Parnavel, tablets 4 mg, 30 pcs.

Parnavel – hypotensive, helps to restore the elasticity of large arterial vessels, reduces the severity of myocardial hypertrophy of the left ventricle, normalizes heart function.

Pharmacodynamics

The ACE inhibitor. ACE suppression leads to a decrease in plasma angiotensin II, resulting in a decrease in aldosterone secretion.

Perindopril acts through its active metabolite perindoprilat. It eliminates the vasoconstrictor effect of angiotensin II, increases the concentration of bradykinin and vasodilator prostaglandins (ACE converts inactive angiotensin I into angiotensin II, which has a vasoconstrictor effect, and also causes degradation of bradykinin and prostaglandin, which have 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 blood 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, and 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 expression of left ventricular myocardial hypertrophy and interstitial fibrosis, normalizes myosin isoenzyme profile; it normalizes heart function.
Decreases preload and postload (decreases systolic and diastolic blood pressure (BP) in “lying” and “standing” position), filling pressure of the left and right ventricles, total peripheral resistance of vessels; increases minute volume of circulation and cardiac index without changing heart rate (in patients with chronic heart failure), in therapeutic doses does not increase heart rate, increases regional blood flow in 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 test). After oral administration of an average single dose, the maximum hypotensive effect is achieved in 4-6 hours and is maintained for 24 hours. Stabilization of the 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%.

The time to reach maximum plasma concentration is 1 h, perindoprilat – 3-4 h. 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. T½ (half-life) of perindopril-1h. Binding of perindoprilat with blood plasma proteins is insignificant, with ACE – less than 30% (depends on concentration). Distribution volume of free perindoprilat is 0.2 l/kg.

Perindoprilat is excreted by the kidneys, T½ of the free metabolite fraction is 3-5 hours. Dissociation of perindoprilat bound to ACE is slow. As a consequence, the “effective” T½ is 25 h. Repeated administration of perindopril does not result in its cumulation, and the T½ of perindoprilat when repeatedly administered corresponds to its period of activity.

The 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 according to creatinine clearance). Dialysis clearance of perindopril is 70 ml/min.

In patients with cirrhosis hepatic clearance of perindopril is decreased 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.

Pharmacological effect

Parnavel is hypotensive, helps restore the elasticity of large arterial vessels, reduces the severity of left ventricular myocardial hypertrophy, and normalizes heart function.

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 decreases.

Perindopril acts through its active metabolite perindoprilate. Eliminates the vasoconstrictor effect of angiotensin II, increases the concentration of bradykinin and vasodilator prostaglandins (ACE converts inactive angiotensin I into angiotensin II, which has a vasoconstrictor effect, and also causes degradation of bradykinin and prostaglandin, which have vasodilatory 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 vascular wall. A decrease in the formation of angiotensin II is accompanied by an increase in plasma renin activity (due to inhibition of negative feedback).

Suppression of ACE 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 restore the elasticity of large arterial vessels (reducing the formation of excess subendothelial collagen), reduces pressure in the pulmonary capillaries, with long-term administration reduces the severity of left ventricular myocardial hypertrophy and interstitial fibrosis, normalizes the myosin isoenzyme profile; normalizes heart function.
Reduces preload and afterload (reduces systolic and diastolic blood pressure (BP) in the “lying” and “standing” positions), filling pressure of the left and right ventricles, total peripheral vascular resistance; increases minute volume of blood circulation and cardiac index without changing heart rate (in patients with chronic heart failure), in therapeutic doses does not increase heart rate, increases regional blood flow in 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, it causes a significant decrease in the severity of clinical signs of heart failure and increases exercise tolerance (according to the bicycle ergometer test). 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. Termination of treatment is not accompanied by the development of withdrawal syndrome.

Pharmacokinetics

Absorption – 25%, bioavailability – 65-70%.

The time to reach the maximum concentration in the blood plasma is 1 hour, perindoprilate – 3-4 hours. During metabolism, 20% is transformed into the active metabolite – perindoprilat (taking perindopril after meals reduces the proportion of perindoprilate formed – has no significant clinical significance); the remaining amount is 5 inactive compounds. T½ (half-life) of perindopril is 1 hour. The association of perindoprilate with plasma proteins is insignificant, with ACE – less than 30% (depending on the concentration). The volume of distribution of free perindoprilate is 0.2 l/kg.

Perindoprilat is excreted by the kidneys, T½ of the free metabolite fraction is 3-5 hours. The dissociation of perindoprilat associated with ACE is slow. As a result, the “effective” T½ is 25 hours. Repeated administration of perindopril does not lead to its cumulation, and T½ of perindoprilat upon repeated administration corresponds to the period of its activity.

The elimination of perindoprilate 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 made depending on creatinine clearance). The dialysis clearance of perindopril is 70 ml/min.

In patients with liver cirrhosis, the hepatic clearance of perindopril is reduced by 2 times, while the total amount of perindoprilate formed does not change and no adjustment of the dosage regimen is required.

Special instructions

The risk of developing arterial hypotension and/or renal failure while taking the drug increases with significant loss of sodium and water (strict salt-free diet, and/or taking diuretics, diarrhea, vomiting) or renal artery stenosis (blockade of the renin-angiotensin system in these situations can lead, especially when first taking 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 already receiving diuretic therapy, it is necessary to stop taking them (3 days before starting Parnavel) and, if necessary, add them to treatment again in the future.

