PRESTARIUM A COATED TAB 5MG N30

Dosage form and composition

Prestarium is produced in the form of tablets for oral use. The active ingredient of the product is perindopril salt. The substance blocks the activity of the enzyme hormone angiotensin, which provokes an increase in blood pressure. The drug has several varieties, differing in dosage and content of auxiliary compounds:

• Prestarium tablets: containing 2, 4 and 8 mg. perindopril;
• Prestarium A: with an increased dosage: 2.5, as well as 5 and 10 mg;
• Bi-Prestarium: tablets in double dosage containing amlodipine, a calcium channel blocker.

All types of Prestarium have a similar effect, but they are prescribed for varying severity of hypertension.

Compound

How does Prestarium work?

The drug reduces the production of the hormone aldosterone, the breakdown of bradykinin and renin activity. The decrease in blood pressure as a result of taking it is not accompanied by a disturbance in heart rate. The use of Prestarium has a beneficial effect on renal blood flow. In this case, the main functions of the organs are not affected. During treatment, the size of the enlarged left ventricle is normalized, and the elasticity of the coronary and other large vessels improves. Prestarium containing amlodipine has a complex effect:

• dilates blood vessels;
• normalizes blood flow in the heart vessels and capillaries;
• reduces the load on the myocardium, improves its blood supply.

The medicine does not affect cholesterol metabolism and does not lead to metabolic disorders. The therapeutic effect develops within 1 hour after taking the tablets. It has a cumulative mechanism of action, the maximum is observed on days 4–5 from the start of the course and persists throughout its entire duration. Metabolites of the drug are excreted in the urine. Its remains do not accumulate inside the body. After withdrawal, patients do not exhibit addiction syndrome.

Pharmacokinetics

Suction. When taken orally, perindopril is rapidly absorbed from the gastrointestinal tract, Cmax in blood plasma is reached after 1 hour. T1/2 of perindopril from blood plasma is 1 hour.

Perindopril has no pharmacological activity. Approximately 27% of the total amount of absorbed perindopril enters the bloodstream in the form of the active metabolite perindoprilate. In addition to perindoprilate, 5 more metabolites are formed that do not have pharmacological activity. Cmax of perindoprilate in blood plasma is achieved 3–4 hours after oral administration.

Eating slows down the conversion of perindopril to perindoprilat, thereby affecting bioavailability. Therefore, the drug should be taken orally once a day, in the morning, before meals.

Distribution. The Vd of free perindoprilate is approximately 0.2 l/kg. The association of perindoprilate with plasma proteins, mainly with ACE, is insignificant and dose-dependent.

Excretion. Perindoprilat is excreted by the kidneys. T1/2 of the free fraction is 3–5 hours. Effective T1/2 is approximately 17 hours, the equilibrium state is reached within 4 days.

Special groups of patients. The elimination of perindoprilate is slowed down in old age, as well as in patients with heart and renal failure. The dialysis clearance of perindoprilate is 70 ml/min.

In patients with liver cirrhosis, the hepatic clearance of perindopril is reduced by 2 times. However, the amount of perindoprilate formed does not decrease, and dose adjustment of the drug is not required (see “Dosage and Administration” and “Special Instructions”).

When is Prestarium shown?

The drug alleviates the physical condition of various cardiovascular pathologies:

• hypertension;
• chronic heart failure;
• for coronary heart disease: in stable condition;
• after a transient ischemic attack;

Prestarium can also be prescribed as a prevention of heart attack as part of complex treatment: in combination with other drugs.

Pharmacodynamics

Mechanism of action

Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II.

ACE, or kininase II, is an exopeptidase that carries out both the conversion of angiotensin I into the vasoconstrictor substance angiotensin II, and the destruction of bradykinin, which has a vasodilatory effect, into an inactive heptapeptide. As a result, perindopril reduces the secretion of aldosterone.

Since ACE inactivates bradykinin, suppression of ACE is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin system, and the PG system is also activated. It is possible that this effect is part of the mechanism of the antihypertensive effect of ACE inhibitors, as well as the mechanism of development of some side effects of drugs of this class (for example, cough).

Perindopril has a therapeutic effect due to the active metabolite perindoprilat. Other metabolites do not have an ACE inhibitory effect in vitro.

