressure in the "lying" and "standing", without compensatory increase in the heart rate (heart rate). Ramipril significantly reduces the overall peripheral resistance of blood vessels (OPSS), virtually without causing changes in renal blood flow and glomerular filtration rate. Antihypertensive effect begins to manifest 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 the course of Tritace®, the antihypertensive effect can gradually increase, usually stabilizing to 3-4 week of regular admission and then remaining 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).

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

In patients with chronic heart failure ramipril reduces OPSS (reduces afterload on the heart), increases the capacity of the venous bed and reduces the filling pressure of the left ventricle, which, accordingly, leads to a decrease in preload on the heart.

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 the renal Insufficiency and time of onset terminal stage need in renal failure and, as a result, reduces the need for hemodialysis or kidney transplantation. At the initial stages of diabetic or nondiabetic nephropathy ramipril reduces the incidence of albuminuria.

In patients with a high risk of developing cardiovascular diseases due to vascular lesions (diagnosed ischemic heart disease, obliterating diseases of peripheral arteries in the anamnesis,a stroke in a history) or diabetes mellitus with at least one additional risk factor (microalbuminuria, hypertension, increased total cholesterol concentrations, a decrease in high density lipoprotein cholesterol (HDL-C) cholesterol, smoking) ramipril addition to standard therapy significantly reduces the incidence of myocardial infarction, stroke, and mortality from cardiovascular reasons. Besides, ramipril

reduces the overall mortality rate, as well as the need for revascularization procedures, and slows the onset or progression of chronic heart failure.

In patients with heart failure with clinical manifestations, developed in the early days of acute myocardial infarction (2-9 days), the use of ramipril, started from 3 to 10 days of acute myocardial infarction, reduced mortality (by 27%), the risk of sudden death (by 30%), the risk of progression of heart failure to severe (III-IV functional class according to the classification of NUNA) / 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 BP, ramipril significantly reduces the risk development of nephropathy and the emergence 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 is subjected to intense presystemic metabolism / activation (mainly in the liver by hydrolysis), which results in the formation of its only active metabolite, ramiprilate, whose activity with respect to ACE inhibition is about 6 times that of ramipril. In addition, as a result of the metabolism of ramipril, a non-pharmacological the activity of diketopiperazine, which is then subjected to conjugation with glucuronic acid, ramiprilate is also glucuronized and metabolized to diketopiperazic 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). Bioavailability of the active metabolite - ramiprilata -after ingestion of 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 reached after 1 and 2 - 4 hours, respectively. The decrease in plasma concentration of ramiprilata occurs in several stages: the distribution and elimination phase with a half-life (T1 / 2) of ramiprilata of about 3 hours, then an intermediate phase with T1 / 2 ramiprilata of about 15 hours and a final phase with a very low concentration of ramiprilate in blood plasma and T1 / 2 ramiprilata, which is approximately 4-5 days. This final phase is due to the slow release of ramiprilata from a strong bond with ACE receptors. Despite the long-term final phase with a single daily ramipril intake at a dose of 2.5 mg or more, the equilibrium plasma concentration of ramiprilate is reached approximately after 4 days of treatment. With the course appointment of the drug "effective" T1 / 2, depending of the dose is 13-17 hours.

The association with blood plasma proteins is about 73% for ramipril, and 56% for ramiprilate.

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 ramiprilata, about 70% of the dose is found in the urine in the form of ramiprilata and its metabolites, in other words, with the intravenous administration of ramipril and ramiprilate, a significant portion of the dose is excreted through the kiwEchine with bile, bypassing the kidneys (50% and 30%, respectively). After ingesting 5 mg of ramipril in patients with bile duct drainage, virtually 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 content of unmetabolized ramipril is approximately 2%.

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

For violations of kidney function with creatinine clearance (CC) less than 60 ml / min. the excretion 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), 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 two weeks of treatment with ramipril in a daily dose of 5 mg there is a 1.5-1.8 fold increase in plasma concentrations of ramiprilate and the area under the pharmacokinetic curve "concentration-time" (AUC).