In patients with chronic heart failure receiving diuretic therapy, if possible, it is necessary to reduce their dose several days before starting Parnavel.

In patients at risk, especially with chronic heart failure in the stage of decompensation, elderly patients, as well as patients with initially low blood pressure, impaired renal function or receiving large doses of diuretics, the initiation of the drug should be monitored. In patients undergoing hemodialysis, the use of polyacrylonitrile membranes should be avoided (the development of anaphylactoid reactions is possible). It is necessary to stop taking it one day before the upcoming surgery and notify the anesthesiologist about taking the drug.

Taking ACE inhibitors is sometimes associated with a syndrome starting with the development of cholestatic jaundice, progressing to fulminant hepatic necrosis, and (sometimes) death. The mechanism of development of this syndrome is not clear. If symptoms of jaundice or increased activity of liver enzymes appear in patients taking ACE inhibitors, drug therapy should be discontinued and appropriate examination should be carried out.

With normal renal function and the absence of other complications, neutropenia rarely occurs. ACE inhibitors are prescribed only in emergency cases in the presence of systemic vasculitis, immunosuppressive therapy, taking allopurinol or procainamide, as well as when combining all of these factors, especially against the background of previous renal failure. There is a risk of developing severe infectious diseases that are resistant to intensive antibiotic therapy. When conducting perindopril therapy in patients with the above factors, it is necessary to regularly monitor the white blood cell count and warn the patient to inform the doctor about the appearance of any symptoms of infection.
During the procedure of apheresis of low-density lipoproteins using dextran-sulfate absorption, when prescribing ACE inhibitors, patients may develop anaphylactic reactions.

Impact on the ability to drive a vehicle and perform work that requires increased attention

Due to the risk of developing arterial 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.

Active ingredient

Perindopril

Composition

Active ingredient:

perindopril erbumine 4 mg.

Excipients:

lactose (milk sugar);

microcrystalline cellulose;

corn starch;

povidone (polyvinylpyrrolidone);

magnesium stearate.

Contraindications

Hypersensitivity to perindopril and other components of the drug or other ACE inhibitors, a history of angioedema during therapy with ACE inhibitors, hereditary or idiopathic angioedema, pregnancy, lactation, age under 18 years, hereditary lactose intolerance, lactase deficiency or impaired absorption of glucose and galactose.

Side Effects

From the cardiovascular system: often – excessive decrease in blood pressure and associated symptoms, rarely – arrhythmia, angina pectoris, myocardial infarction and stroke.

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

From the respiratory system: often – “dry” cough, difficulty breathing; rare bronchospasm, rhinorrhea, eosinophilic pneumonia.

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

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

Allergic reactions: often – skin rash, itching; rarely – urticaria, angioedema; extremely rarely – exudative erythema multiforme.

Laboratory indicators: often – hypercreatininemia, proteinuria, hyperkalemia; hyperuricemia; rarely (with long-term use in high doses) – neutropenia, leukopenia, hypohemoglobinemia, thrombocytopenia, decreased hematocrit; extremely rarely – agranulocytosis, pancytopenia, increased activity of liver enzymes, hyperbilirubinemia, hemolytic anemia (due to glucose-6-phosphate dehydrogenase deficiency).

Other: increased sweating, impaired sexual function.

Interaction

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

Baclofen, tricyclic antidepressants, antipsychotics (neuroleptics), 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 (NSAIDs), including selective cyclooxygenase 2 (COX-2) inhibitors, acetylsalicylic acid (more than 3 g/day) reduce the severity of the hypotensive effect (fluid and electrolyte retention).

Allopurinol, immunosuppressants, including cytostatic agents and systemic glucocorticosteroids, procainamide – when used together with ACE inhibitors – the risk of developing leukopenia.

Potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium supplements increase the risk of developing hyperkalemia.
The simultaneous use of drugs that can cause hyperkalemia and ACE inhibitors is not recommended, except in cases of severe hypokalemia (monitoring serum potassium levels).

When used simultaneously with lithium preparations, it is possible to slow down its elimination from the body (regular monitoring of lithium levels 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 significant hypotension can be reduced by stopping diuretics several days before starting treatment with perindopril.

Perindopril can be prescribed together with acetylsalicylic acid (as an antiplatelet agent), thrombolytics, beta-blockers and/or nitrates. Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors. When prescribing such a combination, it is necessary to evaluate the effectiveness of ACE inhibitors.

When used simultaneously with the drug gold (sodium aurothiomalate) in injection form, patients experienced undesirable effects: “flushes” of blood to the facial skin, nausea, vomiting, arterial hypotension (arterial hypotension is regarded as an increase in the effect of ACE inhibitors under the influence of the drug gold).

Overdose

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

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

If bradycardia develops – atropine, an artificial pacemaker may be required. Monitoring serum electrolytes and CK.

Perindopril can be removed from the systemic circulation by hemodialysis. The use of high-flow polyacrylonitrile membranes should be avoided.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 °C

Shelf life

3 years

Manufacturer

Ozon, Russia