Tritace, tablets 5 mg 28 pcs

Tritace is an antihypertensive drug, an ACE inhibitor. Ramiprilat, the active metabolite of ramipril, is a long-acting ACE inhibitor. In blood plasma and tissues this enzyme catalyzes the transition of angiotensin I into angiotensin II (active vasoconstrictor) and the cleavage of the active vasodilator bradykinin.

Decreasing angiotensin II formation and increasing bradykinin activity leads to vasodilation and contributes to the cardioprotective and endothelioprotective effects of ramipril. Angiotensin II stimulates the release of aldosterone, in this regard, ramipril causes reduction of aldosterone secretion.

The administration of ramipril leads to a significant decrease in RPS, generally without causing changes in renal blood flow and glomerular filtration rate.

The administration of ramipril causes a decrease in BP in both the supine and standing positions without a compensatory increase in HR. Hypotensive effect starts 1-2 hours after oral administration of a single dose of the drug and lasts for 24 hours.

The maximal antihypertensive effect of Tritace usually develops by 3-4 weeks of continuous drug administration and is maintained for a long time. Sudden discontinuation of the drug does not lead to a rapid and significant increase in BP.

The use of the drug reduces mortality (including sudden death), the risk of development of severe heart failure, reduces the number of hospitalizations of patients with clinical signs of chronic heart failure after acute myocardial infarction.

In patients with diabetic and nondiabetic clinically significant nephropathy the drug decreases rate of progression of renal failure, and in preclinical stage of diabetic and nondiabetic nephropathy ramipril decreases albuminuria. The drug favorably influences carbohydrate metabolism and lipid profile, causes reduction of marked myocardial and vascular wall hypertrophy.

Indications

Arterial hypertension.
Chronic heart failure (as part of combination therapy), incl. developing during the first few days after acute myocardial infarction.
Diabetic nephropathy and nephropathy against the background of chronic diffuse kidney diseases (chronic glomerulonephritis with severe proteinuria) – preclinical and clinically pronounced stages.
In order to prevent the development of myocardial infarction, stroke or “coronary death” in patients with coronary artery disease, with an increased risk of cardiovascular diseases, including patients who have had myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting.

Pharmacological effect

Tritace is an antihypertensive drug, an ACE inhibitor. Ramiprilat, the active metabolite of ramipril, is a long-acting ACE inhibitor. In blood plasma and tissues, this enzyme catalyzes the transition of angiotensin I to angiotensin II (an active vasoconstrictor) and the cleavage of the active vasodilator bradykinin.

A decrease in the formation of angiotensin II and an increase in bradykinin activity leads to vasodilation and contributes to the cardioprotective and endothelial protective effects of ramipril. Angiotensin II stimulates the release of aldosterone, and therefore ramipril causes a decrease in aldosterone secretion.

Taking ramipril leads to a significant decrease in peripheral vascular resistance, generally without causing changes in renal blood flow and glomerular filtration rate.

Taking ramipril causes a decrease in blood pressure both in the supine and standing positions without a compensatory increase in heart rate. The hypotensive effect begins 1-2 hours after oral administration of a single dose of the drug and persists for 24 hours.

The maximum antihypertensive effect of Tritace usually develops by 3-4 weeks of continuous use of the drug and is maintained for a long time. Sudden cessation of the drug does not lead to a rapid and significant increase in blood pressure.

The use of the drug reduces mortality (including sudden death), the risk of developing severe heart failure, and reduces the number of hospitalizations of patients with clinical signs of chronic heart failure after acute myocardial infarction.

In patients with diabetic and nondiabetic clinically significant nephropathy, the drug reduces the rate of progression of renal failure, and at the preclinical stage of diabetic and nondiabetic nephropathy, ramipril reduces albuminuria. The drug has a beneficial effect on carbohydrate metabolism and lipid profile, causing a decrease in pronounced hypertrophy of the myocardium and vascular wall.

Special instructions

After taking the first dose, as well as when increasing the dosage of the diuretic and/or ramipril, patients should be under medical supervision for 8 hours to avoid the development of an uncontrolled hypotensive reaction. In patients with CHF, taking the drug can lead to the development of severe arterial hypotension, which in some cases is accompanied by oliguria or azotemia and rarely by the development of acute renal failure.

