Prestarium A pills dispersible 5 mg 30 pcs.
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Active ingredients
Perindopril
Release form
Pills
Composition
Active ingredient: Perindopril arginine (Perindopril arginine) Active ingredient concentration (mg): 5
Pharmacological effect
Perindopril - an ACE inhibitor. ACE, or kininase II, is an exopeptidase that performs both the conversion of angiotensin I into a vasoconstrictor angiotensin II, and the destruction of bradykinin, which has a vasodilating effect, to an inactive heptapeptide. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, in the heptapeptide. plasma renin (by the mechanism of negative feedback) and a decrease in aldosterone secretion. Since ACE inactivates bradykinin, ACE suppression is accompanied by an increase in ktivnosti both circulating and tissue kallikrein-kinin system, the system is also activated prostaglandins. It is possible that this effect is part of the mechanism of the antihypertensive effect of ACE inhibitors, as well as the development mechanism of some side effects of drugs of this class (for example, cough). Perindopril has a therapeutic effect due to an active metabolite, perindoprilat. Other metabolites of the drug do not have an inhibitory effect on ACE in vitro. Clinical efficacy and safety Arterial hypertension Perindopril is effective in the treatment of hypertension of any degree of severity. Against the background of the use of the drug, there is a decrease in both systolic and diastolic blood pressure in the patient lying down and standing. Perindopril reduces OPSS, which leads to a decrease in blood pressure, while peripheral blood flow accelerates without changing heart rate. As a rule, perindopril leads to an increase in renal blood flow, GFR does not change. The antihypertensive effect of the drug reaches a maximum after 4-6 h after a single ingestion and persists for 24 hours. Within 24 hours after ingestion, a pronounced (about 87-100%) residual inhibition of ACE is observed. Reduced blood pressure is achieved quite quickly. In patients with a positive response to treatment, normalization of blood pressure occurs within a month and remains without tachyphylaxis. Discontinuation of treatment is not accompanied by the development of a rebound effect.and also reduces left ventricular hypertrophy. Simultaneous administration of thiazide diuretics increases the severity of the antihypertensive effect. In addition, the combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of developing hypokalemia while taking diuretics. Cerebrovascular diseases patients with a history of cerebrovascular disease. After the introduction period of perindopril tertbutylamine 2 mg (equivalent to perindopril arginine 2.5 mg) 1 time / day for 2 weeks and then 4 mg (equivalent to perindopril arginine 5 mg) 1 time / day for the next 2 weeks, 6105 patients were randomized into two groups: placebo (n = 3054) and perindopril tertbutylamine 4 mg each (corresponding to 5 mg perindopril arginine) (monotherapy) or in combination with indapamide (n = 3051). Indapamide was further prescribed to patients who did not have direct indications or contraindications for the use of diuretics. This therapy was prescribed in addition to standard therapy for stroke and / or arterial hypertension or other pathological conditions. All randomized patients had a history of cerebrovascular disease (stroke or transient ischemic attack) in the last 5 years. The value of blood pressure was not a criterion for inclusion: 2916 patients had arterial hypertension and 3189 - normal blood pressure. After 3.9 years of therapy, blood pressure (systolic / diastolic) decreased by an average of 9/4 mm Hg. It also showed a significant reduction in the risk of recurrent stroke (both ischemic and hemorrhagic, of the order of 28% compared with placebo (10.1% and 13.8%). Additionally, a significant reduction in the risk of fatal or disability-related strokes was shown; including myocardial infarction, including fatal; dementia associated with stroke; severe impairment of cognitive function. This has been observed both in patients with arterial hypertension and in normal blood pressure, independently age, sex, presence or absence of diabetes mellitus and type of stroke. Stable coronary artery disease The effectiveness of perindopril in patients (12,218 patients over 18) with stable coronary artery disease without the clinical symptoms of chronic heart failure was studied during a 4-year study.90% of study participants previously had acute myocardial infarction and / or revascularization procedure. In addition to the study drug, most patients received standard therapy, including antiplatelet agents, lipid-lowering drugs and beta-blockers. As the main criterion of effectiveness, a combined end point was chosen, including cardiovascular mortality, nonfatal myocardial infarction and / or cardiac arrest with successful resuscitation. Perindopril erbumin therapy at a dose of 8 mg / day (equivalent