Clinical efficacy and safety

Arterial hypertension

Perindopril is effective in the treatment of arterial hypertension of any severity. With the use of the drug, there is a decrease in both SBP and DBP in the supine and standing positions.

Perindopril reduces peripheral vascular resistance, which leads to a decrease in blood pressure, while peripheral blood flow accelerates without changing heart rate.

As a rule, perindopril leads to an increase in renal blood flow, while the glomerular filtration rate does not change.

The antihypertensive effect of the drug reaches its maximum 4–6 hours after a single oral dose and persists for 24 hours. 24 hours after oral administration, pronounced (about 80%) residual ACE inhibition is observed.

A decrease in blood pressure is achieved quite quickly. In patients with a positive response to treatment, normalization of blood pressure occurs within a month and is maintained without the development of tachycardia.

Discontinuation of treatment is not accompanied by the development of withdrawal syndrome.

Perindopril has a vasodilating effect, helps restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy.

The simultaneous administration of thiazide diuretics increases the severity of the antihypertensive effect. In addition, the combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of hypokalemia while taking diuretics.

Heart failure

Perindopril normalizes heart function by reducing preload and afterload.

In patients with chronic heart failure treated with perindopril, the following was found:

- decrease in filling pressure in the left and right ventricles of the heart;

— decrease in OPSS;

- increased cardiac output and increased cardiac index.

A study of the drug compared with placebo showed that changes in blood pressure after the first dose of Prestarium® A 2.5 mg in patients with chronic heart failure (functional class II–III according to the NYHA classification) were not statistically significantly different from the changes in blood pressure observed after taking placebo.

Cerebrovascular diseases

Results of the PROGRESS study, which assessed the effect of active therapy with perindopril (monotherapy or in combination with indapamide) for 4 years on the risk of recurrent stroke in patients with a history of cerebrovascular disease. After an introductory period of perindopril tert-butylamine 2 mg (equivalent to perindopril arginine 2.5 mg) once daily for two weeks and then 4 mg (equivalent to perindopril arginine 5 mg) once daily for the next two weeks, 6105 patients were randomized into two groups: placebo (n = 3054) and perindopril tert-butylamine 4 mg (corresponding to 5 mg perindopril arginine) (monotherapy) or in combination with indapamide (n = 3051).

Indapamide was additionally prescribed to patients who did not have direct indications or contraindications for the use of diuretics. This therapy was prescribed in addition to standard therapy for stroke and/or arterial hypertension or other pathological conditions. All randomized patients had a history of cerebrovascular disease (stroke or transient ischemic attack) within the past 5 years. Blood pressure was not an inclusion criterion: 2916 patients had arterial hypertension and 3189 had normal blood pressure. After 3.9 years of therapy, blood pressure (sBP/dBP) decreased by an average of 9/4 mmHg. Art. It also showed a significant reduction in the risk of recurrent stroke (both ischemic and hemorrhagic) of the order of 28% (95% CI (17; 38), p < 0.0001) compared with placebo (10.1 and 13.8%) .

Additionally, significant risk reductions have been shown:

- fatal or disabling strokes;

- major cardiovascular complications, including myocardial infarction, incl. with fatal outcome;

- dementia associated with stroke;

- serious deterioration of cognitive functions.

This was noted both in patients with arterial hypertension and with normal blood pressure, regardless of age, gender, presence or absence of diabetes mellitus and type of stroke.

Stable ischemic heart disease

It has been shown that when taking perindopril tertbutylamine at a dose of 8 mg/day (equivalent to 10 mg perindopril arginine) in patients with stable coronary artery disease, there is a significant reduction in the absolute risk of complications provided for by the main criterion of effectiveness (mortality from cardiovascular diseases, incidence of non-fatal myocardial infarction and/or cardiac arrest followed by successful resuscitation), by 1.9%. In patients who had previously had a myocardial infarction or coronary revascularization procedure, the absolute risk reduction was 2.2% compared with the placebo group.

Contraindications

Prestarium is prohibited for use in the following pathologies:

• angioedema;
• intolerance to ACE inhibitors;
• galactosemia.

