Prestarium A, pills 5mg, 30pcs

Composition

Tablets of 5 mg contain:  Active ingredients:  perindopril arginine 5 mg, which corresponds to 3,395 mg of perindopril. Auxiliary substances:  

• lactose monohydrate 72.58 mg, magnesium stearate 0.45 mg,
• maltodextrin 9.00 mg,
• colloidal hydrophobic silicon dioxide 0.27 mg,
• sodium carboxymethyl starch 2.70 mg;

Shell:  

• premix for plastic shell light green color Sepifilm 4193 [glycerol (E 422a) of 4.5%, hypromellose (E 464) 74,8%, macrogol 6000 1.8%, the magnesium stearate of 4.5%, titanium dioxide (E 171) 14,328%, copper chlorophyllin (E 141(ii)) 0,072%] 1,931 mg, macrogol 6000 to 0.069 mg.

Pharmacological action

PRESTARIUM A is an antihypertensive drug, an ACE inhibitor. ACE, or kininase, is an exopeptidase that performs both the conversion of angiotensin I to the vasoconstrictor angiotensin II, and the destruction of bradykinin, which has a vasodilating effect, to an inactive heptapeptide. ACE inhibition leads to a decrease in the content of angiotensin II in blood plasma, as a result, plasma renin activity increases (due to inhibition of negative feedback, which prevents the release of renin) and aldosterone secretion decreases. Since ACE inhibits bradykinin, ACE inhibition is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin systems, while the prostaglandin system is activated. Perindopril reduces OPSS, which leads to a decrease in blood pressure. In this case, the peripheral blood flow accelerates, but the heart rate does not increase. Perindopril has a therapeutic effect due to its active metabolite, perindoprilat. Other metabolites of the drug do not have an ACE inhibitory effect in vitro. Arterial hypertension In case of arterial hypertension against the background of its use, the drug shows a decrease in both systolic and diastolic blood pressure in the supine and standing positions. Blood pressure reduction is achieved fairly quickly. In patients with a positive response to treatment, blood pressure normalizes within a month. At the same time, the effect of addiction is not observed. Discontinuation of treatment is not accompanied by the development of withdrawal syndrome. Perindopril has a vasodilating effect, helps restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy. Concomitant use of thiazide diuretics increases the hypotensive effect. In addition, the combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of hypokalemia when taking diuretics. Heart failure Perindopril normalizes heart function by reducing preload and afterload. In patients with chronic heart failure treated with perindopril, there was a decrease in filling pressure in the left and right ventricles of the heart; a decrease in OPSS; an increase in cardiac output and an increase in the cardiac index. A study of the drug compared with placebo showed that changes in blood pressure after the first use of Prestarium A at a dose of 2.5 mg in patients with mild to moderate heart failure did not statistically significantly differ from changes in blood pressure observed after taking placebo. The international multicenter study (PROGRESS) evaluated the effect of active therapy with perindopril (monotherapy or in combination with indapamide) for 4 years on the risk of recurrent stroke in patients with a history of cerebrovascular diseases. After an introductory period of 2 mg perindopril tretbutylamine (equivalent to 2.5 mg perindopril arginine) once daily for 2 weeks and then 4 mg (equivalent to 5 mg perindopril arginine) once daily for the next two weeks,6105 patients were randomly assigned to two groups: placebo (n = 3054) and 4 mg perindopril tretbutylamine (equivalent to 5 mg perindopril arginine) (monotherapy) or in combination with indapamide (n = 3051). Indapamide was additionally prescribed to patients who do not have direct indications or contraindications for the use of diuretics. This therapy was prescribed in addition to the standard therapy for stroke and / or arterial hypertension or other pathological conditions. All randomized patients had a history of cerebrovascular diseases (stroke or transient ischemic attack) within the last 5 years. The BP value was not a criterion for inclusion: 2916 patients had arterial hypertension and 3189 had normal BP. After 3.9 years of therapy, blood pressure (systolic/ diastolic) decreased by an average of 9/4 mm Hg. There was also a significant reduction in the risk of recurrent stroke (both ischemic and hemorrhagic) of the order of 28% (95% CI (17; 38), p Additionally, there was a significant reduction in the risk of fatal or disabling strokes; major cardiovascular events, including fatal myocardial infarction; stroke-related dementia; and severe cognitive impairment. These therapeutic benefits are observed both in patients with arterial hypertension and in patients with normal blood pressure, regardless of age, gender, the presence or absence of diabetes mellitus and the type of stroke. Stable CHD In a 4-year, multicenter, randomized, double-blind, placebo-controlled trial EUROPA, the efficacy of perindopril in patients with stable CHD was evaluated. A total of 12,218 patients over 18 years of age participated in the clinical trial: 6110 patients received perindopril tretbutylamine 8 mg (equivalent to 10 mg of perindopril arginine) and 6108 patients received placebo. The main evaluation criteria were cardiovascular mortality, non-fatal myocardial infarction and / or cardiac arrest followed by successful resuscitation. To participate in the study, we selected patients with CHD who had an established myocardial infarction at least 3 months prior to screening, who had undergone coronary revascularization at least 6 months prior to screening, angiographically detected stenosis (at least 70% narrowing of one or more major coronary arteries), or a positive stress test with a history of chest pain. The drug was prescribed in addition to the standard therapy used for hyperlipidemia, arterial hypertension and diabetes mellitus. Most patients received antiplatelet agents, lipid-lowering agents, and beta-blockers. By the end of the study, the ratio of the number of patients taking these groups of drugs was 91%,69% and 63%, respectively. After 4.2 years, treatment with perindopril tretbutylamine 8 mg once daily resulted in a significant 20% (95% CI ) reduction in the relative risk of pre-defined complications: 488 (8%) patients in the perindopril tretbutylamine group and 603 (9.9%) patients in the placebo group (p = 0.0003). The result did not depend on gender, age, blood pressure, or a history of myocardial infarction.