to 10 mg of perindopril arginine) resulted in a significant decrease in absolute the risk of a combined endpoint of 1.9% (relative risk reduction - 20%). In patients who previously had a myocardial infarction or revascularization procedure, the absolute risk decreased by 2.2% (relative risk reduction - 22.4%) compared with the placebo group. Children under 18 years old Effective and safe use of perindopril in children and adolescents under the age of 18 not established. There are data from clinical studies involving 62 patients with arterial hypertension aged 2 to 15 years with GFR> 30 ml / min / 1.73 m2 of body surface area who received perindopril at a dose of 0.07 mg / kg in the it. The dose was adjusted individually, depending on the patient’s general condition and his blood pressure indicators in response to therapy, with a maximum dose of 0.135 mg / kg / day.59 patients participated in the study for 3 months and 36 patients completed the extended study period, which was not less than 24 months (the average duration of participation in the study was 44 months). Indicators of systolic and diastolic blood pressure remained stable throughout the entire study period (from the moment of inclusion in the study before the final assessment) in patients who had previously received other antihypertensive drugs, and decreased in patients who had not previously received antihypertensive therapy. More than 75% of children had a systolic and diastolic blood pressure less than the 95th percentile in the last determination. study is consistent with the already available information regarding the safety of perindopril. The double blockade of RAASI contains data from clinical studies of combination therapy using an ACE inhibitor and an antagonist eptora angiotensin II (ARA II) .Provodilos clinical study in patients,having a history of cardiovascular or cerebrovascular disease, or type 2 diabetes, accompanied by confirmed lesion of the target organ, as well as studies involving patients with type 2 diabetes and diabetic nephropathy. These studies did not reveal a significant positive effect of combination therapy on the occurrence of renal and / or cardiovascular events and on mortality rates, while the risk of developing hyperkalemia, acute renal failure and / or arterial hypotension increased compared to monoterapiey.Prinimaya into account intra similar pharmacodynamic properties of ACE inhibitors and ARA II, these results can be expected for any interaction of other drugs, representatives of the classes of ACE inhibitors and ARA II. Therefore, ACE inhibitors and ARA II should not be used simultaneously in patients with diabetic nephropathy. There are data from a clinical study examining the positive effects of adding aliskiren to standard therapy with an ACE inhibitor or ARA II in patients with type 2 diabetes and chronic kidney disease or cardiovascular disease, or having a combination of these diseases. The study was terminated early due to an increased risk of adverse outcomes. Cardiovascular death and stroke were observed more frequently in the group of patients receiving aliskiren, compared with the placebo group; also adverse events and serious adverse events of particular interest (hyperkalemia, hypotension and renal dysfunction) were recorded more often in the aliskiren group than in the placebo group.
Pharmacokinetics
Absorption and metabolism After oral administration, perindopril is rapidly absorbed from the gastrointestinal tract, Cmax in the blood plasma is reached after 1 hour. T1 / 2 of perindopril from the blood plasma is 1 hour. Perindopril does not possess pharmacological activity. Approximately 27% of the total absorbed perindopril enters the bloodstream as the active metabolite of perindoprilat. Cmax of perindoprilat in blood plasma is reached after 3-4 hours. In addition to perindoprilat, 5 metabolites are formed in the process of metabolism that do not have pharmacological activity. Eating slows down the conversion of perindopril to perindoprilat, thus affecting the bioavailability of the drug.Therefore, the drug should be taken orally once a day, in the morning, before eating. It has been shown that the relationship between the dose of perindopril and its concentration in plasma is linear. Distribution Binding of perindoprilat to plasma proteins, mainly ACE, is 20% and wears dose dependent. Vd of free perindoprilat is approximately 0.2 l / kg. Excretion of Perindoprilat is excreted by the kidneys, the final T1 / 2 of the free fraction is approximately 17 h, as a result, the equilibrium state is reached within 4 days. Pharmacokinetics in special clinical situations with heart and kidney failure. The dialysis clearance of perindopril is 70 ml / min. In patients with liver cirrhosis, the hepatic clearance of perindopril is reduced by 2 times. However, the amount of perindoprilat formed does not decrease and the dose adjustment of the drug is not required (see sections Dosage regimen and Special instructions).