The lower limit of systolic blood pressure for therapy in the early stages of myocardial infarction is considered to be 100 mm Hg. Patients with malignant arterial hypertension or concomitant decompensated CHF should begin treatment in a hospital setting. Before starting and during therapy with ACE inhibitors, it is necessary to count the total number of leukocytes and determine the leukocyte formula (up to 1 time per month in the first 3-6 months of treatment in patients with an increased risk of neutropenia – with impaired renal function, systemic connective tissue diseases or those receiving high doses, as well as at the first signs of infection). If neutropenia is confirmed (the number of neutrophils is less than 2 thousand/μl), therapy with ACE inhibitors should be discontinued.

Before and during treatment, it is necessary to monitor blood pressure, kidney function (creatinine, urea), K+ and other electrolytes in plasma, Hb, and the activity of “liver” enzymes in the blood. Caution must be exercised when prescribing the drug to patients on a low-salt or salt-free diet (increased risk of developing arterial hypotension). In patients with reduced blood volume (as a result of diuretic therapy), with limited salt intake, during dialysis, with diarrhea and vomiting, symptomatic hypotension may develop.

Transient hypotension is not a contraindication for continuing treatment after stabilization of blood pressure. If severe hypotension reoccurs, the dose should be reduced or the drug discontinued. The use of AN69 dialysis membranes in combination with ACE inhibitors is not recommended (due to the possibility of developing anaphylactoid reactions in patients). If there is a history of evidence of the development of angioedema not associated with taking ACE inhibitors, then such patients still have an increased risk of developing it when taking it.

Safety and efficacy in pediatric practice: Close monitoring for hypotension, oliguria and hyperkalemia is recommended for neonates exposed in utero to ACE inhibitors. With oliguria, it is necessary to maintain blood pressure and renal perfusion by administering appropriate fluids and vasoconstrictor drugs.

In neonates and infants there is a risk of oliguria and neurological disorders, possibly due to decreased renal and cerebral blood flow due to the decrease in blood pressure caused by ACE inhibitors (received during pregnancy and postpartum); Lower initial doses and close monitoring are recommended.

Caution should be exercised during exercise or hot weather due to the risk of dehydration and hypotension due to decreased fluid volume. It is not recommended to consume ethanol. Before surgery (including dentistry), the surgeon/anesthesiologist must be warned about the use of ACE inhibitors.

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretic drugs).

Active ingredient

Ramipril

Composition

1 tablet contains:

ramipril 5 mg.

Excipients:

hypromellose,

pregelatinized starch,

microcrystalline cellulose,

sodium stearyl fumarate,

red iron oxide dye.

Contraindications

Hypersensitivity to ramipril or other ACE inhibitors, history of angioedema during therapy with ACE inhibitors, hereditary or idiopathic angioedema, bilateral renal artery stenosis, stenosis of the artery of a solitary kidney, condition after kidney transplantation, hemodynamically significant aortic or mitral stenosis, HOCM, primary hyperaldosteronism, pregnancy, lactation.

With caution. Severe lesions of the coronary and cerebral arteries (danger of decreased blood flow with an excessive decrease in blood pressure), unstable angina, severe ventricular arrhythmias, end-stage CHF, decompensated “pulmonary” heart, diseases requiring the use of corticosteroids and immunosuppressants (lack of clinical experience) – incl. with systemic connective tissue diseases, renal and/or liver failure, hyperkalemia, hyponatremia (including against the background of diuretics and a diet with limited Na+ intake), conditions accompanied by a decrease in blood volume (including diarrhea, vomiting), elderly age, age 18 years (the safety and effectiveness of use have not been studied).

Side Effects

The following undesirable effects are given in accordance with the following gradations of the frequency of their occurrence: very often (≥10%), often (≥1%,

From the cardiovascular system: often – excessive decrease in blood pressure, impaired orthostatic regulation of vascular tone (orthostatic hypotension), syncope; sometimes – myocardial ischemia, including the development of an attack of angina or myocardial infarction, tachycardia, arrhythmias (appearance or intensification), palpitations, peripheral edema, flushes of blood to the skin of the face; rarely – the occurrence or intensification of circulatory disorders against the background of stenotic vascular lesions, vasculitis; frequency unknown – Raynaud’s syndrome.

From the side of the central nervous system: often – headache, a feeling of “lightness” in the head; sometimes – dizziness, ageusia (loss of taste sensitivity), dysgeusia (impaired taste sensitivity), depressed mood, anxiety, nervousness, restlessness, sleep disorders, including drowsiness; rarely – tremor, imbalance, confusion; frequency unknown – cerebral ischemia, including ischemic stroke and transient cerebrovascular accident, impaired psychomotor reactions, paresthesia (burning sensation), parosmia (impaired odor perception), impaired attention.

Parts of the organ of vision: sometimes – visual disturbances, including blurred images; rarely – conjunctivitis.