Indications

• arterial hypertension;
• chronic heart failure;
• prevention of recurrent stroke (combined therapy with indapamide) in patients who have had a stroke or transient ischemic cerebral circulation disorder;
• stable coronary heart disease: to reduce the risk of cardiovascular complications.

Use during pregnancy and lactation

The use of Prestarium® is not recommended in the first trimester of pregnancy. When planning or confirming pregnancy, it is necessary to switch to alternative therapy. No relevant controlled studies have been conducted in humans, so there is insufficient clinical data on the effects of ACE inhibitors in the first trimester of pregnancy. In a limited number of cases of ACE inhibitor use in the first trimester of pregnancy, the appearance of any malformations associated with fetotoxicity (see below) was not observed. Perindopril is contraindicated in the second and third trimesters of pregnancy, since there are data on the manifestation of fetotoxicity (decreased renal function, oligoamnion (pronounced decrease in amniotic fluid volume), delayed formation of cranial bones) and neonatal toxicity (impaired renal function, hypotension, hyperkalemia). If perindopril therapy was performed in the second and/or third trimesters of pregnancy, ultrasound examination of the fetal kidney and skull function should be performed. Breast-feeding periodthe use of perindopril during breast-feeding is not recommended due to the lack of data on the possibility of its penetration into breast milk.

Contraindications

• a history of angioedema (congenital/idiopathic or associated with previous treatment with ACE inhibitor response);
• pregnancy;
• lactation (breastfeeding);
• hypersensitivity to the components of the drug;
• hypersensitivity to other ACE inhibitors;
• lactase insufficiency, galactosemia, a syndrome glucose/galactose malabsorption (due to the fact that the composition of the excipients of the drug includes lactose monohydrate).

Side effects

Common Side Effects >1/100, >< 1/10 Rare Side effects > 1/1000, < 1/10 Rare Side Effects >< 1/100 Extremely Rare Side Effects Sexual dysfunctioncardiovascular disorders: excessive lowering of blood pressure and associated symptoms. Extremely rare: arrhythmia, angina pectoris, myocardial infarction and stroke, may develop secondary severe arterial hypotension in patients at risk. Laboratory parameters: extremely rare: decreased hemoglobin and hematocrit concentrations, thrombocytopenia, leukopenia/neutropenia, isolated cases of agranulocytosis or pancytopenia. The possibility of developing hemolytic anemia against the background of glucose-6-phosphate dehydrogenase deficiency. Rarely: increased urea and creatinine levels in blood plasma, passing hyperkalemia, especially against the background of renal failure, increased activity of “liver” enzymes and liver bilirubin.

