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

Excipients: corn starch partially pregelatinized 43.1 mg or 42.2 mg, or 62.3 mg; lactose monohydrate (sugar milk) - 33.9 mg or 33.1 mg, or 48.9 mg; cellulose microcrystalline - 13.0 mg or 12.7 mg, or 18.8 mg; croscarmellose sodium 5.0 mg or 5 mg or 7.5 mg; talc - 2 mg or 2 mg, or 3.0 mg; magnesium stearate - 1 mg or 1 mg, or 1.5 mg.

Description:Tablets are white or white with a yellowish or creamy hue of color, a flat-cylindrical shape with a bevel. Light marble is allowed.

Pharmacotherapeutic group:inhibitor of angiotensin-converting enzyme (ACE)

ATX: & nbsp

Perindopril

Pharmacodynamics:

Angiotensin-converting enzyme (ACE) inhibitor. Perindopril acts through its active metabolite perindoprilata. Eliminates vasoconstrictor action of angiotensin II, increases the concentration of bradykinin and vasodilator prostaglandins (Pg) (ACE transfers inactive angiotensin I to angiotensin II, which has a vasoconstrictive effect, and also causes degradation of bradykinin and Pg, having vasodilating activity); reduces the production and release of aldosterone, inhibits 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). The suppression of ACE is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin system, as well as the system Pg.

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; burrowsmaligns the work of the heart. Reduces preload and afterload (reduces systolic and diastolic pressure in the "lying" and "standing"), the filling pressure of the left and right ventricles, the total peripheral resistance of the vessels (OPSS); increases the minute blood volume (IOC) and cardiac index,does not increase the heart rate (heart rate) (in patients with chronic heart failure (CHF) moderately reduces (heart rate (heart rate), increases the regional blood flow in muscles.) Increases the concentration of high-density lipoproteins (HDL), in patients with hyperuricemia reduces concentration of uric acid.It increases the renal blood flow, does not change the rate of glomerular filtration.

In patients with CHF causes a significant decrease in the severity of clinical signs of heart failure (CH), increases exercise tolerance (according to the bicycle ergometric test), does not significantly decrease blood pressure. After oral administration 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. The termination of treatment is not accompanied by the development of the "withdrawal" syndrome.

Pharmacokinetics:

Absorption is 25%, bioavailability is 65-70%. Time to reach the maximum concentration of the drug in plasma -1h, perindoprilata - 3-4 hours. The equilibrium concentration is created for 4 days.

In the process of metabolism, 20% is transformed into an active metabolite - perindoprilat (the intake of perindopril after meals reduces the proportion of perindoprilat that is formed - it has no significant clinical significance); The rest is in 5 inactive connections. Half-life of perindopril -1h.

The relationship between perindoprilata and blood plasma proteins is insignificant, with an ACE of less than 30% (dependent on concentration). The volume of distribution of free perindoprilata is 0.2 l / kg.

Perindoprilat is excreted by the kidneys. The half-life of the free fraction of the metabolite is 3-5 hours. The dissociation of perindoprilat, which is associated with ACE, is slow. Consequently, the "effective" half-life is 25 hours. Re-administration of perindopril does not result in its cumulation, and the half-life of perindoprilate upon repeated administration corresponds to the period of its activity. The state of "effective" Css is reached by the end of 4 days.

The excretion of perindoprilat slows in elderly patients, as well as in patients with CHF and chronic renal failure (CRF)

(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, incl. Renovascular, chronic heart failure.

Contraindications:

Hypersensitivity to perindopril or other ACE inhibitors, hypersensitivity to excipients included in the drug, angioedema in history, associated with the administration of ACE inhibitors, hereditary and idiomatic angioedema, pregnancy, lactation, advanced age, children and adolescents aged up to 18 years (efficacy and safety of use not established), lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, the preparation contains lactose.

Carefully:

Angioedema with a history of therapy with ACE inhibitors, hereditary or idiopathic angioedema.

Aortic stenosis, cerebro- and cardiovascular diseases (incl.cerebral circulatory insufficiency, ischemic 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).

Diabetes mellitus (possibly increasing the effect of hypoglycemic drugs).

Two-sided stenosis of the renal arteries, stenosis of the single kidney artery, condition after kidney transplantation (risk of kidney and agranulocytosis), chronic renal failure (especially accompanied by hyperkalemia), diet with restriction of table salt, simultaneous reception of potassium-sparing diuretics, potassium supplements, salt substitutes , surgical intervention / general anesthesia, hyperkalemia, hemodialysis using high-flow membranes (for example, AN69®), conducting desensitizing therapy, condition after kidney transplantation, mitral stenosis, hypertrophic obstructive cardiomyopathy, conditions,accompanied by a decrease in the volume of circulating blood (bcc) (including diarrhea, vomiting).