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

Indications:

Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs, for example, diuretics and blockers of "slow" calcium channels).
Chronic heart failure (as part of combination therapy, in particular, in combination with diuretics).
Diabetic or nondiabetic nephropathy, preclinical and clinically pronounced stages, including those with pronounced proteinuria, especially 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 coronary heart disease, myocardial infarction in history or without it, including patients who survived percutaneous transluminal coronary angioplasty, coronary artery bypass grafting;

in patients with a history of stroke;
in patients with occlusal lesions of peripheral arteries in the anamnesis;
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).

- Cardiac insufficiency with clinical manifestations that 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 Tritace product (see the "Composition" section).
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 of the 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 hemodynamic parameters.
Simultaneous application preparations containing aliskiren, in patients with renal insufficiency (clearance creatinine less than 60 ml / min) and patients with diabetes mellitus.
A hemodynamically significant stenosis of the 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.
Simultaneous use of drugs containing aliskiren, in patients with moderate and severe renal insufficiency (creatinine clearance less than 60 ml / min) and patients with diabetes mellitus.
Simultaneous use with angiotensin II receptor antagonists in patients with diabetic nephropathy.
Hemodynamically significant stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy (GOKMP).
Primary hyperaldosteronism.
Severe renal insufficiency (CC less than 20 ml / min with body surface area 1.73 m2) (clinical experience is not enough).
Hemodialysis (clinical experience is not enough).
Pregnancy.
Lactation period.
Nephropathy, the treatment of which is carried out glucocorticosteroids, non-steroidal anti-inflammatory drugs,
immunomodulators and / or other cytotoxic drugs (experience of clinical use is insufficient, see the section "Interaction with other drugs").
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 such as high-flow membranes from polyacrylonitrile (the risk of developing severe anaphylactoid reactions) (see the sections "Interaction with other drugs", "Special instructions").
Aerate low density lipoproteins using dextran sulfate (a risk of developing severe anaphylactoid reactions) (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 Tritace® in acute stage of myocardial infarction

- severe heart failure (functional class IV according to classification NYHA);

- unstable angina;

- life-threatening ventricular arrhythmias

- "pulmonary heart"

Carefully:

The simultaneous use of Tritace with preparations containing aliskirenor angiotensin II receptor antagonists (with double blockade of the renin-angiotensin-aldosterone system (RAAS), there is an increased risk of a sharp drop in blood pressure, development of hyperkalemia, and impaired renal function compared to monotherapy) (see "Special instructions").

Conditions in which excessive reduction in blood pressure is particularly dangerous (with atherosclerotic lesions of the coronary and cerebral arteries).

Conditions accompanied by an increase in activity (RAAS), in which, with ACE inhibition, there is a risk of a sharp decrease in blood pressure with impaired renal function:

- pronounced arterial gIpertension, 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) - in suchpatients even a slight increase in serum creatinine concentration may be a manifestation of unilateral impairment of renal function;
previous administration of diuretics;
disturbances of water electrolyte balance as a result of insufficient intake of liquid and table salt, diarrhea, vomiting, and profuse sweating.
Dysfunction of the liver Insufficiency of experience of application: it is possible both strengthening, and easing of effects of a preparation Tritace); in the presence of cirrhosis of the liver with ascites and edema in the patients, significant activation of RAAS is possible, see above "Conditions accompanied by increased activity of RAAS").

Impaired renal function (QC more than 20 ml / min with body surface area 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 that can cause changes in the picture of peripheral blood (possibly oppression of bone marrow hematopoiesis, development of neutropenia or agranulocytosis, see section "Interaction with other drugs").

Diabetes mellitus (risk of developing deperkalemia).

Elderly age (risk of increased hypotensive effect).

Hyperkalemia.

Pregnancy and lactation:

Ramipril is contraindicated in pregnancy, as it may adversely affect the fetus: impairment of fetal kidney development, fetal and neonatal fetal decline, 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, treatment with ACE inhibitors should be discontinued.

In case of pregnancy during treatment with Tritace®, it should be stopped as soon as possible and transferred to the patient for taking other drugs, in which the risk to the child will be the least.