Interaction

In the initial period of treatment, some patients with diuretic therapy, especially with excessive excretion of fluids and/or salts, may experience an excessive decrease in blood pressure, the risk of which can be reduced by discontinuing the diuretic, introducing an increased amount of water and/or sodium chloride, as well as prescribing an ACE inhibitor in lower doses. Further increase in the dose of perindopril should be carried out with caution. During therapy with ACE inhibitors, as a rule, the content of potassium in the blood serum remains within normal limits, but sometimes hyperkalemia may develop. The combined use of ACE inhibitors and potassium-sparing diuretics (spironolactone, triamterene and amiloride) and potassium preparations, potassium-containing products and food additives can lead to a significant increase in the concentration of potassium in the blood serum. In this regard, their co-use with ACE inhibitors is not recommended. These combinations should be used only in the case of hypokalemia, taking precautions and constantly monitoring the potassium content in the blood serum. Co-use of ACE inhibitors and lithium preparations may lead to a reversible increase in serum lithium concentrations and the development of lithium toxicity. The additional use of thiazide diuretics in combination with lithium and ACE inhibitors increases the existing risk of lithium toxicity. Co – use of ACE inhibitors and lithium is not recommended. If this combination cannot be avoided, then regular monitoring of the lithium content in the blood serum is necessary. The use of NSAIDs may be accompanied by a weakening of the antihypertensive effect of ACE inhibitors. Moreover, NSAIDs and ACE inhibitors have been found to have an additive effect on increasing serum potassium levels, while possibly also impairing renal function. As a rule, these effects are reversible. In rare cases, acute renal failure may develop, which usually occurs with pre-existing renal dysfunction in elderly patients or against the background of dehydration. The antihypertensive effect of these drugs may be enhanced by concomitant use with ACE inhibitors. The use of nitroglycerin and / or other vasodilators may lead to an additional hypotensive effect. Concomitant use with ACE inhibitors allopurinol, immunosuppressants, including cytostatic agents and systemic corticosteroids, procainamide may increase the risk of leukopenia. The use of ACE inhibitors may increase the hypoglycemic effect of insulin and oral hypoglycemic agents up to the development of hypoglycemia. As a rule, this phenomenon is observed in the first weeks of combined use of these drugs and in patients with renal insufficiency. Concomitant use of tricyclic antidepressants, antipsychotics (neuroleptics), and general anesthesia with ACE inhibitors may lead to an increased hypotensive effect. Sympathomimetics may weaken the antihypertensive effect of ACE inhibitors. When prescribing such a combination, the effectiveness of ACE inhibitors should be regularly evaluated. Antacids reduce the bioavailability of ACE inhibitors. Perindopril can be administered together with acetylsalicylic acid (as a thrombolytic), thrombolytic agents, beta-blockers and / or nitrates. Ethanol enhances the antihypertensive effect of ACE inhibitors.

How to take, course of use and dosage

Inside. It is recommended to take it once a day, in the morning, before meals.

Arterial hypertension The recommended starting dose is 5 mg once daily, in the morning. If the therapy is ineffective for a month, the dose can be increased to 10 mg once a day.

When prescribing ACE inhibitors to patients with a pronounced activated renin – angiotensin-aldosterone system (with renovascular arterial hypertension, impaired water-salt balance, diuretic therapy, severe arterial hypertension, cardiac decompensation), an unpredictable sharp decrease in blood pressure may occur, for the prevention of which it is recommended to stop taking diuretics 2-3 days before the expected start of therapy with Prestarium®.

If diuretics cannot be discontinued, the initial dose of Prestarium® should be 2.5 mg. At the same time, it is necessary to monitor kidney function and the content of potassium in the blood serum. Subsequently, if necessary, the dose can be increased.

In elderly patients, treatment should begin with a dose of 2.5 mg per day, and then, if necessary, gradually increase it up to a maximum dose of 10 mg per day.

Heart failure Treatment of patients with heart failure with Prestarium® in combination with non – potassium-sparing diuretics and/or digoxin and/or beta-blockers is recommended to begin under close medical supervision, prescribing the drug at an initial dose of 2.5 mg once a day, in the morning. Subsequently, depending on the tolerability and response to therapy, after two weeks of treatment, the dose of the drug can be increased to 5 mg once a day.

In patients at high risk of developing symptomatic hypotension, such as those with reduced salt levels with or without hyponatremia, hypovolemia, or diuretics, these conditions should be segregated as far as possible before starting Prestarium®. Parameters such as blood pressure, renal function, and blood potassium levels should be monitored both before and during therapy.

Prevention of recurrent stroke In patients with a history of cerebrovascular disease, Prestarium® therapy should be initiated at a dose of 2.5 mg during the first two weeks prior to indapamide use. Therapy should be started at any time (from two weeks to several years) after a stroke.

Reducing the risk of cardiovascular complications In patients with stable coronary artery disease, Prestarium® therapy should be initiated at a dose of 5 mg once a day for two weeks. Then the daily dose should be increased to 10 mg once a day (depending on renal function).

Elderly patients should start therapy with a dose of 2.5 mg once daily for one week, then 5 mg once daily for the next week before increasing the dose to 10 mg once daily (depending on renal function).

