Perindopril

General characteristics. Structure:

Active ingredient: 4 mg or 8 mg of a perindopril of an erbumin (in terms of 100% substance).

Excipients: sugar milk (lactose) - 0,0331 g, or 0,0489 g; microcrystallic cellulose - 0,0127 g, or 0,0188 g; starch corn (partially prezhelatinizirovanny) - 0,0422 g, or 0,0623 g; croscarmellose sodium - 0,005 g, or 0,0075 g; talc - 0,002 g, or 0,003 g; magnesium stearate - 0,001g, or 0,0015 g.

Antihypertensive drug.

Pharmacological properties:

Pharmacodynamics. APF inhibitor (interacts with Zn2 + in molecule APF and causes its inactivation). Perindopril acts by means of the active metabolite of a perindoprilat. Eliminates vasopressor effect of angiotensin II, increases concentration of bradikinin and vazodilatatorny Pg (APF transfers inactive angiotensin I to the angiotensin II having vasopressor effect and also causes degradation of bradikinin and Pg having vazodilatiruyushchy activity); reduces products and release of Aldosteronum, suppresses release of noradrenaline from the terminations of sympathetic nerve fibrils and formation of endothelin in a wall of vessels.

Decrease in formation of angiotensin II is followed by increase in activity of a renin of a blood plasma (owing to oppression of negative feedback). Suppression of APF is followed by increase in activity as circulating and the fabric kallikrein-kinin system, and also the Pg system. Promotes recovery of elasticity of large arterial vessels (decrease in formation of excess amount of subendothelial collagen), reduces pressure in pulmonary capillaries, at long appointment reduces expressiveness of a hypertrophy of a myocardium of a left ventricle and intersticial fibrosis, normalizes an isofermental profile of a myosin; normalizes cardiac performance. Reduces preloading and an afterload (reduces systolic and diastolic the ABP in situation "lying" and "standing"), filling pressure of the left and right ventricles, the general peripheric resistance of vessels (GPRV); increases the minute volume of blood (MVB) and cardiac index, does not increase the heart rate (HR) (at patients with the chronic heart failure (CHF) moderately urezhat ChSS), strengthens a regional blood stream in muscles. Increases concentration of lipoproteins of the high density (LPVP), at patients with a hyperuricemia reduces concentration of uric acid.

Increases a renal blood stream, does not change a glomerular filtration rate. With HSN causes reliable reduction of expressiveness of clinical signs of the heart failure (HF) in patients, increases tolerance to an exercise stress (according to veloergometrichesky test), the ABP authentically does not reduce. After intake of an average single dose the maximum hypotensive effect is reached in 4-6 h and remains during 24 h. Stabilization of hypotensive effect is observed in 1 month of therapy and remains for a long time. The termination of treatment is not followed by development of a syndrome of "cancellation".

Pharmacokinetics. Absorption – 25%, bioavailability - 65-70%. There is 1 h TCmax, the perindoprilata - 3-4 h Css is created on 4 days. In the course of metabolism of 20% it is transformed to an active metabolite - периндоприлат (reception of a perindopril after food reduces a share of the formed perindoprilat - has no essential clinical value); other quantity - in 5 inactive connections. T½ of a perindopril - 1 h. Communication of a perindoprilat with proteins of a blood plasma - insignificant, with APF - less than 30% (depends on concentration). The volume of distribution of a free perindoprilat – 0,2 l/kg. Perindoprilat is brought by kidneys, T½ of free fraction of a metabolite is 3-5 h.

Dissociation of the perindoprilat connected with APF, slow. Thereof "effective" T½ makes 25 h. Repeated purpose of a perindopril does not lead to its cumulation, and T½ of a perindoprilat at repeated reception corresponds to the period of its activity. The condition of "effective" Css is reached by the end of 4 days.

Removal of a perindoprilat is slowed down at patients of advanced age, and also at sick HSN and a chronic renal failure (at the last dose adjustment should be carried out depending on clearance of creatinine). The dialysis clearance of a perindopril makes 70 ml/min. At patients with cirrhosis the hepatic clearance of a perindopril decreases twice, at the same time total quantity of the formed perindoprilat does not change and correction of the mode of dosing is not required.

Indications to use:

Arterial hypertension, including renovascular, HSN.

Route of administration and doses:

Inside, in the morning, before food, an initial dose - 4 mg/days, if necessary (in 1 month) - increase up to 8 mg/days in one step.

At patients with chronic heart failure, at persons 70 years, against the background of preliminary reception of diuretics, against the background of renovascular hypertensia an initial dose - 2 mg/days are more senior (for 1 reception); if necessary in 1-2 weeks the dose raises to 4-8 mg/days.

At HPN with the klinersy creatine (KC) more than 60 ml/min. - 4 mg/days, at KK of 30-60 ml/min. - 2 mg/days; at KK of 15-30 ml/min. - 2 mg every other day; at KK less than 15 ml/min. - 2 mg in day of dialysis (dialysis clearance of a perindoprilat of 70 ml/min.). Patients with HPN at KK have more than 60 ml/min. or with a liver failure of correction of the mode of dosing it is not required.

Features of use:

The risk of development of arterial hypotension and/or renal failure against the background of administration of drug increases at considerable loss of Na + and waters (a rigid electrolyte-deficient diet, reception of diuretics, the expressed diarrhea or vomiting) or a stenosis of renal arteries (blockade can bring in these situations of RAAS, especially at the first administration of drug and during the first 2 weeks of treatment, to sudden decrease in the ABP and development of HPN).