Breastfeeding and pregnancy at all stages are also reasons to exclude the drug from the treatment regimen. The drug should be used with caution in cases of electrolyte imbalance, after internal organ transplantation, aortic valve stenosis, and systemic connective tissue pathologies. Patients on hemodialysis or taking antidepressants should carefully select the dosage and monitor their well-being. Conditions accompanied by excessive vomiting, diarrhea, dehydration, and renal failure also require special attention.

Instructions for use PRESTARIUM®

Stable ischemic heart disease

If episodes of unstable angina (severe or not) occur during the first month of taking perindopril, it is recommended that a careful assessment of the risk/benefit ratio be carried out before continuing treatment.

Arterial hypotension

ACE inhibitors may cause a decrease in blood pressure. Arterial hypotension with clinical manifestations rarely develops in patients with arterial hypertension without concomitant diseases, more often it occurs in patients with reduced blood volume (taking diuretics, on a diet with limited salt intake, patients on dialysis, patients with diarrhea or vomiting) or in patients with severe renin-dependent hypertension. Symptomatic hypotension has been reported in patients with symptomatic severe heart failure with or without concomitant renal failure. Arterial hypotension may more often develop in patients with more severe heart failure, as a result of taking high-dose loop diuretics, hyponatremia, or functional renal failure. Patients at increased risk of developing symptomatic hypotension should be closely monitored during initiation of therapy and during dose adjustments. A similar approach should also be followed when treating patients with ischemia and/or cerebrovascular disease, in whom severe hypotension can lead to myocardial infarction or stroke.

If arterial hypotension develops, it is necessary to place the patient on his back and, if necessary, replenish the blood volume by intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication for further use of the drug, which can be continued after blood pressure has increased again after an increase in blood volume.

In some patients with congestive heart failure with normal or low blood pressure, taking Prestarium® may lead to an additional decrease in systemic blood pressure (usually does not require discontinuation of the drug). If clinical manifestations of arterial hypotension develop, it may be necessary to reduce the dose or discontinue taking Prestarium®.

Aortic stenosis, mitral stenosis, hypertrophic cardiomyopathy

Like other ACE inhibitors, Prestarium should be administered with extreme caution to patients with mitral valve stenosis and left ventricular outflow obstruction, for example, aortic stenosis or hypertrophic cardiomyopathy.

Renal dysfunction

In case of impaired renal function (creatinine clearance < 60 ml/min), the initial dose should be adjusted according to the patient's creatinine clearance and then depending on the patient's response to treatment. Potassium and creatinine levels need to be monitored.

If arterial hypotension develops at the beginning of therapy with ACE inhibitors in patients with heart failure with clinical manifestations, further deterioration of renal function is possible. There are reports of the development of acute renal failure, which is usually reversible.

In some patients with bilateral renal artery stenosis or solitary renal artery stenosis taking ACE inhibitors, there have been cases of increases in blood urea and serum creatinine, reversible after discontinuation of therapy (more common in patients with renal failure). With renovascular hypertension there is also an increased risk of severe hypotension and renal failure. Treatment of such patients should be initiated under close medical supervision, with low doses and careful dose titration. Since diuretics may be a factor contributing to the development of the conditions described above, in the first weeks of treatment with Prestarium®, diuretics should be discontinued and renal function should be constantly monitored.

In some patients with arterial hypertension without visible renal vascular impairment, an increase in blood urea and serum creatinine concentrations was observed, usually slight and transient, especially in the case of concomitant use of Prestarium® and diuretics. These changes are most likely in patients with existing renal impairment. In this case, it may be necessary to reduce the dose and/or stop taking the diuretic and/or Prestarium.

Patients on hemodialysis

In some patients undergoing hemodialysis using high-flux membranes and simultaneously receiving ACE inhibitors, cases of anaphylactoid reactions have been reported. For such patients, the use of a different type of membrane or a different class of antihypertensive drug should be considered.

Kidney transplant

There is no experience with the use of Prestarium® in patients with recent kidney transplantation.

Hypersensitivity/angioedema

Rarely, angioedema of the face, extremities, lips, mucous membranes, tongue, vocal cords and/or larynx has been reported. These reactions may occur at any time during therapy. In such cases, Prestarium should be stopped immediately and appropriate monitoring should be carried out until symptoms disappear completely. Typically, when swelling affected only the face and lips, it resolved without any treatment, although antihistamines helped relieve symptoms.