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

Dosing and Administration:

Tablets should be swallowed (do not chew), and drink a sufficient amount (1/2 cup) of water regardless of food intake (i.e., tablets may be taken before, during or after a meal) and washed down with sufficient amount (1 /4 glass) of water. You can not chew or take pills before taking. The dose is selected depending on the therapeutic effect and the tolerance of the drug to the patient. Treatment with Tritace® is usually prolonged, 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 arterial hypertension Usually the initial dose is 2.5mg once a day in the morning (in this case, you can use Tritace® tablets 2.5 mg or 5 mg with a risk). If, when taking the drug at this dose for 3 weeks or more, it is not possible to normalize blood pressure, then the dose can be increased to 5 mg of ramipril per day. When Inadequate dose of 5 mg in 2-3 weeks, it can be doubled to the maximum recommended daily dose - 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

Recommended initial dose: 1.25mg once a day (in this case, Tritace® 2.5 tablets can be usedmg with risk). Depending on the response to the patient's 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 more is required, it may be given as a single dose in cducks, and divide into 2 receptions.

The maximum recommended daily dose is 10 mg.

With diabetic or nondiabetic nephropathy

Recommended initial dose:

1.25 mg once a day (in this case, you can use Tritace® tablets 2.5 mg risk). The dose can be increased up to 5 mg once a day. At given conditions of a dose above

5 mg once a day in controlled clinical trials have not been studied enough.

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 (in this case, you can use Tritace® tablets 2.5 mg or 5 mg with a risk).

Depending on the tolerability of the drug, the patient can gradually increase the dose.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.

In heart failure with clinical manifestations that developed during the first few days (from the 2nd to the 9th day) after an acute myocardial infarction

The recommended initial 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 (in this case, Tritace® 2.5 mg or 5 mg with risk can be used). If the patient does not tolerate this initial dose (there is an excessive decrease in blood pressure), then it is recommended that he take 1.25 mg twice a day for two days (in this case, 2.5 mg of Tritace tablets with a risk can be used).

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.

Currently, the experience of treating patients with severe heart failure (III-IV functional class by classification NYHA), which appeared immediately after an acute myocardial infarction, is insufficient. If such patients decide to undergo treatment with Tritace®, it is recommended that treatment start with the lowest possible dose, 1.25 mg once a day (in this case Tritace® tablets 2.5 mg with a risk can be used), and a special caution should be observed at each dose increase.

Use of Tritace® in selected patient groups

Patients with impaired renal function

With SC from 50 to 20 ml / min at 1.73 m^{2 areas}Surface of the body, the initial daily dose is usually 1.25 mg (in this case you can use Tritace® tablets 2.5 mg with a risk). The maximum allowable daily dose is 5 mg

Patients with incompletely adjusted loss of fluid and electrolytes, patients with severe hypertension, as well as patients for whom excessive BP reduction poses a certain risk (for example, in severe atherosclerotic lesions of the coronary and cerebral arteries) The initial dose is reduced to 1.25 mg / day (in this case you can use Tritace® tablets 2.5 mg with a risk).

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 Tritace® or at least reduce the dose of diuretics taken Treatment of these patients should begin with the lowest dose of 1.25 mg of ramipril (in this case, Tritace® tablets 2.5 mg with a risk) can be used, 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 per day (in this case, Tritace® tablets 2.5 mg with a risk can be used).

Patients with hepatic impairment

The reaction of blood pressure to the Tritace® preparation can both be increased (by slowing the elimination of ramiprilate), and weaken (forthe slowing down of the conversion of low-active ramipril to active ramiprilate). Therefore, at the beginning of treatment, a thorough medical supervision. The maximum allowable daily dose is 2.5 mg (in this case Tritace® tablets 2.5 mg or 5 mg with a risk can be used).

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%); sometimes: (> 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

Sometimes: myocardial ischemia, including the development of an attack of angina or infarction

myocardium, tachycardia, arrhythmias (appearance or gain), palpitation, peripheral edema.

Vascular disorders

Often: excessive decrease in blood pressure, violation of orthostatic regulation

vascular tonus (orthostatic hypotension), syncopal conditions.

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

Rarely: occurrence or intensification of circulatory disorders in the background

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.

Sometimes: 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

Sometimes: visual disorders, including vagueness of the image.

Rarely: conjunctivitis.

