Arentopres - instructions for use, dose, side effects, contraindications

ACE inhibitor. Suppression of ACE leads to a decrease in angiotensin II in the blood plasma, as a result of which it decreases: the secretion of aldosterone. Perindopril acts through its active metabolite perindoprilata. It eliminates the vasoconstrictor action of angiotensin I. increases the concentration of bradykinin and prostaglandins vazodilatagornyh (ACE converts the inactive angiotensin I to angiotensin II, providing vasoconstrictor effect, as well as causing the degradation of bradykinin and prostaglandin having vasodilating activity); reduces the production and release of aldosterone,suppresses the release of norepinephrine from the endings of sympathetic nerve fibers and the formation of endothelin in the vessel wall. Reduction of the formation of angiotensin II is accompanied by an increase in the activity of renin of the blood plasma (due to the inhibition of negative feedback). Suppression of ACE is accompanied by an increase in the activity of both circulating and tissue kallikrein-kinin system, while the system of prostaglandins is also activated.

Helps restore the elasticity of large arterial vessels (reducing the formation of excessive amounts of subendothelial collagen), reduces pressure in the pulmonary capillaries, with long-term administration reduces the severity of myocardial hypertrophy of the left ventricle and interstitial fibrosis, normalizes the isozyme profile of myosin; normalizes the work of the heart.

Reduces afterload and afterload (reduces systolic and diastolic blood pressure (BP) in the "lying" and "standing"), the filling pressure of the left and right ventricles, the total peripheral resistance of the vessels; increases the minute volume of blood and cardiac index without changing the frequency of cardiac contractions (in patients with chronic heart failure), does not increase the heart rate, increases regional blood flow in the muscles.

After ingestion of the median single dose, the maximum hypotensive effect is achieved after 4-6 hours and persists for 24 hours. Stabilization of the hypotensive effect occurs after 1 month of therapy and persists for a long time. The termination of treatment is not accompanied by the development of the "withdrawal" syndrome.

Increases the concentration of high density lipoproteins, in patients with hyperuricemia reduces the concentration of uric acid. Increases renal blood flow, does not change the rate of glomerular filtration.

In patients with chronic heart failure causes a significant decrease in the severity of clinical signs of heart failure, increases exercise tolerance (according to the veloergometric test), does not significantly reduce blood pressure.

Pharmacokinetics:

Absorption is 25%, bioavailability is 65-70%. Time to reach the maximum concentration in blood plasma - 1 hour, perindoprilata-3-4 hours.

In the process of metabolism, 20% is transformed into an active metabolite - perindoprilat (receptionPerindopril after meals reduces the proportion of perindoprilat formed - no significant clinical significance); The rest is in 5 inactive Compounds. T1 / 2 (half-life) perindopril - 1 hour. The relationship between perindoprilata and blood plasma proteins is insignificant, with ACE less than 30% (depending on concentration). The volume of distribution: free perindoprilata - 0.2 l / kg. Perindoprilat is excreted by the kidneys, T1 / 2 of the free fraction of the metabolite is 3-5 hours. Dissociation of perindoprilat, associated with ACE, is slow. Therefore, the "effective" T1 / 2 is 25 hours. Repeated administration of perindopril does not lead to its cumulation, and T1 / 2 perindoprilata with repeated admission corresponds to the period of its activity.

The excretion of perindoprilat is slowed down in elderly patients, as well as in patients with chronic heart failure and chronic renal insufficiency (in the latter, dose adjustment should be performed depending on the creatinine clearance). The dialytic clearance of perindopril is 70 ml / min.

In patients with liver cirrhosis, the liver clearance of perindopril is reduced by a factor of 2, while the total amount of perindoprilat formed does not change and correction of the dosing regimen is not required.

Indications:

Arterial hypertension; chronic heart failure.

Contraindications:Hypersensitivity: to perindopril and other components of the drug or other ACE inhibitors, angioedema in the history of therapy with ACE inhibitors, hereditary or idiopathic angioedema, pregnancy, lactation, age up to 18 children (efficacy and safety not established); hereditary intolerance to galactose, insufficiency of lactase or impaired absorption of glucose and galactose.

Carefully:Stenosis of the aortic valve, hypertrophic obstructive cardiomyopathy, cerebrovascular diseases (including cerebral circulatory insufficiency), coronary heart disease, coronary insufficiency - the risk of excessive decrease in blood pressure and concomitant ischemia. Heavy autoimmune systemic diseases of connective tissue (including systemic lupus erythematosus, scleroderma), oppression of bone marrow hematopoiesis against immunosuppressant therapy (increased probability of neutropenia development). Renovascular hypertension, bilateral stenosis of the renal arteries,stenosis of the artery of a single kidney, condition after kidney transplantation (risk of kidney and agranulocytosis), chronic renal failure (especially accompanied by hyperkalemia), hyperkalemia, diet with sodium restriction, conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting, diuretics), diabetes mellitus, advanced age, surgical intervention (general anesthesia).

