Prestarium A, Dispersible pills 10mg, 30pcs

Composition

The Active ingredient of Prestarium A tablets contains:

perindopril arginine 10 mg.

Auxiliary substances:

titanium dioxide,

maltodextrin,

lactose monohydrate,

magnesium stearate,

colloidal hydrophobic silicon dioxide,

sodium carboxymethyl starch,

glycerol,

hypromellose,

macrogol 6000.

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.

Heart failure Perindopril normalizes the functioning of the heart, 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.

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 With 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.

Cerebrovascular diseases 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 coronary heart disease The 4-year, multicenter, randomized, double-blind, placebo-controlled EUROPA trial examined the efficacy of perindopril in patients with stable coronary heart disease. 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.

In 4.2 the result of years of therapy with perindopril tertbutylamine a dose of 8 mg 1 time/day, there was a significant relative risk reduction of 20% (95% CI ) of development of the pre-defined complications: at 488 (8%) of patients receiving perindopril tertbutylamine, and 603 (9.9%) patients of the placebo group (p = 0.0003). The result did not depend on gender, age, blood pressure, or a history of myocardial infarction.

Indications

prevention of recurrent stroke (combined therapy with indapamide) in patients who have had a stroke or transient ischemic cerebral circulation disorder;

arterial hypertension;

chronic heart failure;

stable coronary heart disease: to reduce the risk of cardiovascular complications.

Contraindications

a history of angioedema (congenital/idiopathic or associated with previous treatment with ACE inhibitor response); pregnancy and lactation (breastfeeding);

hypersensitivity to the drug and other ACE inhibitors;

galactosemia, lactase deficiency syndrome glucose/galactose malabsorption (due to the fact that the composition of the excipients of the drug includes lactose monohydrate).

Side effects

Extremely Rare Side effects < 1 / 10,000 Rare Side effects > 1/1000, < 1/ 10,000 Rare Side effects >< 1/100 Frequent Side effects >1/100, < 1/100 Frequent Side effects >< 1/10

Urinary system: rarely-Decreased renal function, extremely rarely-Acute renal failure

Allergic reactions: often – Skin rash, pruritus, rarely-Urticaria, extremely rarely-Erythema multiforme

Respiratory system: often-Cough, difficulty breathing, rarely-Bronchospasm, angioedema, extremely rare-Eosinophilic pneumonia, rhinitis

Digestive system: often – Nausea, vomiting, abdominal pain, taste disorders diarrhea, constipation, decreased appetite, rarely-Dry mouth, extremely rarely-Cholestatic or cytolytic jaundice, pancreatitis

Nervous system: often – Headache, asthenia, dizziness, ringing in the ears, visual disturbances, muscle cramps, paresthesia, rarely-Decreased mood, sleep disorders, extremely rarely-Confusion

Other: rarely-Sweating. Sexual dysfunction

Cardiovascular 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

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. 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.

How to take, course of use and dosage

Assign inside 1 time/day in the morning, before meals.

Overdose

Symptoms: renal failure, hyperventilation, tachycardia, marked decrease in blood pressure, shock, electrolyte disturbances (such as increased potassium ion concentration, decreased sodium); dizziness, bradycardia, restlessness and cough.

Treatment: if there is a significant decrease in blood pressure, the patient should be placed in a supine position and immediately replenish the BCC, if possible, conduct an infusion of angiotensin II and/or introduce intravenous catecholamines.

With the development of persistent pronounced bradycardia, it may be necessary to use an artificial pacemaker. Constant monitoring of vital body functions, serum electrolytes and creatinine clearance is required.

Perindopril can be removed from the systemic circulation by hemodialysis. High-flow polyacrylonitrile membranes should be avoided during dialysis.

Special instructions

In patients with stable coronary artery disease, if an episode of unstable angina occurs (significant or not) during the first month of Prestarium A therapy, the benefits and risks should be evaluated before continuing treatment. ACE inhibitors can cause a sharp decrease in blood pressure.

Symptomatic hypotension rarely develops in patients without concomitant diseases. The risk of excessive blood pressure reduction is increased in patients with reduced BCC, which can be observed against the background of diuretic therapy, with a strict salt-free diet, hemodialysis, as well as with vomiting and diarrhea.

In most cases, episodes of a marked decrease in blood pressure are observed in patients with severe heart failure, both in the presence of concomitant renal failure and in the absence of CE. Most often, this side effect is observed in patients receiving high-dose loop diuretics, as well as on the background of hyponatremia or with impaired renal function. In such patients, treatment should begin under close medical supervision, preferably in a hospital setting. In this case, the drug is prescribed in small doses, followed by careful titration of the dose.

If possible, diuretic therapy should be temporarily discontinued. This approach is also used in patients with angina pectoris or with cerebrovascular diseases, in which severe arterial hypotension can lead to the development of myocardial infarction or cerebrovascular complications. Before prescribing Prestarium A, as well as other ACE inhibitors, and during its use, you should carefully monitor the level of blood pressure, indicators of renal function and the concentration of potassium ions in the blood serum.

In order to reduce the likelihood of developing symptomatic arterial hypotension in patients receiving high-dose diuretic therapy, the dose of diuretics should, if possible, be reduced several days before the start of Prestarium use And In case of arterial hypotension, the patient should be transferred to the supine position. If necessary, BCC should be replenished with intravenous saline solution.

A marked decrease in blood pressure at the first dose of the drug is not an obstacle to further use of the drug. After recovery of BCC and blood pressure, treatment can be continued, provided that the dose of the drug is carefully selected. In patients with symptomatic heart failure, hypotension that develops during the initial period of ACE inhibitor therapy may lead to deterioration of renal function.

