Perindopril-Richter

Perindopril-Richter is an antihypertensive drug; the active ingredient is perindopril, which inhibits the action of angiotensin-converting enzyme, which is a catalyst for the conversion of angiotensin-1 to angiotensin-2 (peptide component), which has a vasoconstrictor effect. As a result, its stimulating effect on adrenal secretion of aldosterone is blocked.

Perindopril exhibits therapeutic activity due to the metabolic component perindoprilat. Other metabolic products do not inhibit the action of ACE in vitro. [ 1 ]

Indications Perindopril-Richter

It is used to treat the following disorders:

• increased blood pressure;
• CH (to increase survival, reduce the need for hospitalization and delay the progression of the pathology);
• prevention of recurrence of ischemic stroke in individuals with cerebrovascular forms of disease;
• prevention of complications associated with the functioning of the cardiovascular system in people with stable (diagnosed) coronary artery disease.

Release form

The medicinal substance is released in tablet form (volume 4 or 8 mg), 10 pieces inside a cell plate. Inside the box - 3 such plates.

Pharmacodynamics

Perindopril slows the action of ACE, which converts angiotensin-1 to angiotensin-2.

The ACE element (or kininase 2) is an exopeptidase that facilitates the transformation of angiotensin-1 into the vasoconstrictor component angiotensin-2, and in addition, the destruction of bradykinin (which has a vasodilating effect) to an inactive heptapeptide. Slowing down the action of ACE causes a decrease in plasma angiotensin-2 levels, which results in an increase in plasma renin activity (the principle of "negative feedback") and a decrease in the volume of aldosterone released. [ 2 ]

Due to the inactivation of bradykinin under the influence of ACE, when the latter is suppressed, an increase in the activity of the tissue and circulating kallikrein-kinin structure is observed; along with this, the activation of the PG system is also carried out. There is an assumption that this effect is an integral part of the developing hypotensive effect of ACE inhibitors and the appearance of individual negative symptoms characteristic of this class of drugs (for example, cough). [ 3 ]

Elevated blood pressure values.

Perindopril demonstrates high efficiency in the treatment of elevated blood pressure of any intensity. When used, it reduces the level of diastolic and systolic blood pressure (with the patient in vertical and horizontal positions).

Perindopril reduces the severity of OPSS, resulting in a decrease in blood pressure; at the same time, the peripheral blood circulation rate increases (without changing heart rate values).

Often the drug increases the rate of renal blood flow, while the rate of CF remains unchanged.

The hypotensive effect of Perindopril-Richter reaches its peak level after 4-6 hours from the moment of a single oral administration and lasts for 24 hours. After 24 hours, there is a significant (approximately 87-100%) residual slowing of the ACE action.

A decrease in blood pressure values is observed quite quickly. In individuals with a positive response to therapy, these values stabilize after a month, remaining without the appearance of tachyphylaxis.

After completion of therapy, there is no rebound reaction.

Perindopril exhibits a vasodilating effect, helping to restore the elasticity of large arteries, as well as the structure of the vascular membranes of small arteries. At the same time, the drug reduces left ventricular hypertrophy.

Use in combination with thiazide-type diuretics potentiates the intensity of the hypotensive effect. At the same time, the combination of ACE inhibitors with a thiazide diuretic reduces the likelihood of hypokalemia associated with the administration of diuretic drugs.

Taking medication for CHF.

The drug stabilizes cardiac function by reducing post- and preload relative to the heart. In individuals with CHF who took perindopril, the following is noted:

• decrease in the level of filling pressure inside the right and left ventricles of the heart;
• decrease in the intensity of OPSS;
• increase in cardiac index and cardiac output.

It was found that the change in blood pressure values with the first use of the drug in a 2.5 mg dose in people with CHF (grades 2-3 according to the NYHA registry), according to statistics, was the same as in the placebo group.

Cerebrovascular pathologies.

In people with a history of cerebrovascular diseases, active use of the drug for a period of 4 years (monotherapy or combination with indapamide), supplementing standard treatment, led to a decrease in blood pressure (diastolic and systolic). In addition, there was a significant decrease in the likelihood of fatal or disabling strokes, major complications associated with the cardiovascular system (including myocardial infarction, which can also lead to death), dementia due to stroke, and in addition to this, a significant deterioration in cognitive activity.

The above effects were observed in individuals with elevated blood pressure and normal blood pressure, regardless of gender and age, as well as the type of stroke and the absence/presence of diabetes.

Stable form of coronary heart disease.

In people with a stable type of coronary heart disease, administration of the drug at a dosage of 8 mg per day over a 4-year period caused a significant decrease in the absolute probability of complications (death from cardiovascular diseases, non-fatal myocardial infarction, or cardiac arrest with successful resuscitation) by 1.9%.