Pregnancy and lactation:

In pregnancy, the use of the drug is contraindicated. It should not be used in the first trimester of pregnancy, so when the pregnancy is confirmed, the drug Perindopril you must cancel as soon as possible. The drug is contraindicated in the II-III trimesters of pregnancy, because in the II-III trimesters pregnancy can cause fetotoxic effects (decreased kidney function, low blood pressure, slowing ossification of the fetal bones) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). If nevertheless applied drug in the II-III trimesters of pregnancy, it is necessary to conduct an ultrasound examination of the kidneys and bones of the fetal skull.

Application of the drug Perindopril in the period of breastfeeding is not recommended, due to the lack of data on the possibility of its penetration into breast milk. If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, in the morning, before eating.For the treatment of essential hypertension, the recommended initial dose is 4 mg / day, if necessary (after 1 month) - an increase to 8 mg / day in one session.

In patients with chronic heart failure, in patients older than 70 years, with a preliminary dose of diuretics, against the background of renovascular hypertension, the initial dose is 2 mg / day (for 1 dose); if necessary, after 2 weeks, the dose increases to 4-8 mg / day.

In chronic renal insufficiency with creatinine clearance (CC) more than 60 ml / min - 4 mg / day, with KK 30-60 ml / min - 2 mg / day; with QC 15-30 ml / min - 2 mg every other day; with QC less than 15 ml / min - 2 mg per day of dialysis (dialysal clearance of perindoprilat 70 ml / min).

In patients with chronic renal failure with QC greater than 60 ml / min or with liver failure correction of the dosing regimen is not required.

In elderly patients, treatment 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.

Side effects:

The frequency of adverse reactions listed below was determined according to the following (classification of the World Health Organization): very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0,01%,but less than 0.1%; very rarely - less than 0.01%, including individual reports; the frequency is unknown - according to the available data, it is not possible to determine the incidence of undesirable effects.

From the central and peripheral nervous system: often - headache, dizziness, paresthesia; infrequently - sleep or mood disturbances; very rarely confusion.

From the side of the organ of vision: often - impaired vision.

From the side of the organ of hearing: often - noise in the ears.

From the cardiovascular system: often - a pronounced decrease in blood pressure; very rarely - arrhythmias, angina pectoris, myocardial infarction or stroke, possibly secondary, due to severe arterial hypotension in high-risk patients; vasculitis (frequency unknown).

On the part of the respiratory system: often - cough, shortness of breath; infrequently bronchospasm; very rarely - eosinophilic pneumonia, rhinitis.

On the part of the digestive tract: often - nausea, vomiting, abdominal pain, dysgeusia, indigestion, diarrhea, constipation; infrequent - dryness of the oral mucosa; rarely - pancreatitis; very rarely - cytolytic or cholestatic hepatitis, angioedema of the intestine.

From the skin: often - skin rash, itching; rarely angioedema, swelling of the face, limbs, urticaria; very rarely erythema multiforme.

From the musculoskeletal system: often - muscle cramps. From the genitourinary system: infrequently - renal failure, impotence; very rarely acute renal failure.

Common disorders: often - asthenia; infrequently - increased sweating. From the organs of hematopoiesis and lymphatic system: very rarely, with prolonged use in high doses, it is possible to reduce hemoglobin and hematocrit, thrombocytopenia, leukopenia / neutropenia, agranulocytosis, pancytopenia; very rarely - hemolytic anemia (in patients with congenital deficiency of glycose-6-phosphate dehydrogenase).

Laboratory indices: increased urea concentration in blood serum and plasma creatinine, and hyperkalemia reversible after discontinuation of the drug (especially in patients with renal insufficiency, severe CHF and reno- vascular hypertension); rarely - increased activity of "hepatic" enzymes and bilirubin in the blood serum; hypoglycemia.

Overdose:

Overdose

Symptoms: marked decrease in blood pressure, shock, stupor, bradycardia, disturbance of water-electrolyte balance (hyperkalemia, hyponatremia), renal failure, hyperventilation, tachycardia, palpitation, dizziness, anxiety, cough.

