Prestarium A pills 5 mg 14 pcs
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Active ingredients
Perindopril
Release form
Pills
Composition
Perindopril arginine 5 mg, which corresponds to the content of perindopril 3.395 mg. Adjuvants: lactose monohydrate - 72.58 mg, magnesium stearate - 0.45 mg, maltodextrin - 9 mg, silicon colloidal hydrophobic dioxide - 0.27 mg, sodium carboxymethyl starch - 2.7 mg. shell green color Sepifilm 4193 (glycerol (E422a) - 4.5%, hypromellose (E464) - 74.8%, macrogol 6000 - 1.8%, magnesium stearate - 4.5%, titanium dioxide (E171) - 14.328%, copper chlorophyllin (E141 ( ii)) - 0.072%) - 1.931 mg, macrogol 6000 - 0.069 mg.
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 persists without developing tachyphylaxis. The cessation of treatment is not accompanied by the development of a rebound effect. The 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, includingfatal; dementia associated with stroke; serious deterioration of cognitive functions. This was observed in patients with arterial hypertension and in normal blood pressure, regardless of age, gender, presence or absence of diabetes mellitus and stroke type. Stable IBS Effectiveness of perindopril use in patients (12 218 patients over 18) with stable coronary artery disease without 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 I am before the final assessment) in patients who previously received other antihypertensive drugs, and decreased in patientsMore than 75% of children in the latter definition had systolic and diastolic blood pressure less than the 95th percentile. The safety data obtained in this study is consistent with the already available information regarding the safety of perindopril. The dual blockade of RAASI is combined with clinical data from combined treatment with an ACE inhibitor and an angiotensin II receptor antagonist (ARA II). A clinical study was conducted with patients with a history of cardiovascular ovascular or cerebrovascular disease, or diabetes mellitus type 2, accompanied by confirmed lesions 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 with monotherapy. Taking into account the similar intragroup pharmacodynamic properties of ACE inhibitors and ARA II, these results can be expected for the interaction of any 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 (combination therapy with indapamide) in patients who have had a stroke or transient cerebral circulation in ischemic type; - stable ischemic heart disease: to reduce the risk of cardiovascular complications.
Contraindications
- hypersensitivity to the active substance, other ACE inhibitors and excipients (see section Composition and release form), which are part of the preparation; - angioedema (angioedema) in history,associated with taking an ACE inhibitor; hereditary / idiopathic angioedema; simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or renal impairment (GFR <60 ml / min / 1.73 m2 of body surface area) (see Pharmacological action and drug interactions); - pregnancy (see section Pregnancy and lactation); - breastfeeding period (see section Pregnancy and lactation); - age up to 18 years (efficacy and safety have not been established) .- deficiency la ktazy, lactose intolerance, glucose-galactose malabsorption syndrome; With caution (see also sections Special Instructions and Drug Interactions) the drug should be used for bilateral renal artery stenosis or 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.
Precautionary measures
During treatment, psoriasis may worsen. During pheochromocytoma, propranolol can only be used after taking an alpha blocker. After a long course of treatment, propranolol should be discontinued gradually, under the supervision of a physician. during anesthesia, you must stop taking propranolol or find a remedy for anesthesia with minimal negative inotropic effects.The impact on the ability to drive vehicles and control mechanisms of patients whose activities require increased attention, the question of the use of propranolol on an outpatient basis should be addressed only after evaluating the individual response of the patient.
