Description
Pharmacological action
Pharmacodynamics:
ACE inhibitor. Suppression of ACE leads to a decrease in the content of angiotensin II in the blood plasma, as a result of which the secretion of aldosterone is reduced. Perindopril acts through its active metabolite, perindoprilat. Eliminates the vasoconstrictor effect of angiotensin II, increases the concentration of bradykinin and vasodilator prostaglandins (ACE converts inactive angiotensin I to angiotensin II, having a vasoconstrictor effect, and also causes the degradation of bradykinin and prostaglandin, which have vasodilating activity) reduces the production and release of aldosterone, inhibits the release of norepinephrine from the ends of the sympathetic nerve fibers and the formation of endothelin in the vessel wall. A decrease in the formation of angiotensin II is accompanied by an increase in plasma renin activity (due to inhibition of negative feedback). ACE suppression is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin system, while the prostaglandin system is also activated.
Helps to restore the elasticity of large arterial vessels (reducing the formation of excess subendothelial collagen), reduces pressure in the pulmonary capillaries, with prolonged administration, it reduces the severity of left ventricular myocardial hypertrophy and interstitial fibrosis, normalizes the isoenzyme profile of myosin and normalizes the functioning of the heart.
Reduces preload and afterload (reduces systolic and diastolic blood pressure while lying and standing), filling pressure of the left and right ventricles, total peripheral vascular resistance increases cardiac output and cardiac index without changing heart rate (in patients with chronic heart failure) , does not increase heart rate, enhances regional blood flow in the muscles.
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 glomerular filtration rate. In patients with chronic heart failure, it causes a significant decrease in the severity of clinical signs of heart failure, increases exercise tolerance (according to the bicycle ergometry test), and does not significantly reduce blood pressure. After ingestion of an average single dose, the maximum hypotensive effect is achieved after 4-6 hours and persists for 24 hours. Stabilization of the hypotensive effect is observed after 1 month of therapy and persists for a long time. Discontinuation of treatment is not accompanied by the development of withdrawal syndrome.
Pharmacokinetics:
Absorption – 25%, bioavailability – 65-70%. The time to reach maximum plasma concentration is 1 hour, perindoprilat is 3-4 hours. In the process of metabolism, 20% is transformed into the active metabolite – perindoprilat (taking perindopril after a meal reduces the proportion of perindoprilat formed – does not have significant clinical value) the rest – in 5 inactive compounds. T1 / 2 (half-life) of perindopril – 1 hour. The relationship of perindoprilat with plasma proteins is insignificant, with ACE – less than 30% (depending on concentration). The distribution volume of free perindoprilat is 0.2 l / kg. Perindoprilat is excreted by the kidneys, T1 / 2 of the free fraction of the metabolite is 3-5 hours. The dissociation of perindoprilat associated with ACE is slow. As a result of this, effective T1 / 2 is 25 hours. Repeated administration of perindopril does not lead to its accumulation, and T1 / 2 of perindoprilat at repeated administration corresponds to the period of its activity.
Excretion of perindoprilat slows down in elderly patients, as well as in patients with chronic heart failure and chronic renal failure (in the latter, dose adjustment should be carried out depending on creatinine clearance). The dialysis clearance of perindopril is 70 ml / min.
In patients with cirrhosis, the hepatic clearance of perindopril is reduced by 2 times, while the total amount of perindoprilat formed does not change and correction of the dosage regimen is not required.
Indications
Arterial hypertension
chronic heart failure.
Contraindications
Hypersensitivity to perindopril and other components of the drug or other ACE inhibitors, history of angioedema in the background, therapy with inhibitors. ACE, hereditary or idiopathic angioedema, pregnancy, lactation, age under 18 years (efficacy and safety have not been established).
Caution: aortic valve stenosis, hypertrophic obstructive cardiomyopathy, cerebrovascular diseases (including cerebrovascular insufficiency, coronary heart disease, coronary insufficiency – the risk of developing an excessive decrease in blood pressure and concomitant ischemia).
Severe autoimmune systemic diseases of the connective tissue (including systemic lupus erythematosus, scleroderma), inhibition of bone marrow hematopoiesis while receiving immunosuppressants (increased likelihood of developing neutropenia).
Renovascular hypertension, bilateral renal artery stenosis, stenosis of a single kidney artery, condition after kidney transplantation (risk of impaired renal function and agranulocytosis), chronic renal failure (especially accompanied by hyperkalemia), hyperkalemia, a diet with a sodium restriction, conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting, taking diuretics), diabetes mellitus, old age, surgical intervention (general anesthesia).
Use during pregnancy and lactation
The use of the drug Perindopril-SZ during pregnancy and during lactation is contraindicated.
Special instructions
The risk of developing arterial hypotension and / or renal failure while taking the drug increases with a significant loss of sodium and water (strict salt-free diet, and / or diuretics, diarrhea, vomiting) or renal artery stenosis (renin block in these situations -angiotensin system can lead, especially at the first dose 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 starting and during therapy, it is recommended to determine the concentration of creatinine, electrolytes and urea (within 1 month).
In patients with arterial hypertension who are already receiving diuretic therapy, it is necessary to stop taking them (3 days before the start of prescribing Perindopril) and, if necessary, add them to the treatment again later.