In individuals who had previously had a myocardial infarction or undergone revascularization, the absolute probability reduction was 2.2% compared with the placebo category.

Pharmacokinetics

Absorption.

After oral administration, perindopril is rapidly absorbed in the gastrointestinal tract, reaching plasma levels of Cmax after 1 hour. The plasma half-life is 1 hour. Perindopril does not exhibit medicinal activity.

About 27% of the total volume of the absorbed substance penetrates into the circulatory system in the form of the active metabolic element perindoprilat. In addition to perindoprilat, 5 more metabolic components are formed that do not have medicinal activity.

The plasma Cmax of perindoprilat is observed after 3-4 hours from the moment of oral administration. Eating food reduces the rate of transformation of perindopril into perindoprilat, which changes the bioavailability value. Because of this, the drug should be taken orally once a day, in the morning, before breakfast.

It was found that the drug dosage size and its plasma level have a linear relationship.

Distribution processes.

The distribution volumes of free perindoprilat are approximately 0.2 l/kg. Among proteins, the substance is synthesized mainly with ACE - equals 20% and depends on the size of the drug portion.

Excretion.

Perindoprilat is excreted via the kidneys, with a terminal half-life of the free fraction of approximately 17 hours; thus, steady-state drug levels are observed after 4 days.

Pharmacokinetic parameters in specific patient categories.

In elderly people and people with renal insufficiency or CHF, the excretion of perindoprilat is slowed. The dialysis clearance of perindoprilat is 70 ml/min.

In patients with liver cirrhosis, the intrahepatic clearance of perindopril is reduced by half. However, the total volume of perindoprilat formed does not change, so the dosage regimen does not need to be adjusted.

Dosing and administration

Perindopril-Richter is taken once a day, orally (recommended in the morning, before meals). The initial dosage is 2-4 mg, and the maintenance dosage is 8 mg.

• Application for children

Perindopril-Richter is prohibited for use in pediatrics.

Use Perindopril-Richter during pregnancy

The medication is not used when planning conception, pregnancy, or during breastfeeding.

Contraindications

It is contraindicated to use the medicine in case of intolerance to its components.

Caution is required in the following cases:

• hereditary or idiopathic type of Quincke's edema;
• allergy to other medications from the ACE inhibitor subgroup;
• Quincke's edema that developed after taking medications (in anamnesis);
• aortic stenosis;
• cardio- or cerebrovascular pathologies (including insufficiency of cerebral blood flow processes, coronary heart disease and coronary insufficiency);
• narrowing of the arteries of both kidneys (bilateral stenosis) or stenosis affecting the artery of a single kidney, as well as the condition after kidney transplantation;
• severe stages of autoimmune collagenoses (scleroderma or SLE);
• suppression of hematopoietic processes within the bone marrow associated with the administration of immunosuppressants;
• diabetes mellitus;
• CRF (especially when combined with hyperkalemia);
• conditions against which a decrease in circulating blood volume is observed;
• old age.

Side effects Perindopril-Richter

The following side effects may be observed:

• decreased blood pressure, fatigue, headaches, fainting, dizziness;
• nausea, xerostomia, glossitis, diarrhea, abdominal pain, dysfunction of taste buds;
• muscle spasms, myalgia, vasculitis, arthritis or arthralgia;
• dry cough, bronchial spasm, itching, rashes, hyperhidrosis, urticaria, psoriasis, Quincke's edema, erythema multiforme, alopecia, photosensitivity and dermatitis of allergic origin;
• anemia, agranulocytosis, thrombocyto- or leukopenia;
• cholestatic jaundice, increased liver transaminase levels, urea, plasma creatinine, cholestatic or hepatocellular hepatitis, liver failure and pancreatitis;
• sinusitis, bronchitis, runny nose, change in voice timbre, pneumonia or eosinophilic alveolitis;
• proteinuria, anuria or oliguria, and renal dysfunction;
• tachycardia, orthostatic symptoms, palpitations, fever and arrhythmia;
• impotence or gynecomastia.

Overdose

Signs of poisoning include: agitation, decreased blood pressure, shock and anxiety, vascular insufficiency, fainting and bradycardia, as well as dizziness, cough, renal/liver failure, arrhythmia, salt imbalance and hyperventilation.

It is necessary to perform procedures that allow the drug to be excreted from the body (gastric lavage and use of enterosorbents). The patient must be placed in a horizontal position. Excretion can be performed through dialysis.

Interactions with other drugs

The likelihood of hyperkalemia increases in the case of combined use of drugs with other substances that can provoke this disorder: potassium salts or potassium-sparing diuretics, aliskiren, as well as aliskiren-containing agents, heparin, trimethoprim, ACE inhibitors, NSAIDs, angiotensin-2 reuptake inhibitors and immunosuppressants (including tacrolimus or cyclosporine).