From the organ of hearing: rarely – hearing impairment, ringing in the ears.

From the respiratory system: often – dry cough (worsening at night and when lying down), bronchitis, sinusitis, shortness of breath; sometimes – bronchospasm, including worsening of bronchial asthma, nasal congestion.

From the digestive system: often – inflammatory reactions in the stomach and intestines, digestive disorders, discomfort in the abdominal area, dyspepsia, diarrhea, nausea, vomiting; sometimes – pancreatitis, incl. with a fatal outcome (cases of pancreatitis with a fatal outcome when taking ACE inhibitors were observed extremely rarely), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, abdominal pain, gastritis, constipation, dry oral mucosa; rarely – glossitis; frequency unknown – aphthous stomatitis (inflammatory reaction of the oral mucosa).

From the hepatobiliary system: sometimes – increased activity of liver enzymes and the concentration of conjugated bilirubin in the blood plasma; rarely – cholestatic jaundice, hepatocellular lesions; frequency unknown – acute liver failure, cholestatic or cytolytic hepatitis (death was extremely rare).

From the kidneys and urinary tract: sometimes – impaired renal function, including the development of acute renal failure, increased urine output, increased pre-existing proteinuria, increased concentrations of urea and creatinine in the blood.

From the reproductive system and mammary glands: sometimes – transient impotence due to erectile dysfunction, decreased libido; frequency unknown: gynecomastia.

From the hematopoietic system: sometimes – eosinophilia; rarely – leukopenia, including neutropenia and agranulocytosis, a decrease in the number of red blood cells in the peripheral blood, a decrease in hemoglobin concentration, thrombocytopenia; frequency unknown – suppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.

From the skin and mucous membranes: often – skin rash (in particular maculopapular); sometimes – angioedema, incl. with a fatal outcome (swelling of the larynx can cause airway obstruction, leading to death), itching, hyperhidrosis; rarely – exfoliative dermatitis, urticaria, onycholysis; very rarely – photosensitivity reactions; frequency unknown – toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (lichenoid) exanthema or enanthema, alopecia.
From the musculoskeletal system: often – muscle cramps, myalgia; sometimes – arthralgia.

Metabolic, nutritional and laboratory disorders: often – increased potassium concentration in the blood; sometimes – anorexia, loss of appetite; frequency unknown – decreased sodium concentration in the blood.

From the immune system: frequency unknown – anaphylactic or anaphylactoid reactions (with ACE inhibition, the number of anaphylactic or anaphylactoid reactions to insect venoms increases), increased concentration of antinuclear antibodies.

General disorders: often – chest pain, feeling tired; sometimes – increased body temperature; rarely – asthenia (weakness).

Interaction

When using potassium salts and potassium-sparing diuretics (for example, amiloride, triamterene, spironolactone) with Tritace, hyperkalemia is observed (control of potassium levels in the blood serum is necessary).

The simultaneous use of Tritace with antihypertensive drugs (in particular, diuretics) and other drugs that lower blood pressure leads to increased effects of ramipril.

When used simultaneously with sleeping pills, opioids and analgesics, a sharp decrease in blood pressure is possible.

Vasopressor sympathomimetic drugs (epinephrine) and estrogens may reduce the effect of ramipril.

With the simultaneous use of Tritace with allopurinol, procainamide, cytostatic agents, immunosuppressants, systemic corticosteroids and other drugs that can change the blood picture, a decrease in the number of leukocytes in the blood is possible.

When used simultaneously with lithium preparations, it is possible to increase the concentration of lithium in plasma, which leads to increased cardio- and neurotic effects of lithium.

When Tritace is used simultaneously with oral hypoglycemic agents (sulfonylurea derivatives, biguanides), insulin, hypoglycemia increases. NSAIDs (indomethacin, acetylsalicylic acid) may reduce the effectiveness of ramipril.

When used simultaneously with heparin, an increase in the concentration of potassium in the blood serum is possible.

Table salt reduces the effectiveness of ramipril.

Ethanol enhances the hypotensive effect of ramipril.

Overdose

Symptoms: marked decrease in blood pressure, shock, severe bradycardia, water and electrolyte imbalance, acute renal failure, stupor.

Treatment: gastric lavage, taking adsorbents, sodium sulfate (if possible during the first 30 minutes). In the event of the development of arterial hypotension, the administration of alpha 1-adrenergic stimulants (norepinephrine, dopamine) and angiotensin II (angiotensinamide) can be added to therapy to replenish blood volume and restore salt balance.

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

5 years

Manufacturer

Sanofi S.R.L., Italy