Hearing disorders

Rarely: hearing impairment, ringing in the ears.

Disorders from the psyche

Sometimes: depressed mood, anxiety, nervousness, impellent

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.

Sometimes: bronchospasm, including weighting of the course of bronchial asthma,

nasal congestion.

Disturbances from the digestive tract

Often: inflammatory reactions in the stomach and intestines, disorders

digestion, a feeling of discomfort in the abdomen, dyspepsia, diarrhea, nausea, vomiting.

Sometimes: pancreatitis, including fatal (cases of pancreatitis with

lethal outcome when taking ACE inhibitors were very rare), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, abdominal pain, gastritis, constipation, dryness of the oral mucosa.

Rarely: glossitis

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

Disorders from the hepatobiliary system

Sometimes: increased activity of "liver" enzymes and concentration

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

Sometimes: a violation of kidney function, including the development of acute renal

insufficiency, increased urine output, increased pre-existing proteinuria, increased urea and creatinine levels in the blood.

Disorders from the reproductive system and mammary glands

Sometimes: transient impotence due to erectile dysfunction, decrease

libido.

The frequency is unknown: gynecomastia.

Violations of the blood and lymphatic system

Sometimes: eosinophilia.

Rarely: leukopenia, including neutropenia and agranulocytosis, decrease

the number of erythrocytes in the peripheral blood, a decrease in the concentration of 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.

Sometimes: angioedema, including fatal outcome (swelling

larynx can cause airway obstruction leading to death), skin itching, hyperhidrosis (excessive sweating).

Rarely: exfoliative dermatitis, urticaria, onycholysis.

Very rarely: photosensitization reactions.

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

Disorders from the musculoskeletal system and connective tissue

Often: muscle cramps, myalgia

Sometimes: arthralgia

Disorders from the metabolism, nutrition and laboratory indicators

Often: increase in the concentration of potassium in the blood.

Sometimes: 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), an increase in the concentration of antinuclear antibodies.

Common violations

Often: chest pain, fatigue.

Sometimes: fever.

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: gastric lavage, intake of adsorbents, sodium sulfate (if possible within the first 30 minutes). In the case of a marked decrease in blood pressure to therapy for replenishing the volume of circulating blood and restoringelectrolyte balance, the administration of alpha-adrenergic agonists (norepinephrine, dopamine) and angiotensin-P (angiotensinamide). In the case of refractory to medical treatment of bradycardia, 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-flux membranes with a negatively charged surface (for example, polyacrylonitrile membranes) during hemodialysis or hemofiltration; use of dextran sulfate in the apheresis of low density lipoproteins Risk of development of severe anaphylactoid reactions. If the patient needs these procedures, then other types of membranes should be used (in the case of plasmapheresis and hemofiltration) or the patient should be taken to receive other types of antihypertensive drugs.
The simultaneous use of Tritace® and preparations containing aliskiren The simultaneous use of Tritace® and preparations containing aliskiren, in patients with diabetes mellitus or moderate or severe renal insufficiency with creatinine clearance <60 ml / min is contraindicated and not recommended in other patients (see the sections "Contraindications", "With caution", "Special instructions").

- The simultaneous use of Tritace® and angiotensin receptor antagonists II The simultaneous use of Tritace and antagonists of angiotensin II receptors in patients with diabetic nephropathy is contraindicated and not recommended in other patients (see the sections "Contraindications", "With caution", "Special instructions").

Unrecommended combinations

- With potassium salts, potassium-sparing diuretics (for example, amiloride, triamterene, spiroeolactone), other drugs capable of increasing serum potassium levels (including angiotensin receptor antagonists D trimethoprim, tacrolimus., ciclosporin)

Perhaps more pronounced increase in potassium in the blood serum (with the simultaneous use requires careful monitoring of potassium in the blood serum).

Combinations that should be used with caution

- With antihypertensive medications (eg diuretics) and other drugs that can reduce blood pressure (nitrates, tricyclic antidepressants and, in general, for general and local anesthesia, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin)

Potentiation antihypertensive effect; for the combination with diuretics, see also the sections "Dosage and administration", "Side effects", "Special instructions", when combined with diuretics, the sodium content in serum should be monitored regularly.
- With sleeping pills, narcotic and anesthetic drugs
Perhaps a more pronounced decrease in blood pressure.