Administration together with aliskiren in diabetics or individuals with renal dysfunction (SCF <60 ml/min) increases the likelihood of hyperkalemia, decreased renal function and an increased incidence of cardiovascular diseases and mortality from them (in individuals from these categories, such a combination is prohibited).

Literary sources report that in individuals with diagnosed atherosclerotic pathology, heart failure or diabetes mellitus, which are accompanied by damage in the area of target organs, the introduction of ACE inhibitors together with angiotensin-2 terminals leads to an increased frequency of fainting, hypotension, hyperkalemia and weakening of renal function (this includes acute renal failure) compared to the use of only one drug that acts on the RAAS. Dual-type blockade (for example, when combining an ACE inhibitor with an angiotensin-2 terminal antagonist) should be limited to individual situations when careful monitoring of renal function and blood pressure and potassium levels is performed.

Use together with estramustine may increase the likelihood of side effects (including Quincke's edema).

Combination of the drug with lithium substances may reversibly increase serum lithium levels and the resulting toxic symptoms (therefore, such a compound is not used).

Administration together with antidiabetic drugs (oral hypoglycemic drugs and insulin) should be done with extreme caution, since ACE inhibitors, including perindopril, can potentiate the antidiabetic activity of these drugs, up to the occurrence of hypoglycemia. Usually, such an effect develops during the first weeks of combined treatment in individuals with renal dysfunction.

Baclofen potentiates the hypotensive effect of the drug; in the case of such a combination of drugs, it may be necessary to adjust the dose of the latter.

In individuals using diuretics (especially those that excrete salts or fluid), a strong decrease in blood pressure values is possible at the initial stage of treatment with Perindopril-Richter (this risk can be reduced by discontinuing the diuretic and replenishing the loss of salts or fluid before starting to use the drug). In addition, a method can be used with the introduction of perindopril in a small initial portion with its subsequent gradual increase.

In case of CHF, when using diuretics, the drug is administered in a low dose, possibly after reducing the potassium-sparing diuretic administered in combination. With any scheme, during the first weeks of using ACE inhibitors, it is necessary to monitor renal function (creatinine level).

Use of spironolactone or eplerenone in doses of 12.5-50 mg per day, as well as ACE inhibitors (including perindopril) in low doses.

In case of treatment of HF functional type 2-4 according to NYHA rating with left ventricular ejection fraction <40%, as well as previously used ACE inhibitors and loop diuretics, there is a risk of hyperkalemia (fatal outcome is possible), especially if the instructions regarding this combination are not followed. Before starting to use this combination, it is necessary to make sure that the patient does not have renal dysfunction and hyperkalemia. It is necessary to constantly monitor blood potassium and creatinine levels - every week during the 1st month of therapy, and then every month.

The use of the drug in combination with NSAIDs (aspirin in a dosage that has anti-inflammatory activity, non-selective NSAIDs and substances that inhibit the action of COX-2) can provoke a decrease in the hypotensive activity of ACE inhibitors.

The use of ACE inhibitors in combination with NSAIDs causes deterioration of renal function (e.g., acute renal failure) and an increase in serum potassium levels, especially in individuals with impaired renal function. This combination should be used with caution in the elderly. Patients should consume sufficient fluids; renal function should be closely monitored (at the beginning of therapy and later in the course of therapy).

The antihypertensive effect of perindopril is potentiated in case of combined use with other antihypertensive drugs and vasodilators (including nitrates with prolonged and short-acting effects).

The use of ACE inhibitors in combination with gliptins (saxagliptin with linagliptin, vitagliptin and sitagliptin) increases the likelihood of developing angioedema due to gliptin's inhibition of dipeptidyl peptidase-4 activity.

Taking the medication with antipsychotics, tricyclics and general anesthetics may cause potentiation of the hypotensive effect.

The administration of sympathomimetics may reduce the hypotensive activity of Perindopril-Richter.

The use of ACE inhibitors in people who receive intravenous gold substances (such as sodium aurothiomalate) causes the development of a symptom complex, which includes vomiting, facial hyperemia, decreased blood pressure, and nausea.

Storage conditions

Perindopril-Richter must be stored at temperatures between 15-30°C.

Shelf life

Perindopril-Richter can be used for a period of 36 months from the date of sale of the therapeutic agent.

Analogues

The analogs of the drug are the medications Viacoram, Kosirel and Amlessa with Bi-Prestarium, and also Coverex, Peristar with Amlodipine + Perindopril, Parnavel and Amlopress. In addition, the list includes Perlicor, Noliprel and Arentopress, Perinpress with Co-Prenessa, Erupnil and Hypernik with Ordilat, as well as Hiten and Piristar.