Angioedema that extends to the larynx can be fatal. If there is swelling of the tongue, vocal cords or larynx, which may lead to airway obstruction, appropriate measures should be taken immediately. Emergency care may include giving epinephrine (adrenaline) and/or maintaining an airway. The patient should be under medical supervision until symptoms disappear completely and permanently.

An increased risk of developing angioedema while taking ACE inhibitors exists for patients who have had angioedema not associated with taking ACE inhibitors.

In rare cases, angioedema of the intestine has been reported in patients treated with ACE inhibitors. These patients experienced abdominal pain (with or without nausea and vomiting); in several cases there was no previous facial edema and C-1 esterase levels were normal. Angioedema was diagnosed by abdominal CT, ultrasound, or surgery; symptoms resolved after discontinuation of ACE inhibitors. The development of angioedema of the intestine should be taken into account in the differential diagnosis of patients with abdominal pain during treatment with ACE inhibitors.

Anaphylactoid reactions during hemodialysis or LDL apheresis procedures

Rare cases of life-threatening anaphylactoid reactions have been reported in some patients undergoing hemodialysis using high-flux membranes or receiving LDL apheresis using dextran sulfate absorption when prescribed ACE inhibitors. These reactions can be avoided by temporarily discontinuing the ACE inhibitor each time before apheresis.

Anaphylactoid reactions during desensitization

Anaphylactoid reactions have occurred in some patients receiving ACE inhibitors during desensitization therapy (eg, hymenopteric venom). In some patients, these reactions were avoided by temporarily discontinuing the ACE inhibitor, but they occurred again if the drug was taken carelessly.

Liver dysfunction

In rare cases, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not yet clear. In patients receiving ACE inhibitors, if jaundice or a marked increase in liver enzyme activity develops, the ACE inhibitor should be discontinued and a thorough medical examination should be performed.

Neutropenia, agranulocytosis, thrombocytopenia, anemia

Neutropenia/agranulocytosis, thrombocytopenia and anemia were observed while taking ACE inhibitors. In patients with normal liver function and in the absence of other complicating factors, neutropenia rarely develops. Perindopril should be used with extreme caution in patients with diffuse connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with pre-existing liver dysfunction. Some of these patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.

Cough

Taking an ACE inhibitor may cause a dry cough. The cough is non-productive and persists while taking the drug, but disappears when it is discontinued. This symptom may have an iatrogenic etiology. Cough caused by taking an ACE inhibitor should be considered in the differential diagnosis of cough.

Surgery, anesthesia

During surgery or during anesthesia with drugs that cause arterial hypotension, Prestarium® can block the formation of angiotensin II, as a result of compensatory release of renin. It is recommended to stop treatment the day before surgery. When arterial hypotension occurs, which is presumably associated with this mechanism of action, the blood volume should be increased.

Hyperkalemia

In some patients treated with ACE inhibitors, incl. perindopril, cases of elevated serum potassium levels have been reported. Risk factors for the development of hyperkalemia include renal failure, deterioration of renal function, age (>70 years), diabetes mellitus, intercurrent events such as dehydration, acute heart failure, metabolic acidosis, concomitant use of potassium-sparing diuretics (eg, spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes, or taking other drugs that cause increases in serum potassium (eg, heparin). Taking potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes, especially in patients with impaired renal function, may result in significant increases in serum potassium levels. Hyperkalemia can cause serious arrhythmias, sometimes fatal. If concomitant administration of perindopril or the above drugs is considered necessary, they should be taken with caution and with regular monitoring of serum potassium levels.

Diabetes

In diabetic patients already taking oral hypoglycemic agents or insulin, glycemic levels should be carefully monitored, especially during the first month of taking an ACE inhibitor.

Lithium preparations

The combined use of perindopril and lithium is usually not recommended.

Potassium-sparing diuretics, potassium supplements, and potassium-containing salt substitutes

The combination of perindopril with potassium-sparing diuretics, potassium supplements, and potassium-containing salt substitutes is generally not recommended.