FROM vasopressor sympathomimetics (epinephrine (adrenaline), isoproterenol, dobutamine, dopamine) Reduction of the antihypertensive effect of the Tritace® preparation, particularly careful control of blood pressure is recommended.
FROM Allopurinol, procainamide, cytostatics, immunosuppressants, corticocmeroids (glucocorticosteroids and mineralocorticosteroids) and other medicinal means that can affect hematological parameters A joint application of
increases the risk of development of hematologic reactions (see section "Special instructions"),
- With lithium salts
Increase serum the concentration of lithium and the enhancement of the cardio- and neurotoxic effects of lithium. Therefore, the concentration of lithium in serum should be monitored.
- With hypoglycemic agents for oral administration (derivatives of sulfonylureas, biguanides), insulin
In connection with a decrease in insulin resistance under
effect of ACE inhibitors is possible gain
hypoglycemic effect of these drugs until the development of hypoglycemia. Recommended
especially careful monitoring of blood glucose concentrations at the beginning of their combined use with ACE inhibitors.
means that may affect hematological indicators Joint use increases the risk of hematological reactions (see section "Special instructions").
- With lithium salts
- With hypoglycemic agents (for example, insulin, hypoglycemic agents for oral administration (derivatives of sulfonylureas))
In connection with the decrease in insulin resistance under the influence of ACE inhibitors, it is possible to increase the hypoglycemic effect of these drugs, up to the development of hypoglycemia.A particularly careful monitoring of blood glucose concentrations at the beginning of their joint use with ACE inhibitors.
- With vildagliptin
In patients taking both ACE inhibitors and vildagliptin, there was an increase in the incidence of angioedema.
- With inhibitors mTOR (mammalian Target of Rapamycin - a target of rapamycin in mammalian cells), for example, tessirolimus
In patients taking both ACE inhibitors and inhibitors mTOR, there was an increase in the incidence of angioedema.

Combinations that should be taken into account
- With non-steroidal anti-inflammatory agents (indomethacin, acetylsalicylic acid) It is possible to weaken the action of Tritace®, increase the risk of renal dysfunction and increase the potassium content in the blood serum.
- With heparin It is possible to increase the potassium content in the blood serum.
  - With sodium chloride Weakening of the antihypertensive effect of Tritace® and less effective treatment of symptoms of chronic heart failure.
  - With ethanol Increased symptoms of vasodilation.The drug Tritace® can enhance the effect of ethanol on the body.
  - With estrogens Weakening of the antihypertensive effect of Tritace® (fluid retention).
  - Desensitizing therapy with hypersensitivity to insect venoms
  ACE inhibitors, including Tritace®, increase the likelihood of severe anaphylactic or anaphylactoid reactions to insect venoms. It is assumed that this effect can occur when other allergens are used.

Special instructions:PBefore starting treatment with Tritace®, 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 Tritace® (in this case, carefully monitor the condition of patients with chronic heart failure, due to the possibility of developing them decompensation with increasing 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 Tritace® is used for the first time or at a high dose in patients with increased activity of RAAS, then they should be closely monitored by AD, especially at the beginning of treatment, as these patients have an increased risk of excessive blood pressure lowering (see "With caution").

With malignant arterial hypertension and heart failure, especially in the acute stage of myocardial infarction, treatment with Tritace^ь 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 that the parameters of kidney function are monitored during the initial phase of treatment (see also section "Method of administration and dose").

Have 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 due to 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 sodium content in the blood.

During treatment with Tritace it is not recommended to drink alcohol (ethanol). The transient excessive decrease in blood pressure is not a contraindication for the continuation of treatment after stabilization of blood pressure. In case of repeated development of a marked decrease in blood pressure, the dose should be reduced or the drug should be withdrawn.