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
Inside 1 tablet 1 time per day, preferably in the morning, before eating. When choosing a dose, take into account the specifics of the clinical situation (seesection Special instructions) and the degree of reduction in blood pressure on the background of the therapy. Arterial hypertension Prestarium A can be used both as monotherapy and as part of combination therapy (see sections Contraindications, Special instructions and Pharmacological action). The recommended initial dose is 5 mg 1 time per day If necessary, one month after the start of therapy, you can increase the dose of the drug to 10 mg 1 time / day. The maximum daily dose is 10 mg. Patients with pronounced activity of the RAAS (especially in case of renovascular hypertension, hypovolemia and / or reduction of electrolytes in blood plasma, decompensation of chronic heart failure or severe arterial hypertension) after taking the first dose of the drug can develop a marked decrease in blood pressure. At the beginning of therapy, such patients should be under close medical supervision. The recommended initial dose for these patients is 2.5 mg 1 time / day. At the beginning of treatment with Prestarium A, symptomatic arterial hypotension may occur. In patients receiving diuretics at the same time, the risk of arterial hypotension is higher due to possible hypovolemia and a decrease in the electrolyte content of blood plasma. Caution must be exercised when using the drug Prestarium A in this group of patients. It is recommended, if possible, to stop taking diuretics 2-3 days before the intended start of therapy with Prestarium A (see section Special instructions). If it is impossible to cancel diuretics, the initial dose of Prestarium A is 2.5 mg. It is necessary to control the kidney function and the content of potassium in the serum. In the future, if necessary, the dose of the drug may be increased. If necessary, the use of diuretics can be resumed. Elderly patients should begin treatment with a dose of 2.5 mg / day. If necessary, one month after starting therapy, the dose can be increased to 5 mg / day, and then up to a maximum dose of 10 mg / day, taking into account the state of kidney function (see table). Heart failure Treatment of patients with chronic heart failure with Prestarium A in combination It is recommended to start with non-calcium-saving diuretics and / or digoxin and / or beta-blockers, under careful medical supervision, prescribing the drug in an initial dose of 2.5 mg 1 time / day, in the morning.After 2 weeks of treatment, the dose of the drug can be increased up to 5 mg 1 time / day, provided that the dose of 2.5 mg is well tolerated and the patient responds satisfactorily to therapy. In patients with severe heart failure, as well as in patients from high risk groups and a tendency to impair water-electrolyte balance, patients receiving diuretics and / or vasodilator drugs at the same time), treatment should be initiated under close medical supervision (see the section Special Azania) .u patients with high risk of symptomatic hypotension, e.g., with a reduced electrolyte content, with or without hyponatremia, hypovolemia or diuretics, before receiving the Drug A Prestarium as possible listed states must be adjusted. Indicators such as blood pressure, kidney function and potassium in the blood plasma should be monitored both before and during the treatment. Prevention of recurrent stroke (combination therapy with indapamide) In patients with a history of cerebrovascular disease, Prestarium A should start with doses of 2.5 mg for the first 2 weeks, then increasing the dose to 5 mg over the next 2 weeks before starting the use of indapamide. Therapy should be started at any time (from 2 weeks to several years) after stroke. IBS: reducing the risk of cardiovascular complications in patients who have previously had myocardial infarction and / or coronary revascularization. With stable ischemic heart disease, Prestarium A should be started with a dose of 5 mg 1 time / day. After 2 weeks, with good tolerance and taking into account the state of kidney function, the dose can be increased to 10 mg 1 time / day. In elderly patients, therapy should be started with a dose of 2.5 mg 1 time / day for 1 week, then 5 mg 1 time / day during the next week. Then, taking into account the state of kidney function, the dose can be increased to 10 mg 1 time / day (see table). It is possible to increase the dose of the drug only if it is well tolerated at the previously recommended dose. When prescribing the drug to patients with impaired liver function, dose adjustment is not required (see the Pharmacokinetics and Special Instructions sections). - due to the lack of data on the efficacy and safety of the drug in patients of this age group (see Contraindications).Currently, there are insufficient data on the safety and efficacy of perindopril in children and adolescents under the age of 18 years. The available data described in the section Pharmacological action does not allow making recommendations on the method of administration and dosages of the drug in patients of this age group.
