Perindopril-SZ, tablets 4 mg 30 pcs

Pharmacotherapeutic group:

An angiotensin-converting enzyme inhibitor (ACE).

The ATX code: [C09AA04].

Pharmacological properties.

Pharmacodynamics.

The ACE inhibitor. Suppression of ACE leads to a decrease in plasma angiotensin II, resulting in a decrease in aldosterone secretion. Perindopril acts through its active metabolite perindoprilat.

Corrects the vasoconstrictor effect of angiotensin II, increases the concentration of bradykinin and vasodilator prostaglandins (ACE converts inactive angiotensin I into angiotensin II with vasoconstrictor effect and also causes degradation of bradykinin and prostaglandin with vasodilator activity); reduces the production and release of aldosterone, suppresses the release of norepinephrine from the sympathetic nerve fiber endings and the formation of endothelin in the vascular wall. Decrease of angiotensin II formation is accompanied by increase of plasma renin activity (due to inhibition of negative feedback).

The suppression of ACE is accompanied by increased activity of both circulating and tissue kallikrein-kinin system, while the prostaglandin system is also activated. It promotes restoration of elasticity of large arterial vessels (decrease of formation of excessive amount of subendothelial collagen), reduces pressure in pulmonary capillaries, with long-term prescription it reduces severity of left ventricular myocardial hypertrophy and interstitial fibrosis, normalizes myosin isoenzyme profile; normalizes heart function.

Limits preload and postload (reduces systolic and diastolic blood pressure in the “lying” and “standing” position), the filling pressure of the left and right ventricles, total peripheral vascular resistance; increases the minute circulatory volume and cardiac index without changing the heart rate (in patients with chronic heart failure), does not increase the heart rate, increases 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 glomerular filtration rate. in patients with chronic heart failure causes significant reduction of clinical signs of heart failure, increases exercise tolerance (by ergometer testing), does not significantly reduce blood pressure.

After oral administration of an average single dose the maximal hypotensive effect is reached after 4-6 hours and is maintained during 24 hours. Stabilization of hypotensive effect is observed after 1 month of therapy and is maintained for a long time. Discontinuation of treatment is not accompanied by development of “withdrawal” syndrome.

Pharmacokinetics.

Absorption – 25%, bioavailability – 65-70%. Time of reaching maximum concentration in blood plasma – 1 hour, perindoprilat – 3-4 hours. During metabolism 20% is transformed into active metabolite – perindoprilat (taking perindopril after meals reduces the proportion of perindoprilat formed – significant clinical significance); the remaining amount – into 5 inactive compounds. T1/2 (elimination half-life) of perindopril is 1 hour.

Binding of perindoprilat with blood plasma proteins is insignificant, with ACE – less than 30% (it depends on concentration). Distribution volume of free perindoprilat is 0.2 l/kg. Perindoprilat is excreted by the kidneys, T1/2 of free metabolite fraction is 3-5 hours. Dissociation of perindoprilat bound to ACE is slow. Due to this “effective” T1/2 is 25 h.

The repeated administration of perindopril does not result in its cumulation, and the T1/2 of perindoprilat when repeatedly administered corresponds to its period of activity. Excretion of perindoprilat is slower in elderly patients, as well as in patients with chronic heart failure and chronic renal failure (in the latter the dose should be adjusted depending on creatinine clearance).

The dialysis clearance of perindopril is 70 ml/min. In patients with cirrhosis, hepatic clearance of perindopril is reduced by half, while the total amount of perindoprilate produced does not change and dosing regimen adjustment is not required.

Indications

Arterial hypertension, chronic heart failure.

Active ingredient

Composition

How to take, the dosage

Ingestion, in the morning, before meals. The initial dose for the treatment of arterial hypertension is 4 mg/day, if necessary (after 1 month) the dose may be increased to 8 mg/day in one dose. When prescribing ACE inhibitors in patients receiving diuretics therapy a sharp decrease of BP may be noted, for prevention of which it is recommended to stop diuretics 2-3 days before the expected start of Perindopril therapy or to prescribe the drug in lower doses – 2 mg once daily.

In patients with renovascular hypertension, the initial dose is 2 mg once daily. If necessary, the dose can be subsequently increased.

In elderly patients, therapy should be started with a dose of 2 mg daily and then, if necessary, gradually increased up to a maximum dose of 8 mg daily.

The treatment of patients with heart failure in combination with a non-caliber diuretic and/or digoxin is recommended to start under close medical supervision, Perindopril should be administered in an initial dose of 2 mg once daily, in the morning. Later, after 1-2 weeks of therapy, the drug dose may be increased to 4 mg once daily.

In patients with impaired renal function, the drug dose should be adjusted according to the degree of renal failure: depending on creatinine clearance (CK). In case of IQ 30-60 ml/min – 2 mg once a day; in case of IQ 15-30 ml/min – 2 mg every other day; for patients on hemodialysis (IQ less than 15 ml/min) – 2 mg per dialysis day. If IQ is more than 60 ml/min, 4 mg per day. Patients with impaired liver function do not need to change Perindopril dosage.

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Interaction

In concomitant use with antihypertensives, muscle relaxants, anesthetics may increase the antihypertensive effect.

In concomitant use with loop diuretics, thiazide diuretics may increase the antihypertensive effect. Significant arterial hypotension, especially after the first dose of diuretic appears to be due to hypovolemia, which leads to transient enhancement of hypotensive effect of perindopril. There is an increased risk of impaired renal function.

Concomitant use with sympathomimetics may decrease the antihypertensive effect of perindopril.

Concomitant use with tricyclic antidepressants, antipsychotics (neuroleptics) increases the risk of postural hypotension.

Concomitant use with indomethacin decreases antihypertensive effect of perindopril, probably due to inhibition by NSAIDs of prostaglandin synthesis (which is believed to play a role in development of hypotensive effect of ACE inhibitors).

Concomitant use with insulin and hypoglycemic agents with sulfonylurea derivatives may lead to hypoglycemia due to increased glucose tolerance.

In concomitant use with potassium-saving diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and food supplements containing potassium, hyperkalemia may develop (especially in patients with impaired renal function).Because ACE inhibitors decrease the content of aldosterone, which leads to potassium retention in the body against the background of potassium excretion restriction or its additional intake.

Concomitant use with lithium carbonate may decrease the excretion of lithium from the body.

Special Instructions

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

Before and during therapy it is recommended to determine creatinine, electrolytes and urea concentrations (within 1 month). In patients with arterial hypertension who are already receiving therapy with diuretics, it is necessary to stop their intake (3 days before Perindopril administration) and if necessary to add them again to the treatment in future.

In patients with chronic heart failure receiving therapy with diuretics, if possible, their dose should also be reduced several days before the start of administration. In patients belonging to risk group, especially in patients with chronic heart failure in decompensation stage, elderly patients as well as in patients with baseline low blood pressure, impaired renal function or those receiving high doses of diuretics the start of the drug should be controlled.

In patients on hemodialysis the use of polyacrylonitrile membranes should be avoided (possible development of anaphylactoid reactions). It is necessary to discontinue use 12 hours before the upcoming surgical treatment and to warn the anesthesiologist about the drug intake.

Impact on the ability to drive and perform work requiring increased attention.

Due to the risk of arterial hypotension and dizziness, ACE inhibitors should be used with caution in persons driving motor vehicles and engaged in activities requiring increased attention and rapid motor reaction.

Contraindications

Side effects

Overdose

Similarities