Pregnancy and lactation:Contraindicated.

Dosing and Administration:

Inside, in the morning, before eating.

The initial dose for the treatment of hypertension is 4 mg / day, if necessary (after 1 month) the dose can be increased to 8 mg / day in one session.

In the appointment of ACE inhibitors, patients receiving diuretic therapy may experience a sharp decrease in blood pressure, for the prevention of which it is recommended to stop taking diuretics 2-3 days before the proposed initiation of therapy with Arentopres, or to prescribe the drug at lower doses of 2 mg once a day.

In patients with renovascular hypertension, the initial dose is 2 mg 1 time per day.

If necessary, the dose may be increased later.

In elderly patients, therapy should begin with a dose of 2 mg per day, and then, if necessary, gradually increase it up to a maximum dose of 8 mg per day.

Treatment of patients with chronic heart failure in combination with a potassium-sparing diuretic and / or digoxin is recommended to begin under careful medical supervision, the drug should be administered at an initial dose of 2 mg once a day in the morning.

In the future, after 1-2 weeks of therapy, the dose of the drug can be increased to 4 mg once a day.

In patients with impaired renal function, the dose of Arentopres Preparation should be selected taking into account the degree of renal failure: depending on the creatinine clearance.

At the clearance of creatinine 30-60 ml / min. - 2 mg once a day; with the clearance of creatinine 15-30 ml / min. - 2 mg every other day; patients on hemodialysis (creatinine clearance less than 15 ml / min.) - 2 mg per day of dialysis.

In case of creatinine clearance more than 60 ml / min. - 4 mg per day.

Patients with impaired liver function do not need to change the dose.

Side effects:

From the side of the cardiovascular system: often - excessive reduction in blood pressure and related symptoms, rarely - arrhythmia, angina, myocardial infarction and stroke.

From the urinary system: decreased kidney function, acute renal failure.

On the part of the respiratory system: often - a "dry" cough, difficulty breathing; rarely - bronchospasm, rhinorrhea, eosinophilic pneumonia.

From the digestive system: often - nausea, vomiting, abdominal pain, taste change, diarrhea or constipation, dry mouth, decreased appetite, cholestatic or cytolytic jaundice, pancreatitis, intestinal edema.

From the central nervous system: often - headache, asthenia, fatigue, dizziness, ringing in the ears, visual impairment, muscle cramps, paresthesia; rarely - decreased mood, insomnia; extremely rare - confusion consciousness.

Allergic reactions: often - skin rash, itching; rarely - hives, angioedema; extremely rarely - multiforme exudative erythema. Laboratory indicators: often - hypercreatininaemia, proteinuria, hyperkalemia; hyperuricemia; rarely (with prolonged use in high doses) - neutropenia, leukopenia,hypogemoglobinaemia, thrombocytopenia, reduction of hematocrit; extremely rare - agranulocytosis, pancytopenia, increased activity of "hepatic" enzymes, hyperbilirubinemia, hemolytic anemia (against the background of a deficiency of pyocose-6-phosphate dehydrogenase).

Other: increased sweating, violation of sexual function.

Overdose:

Symptoms: marked decrease in blood pressure, shock, stupor, bradycardia, tachycardia, anxiety and cough, dizziness, electrolyte disorders (hyperkalaemia, hyponatremia), renal failure.

Treatment: gastric lavage, restoration of water-electrolyte balance, intravenous injection of 0.9% sodium chloride solution. In the case of a marked decrease in blood pressure, the patient should be placed in a horizontal position, lifting his legs up, replenish the volume of circulating blood.

With the development of bradycardia - atropine, an artificial pacemaker may be required. Control of serum electrolytes and QC.

Perindopril can be removed from the systemic blood flow by hemodialysis. It is necessary to avoid the use of high-flow polyacrylonitrile membranes.

Interaction:

Increases the severity of hypoglycemic action of insulin and sulfonylurea derivatives.

Baclofen, tricyclic antidepressants, antipsychotics (antipsychotics), saluretics increase the hypotensive effect and increase the risk of orthostatic hypotension (additive effect), antacids reduce the bioavailability of ACE inhibitors.

Glucocorticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase 2 (COX-2), acetylsalicylic acid (more than 3 g / day) reduce the severity of hypotensive action (fluid retention and electrolytes).