The simultaneous use of Tritace '¹ with preparations containing aor angiotensin II receptor antagonists, resulting in a double blockade of RAAS, is not recommended due to the risk of excessive blood pressure lowering, the development of hyperkalemia, and impaired renal function compared to monotherapy. The simultaneous use of Tritace® with preparations containing aliskiren, in patients with diabetes mellitus and / or moderate and severe renal insufficiency with creatinine clearance <60 ml / min is contraindicated (see.sections "Contraindications" and "Interaction with other medicinal products"). Simultaneous use with antagonists of angiotensin II receptors in patients with diabetic nephropathy is contraindicated (see the sections "Contraindications" and "Interaction with other drugs").

Patients treated with ACE inhibitors experienced cases of angioedema of the face, extremities, lips, tongue, pharynx andwhether the 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) followed by the use of glucocorticosteroids (iv, in / m or inside); It is also recommended intravenous administration of antihistamines (antagonists of H₁ and H₂-gistaminovyh receptors), and in the case of deficiency of inactivators of the enzyme C1-esterase, it may be necessary to consider the addition of inhibitors of the enzyme C1-esterase in addition to epinephrine (adrenaline). The patient should be gis overshadowed, and monitoring should be carried out until 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, it is necessary to consider the possibility of developing an intestinal angioedema in the course of a differential diagnosis.

Treatment aimed at desensitization to the poison of insects (such as 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 (such as 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 the appropriate drug of the other group.

With the use of ACE inhibitors, life-threatening, rapidly developing anaphylactoid reactions have been described, sometimes up to the development of shock during hemodialysis or plasma filtration using certain high-flow membranes (eg, polyacrylonitrile membranes) (see also membrane manufacturers instructions). It is necessary to avoid the joint use of Tritace¹'and the use of this type of membrane, for example, for urgent hemodialysis or hemofiltration. In this case, preferablyUse of other types of membranes or exclusion 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 Tritace * treatment may be either exacerbated or weakened. In addition, in patients with severe 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), the surgeon / anesthesiologist should be warned about taking ACE inhibitors. It is recommended that careful monitoring of newborns exposed to intrauterine exposure andACE inhibitors, for the detection of arterial hypotension, oliguria and hyperkalemia. In oliguria it is necessary to maintain BP and renal perfusion by introducing appropriate fluids and vasoconstrictors. In such newborns, there is a risk of developing oliguria and neurological disorders, possibly due to a reduction in renal and cerebral blood flow due to a reduction in blood pressure caused by ACE inhibitors.

Control of laboratory indicators before and during treatment with Tritace® (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 and in the following it is recommended to monitor the function of the kidneys. Particularly careful monitoring is required for patients with acute and chronic heart failure, impaired renal function, after transplantationglasses, patients with renovascular diseases, including patients with hemodynamically significant unilateral stenosis of the renal artery in the presence of two kidneys (in such patients, even a slight increase in serum creatinine concentration may be indicative of a decrease in renal function).

Control of the content of electrolytes Regular monitoring of the potassium and sodium content in serum is recommended. Particularly careful monitoring of potassium in the blood serum is required for patients with impaired renal function, significant disturbances in water-electrolyte balance, chronic heart failure.

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

It is recommended to monitor the parameters of the general blood test, for Possible manifestations of 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 picture 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 appearance of signs to(small petechiae, red-brown rashes on the skin and mucous membranes), control of the number of platelets in the peripheral blood is also necessary.

Determination of the activity of "liver" enzymes, the concentration of bilirubin in the blood When jaundice or a significant increase in the activity of "liver" enzymes, treatment with Tritace should be stopped and medical supervision of the patient should be provided.

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

During the treatment with Tritace®, it is necessary to 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:

Tablets of 10 mg. For 14 tablets in a blister, made of PVC / aluminum foil. 2 blisters together with instructions for use in a cardboard box.

Packaging:For 14 tablets in a blister, made of PVC / aluminum foil. 2 blisters together with instructions for use in a cardboard box.

Storage conditions:

List B. At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:3 of the year. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008998/09

Date of registration:09.11.2009

The owner of the registration certificate:Sanofi-Aventis Deutschland GmbHSanofi-Aventis Deutschland GmbH Germany

Manufacturer: & nbsp

SANOFI-AVENTIS, S.p.A. Italy

Information update date: & nbsp15.07.2014

Illustrated instructions

Instructions

Tritace® (Tritace®)