Indications
Arterial hypertension; chronic heart failure; prevention of recurrent stroke; stable ischemic heart disease.
Contraindications
Hypersensitivity to the active substance, angioedema (angioedema); hereditary / idiopathic angioedema; pregnancy; breastfeeding period; simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes or renal impairment; lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome; age up to 18 years.
Precautionary measures
Do not exceed the recommended dose. With caution (see also sections Special Instructions and Drug Interactions) the drug should be used in case of bilateral stenosis of the renal arteries or in the presence of only one functioning kidney; renal failure; systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma); therapy with immunosuppressants, allopurinol, procainamide (risk of developing neutropenia, agranulocytosis); reduced bcc (diuretic intake, salt-free diet, vomiting,diarrhea); angina pectoris; cerebrovascular diseases; renovascular hypertension; diabetes; chronic heart failure IV FC classification NYHA; simultaneous use of potassium-saving diuretics, potassium preparations, potassium-containing salt substitutes, lithium preparations; hyperkalemia; surgical intervention / general anesthesia; hemodialysis using high-flow membranes; desensitizing therapy; apheresis LDL; condition after kidney transplantation; aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy; in patients of the Negroid race.
Use during pregnancy and lactation
Prestarium A is contraindicated for use in pregnancy (see section Contraindications). There are currently no conclusive epidemiological data on the teratogenic risk of taking ACE inhibitors in the first trimester of pregnancy. However, a slight increase in the risk of fetal developmental disorders cannot be ruled out. When planning pregnancy or its occurrence while using Prestarium A, you should immediately stop taking the drug and, if necessary, prescribe another antihypertensive therapy with a proven safety profile during pregnancy. It is known that the effect of ACE inhibitors on the fetus during the second and third trimesters of pregnancy may result to the disruption of its development (reduction of renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (renal failure, hypotension, hyperkalemia). If the patient received ACE inhibitors in the second and third trimesters of pregnancy, an ultrasound scan is recommended to assess the state of the skull bones and kidney function. Neonates whose mothers received ACE inhibitors during pregnancy should be monitored because of the risk of arterial hypotension. Breastfeeding period. At present, it has not been established whether perindopril is excreted into breast milk. Due to the lack of information regarding the use of perindopril during breastfeeding, its reception is not recommended. It is preferable to use other drugs with a more studied safety profile during breastfeeding, especially when feeding newborns or premature babies. Fertility In preclinical studies, it was shown that perindopril does not affect reproductive function in rats of both sexes.
Dosage and administration
InsideIt is recommended to take once a day, in the morning, before eating.
Side effects
Dizziness, headache, paresthesia, vertigo, visual disturbances, tinnitus, excessive decrease in blood pressure, cough, shortness of breath, abdominal pain, constipation, diarrhea, taste disturbance, dyspepsia, nausea, vomiting, skin itch, skin rash, muscle spasms and asthenia.
Overdose
Data on drug overdose is limited. Symptoms: pronounced decrease in blood pressure, shock, impaired water and electrolyte balance, renal failure, hyperventilation, tachycardia, feeling of heartbeat, bradycardia, dizziness, anxiety, cough.Treatment: when there is a marked decrease in blood pressure, put the patient in a lying position on the back with raised legs; If necessary, you should enter into / in 0.9% sodium chloride solution, catecholamine solution. Perindoprilat, the active metabolite of perindopril, can be removed from the body by dialysis. With the development of treatment-resistant bradycardia, it may be necessary to install an artificial pacemaker. It is necessary to constantly monitor the indicators of the main vital functions of the body, the concentration of creatinine and electrolytes in the serum.