Allopurinol, immunosuppressants, including cytotoxic drugs and systemic glucocorticosteroids, procainamide - when combined with ACE inhibitors - the risk of developing leukopenia.

Potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations increase the risk of hyperkalemia.

It is not recommended simultaneous use of drugs that can cause hyperkalemia, and ACE inhibitors, except in cases of severe hypokalemia (control of potassium in the blood serum).

With simultaneous use with lithium preparations, it is possible to slow its removal from the body (regular monitoring of lithium content in the blood is necessary). Diuretics, medicines for general anesthesia and muscle relaxants, ethanol increase the risk of excessive blood pressure lowering. The risk of developing clinically pronounced arterial hypotension can be reduced by stopping diuretics several days before the start of treatment with perijopril.

Perindopril can be administered together with acetylsalicylic acid (as a thrombolytic agent), thrombolyticamia, beta-blockers and / or nitrates.

Sympathomimetics can weaken the antihypertensive effect of ACE inhibitors. When this combination is prescribed, it is necessary to evaluate the efficacy of ACE inhibitors.

At simultaneous, application with a preparation of gold (sodium aurotomy malate) in the injecting form, undesirable phenomena were observed in the patients: "flushes" of blood to the skin of the face, nausea, vomiting, arterial hypotension (arterial hypotension is regarded as an intensification of the effect of ACE inhibitors under the influence of the gold preparation).

Special instructions:

The risk of arterial hypotension and / or renal failure increases with a significant loss of sodium and water (strict salt-free diet, and / or diuretics, diarrhea, vomiting) or renal artery stenosis (blockade in these situations of the renin-angiotensin system may result , especially with the first intake of the drug and during the first 2 weeks of treatment, to a sudden decrease in blood pressure and the development of chronic renal failure).

Before and during the therapy it is recommended to determine the concentration of creatinine, electrolytes and urea (within 1 month).

In patients with hypertension who are already receiving diuretic therapy, it is necessary to stop taking them (3 days before the appointment of the drug Aren Hopress) and, if necessary, continue to add to the treatment again.

In patients with chronic heart failure who are receiving diuretic therapy, if possible, it is necessary to reduce their dose several days before the start of Arentopresa.

In patients at risk, especially with chronic heart failure in the stage of decompensation, elderly patients,as well as patients with baseline low blood pressure, impaired renal function or receiving large doses of diuretics, initiation, use of the drug should be controlled.

Patients on hemodialysis should avoid the use of polyacrylonitrile membranes (possibly the development of anaphylactoid reactions). It is necessary to stop receiving before the forthcoming surgical intervention for a day and to warn the anesthetist about taking the drug.

Acceptance of ACE inhibitors is sometimes associated with a syndrome that begins with the development of cholestatic jaundice, progressing to fulminant liver necrosis, and (sometimes) death. - The mechanism of development of this syndrome is not clear. If symptoms of jaundice appear or the activity of "liver" enzymes increases in patients taking ACE inhibitors, discontinue drug therapy and conduct an appropriate examination.

With normal kidney function and the absence of other complications, neutropenia occurs - rarely. ACE inhibitors are prescribed only in emergency cases in the presence of systemic vasculitis, immunosuppressive therapy, reception of allopurinol or procainamide,as well as when combining all these factors, especially against the background of previous renal failure. There is a risk of developing severe infectious diseases 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 doctor about the appearance of any symptoms of infection.

In the procedure of apheresis of low density lipoproteins with dextran-sulphate absorption, anaphylactic reactions may develop in patients with ACE inhibitors.

Effect on the ability to drive transp. cf. and fur:

In connection with the danger of developing arterial hypotension and dizziness, ACE inhibitors should be cautiously prescribed to persons managing motor vehicles and engaged in activities requiring increased attention and rapid motor reaction.

Form release / dosage:

Tablets 2 mg, 4 mg.

Packaging:10 tablets in a blister of aluminum foil. 3 or 10 blisters in a cardboard box together with instructions for use.

Storage conditions:

Store at a temperature of no higher than 25 ° C in a dry, protected from light place. Keep out of the reach of children.

Shelf life:

2 years. Do not use after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006573/09

Date of registration:17.08.2009

Expiration Date:Unlimited

The owner of the registration certificate:Torrent Pharmaceuticals Co., Ltd.Torrent Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

TORRENT PHARMACEUTICALS, Ltd. India

Representation: & nbspTORRENT PHARMACEUTICALS LTD. TORRENT PHARMACEUTICALS LTD. India

Information update date: & nbsp12.09.2017

Illustrated instructions

Instructions

Arentopres (Arentopres)