In patients with chronic heart failure receiving diuretic therapy, if possible, their dose should also be reduced several days before the start of treatment.
In patients at risk, especially with chronic heart failure in the decompensation stage, elderly patients, as well as patients with initially low blood pressure, impaired renal function or receiving high doses of diuretics, the start of the drug should be controlled.
In patients undergoing hemodialysis, the use of polyacrylonitrile membranes should be avoided (anaphylactoid reactions may develop).
It is necessary to stop taking before the upcoming surgical treatment for 12 hours and to warn the anesthetist about taking the drug.
Influence on the ability to drive a car and perform work that requires increased attention
Due to the risk of developing hypotension and dizziness, ACE inhibitors should be prescribed with caution to persons driving vehicles and engaging in activities that require increased attention and rapid motor response.
Composition
Composition (1 table): active substance: perindopril erbumin 8 mg
excipients: lactose (milk sugar) cellulose microcrystalline croscarmellose sodium (primrose) silicon dioxide colloidal (aerosil) magnesium stearate.
Dosage and administration
Inside, in the morning, before meals.
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 dose.
When prescribing ACE inhibitors to patients receiving diuretic therapy, there may be a sharp decrease in blood pressure, for the prevention of which it is recommended to stop taking diuretics 2-3 days before the intended initiation of perindopril therapy or to prescribe a drug in lower doses – 2 mg once a day.
In patients with renovascular hypertension, the initial dose is 2 mg 1 time per day. If necessary, the subsequent dose may be increased.
In elderly patients, therapy should be started 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.
The treatment of patients with heart failure in combination with a non-potassium-sparing diuretic and / or digoxin, it is recommended to start under close medical supervision, appoint Perindopril in an initial dose of 2 mg once a day, in the morning.
Further, 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 the drug should be selected taking into account the degree of renal failure: depending on the clearance of creatinine (CC).
With KK 30-60 ml / min – 2 mg once a day with KK 15-30 ml / min – 2 mg every other day for patients on hemodialysis (KK less than 15 ml / min) – 2 mg per day of dialysis. With CC more than 60 ml / min 4 mg per day.
Patients with impaired liver function, changes in the dose of perindopril is not required.
Side effects of
From the cardiovascular system: often an excessive decrease in arterial pressure and related symptoms, rarely arrhythmia, angina pectoris, myocardial infarction and stroke.
From the urinary system: decreased renal function, acute renal failure.
On the part of the respiratory system: often – dry cough, difficulty breathing rarely – bronchospasm, rhinorrhea.
From the digestive system: often – nausea, vomiting, abdominal pain, taste change, diarrhea or constipation, dry mouth, decreased appetite, cholestatic jaundice, pancreatitis, intestinal edema.
From the central nervous system: often – headache, asthenia, fatigue, dizziness, ringing in the ears, visual impairment, muscle cramps, paresthesias rarely – decreased mood, insomnia extremely rare – confusion.
Allergic reactions: often – skin rash, itching rarely – urticaria, angioedema extremely rare – erythema multiforme exudative.
Laboratory indicators: often – hypercreatininemia, proteinuria, hyperkalemia, hyperuricemia rarely (with prolonged use in high doses) – neutropenia, leukopenia, hypogemoglobinemia, thrombocytopenia, hematocrit reduction is extremely rare – agranulocytosis, pancytopenia, increased activity of liver enzymes, hyperbilirubinemia, hemolytic anemia (against the background of deficiency of glucose-6-phosphate dehydrogenase).
Other: increased sweating, impaired sexual function.
Drug interaction
Increases the severity of the hypoglycemic effect of insulin and sulfonylurea derivatives. Baclofen, tricyclic antidepressants, antipsychotic drugs (antipsychotics), saluretics enhance 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 reduce the severity of the hypotensive effect (fluid and electrolyte retention).
Potassium-sparing diuretics (spironolactone, triamteren, amiloride), potassium preparations increase the risk of hyperkalemia. The simultaneous use of drugs that can cause hyperkalemia and ACE inhibitors is not recommended, except in cases of severe hypokalemia (serum potassium monitoring).
With simultaneous use with lithium preparations, it is possible to slow its elimination from the body (regular monitoring of lithium content in the blood is necessary).
Diuretics, drugs for general anesthesia and muscle relaxants, ethanol increase the risk of developing an excessive decrease in blood pressure. The risk of developing clinically pronounced arterial hypotension can be reduced by stopping the use of diuretics several days before starting treatment with Perindopril.
Overdose
Symptoms: marked decrease in blood pressure, shock, stupor, bradycardia, electrolyte disturbances (hyperkalemia, hyponatremia), renal failure.
Treatment: gastric lavage, restoration of water-electrolyte state, intravenous administration of 0.9% sodium chloride solution. In the case of a pronounced decrease in blood pressure, the patient should be laid horizontally, lifting his legs up. Hemodialysis is effective (do not use highly permeable polyacrylonitrile membranes). With the development of bradycardia – atropine, the production of an artificial pacemaker may be required.
Storage conditions
In a dry, dark place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.
Expiration
2 years.
Deystvuyuschee substances
Perindopril
Terms of delivery p1460 pharmacy and from pharmacies
Prescription
Dosage Form
tablet
North Star, Russia