Double blockade of the RAAS

Cases of hypotension, syncope, stroke, hyperkalemia, and impaired renal function (including acute renal failure) have been reported in susceptible patients, particularly when receiving combined medications that affect this system. In this regard, double blockade of the RAAS by combined administration of an ACE inhibitor and an angiotensin II receptor antagonist or aliskiren is not recommended.

Combined use with aliskiren in patients with diabetes mellitus or renal failure (GFR < 60 ml/min/1.73 m2) is contraindicated.

Race

When treated with ACE inhibitors, angioedema develops more often in patients of the Black race than in patients of other races.

Like other ACE inhibitors, the effectiveness of perindopril in lowering blood pressure may be lower in patients of the black race than in patients of other races, perhaps the reason for this is that hypertension in black patients very often resolves against the background of low renin levels.

Excipients

Prestarium® tablets contain lactose, so the drug should not be prescribed to patients with rare problems of hereditary lactose intolerance, glucose-galactose malabsorption or lapp lactase deficiency.

Use in pediatrics

Safety and effectiveness of Prestarium in children and adolescents under 18 years of age

have not been established, so prescribing the drug to this category of patients is not recommended.

Impact on the ability to drive vehicles and operate machinery

Prestarium® does not affect the ability to concentrate and the speed of psychomotor reactions. However, in some patients, especially at the beginning of treatment or when combined with other antihypertensive drugs, individual reactions may develop with a decrease in blood pressure. This leads to a deterioration in the ability to drive vehicles and operate machinery.

Preclinical safety data

Reversible renal impairment was observed in oral chronic toxicity studies in rats and monkeys. No mutagenicity was observed in in vivo or in vitro studies. No carcinogenicity was observed in rats or mice with long-term administration.

Reproductive toxicity studies (in rats, mice, rabbits and monkeys) showed no evidence of embryotoxicity or teratogenicity. However, ACE inhibitors as a class have been shown to have adverse effects on late fetal development, resulting in fetal death and congenital disorders in rodents and rabbits; kidney damage and an increase in perinatal and postnatal mortality were observed. No effects on fertility were observed in male or female rats.

Side effects

Prestarium can cause the following undesirable reactions from the body:

• nausea, dry mouth, loss of appetite;
• dry cough;
• increased uric acid levels;
• dizziness, headaches;
• physical weakness, apathy, increased drowsiness;
• depression;
• swelling of the ankles;
• thrombocytopenia, decreased hemoglobin, red blood cells and other blood count disorders.

Allergic reactions may cause skin itching, rashes, swelling of the mucous membranes and skin, and respiratory problems. Men may experience decreased libido. In case of overdose, vascular collapse, bradycardia, and impaired coordination of movements are likely.

Side effects

The safety profile of perindopril is consistent with the safety profile of ACE inhibitors.

The most common adverse events reported in clinical studies and observed with perindopril are: dizziness, headache, paresthesia, vertigo, visual disturbances, tinnitus, excessive decrease in blood pressure, cough, shortness of breath, abdominal pain, constipation, diarrhea, taste disturbance, dyspepsia, nausea, vomiting, itching, skin rash, muscle spasms and asthenia.

The frequency of adverse reactions that were noted during clinical trials and/or post-registration use of perindopril is given in the following gradation: very often (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); unspecified frequency (frequency cannot be calculated from available data). The classification of frequency indicators is recommended by WHO.

From the circulatory and lymphatic system: infrequently* - eosinophilia; very rarely - decreased hemoglobin and hematocrit, thrombocytopenia, leukopenia/neutropenia, agranulocytosis, pancytopenia, hemolytic anemia in patients with congenital deficiency of glucose-6-phosphate dehydrogenase (see "Special Instructions").

Metabolic disorders: uncommon* - hypoglycemia (see "Special Instructions" and "Interactions"), hyperkalemia, reversible after discontinuation of the drug (see "Special Instructions"), hyponatremia.

From the side of the central nervous system: often - paresthesia, headache, dizziness, vertigo; uncommon - sleep disturbance, mood lability, drowsiness*, fainting*; very rarely - confusion.

From the side of the organ of vision: often - visual impairment.