Side effects
The safety profile of perindopril is consistent with the safety profile of ACE inhibitors. The most common adverse events reported in clinical studies that were observed with perindopril are: dizziness, headache, paresthesia, vertigo, visual impairment, tinnitus, excessive decrease in blood pressure, cough, shortness of breath, abdominal pain, constipation, diarrhea, taste disturbance, dyspepsia, nausea, vomiting, pruritus, skin rash, muscle spasms and asthenia. Determination of the frequency of adverse reactions (according to recommendation WHO), which were noted during clinical trials and / or post-registration use of perindopril: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10,000, <1/1000); very rarely (<1/10 000); unspecified frequency (frequency cannot be calculated from available data). On the part of the blood and lymphatic system: infrequently * - eosinophilia; very rarely, hemoglobin and hematocrit decrease, thrombocytopenia, leukopenia / neutropenia, agranulocytosis, pancytopenia, hemolytic anemia in patients with congenital glucose-6-phosphate dehydrogenase deficiency (see Special Instructions section). sections Special Instructions and Drug Interactions), hyperkalemia, reversible after discontinuation of the drug (see section Special Instructions), hyponatremia. For the CNS: often - paresthesia, headache, dizziness, vertigo; infrequently - sleep disturbances, mood lability, drowsiness *, fainting *; very rarely - confusion. From the sense organs: often - visual disturbances, tinnitus. From the cardiovascular system: often - excessive decrease in blood pressure and associated symptoms; infrequently * - vasculitis, tachycardia, palpitations; very rarely, cardiac arrhythmias, angina pectoris, myocardial infarction and stroke, possibly due to an excessive decrease in blood pressure in high-risk patients (seesection Special instructions). On the part of the respiratory system: often - cough, shortness of breath; infrequently - bronchospasm; very rarely - eosinophilic pneumonia, rhinitis. From the digestive system: often - constipation, nausea, vomiting, abdominal pain, taste disturbance, dyspepsia, diarrhea; infrequently - dryness of the oral mucosa; very rarely - pancreatitis. From the side of the liver and biliary tract: very rarely - hepatitis (cholestatic or cytolytic) (see section Special Instructions). From the side of the skin and subcutaneous fat: often - itchy skin, rash; infrequently * - photosensitization, pemphigus, increased sweating; very rarely - erythema multiforme. Allergic reactions: infrequently - angioedema of the face, lips, upper and lower extremities, mucous membranes, tongue, vocal folds and / or larynx, urticaria (see Specific instructions). For musculoskeletal system: often - muscle spasms; infrequently * - arthralgia, myalgia. From the kidneys and urinary tract: infrequently - renal failure; very rarely - acute renal failure. From the reproductive system: infrequently - erectile dysfunction. Common disorders and symptoms: often - asthenia; infrequently - chest pain *, peripheral edema *, weakness *, fever *, falling *. From laboratory indicators: rarely - increased activity of hepatic transaminases and serum bilirubin; infrequently * - an increase in the concentration of urea and creatinine in the blood plasma. * Evaluation of the incidence of adverse reactions identified by spontaneous reports was carried out on the basis of data from clinical studies. Adverse events noted in clinical studies In the EUROPA study, only serious adverse events were recorded. Serious adverse events were observed in 16 (0.3%) patients in the perindopril group and in 12 (0.2%) patients in the placebo group. In the group of perindopril in 6 patients, a marked decrease in blood pressure was observed, in 3 patients - angioedema, in 1 patient - sudden cardiac arrest. The frequency of drug withdrawal due to cough, pronounced decrease in blood pressure or other cases of intolerance was higher in the perindopril group compared to the placebo group.
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 (see section Contraindications) Aliskiren: in patients with diabetes mellitus or impaired renal function, the risk of hyperkalemia increases, renal function decreases and cardiovascular morbidity and mortality increases. Simultaneous use is not recommended (see section Special instructions) Aliskiren: in patients without diabetes mellitus or renal dysfunction, the risk of hyperkalemia may increase, Yeniya kidney function and increase the frequency of cardiovascular morbidity and mortality. Joint therapy with ACE inhibitors 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. When