Selection of doses for renal failure: if the patient has impaired renal function, the dose of Prestarium® should be selected taking into account the degree of renal insufficiency and with regular monitoring of potassium content and creatinine clearance (CC).

Overdose

Symptoms: marked decrease in blood pressure, shock, electrolyte disturbances (such as increased potassium ion concentration, decreased sodium); renal failure, hyperventilation, tachycardia, dizziness, bradycardia, restlessness and cough. Treatment: with a significant decrease in blood pressure, the patient should be placed in a supine position and immediately replenish the volume of circulating blood, if possible, an infusion of angiotensin II and/or an intravenous solution of catecholamines should be administered. If persistent severe bradycardia develops, it may be necessary to use an artificial heart driver. The main vital functions of the body, blood serum electrolytes and creatinine clearance should be constantly monitored. Perindopril can be removed from the systemic circulation by hemodialysis. The use of high-flow polyacrylonitrile membranes should be avoided.

Special instructions

Diuretics In the initial period of treatment, some patients with diuretic therapy, especially with excessive fluid and/or salt excretion, may experience an excessive decrease in blood pressure at the very beginning of perindopril therapy, the risk of which can be reduced by discontinuing the diuretic, introducing an increased amount of water and/or sodium chloride, as well as prescribing an ACE inhibitor in lower doses. Further increase in the dose of perindopril should be carried out with caution.Potassium-sparing diuretics or potassium preparations, potassium-containing products and dietary supplements during therapy with ACE inhibitors, as a rule, the content of potassium in the blood serum remains within normal limits, but sometimes hyperkalemia may develop. The combined use of ACE inhibitors and potassium-sparing diuretics (spironolactone, triamterene and amiloride) and potassium preparations, potassium-containing products and food additives can lead to a significant increase in the concentration of potassium in the blood serum. In this regard, their co-use with ACE inhibitors is not recommended. Prescribe these combinations only in the case of hypokalemia, taking precautions and constantly monitoring the content of potassium in the blood serum. Lithium-couse of ACE inhibitors and lithium preparations can lead to a reversible increase in serum lithium concentrations and the development of lithium toxicity. The additional use of thiazide diuretics in combination with lithium and ACE inhibitors increases the already existing risk of lithium toxicity. Co – use of ACE inhibitors and lithium is not recommended. If it is impossible to avoid this combination, it is necessary to conduct regular monitoring of the lithium content in the blood serum. Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (aspirin) ≥ 3 g / day. The use of NSAIDs may be accompanied by a weakening of the antihypertensive effect of ACE inhibitors. Moreover, NSAIDs and ACE inhibitors have been found to have an additive effect on increasing serum potassium levels, while possibly also impairing renal function. As a rule, these effects are reversible. In rare cases, acute renal failure may develop, which usually occurs with pre-existing renal dysfunction in elderly patients or against the background of dehydration. Antihypertensive and vasodilating agents The antihypertensive effect of drugs may be enhanced by combined use with ACE inhibitors. The use of nitroglycerin and / or other vasodilators may lead to an additional hypotensive effect. Allopurinol, immunosuppressants, including cytostatic agents and systemic glucocorticosteroids, Procainamide co-use with ACE inhibitors may increase the risk of leukopenia. Hypoglycemic agents use of ACE inhibitors may increase the hypoglycemic effect of insulin and oral hypoglycemic agents up to the development of hypoglycemia. As a rule, this phenomenon is observed in the first weeks of combined use of these drugs and in patients with renal insufficiency. Tricyclic Antidepressants/ Antipsychotics (neuroleptics)/ General anaesthetic agents Co-administered with ACE inhibitors may lead to an increased hypotensive effect. Sympathomimetics may weaken the antihypertensive effect of ACE inhibitors. When prescribing such a combination, the effectiveness of ACE inhibitors should be regularly evaluated. Antacids reduce the bioavailability of ACE inhibitors. Acetylsalicylic acid, thrombolytic agents, beta-blockers, nitraty Perindopril can be prescribed together with acetylsalicylic acid (as a thrombolytic), thrombolytic agents, beta-blockers and / or nitrates. Alcohol increases the hypotensive effect of ACE inhibitors.

Form of production

Oblong tablets, film-coated, rounded on both sides, light green in color, with notches on both sides and engraved in the form of the company’s logo on one of the front sides.

Storage conditions

No special storage conditions are required

Shelf life

3 years

Active ingredient

Perindopril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Prevention of heart attacks and strokes, Angina, Hypertension, Heart failure