Interaction with other drugs
Data from clinical studies show that double blockade of RAAS as a result of the simultaneous use of ACE inhibitors, ARA II or aliskiren leads to an increase in the incidence of adverse events such as arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure), compared with situations when only one drug is used that affects the RAAS (see sections Contraindications, Special Instructions and Pharmacological Effects). Drugs that cause hypercal emiyuNekotorye drugs or other pharmacological classes of drugs may increase the risk of hyperkalemia: aliskiren and aliskirensoderzhaschie drugs, salts of potassium, potassium-sparing diuretics, ACE inhibitors, ARA II, NSAID, heparin, immunosuppressants, such as cyclosporin or tacrolimus, trimethoprim. The combination of these drugs increases the risk of hyperkalemia. Simultaneous use is contraindicated (seeContraindications section) Aliskiren: in patients with diabetes mellitus or impaired renal function, the risk of hyperkalemia, deterioration of renal function and an increase in the incidence of cardiovascular morbidity and mortality increases. Simultaneous use is not recommended (see Special Instructions) Aliskiren: in patients without diabetes mellitus or impaired renal function, possibly increasing the risk of hyperkalemia, worsening renal function and increasing the incidence of cardiovascular morbidity and mortality. Joint therapy is an inhibitor ramie ACE and angiotensin receptor antagonists. In the literature, it was reported that in patients with established atherosclerotic disease, heart failure or diabetes mellitus with target organ damage, concurrent therapy with an ACE inhibitor and ARA II is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and impaired renal function failure) compared with the use of only one drug that affects the RAAS. Double blockade (for example, when combining an ACE inhibitor with ARA II) should be limited to individual cases with careful monitoring of kidney function, potassium and BP. Estramustin. Simultaneous use may lead to increased risk of side effects, such as angioedema. Kaliysaving diuretics (such as triamterene, amiloride), potassium salts. Hyperkalemia (possibly fatal), especially in case of impaired renal function (additional effects associated with hyperkalemia). The combination of perindopril with the above-mentioned drugs is not recommended (see section Special instructions). If, however, simultaneous administration is indicated, they should be used, taking precautions and regularly monitoring the content of potassium in the blood serum. Features of the use of spironolactone in heart failure are described further in the text. The drugs lithium. With the simultaneous use of lithium preparations and ACE inhibitors, there may be a reversible increase in the concentration of lithium in the blood serum and the associated toxic effects. The simultaneous use of perindopril and lithium preparations is not recommended.If necessary, such therapy should be regularly monitored for the concentration of lithium in the blood plasma (see section Special Instructions). Simultaneous use that requires special caution. Hypoglycemic agents (insulin, hypoglycemic agents for oral administration). The use of ACE inhibitors can enhance the hypoglycemic effect of insulin and hypoglycemic agents for oral administration up to the development of hypoglycemia. As a rule, this is observed in the first weeks of simultaneous therapy and in patients with impaired renal function. Baclofen enhances the antihypertensive effect of ACE inhibitors. The level of blood pressure and, if necessary, the dosage of antihypertensive drugs should be carefully monitored. Kaliene-sparing diuretics. In patients taking diuretics, especially those taking liquid and / or salts, at the beginning of perindopril therapy, an excessive decrease in blood pressure can be observed, the risk of which can be reduced by canceling the diuretic, replenishing fluid or salt loss before starting perindopril and dose with a further gradual increase. In hypertension in patients receiving diuretics, especially excreting fluid and / or salts, diuretics should be either canceled before using the ACE inhibitor (and the potassium-sparing diuretic can later be reappointed), or the ACE inhibitor should be prescribed in its further gradual increase. When using diuretics in the case of chronic heart failure, the ACE inhibitor should be prescribed in a low dose, possibly after reducing the dose of a potassium-sparing diuretic used simultaneously. In all cases, the kidney function (creatinine concentration) should be monitored in the first weeks of use of ACE inhibitors. Calis-saving diuretics (eplerenone, spironolactone). The use of eplerenone