On the part of the hearing organ: often - tinnitus.

From the cardiovascular system: often - excessive decrease in blood pressure and associated symptoms; uncommon* - vasculitis, tachycardia, palpitations; very rarely - cardiac arrhythmias, angina pectoris, myocardial infarction and stroke, possibly due to an excessive decrease in blood pressure in high-risk patients (see "Special Instructions").

From the respiratory system: often - cough, shortness of breath; uncommon - bronchospasm; very rarely - eosinophilic pneumonia, rhinitis.

From the digestive system: often - constipation, nausea, vomiting, abdominal pain, taste disturbance, dyspepsia, diarrhea; infrequently - dryness of the oral mucosa; very rarely - pancreatitis.

From the liver and biliary tract: very rarely - hepatitis (cholestatic or cytolytic) (see "Special Instructions").

On the part of the skin and subcutaneous fat: often - skin itching, rash; uncommon - angioedema of the face, lips, upper and lower extremities, mucous membranes, tongue, vocal folds and/or larynx; urticaria (see “Special Instructions”); very rarely - erythema multiforme; uncommon* - photosensitivity, pemphigus, increased sweating.

From the musculoskeletal system and connective tissue: often - muscle spasms; infrequently* - arthralgia, myalgia.

From the kidneys and urinary tract: infrequently - renal failure; very rarely - acute renal failure.

From the reproductive system: infrequently - erectile dysfunction.

General disorders and symptoms: often - asthenia; Uncommon: chest pain*, peripheral edema*, weakness*, fever*, falls*.

Laboratory indicators: rarely - increased activity of liver transaminases and bilirubin in the blood serum; infrequently* - increased concentrations of urea and creatinine in the blood plasma.

*Evaluation of the frequency of adverse reactions identified by spontaneous reports was based on data from the results of clinical studies.

Adverse events noted in clinical studies

The EUROPA study recorded only serious adverse events. Serious adverse events were reported in 16 (0.3%) patients in the perindopril group and 12 (0.2%) patients in the placebo group. In the perindopril group, a marked decrease in blood pressure was observed in 6 patients, angioedema in 3 patients, and sudden cardiac arrest in 1 patient. The rate of drug discontinuation due to cough, severe decrease in blood pressure, or other cases of intolerance was higher in the perindopril group compared with the placebo group.

How to use Prestarium: instructions

The doctor prescribes the exact treatment regimen depending on the type of disease and the age of the patient. General recommendations:

• The tablets must be taken on an empty stomach, in the morning, with plenty of water; there is no need to chew the drug;
• the prescribed dose is taken once: it can range from 2 to 8 mg per day;
• in acute conditions, the drug is taken no earlier than complete normalization and remission.

For elderly people and other risk groups, the dosage is adjusted downwards. It is prohibited to change the number of tablets on your own. The course of treatment is continued until the physical condition is stabilized and the existing pathologies are normalized. If necessary, Prestarium is taken for several months in a row or continuously. It is allowed to combine it with diuretic medications.

The drug is incompatible with narcotic analgesics, corticosteroid hormones, immunosuppressants, cytostatics, diabetes treatments, antipsychotics, since when taken simultaneously, the risk of side effects mutually increases.

Use during pregnancy and breastfeeding

Pregnancy

Prestarium® A is contraindicated for use during pregnancy (see “Contraindications”).

Prestarium® A should not be used in the first trimester of pregnancy. If you are planning pregnancy or if it occurs while using the drug Prestarium® A, you should immediately stop taking the drug and, if necessary, prescribe other antihypertensive therapy with a proven safety profile for use during pregnancy.

It is known that the effect of ACE inhibitors on the fetus in the second and third trimesters of pregnancy can lead to disruption of its development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

If the patient received ACE inhibitors during the second or third trimester of pregnancy, it is recommended to conduct an ultrasound examination of the newborn to assess the condition of the skull bones and renal function.

Breastfeeding period

It is not known whether perindopril passes into breast milk. Therefore, the use of Prestarium® A during breastfeeding is not recommended. If the use of the drug is necessary during lactation, then breastfeeding should be discontinued.

Fertility

Preclinical studies have shown no effect of perindopril on reproductive function in rats of both sexes.