Prestarium A, dispersible tablets 5 mg, 30 pcs.

Prestarium A

Use during pregnancy and breastfeeding

Prestarium® A is contraindicated for use during pregnancy.
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 alternative 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 in 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 kidney function.

It is not known whether perindopril is excreted in breast milk, therefore the use of Prestarium® A during lactation (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.

Use for liver dysfunction

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 no changes in the dose of the drug are required.

When prescribing the drug to patients with impaired liver function, no dose changes are required.

Use for renal impairment

The drug should be used with caution in cases of bilateral renal artery stenosis or the presence of only one functioning kidney; renal failure.

There are no data on the use of Prestarium® A in patients after kidney transplantation.

If renal function is impaired, the dose of Prestarium® A should be selected taking into account the degree of renal failure and under regular monitoring of potassium and QC levels.

* dialysis clearance of perindoprilate: 70 ml/min. The drug should be taken after the dialysis procedure.

Use in children

The use of the drug is contraindicated in patients under the age of 18 years (the effectiveness and safety of use have not been established).

Use in elderly patients

For arterial hypertension in elderly patients, treatment should begin with a dose of 2.5 mg/day. If necessary, a month after the start of therapy, the dose can be increased to 5 mg/day, and then to a maximum dose of 10 mg/day, taking into account the state of renal function.

For coronary artery disease, to reduce the risk of cardiovascular complications in patients who have previously suffered a myocardial infarction and/or coronary revascularization, elderly patients should begin therapy with a dose of 2.5 mg 1 time / day for 1 week, then 5 mg 1 time / day in over the next week. Then, taking into account the state of renal function, the dose can be increased to 10 mg 1 time / day (see table). The dose of the drug can be increased only if it is well tolerated at the previously recommended dose.

special instructions

IHD: reducing the risk of cardiovascular complications in patients who have previously had myocardial infarction and/or coronary revascularization

In patients with coronary artery disease, if an episode of unstable angina occurs during the first month of therapy with Prestarium® A, the benefits and risks should be assessed before continuing treatment.

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients with uncomplicated arterial hypertension. The risk of an excessive decrease in blood pressure is increased in patients with reduced blood volume, which can be observed during therapy with diuretics, while following a strict salt-free diet, hemodialysis, vomiting and diarrhea, as well as in patients with severe arterial hypertension with high renin activity. In patients at increased risk of developing symptomatic hypotension, blood pressure, renal function, and serum potassium levels should be carefully monitored during therapy with Prestarium® A. A similar approach is also used in patients with coronary artery disease or cerebrovascular disease, in whom severe hypotension may lead to to the development of myocardial infarction or cerebrovascular complications.

If arterial hypotension develops, the patient should be placed in a horizontal position with a low headboard. If necessary, the blood volume should be replenished using intravenous administration of saline. Transient arterial hypotension is not an obstacle to further use of the drug. After restoration of blood volume and blood pressure, treatment can be continued.

In some patients with chronic heart failure and normal or low blood pressure, Prestarium® A may cause an additional decrease in blood pressure. This effect is predictable and does not usually require discontinuation of therapy. If symptoms of a pronounced decrease in blood pressure appear, the dose of the drug should be reduced or discontinued.

Mitral stenosis/aortic stenosis/hypertrophic obstructive cardiomyopathy

Prestarium® A, like other ACE inhibitors, should be prescribed with caution to patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as to patients with mitral stenosis.

Renal dysfunction

In patients with renal failure (creatinine clearance <60 ml/min), the initial dose of Prestarium® A should be adjusted depending on the clearance value and then depending on the therapeutic effect. For such patients, regular monitoring of serum creatinine and potassium concentrations is necessary.

Hypotension, which sometimes develops when initiating ACE inhibitors in patients with symptomatic chronic heart failure, can lead to deterioration of renal function. Acute renal failure may develop, usually reversible.

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney (especially in the presence of renal failure), during therapy with ACE inhibitors, there may be an increase in the concentration of urea and creatinine in the blood serum, which usually resolves when therapy is discontinued. The additional presence of renovascular hypertension causes an increased risk of severe hypotension and renal failure in such patients. Treatment of such patients begins under close medical supervision using low doses of the drug and further adequate selection of doses. Treatment with diuretics should be temporarily discontinued and plasma potassium and creatinine levels should be regularly monitored during the first few weeks of therapy.

In some patients with arterial hypertension without indication of pre-existing renal vascular disease, serum urea and creatinine concentrations may increase, especially with simultaneous use of diuretics. These changes are usually mild and reversible. The likelihood of developing these disorders is higher in patients with a history of renal failure. In such cases, it may be necessary to discontinue or reduce the dose of Prestarium® A and/or the diuretic.

Hemodialysis

In patients undergoing hemodialysis using high-flux membranes (eg, AN69®), several cases of persistent, life-threatening anaphylactic reactions have been reported during therapy with ACE inhibitors. Prescription of ACE inhibitors should be avoided when using this type of membrane.

Kidney transplant

There are no data on the use of Prestarium® A in patients after kidney transplantation.

Hypersensitivity/angioedema

When using ACE inhibitors, incl. perindopril, in rare cases and during any period of therapy, the development of angioedema of the face, upper and lower extremities, lips, mucous membranes, tongue, vocal folds and/or larynx may be observed. If symptoms appear, use of the drug should be stopped immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. When such symptoms appear, emergency treatment is required, incl. subcutaneous administration of epinephrine (adrenaline) and/or ensuring airway patency. The patient should be under medical supervision until symptoms disappear completely and permanently.

Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group.

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal levels of C1-esterase. The diagnosis was made using abdominal computed tomography, ultrasound, or surgery. Symptoms disappeared after stopping the ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

Anaphylactoid reactions during LDL apheresis

In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.