or spironolactone in doses of 12.5 mg to 50 mg per day and low doses of ACE inhibitors: when treating heart failure II-IV FC according to the NYHA classification with a left ventricular ejection fraction <40% and previously used ACE inhibitors and loop diuretics, there is a risk hyperkalemia (possibly fatal), especially in the case of non-compliance with the recommendations regarding this combination of drugs. Before using this combination of drugs, you must ensure that there is no hyperkalemia and renal dysfunction.It is recommended to regularly monitor the concentration of creatinine and potassium in the blood: weekly in the first month of treatment and every month thereafter. NSAIDs, including high doses of acetylsalicylic acid (≥3 g / day): simultaneous use of ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose that has anti-inflammatory effect , COX-2 inhibitors and non-selective NSAIDs), can lead to a decrease in the antihypertensive effect of ACE inhibitors. The simultaneous use of ACE inhibitors and NSAIDs can lead to a deterioration in renal function, including the development of acute renal failure, and an increase in serum potassium, especially in patients with reduced kidney function. Care should be taken in the appointment of this combination, especially in elderly patients. Patients should receive an adequate amount of fluid, and it is recommended that the kidney function be carefully monitored, both at the beginning and during the treatment. Simultaneous use, which requires some caution. Antihypertensive drugs and vasodilators. The antihypertensive effect of perindopril can be enhanced with simultaneous use with other antihypertensives, vasodilators, including nitrates of short and prolonged action. Glyptins (linagliptin, saxagliptin, sitagliptin, vildagliptin): combined use with ACF inhibitors may increase the risk of developing angioneurotic syndrome. DPP-IV) glyptin. Tricyclic antidepressants, antipsychotics (neuroleptics) and general anesthetics sion: concurrent use of ACE inhibitors may lead to enhanced antihypertensive effects (see Specific guidance.) .Simpatomimetiki can weaken the antihypertensive effect APF.Preparaty gold inhibitors. When using ACE inhibitors, incl. perindopril, patients receiving IV gold preparation (sodium aurothiomalate) have described nitritoid reactions — a symptom complex that includes facial flushing, nausea, vomiting, and arterial hypotension.
special instructions
CHD: reducing the risk of cardiovascular complications in patients who have previously had a myocardial infarction and / or coronary revascularization. If unstable angina develops during the first month of treatment with Prestarium A, the benefits and risks should be assessed before continuing therapy. Arterial hypotension ACE inhibitors can cause a sharp decrease in AD.Symptomatic arterial hypotension rarely develops in patients with uncomplicated arterial hypertension. The risk of an excessive decrease in blood pressure is increased in patients with reduced BCC, which can occur during diuretic therapy, with a strict salt-free diet, hemodialysis, vomiting and diarrhea, as well as in patients with severe arterial hypertension with high renin activity (see the sections interaction and side effects). Symptomatic arterial hypotension can be observed in patients with clinical manifestations of heart failure, both with and without renal failure. This risk is more likely in patients with severe heart failure, as a reaction to taking high-dose loop diuretics, hyponatremia, or functional renal failure. In patients with an increased risk of symptomatic arterial hypotension, blood pressure, kidney function and serum potassium should be carefully monitored during Prestarium A. therapy. A similar approach is also used in patients with coronary artery disease and cerebrovascular diseases in whom severe arterial hypotension can lead to a heart attack myocardial or cerebral circulatory disorders. In the event of arterial hypotension, the patient must be placed in a horizontal position with a low headboard eat. If necessary, the BCC should be replenished with IV injection of a 0.9% sodium chloride solution. Transient hypotension is not an obstacle to further use of the drug. After the restoration of BCC and blood pressure, treatment may be continued. In some patients with chronic heart failure and normal or decreased blood pressure, Prestarium A may cause an additional decrease in blood pressure. This effect is predictable and usually does not require cessation of therapy. If symptoms of pronounced decrease in blood pressure occur, reduce the dose of the drug or discontinue it. Mitral stenosis / aortic stenosis / hypertrophic obstructive cardiomyopathy ), as well as in patients with