Before the beginning and against the background of therapy it is recommended to define concentration of creatinine, electrolytes and urea (within 1 month). At the patients with arterial hypertension who are already receiving therapy by diuretics it is necessary to stop their reception (in 3 days prior to purpose of a perindopril) and in need of further to add to treatment again. At patients from HSN receiving therapy by diuretics, whenever possible their dose also has to be reduced some days before the beginning of reception. At the patients belonging to risk group, especially from dekompensirovanny HSN, patients of advanced age, and also patients with initially low ABP, a renal failure or receiving high doses of diuretics, the beginning of use of drug has to be carried out under control of medical personnel.

At the patients who are on a hemodialysis it is necessary to avoid use of polyacrylonitrile membranes (possibly development of anaphylactoid reactions). It is necessary to stop reception before the forthcoming surgical treatment for 12 h and to warn the anesthesiologist about administration of drug.

With care to apply in operating time to drivers of vehicles and people whose profession is connected with the increased concentration of attention.

Side effects:

Frequent side effects - 1-10%; rare – 0,1-1%; extremely rare - less than 0,1%. From CCC: often - excessive decrease in the ABP and the symptoms connected with it.

From an urinary system: seldom - aggravation or development of a renal failure.

From a respiratory organs: often - Sukhoi cough, breath difficulties; seldom - a bronchospasm.

From the alimentary system: often - nausea, vomiting, an abdominal pain, taste change, diarrhea or locks, dryness in a mouth.

From a nervous system: often - a headache, excessive fatigue, dizziness, a loss of appetite, a ring in ears, a vision disorder, spasms, paresthesias; seldom - decrease in mood, sleeplessness; extremely seldom - confusion of consciousness.

Allergic reactions: often - skin rashes, an itch; seldom - a small tortoiseshell, a Quincke's disease; extremely seldom - a multiformny exudative erythema.

Laboratory indicators: often - a giperkreatininemiya, a proteinuria, a hyperpotassemia; hyperuricemia; seldom (at prolonged use in high doses) - a neutropenia, a leukopenia, a hypohaemoglobinaemia, thrombocytopenia, decrease in a hematocrit; extremely seldom - an agranulocytosis, a pancytopenia, increase in activity of "hepatic" transaminases, a hyperbilirubinemia, hemolitic anemia (against the background of deficit glyukozo-6-fosfatdegidroge-nazy).

Interaction with other medicines:

Increases expressiveness of hypoglycemic effect of insulin and drugs of sulphonylurea.

Baclofenum, tricyclic antidepressants, antipsychotic HP (neuroleptics), saluretics strengthen hypotensive action and increase risk of development of orthostatic hypotension (the additive effect).

GKS, NPVP reduce expressiveness of hypotensive action (a delay of water and electrolytes). Kaliysberegayushchy diuretics, the drugs K+ increase risk of development of a hyperpotassemia. Simultaneous use of the HP capable to cause a hyperpotassemia, and APF inhibitors, except for cases of a heavy hypopotassemia is not recommended.

At simultaneous use with the drugs Li + delay of its removal from an organism is possible.

Diuretics, HP for the general anesthesia and muscle relaxants increase risk of development of excessively expressed decrease in the ABP.

The risk of development of clinically expressed arterial hypotension can be reduced, having stopped reception of diuretics some days before an initiation of treatment perindoprily.

Myelotoxic HP - strengthening of myelotoxic action.

Contraindications:

Hypersensitivity to a perindopril or the APF other inhibitors, pregnancy, the lactation period.

With care. A Quincke's disease in the anamnesis against the background of therapy by APF inhibitors, a hereditary or idiopathic Quincke's disease. An aortal stenosis, tserebro-and cardiovascular diseases (including insufficiency of cerebral circulation, coronary heart disease, coronary insufficiency - danger of development of excessive decrease in the ABP and the accompanying ischemia). Serious autoimmune general diseases of connecting fabric (including hard currency, a scleroderma), oppression of a marrowy hemopoiesis against the background of reception of immunodepressants (increase in probability of development of a neutropenia).

Diabetes mellitus (strengthening of action of hypoglycemic HP is possible).

Bilateral stenosis of renal arteries, stenosis of an artery of the only kidney, state after transplantation of kidneys (risk of development of a renal failure and agranulocytosis), HPN (which is especially followed by a hyperpotassemia), a diet with restriction of Na+, the states which are followed by decrease in volume of the circulating blood (including diarrhea, vomiting), advanced age, age up to 18 years (safety and efficiency of use are not studied).

Overdose:

Symptoms: decrease in the ABP, shock, stupor, bradycardia, electrolytic disturbances, renal failure.

Treatment: a gastric lavage, recovery of water and electrolytic balance, in/in introduction of 0,9% of NaCl solution. In case of the expressed decrease in the ABP of the patient it is necessary to put horizontally, having raised legs up. The hemodialysis is effective (not to use high-permeability poliakrilnitrilovy membranes). At development of bradycardia - atropine, statement of an artificial pacemaker can be required.

Storage conditions:

In the dry, protected from light place at a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 4 mg and 8 mg. 3 blister strip packagings together with the application instruction place in a pack from a cardboard.