Treatment: with a pronounced decrease in blood pressure - give the patient a horizontal position with raised legs and take measures to replenish the volume of circulating blood (BCC). With the development of severe bradycardia, which is not amenable to drug therapy (including atropine), an artificial pacemaker is shown. It is necessary to monitor the vital functions and concentrations of creatinine and electrolytes in the blood serum. Perindopril can be removed from the systemic blood flow by hemodialysis. It is necessary to avoid the use of high-flow polyacrylonitrile membranes.

Repeated determinations of the content of electrolytes and creatinine in the blood serum, gastric lavage, prescribe absorbents and magnesium sulfate within 30 minutes after taking an ACE inhibitor. Gastric lavage, restoration of water-electrolyte equilibrium, intravenous administration of 0, 9% solution of sodium chloride.

Interaction:

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

Baclofen, tricyclic antidepressants, antipsychotic drugs (neuroleptics), saluretics increase the hypotensive effect and increase the risk of developing orthostatic hypotension (additive- effect).

Glucocorticosteroids, non-steroidal anti-inflammatory drugs, including acetylsalicylic acid in doses of 3 g / day or more reduce the severity of hypotensive action (water retention and electrolytes). Sympathomimetics can weaken the antihypertensive effect of ACE inhibitors. When this combination is prescribed, the effectiveness of ACE inhibitors should be evaluated regularly.

Ethanol enhances the hypotensive effect of ACE inhibitors. Potassium-sparing diuretics, preparations of potassium ions 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.

With the simultaneous use of lithium ions with drugs, it is possible to slow its removal from the body.

Diuretics, medicines (drugs) for general anesthesia and myorelaxitis 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 starting treatment with perindopril.

Myelotoxic drugs - increased myelotoxic effect.

With simultaneous use of ACE inhibitors and preparations of gold for parenteral administration (sodium aurotomy malate) describes a symptom complex, which includes facial flushing, nausea, vomiting and lowering blood pressure. Perindopril can be administered together with acetylsalicylic acid (as an anti-aggregate agent), thrombolytic agents, beta-blockers and / or nitrates.

Special instructions:

The risk of developing arterial hypotension and / or renal failure against the background of taking the drug is increased with a significant loss of sodium and water ions (strict salt-free diet, diuretics, severe diarrhea or Q vomiting) or stenosis of the renal arteries (blockade in these situations of renin-angiotensin-aldosterone system can lead, 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 CRF).

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 perindopril) and, if necessary, add to the treatment in the future again. In patients with CHF who receive diuretic therapy, if possible, their dose should also be reduced a few days before the start of admission.

In patients at risk, especially with decompensated CHF, elderly patients, as well as patients with baseline low blood pressure, impaired renal function or receiving large doses of diuretics, the beginning of the drug should be administered under the supervision of a doctor.

Patients on hemodialysis should avoid the use of polyacrylonitrile membranes (possibly the development of anaphylactoid reactions).

It is necessary to stop taking before the forthcoming surgery under general anesthesia for 12 hours and to warn the doctor / anesthesiologist about taking the drug.

It should be borne in mind that in patients of the Negroid race the risk of angioedema development is higher.Like other ACE inhibitors, perindopril is less effective as an antihypertensive agent in patients of the Negroid race. This effect is probably associated with a marked predominance of low-grade status in patients of the Negroid race with arterial hypertension.

During therapy with ACE inhibitors, it is sometimes possible to develop a syndrome that starts with cholestatic jaundice and then progresses to fulminant liver necrosis, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If jaundice appears during the administration of an ACE inhibitor or an increase in the activity of "liver" enzymes occurs, the ACE inhibitor should be immediately discontinued and the patient should be closely monitored. It is also necessary to conduct an appropriate examination.

Effect on the ability to drive transp. cf. and fur:In connection with the danger of developing arterial hypotension and dizziness, perindopril caution should be given to persons managing transport and engaged in activities that require increased concentration of attention and rapid motor reaction.

Form release / dosage:

Tablets 2 mg, 4 mg and 8 mg.10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

20 or 30 tablets in a polymer can with a first-tier control cover or a can of light-protective glass such as BTS, sealed with a lid with a sealing element. Free space in the bank is filled with cotton hygroscopic cotton.

Each jar, 1, 2 or 3 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In dry, the dark place at a temperature of no higher than 30 ° C. Keep out of the reach of children.

Shelf life:2 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001215

Date of registration:16.11.2011

The owner of the registration certificate:BIOCHEMIST, OJSC BIOCHEMIST, OJSC Russia

Manufacturer: & nbsp

BIOCHEMIST, OJSC Russia

Information update date: & nbsp28.08.2015

Illustrated instructions

Instructions

Perindopril (Perindopril)