Anaphylactoid reactions during desensitization

There are isolated reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitization therapy, such as hymenoptera venom. ACE inhibitors should be used with caution in patients susceptible to allergic reactions undergoing desensitization procedures. The use of ACE inhibitors should be avoided in patients receiving bee venom immunotherapy. However, this reaction can be avoided by temporarily discontinuing the ACE inhibitor before starting the desensitization procedure.

Liver dysfunction

In rare cases, during the use of ACE inhibitors, a syndrome of development of cholestatic jaundice with transition to fulminant liver necrosis, sometimes with death, was observed. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of liver enzymes occurs during the use of ACE inhibitors, the drug should be stopped and the patient should be under appropriate medical supervision.

Neutropenia/agranulocytosis/thrombocytopenia/anemia

Neutropenia/agranulocytosis, thrombocytopenia and anemia may occur during the use of ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. Prestarium® A should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function.

Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing Prestarium® A in such patients, it is recommended to periodically monitor the level of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.

Ethnic differences

It should be taken into account that patients of the Negroid race have a higher risk of developing angioedema. Like other ACE inhibitors, perindopril is less effective as an antihypertensive agent in black patients. This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.

Cough

During therapy with an ACE inhibitor, a persistent dry cough may occur, which stops after discontinuation of the drug. This should be taken into account when carrying out the differential diagnosis of cough.

Surgery/general anesthesia

The use of ACE inhibitors in patients whose condition requires surgery and/or general anesthesia may lead to an excessive decrease in blood pressure, especially when using drugs for general anesthesia that have an antihypertensive effect. Taking Prestarium® A should be stopped one day before surgery. If arterial hypotension develops, blood pressure should be maintained by replenishing blood volume. It is necessary to warn the surgeon/anesthesiologist that the patient is taking ACE inhibitors.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, incl. perindopril. Risk factors for hyperkalemia are renal failure, decreased renal function, age over 70 years, diabetes mellitus, some concomitant conditions (dehydration, acute heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride) , potassium supplements/preparations or potassium-containing table salt substitutes, as well as the use of other drugs that increase potassium levels in the blood (for example, heparin). The use of potassium supplements/preparations, potassium-sparing diuretics, and potassium-containing table salt substitutes can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function. Hyperkalemia can cause serious, sometimes fatal, abnormal heart rhythms. If simultaneous use of Prestarium® A and the above drugs is necessary, treatment should be carried out with caution against the background of regular monitoring of potassium levels in the blood serum.

Patients with diabetes mellitus

When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic drugs for oral administration or insulin, during the first month of therapy it is necessary to regularly monitor the concentration of glucose in the blood.

Lithium preparations

The simultaneous use of Prestarium® A and lithium preparations is not recommended.

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

The simultaneous administration of Prestarium® A and potassium-sparing diuretics, as well as potassium preparations, potassium-containing table salt substitutes and food additives is not recommended.

Double blockade of the RAAS

Cases of hypotension, syncope, stroke, hyperkalemia and renal dysfunction (including acute renal failure) have been reported in susceptible patients, especially when used concomitantly with drugs that affect this system. Therefore, dual blockade of the RAAS by combining an ACE inhibitor with an angiotensin II receptor antagonist or aliskiren is not recommended.

Combination with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (GFR <60 ml/min/1.73 m2).

Impact on the ability to drive vehicles and operate machinery

Prestarium® A should be prescribed with caution to patients driving vehicles and engaging in activities that require increased concentration and speed of psychomotor reactions, due to the risk of developing arterial hypotension and dizziness.

It is known that the level of blood pressure in the morning upon awakening, according to 24-hour monitoring, is a more significant risk factor for serious cardiovascular complications than the level of blood pressure at any other time of the day or the average blood pressure values ​​per day. However, there have never been any well-designed studies that directly compared the effect of antihypertensive therapy depending on the timing of its administration.

In addition, the prescription of antihypertensive drugs before bedtime has a certain pathophysiological justification: for example, it is known that the activity of the RAAS is maximum at night.

The European Heart Journal published the results of an open-label, prospective study of Hygia Chronotherapy conducted in primary care clinics in Spain.

The study included 19,084 patients with arterial hypertension, the course of which allowed a single dose of antihypertensive drugs (both monotherapy and combinations). Patients were divided into 2 groups: taking standard medications in the morning or taking the same medications before bed. It was allowed to take small doses of diuretics (hypothiazide no more than 25 mg). It was assumed that such a dose of diuretics would not disturb the patients' sleep at night. At each visit (at least once a year), two-day blood pressure monitoring was carried out, and adverse events were recorded. The average follow-up duration was 6 years.

It turned out that in the group taking antihypertensive drugs before bedtime, daytime blood pressure was slightly lower, and patients were less likely to be classified as non-dippers. In addition, it turned out that such a regimen of taking antihypertensive drugs was associated with a decrease in the incidence of the combined endpoint of cardiovascular death/MI/coronary revascularization/CHF/stroke. After adjustment for major risk factors, the OR was 0.55 (95% CI 0.50–0.61), P < 0.001. -=»» 0=»» 44=»» 34=»» 56=»» p=»»>Such impressive results are difficult to explain solely by a decrease in blood pressure, since the differences in the degree of blood pressure reduction with the standard therapy group were quite modest. Perhaps there were some pleiotropic effects that normalized circadian rhythms in the functioning of the cardiovascular system.

Of course, randomized placebo-controlled studies are required to confirm the results obtained.

Based on materials:

Ramon C Hermida, et al. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial, European Heart Journal, ehz754, https://doi.org/

Text: Ph.D. Shakhmatova O.O.