Sometimes acute renal failure develops in this case, as a rule, is reversible. In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney (especially in the presence of renal insufficiency), urea and creatinine concentrations in the blood serum may increase during therapy with ACE inhibitors.

The use of ACE inhibitors in patients with renovascular arterial hypertension is associated with an increased risk of developing severe arterial hypotension and renal failure. Treatment of such patients begins under close medical supervision with the appointment of the drug in small doses and further adequate dose selection.

During the first few weeks of therapy, diuretic therapy should be temporarily discontinued and renal function monitored. In some patients with arterial hypertension, in the presence of previously undetected renal insufficiency, especially with concomitant use of diuretics, the concentration of urea and creatinine in the blood serum may increase.

These changes are usually minor and reversible. In this case, it is recommended to reduce the dose of Prestarium A and / or cancel the diuretic. Several cases of persistent, life-threatening anaphylactic reactions have been reported in patients undergoing hemodialysis using high-flow membranes. ACE inhibitors should be avoided when using this type of membrane.

There are no data on the use of Prestarium A in kidney transplantation. Angioedema of the face, extremities, lips, mucous membranes, tongue, glottis, and / or larynx may develop in patients receiving ACE inhibitors, especially during the first few weeks of therapy. In rare cases, severe angioedema may occur with prolonged use of an ACE inhibitor.

In such cases, treatment with an ACE inhibitor should be stopped immediately, and drugs of a different pharmacotherapeutic group should be prescribed as a replacement. Angioedema of the tongue, glottis, or larynx can be fatal. If it develops, emergency therapy includes, among other prescriptions, immediate subcutaneous use of an epinephrine (epinephrine)solution 1: 1000 (1 mg/ml) 0.3-0.5 ml or slow intravenous use (in accordance with the instructions for preparing the infusion solution) under the control of ECG and blood pressure.

The patient should be hospitalized for treatment and follow-up for at least 12-24 hours and until the symptoms of this reaction completely disappear. During the procedure of LDL apheresis using dextran sulfate absorption, when prescribing ACE inhibitors, patients may develop anaphylactic reactions. There are isolated reports of the development of life-threatening anaphylactic reactions in patients receiving ACE inhibitors during desensitizing therapy with bee venom (bees, wasps).

ACE inhibitors should be used with caution in patients with a predisposition to allergic reactions undergoing desensitization procedures.ACE inhibitors should be avoided in patients receiving bee venom immunotherapy. However, this reaction can be avoided by temporarily discontinuing the ACE inhibitor prior to the procedure. Taking ACE inhibitors is sometimes associated with a syndrome that begins with the development of cholestatic jaundice, progressing to fulminant liver necrosis, and (sometimes) with a fatal outcome.

The mechanism of development of this syndrome is not clear. If symptoms of jaundice or increased liver enzyme activity occur in patients taking ACE inhibitors, discontinue therapy with the drug and conduct an appropriate examination. Neutropenia, agranulocytosis, thrombocytopenia, and anemia may develop during ACE inhibitor therapy. Neutropenia is rare in patients with normal renal function and no other complications.

ACE inhibitors are prescribed only in emergency cases in the presence of systemic vasculitis, immunosuppressive therapy, taking allopurinol or procainamide, as well as with a combination of all these factors, especially against the background of previous renal failure. There is a risk of developing severe infectious diseases that are resistant to intensive antibiotic therapy.

When conducting perindopril therapy in patients with the above factors, it is necessary to regularly monitor the number of white blood cells and warn the patient about the need to inform the attending physician about the appearance of any symptoms of infection. It should be borne in mind that patients of the black race have a higher risk of developing angioedema. Like other ACE inhibitors, perindopril is less effective as an antihypertensive agent in black patients. This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.

Against the background of ACE inhibitor therapy, a dry, unproductive cough may occur, which stops after discontinuation of the drug. The use of ACE inhibitors in patients whose condition requires surgical intervention and / or, if necessary, general anesthesia, can lead to the development of arterial hypotension or collapse, which is due to a sharp increase in the antihypertensive effect. Perindopril should be discontinued one day before surgery.

With the development of arterial hypotension, it is necessary to maintain blood pressure by replenishing the BCC. Hyperkalemia may develop during ACE inhibitor therapy, especially if the patient has renal and / or heart failure, uncontrolled diabetes mellitus. It is generally not recommended to prescribe potassium supplements, potassium-sparing diuretics, or other medications associated with a risk of increased potassium levels (for example, heparin) due to the possibility of severe hyperkalemia.

If the combined use of these drugs is necessary, then therapy should be accompanied by regular monitoring of the potassium content in the blood serum. In patients taking oral hypoglycemic agents or insulin, blood glucose should be carefully monitored during the first month of ACE inhibitor therapy. It is not recommended to use lithium preparations, potassium-sparing diuretics, potassium preparations, potassium-containing products and food additives simultaneously with perindopril.

Due to the fact that the excipients of the drug include lactose monohydrate, Prestarium A is contraindicated in patients with lactose deficiency, galactosemia or glucose/galactose malabsorption syndrome. Prestarium A tablets of 2.5 mg,5 mg and 10 mg contain 36.29 mg,72.58 mg and 145.16 mg of lactose monohydrate, respectively.

Form of production

Pills.

Storage conditions

Keep out of reach of children.

Shelf life

3 years

Active ingredient

Perindopril

Conditions of release from pharmacies

By prescription

Dosage form

tablets for resorption

Purpose

For adults as directed by your doctor

Indications

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