mitral stenosis. Impaired renal functionPatients with renal insufficiency (CC <60 ml / min), the initial dose of the drug Pres arium A should be selected depending on the value of CC (see.section Dosage regimen) and then - depending on the therapeutic effect. For these patients, regular monitoring of serum creatinine and potassium levels is necessary (see the section Side Effects). Arterial hypotension, which sometimes develops at the beginning of the use of ACE inhibitors in patients with symptomatic chronic heart failure, can lead to a deterioration in renal function. Perhaps the development of acute renal failure, usually reversible. In patients with bilateral renal artery stenosis or arterial stenosis of a single kidney (especially in the presence of renal failure) during therapy with ACE inhibitors, there may be an increase in serum urea and creatinine levels, usually with withdrawal of therapy . The additional presence of renovascular hypertension causes an increased risk of developing severe arterial hypotension and renal failure in these patients. The treatment of these patients begins under close medical supervision with the use of low doses of the drug and further adequate selection of doses. Treatment with diuretics should be temporarily discontinued and regular monitoring of the content of potassium and creatinine in the blood plasma during the first few weeks of therapy. Some patients with arterial hypertension without indicating the presence of a prior kidney disease may increase the concentration of urea and creatinine in the blood serum, especially while the use of diuretics. These changes are usually expressed slightly and are reversible. The likelihood of developing these disorders is higher in patients with renal insufficiency in history. In such cases, it may be necessary to cancel or reduce the dose of Prestarium A and / or diuretic. Hemodialysis In patients undergoing hemodialysis using high-flow membranes, several cases of anaphylactic reactions occurring during therapy with ACE inhibitors. The use of ACE inhibitors when using this type of membrane should be avoided. In such situations, the use of another type of antihypertensive drug or the use of another type of dialysis membrane should be considered. Renal transplantation There is no data on the use of Prestarium A in patients after kidney transplantation. Hypersensitivity / angioedema When taking ACE inhibitors, includingperindopril, in rare cases and in any period of therapy, angioedema of the face, upper and lower extremities, lips, mucous membranes, tongue, vocal folds and / or larynx may develop (see the Adverse Effects section). If symptoms occur, the drug should be stopped immediately, and the patient should be observed until the signs of edema disappear completely. If the edema affects only the face and lips, then its manifestations usually go away on their own, although antihistamines can be used to treat the symptoms. Angioedema, accompanied by laryngeal edema, can be fatal. Swelling of the tongue, vocal cords or larynx can lead to airway obstruction. At occurrence of such symptoms, emergency treatment is required, incl. s / c administration of epinephrine (adrenaline) and / or ensuring the airway. The patient should be under medical supervision until the symptoms are completely and persistently. Patients with angioedema and a history not associated with taking ACE inhibitors may have an increased risk of developing it when taking this group of drugs (see Contraindications). In rare cases, against the background of therapy with ACE inhibitors, angioedema of the intestines develops. At the same time, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without prior angioedema of the face and at a normal level of C1-esterase. The diagnosis was established using computed tomography of the abdominal area, ultrasound, or during surgery. Symptoms disappeared after discontinuation of ACE inhibitors. Therefore, in patients with pain in the abdomen who are receiving ACE inhibitors, differential diagnosis must take into account the possibility of developing angioedema of the intestine (see the section Side Effects). apheresis of LDL using dextran sulfate can develop life-threatening anaphylactoid reactions.To prevent an anaphylactoid reaction, the ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure. Anaphylactoid reactions during desensitization. There are some reports on the development of anaphylactoid reactions in patients who receive ACE inhibitors during desensitization therapy, such as a venom of venter. In these patients, these reactions were prevented by the temporary abolition of ACE inhibitors, but with an accidental or inaccurate resumption of treatment, the reactions could develop again.