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Prestilol tabs 5mg + 5mg #30

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  • $29.50
  • 3 or more $29.28
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Prestilol instructionYou can buy Prestilol hereCompositionactive ingredients: bisoprolol fumarate / perindopril arginine;Prestilol 5 mg / 5 mg1 tablet contains 5 mg of bisoprolol fumarate (which corresponds to 4.24 mg of bisoprolo..

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Prestilol instruction

You can buy Prestilol here

Composition

active ingredients: bisoprolol fumarate / perindopril arginine;
Prestilol 5 mg / 5 mg
1 tablet contains 5 mg of bisoprolol fumarate (which corresponds to 4.24 mg of bisoprolol) and 5 mg of perindopril arginine (which corresponds to 3.395 mg of perindopril)
Prestilol 5 mg / 10 mg
1 tablet contains 5 mg of bisoprolol fumarate (which corresponds to 4.24 mg of bisoprolol) and 10 mg of perindopril arginine (which corresponds to 6.790 mg of perindopril)
Prestilol 10 mg / 5 mg
1 tablet contains 10 mg of bisoprolol fumarate (which corresponds to 8.49 mg of bisoprolol) and 5 mg of perindopril arginine (which corresponds to 3.395 mg of perindopril)
Prestilol 10 mg / 10 mg
1 tablet contains 10 mg of bisoprolol fumarate (which corresponds to 8.49 mg of bisoprolol) and 10 mg of perindopril arginine (which corresponds to 6.790 mg of perindopril)
Excipients: microcrystalline cellulose (type 102), calcium carbonate, corn starch (maize), sodium starch (type A), colloidal silicon dioxide, magnesium stearate (E 470b), croscarmellose sodium;
film shell: glycerin (E 422), hypromellose (E 464), macrogol 6000, magnesium stearate (E 470b), titanium dioxide (E 171), ferric oxide yellow (E172), ferric oxide red (E 172).
Dosage Form
Tablets, film coated.

Main physical and chemical properties

Prestilol 5 mg / 5 mg pink-beige color, oblong tablet-coated, with a notch and embossed "" on one side and "5/5" - on the other. The tablet is to be divided into two parts.
Prestilol 5 mg / 10 mg is pink-beige, oblong-shaped tablet, coated, with a notch and embossed "" on one side and "5/10" - on the other. The tablet is to be divided into two parts.
Prestilol 10 mg / 5 mg is pink-beige, a round tablet-coated with an embossed “” on one side and “10/5” on the other.
Prestilol 10 mg / 10 mg is pink-beige, oblong tablet coated with embossed “” on one side and “10/10” - on the other.

Mechanism of action

bisoprolol

Bisoprolol is a highly selective blocker of β 1 -adrenoreceptors, it has no internal sympathomimetic and pronounced membrane stabilizing activity. It has a low affinity for the β 2 receptors of the smooth muscles of the bronchi and blood vessels, as well as the β 2 receptors responsible for the regulation of metabolism. Therefore, bisoprolol in general should not affect airway resistance and β 2 mediated metabolic effects. Its β 1 selectivity extends beyond therapeutic dosing.

perindopril

Perindopril is an enzyme inhibitor that converts angiotensin I to angiotensin II (ACE). The transformative enzyme, or kinase, is exopeptidase, which makes it possible to convert angiotensin I into vasoconstrictor angiotensin II, and also causes the breakdown of the bradykinin vasodilator to inactive heptapeptide. Inhibition of ACE leads to a decrease in plasma angiotensin II concentration, which increases renin activity in blood plasma (by inhibiting negative feedback from renin release) and reduces aldosterone secretion. Since ACE inactivates bradykinin, inhibiting ACE also leads to an increase in the activity of the circulating and local kallikrein-kinin systems (and, thus, also leads to activation of the prostaglandin system). This mechanism of action leads to a decrease in blood pressure by ACE inhibitors and is partly responsible for the appearance of some side effects (for example, cough).
Perindopril acts through its active metabolite, perindoprilat. Other metabolites show no activity in suppressing ACE in vitro.

pharmacodynamic effects

bisoprolol

Bisoprolol does not have a pronounced negative inotropic effect. The maximum effect of bisoprolol is achieved in 3-4 hours after application. Due to its half-life of 10–12 hours, bisoprolol retains a therapeutic effect for 24 hours. The maximum antihypertensive effect of bisoprolol is usually achieved after two weeks of use.
With a single use in patients with ischemic heart disease without chronic heart failure, bisoprolol reduces heart rate and stroke volume and, thus, reduces cardiac output and oxygen consumption. With prolonged use, initially increased peripheral resistance is reduced. A decrease in plasma renin activity is likely to cause the antihypertensive effect of β-blockers.
Bisoprolol reduces the sympathoadrenergic reaction by blocking the heart's β-adrenoreceptors, which leads to a decrease in heart rate and contractility. This, in turn, leads to a decrease in myocardial oxygen consumption, which is necessary in the treatment of angina pectoris in ischemic heart disease.

perindopril

Perindopril effectively reduces blood pressure in all degrees of hypertension (mild, moderate and severe) a decrease in systolic and diastolic blood pressure is observed in a patient in the supine or standing position.
Perindopril reduces the resistance of peripheral vessels, which leads to a decrease in blood pressure. As a result, peripheral blood flow increases without affecting the heart rate.
As a rule, the renal blood flow also increases, while the glomerular filtration rate (GFR) usually does not change.
The maximum antihypertensive effect develops 4-6 hours after a single dose and lasts for at least 24 hours: the residual effect is about 87-100% of the peak effect.
Blood pressure drops rapidly. In patients who responded to treatment, normalization of blood pressure occurs within a month and is maintained without the occurrence of tachyphylaxis. Termination of treatment is not accompanied by a cancellation effect. Perindopril reduces left ventricular hypertrophy.
Clinical studies have shown that perindopril has vasodilating properties. It improves the elasticity of large arteries and reduces the ratio of wall thickness to the vessel lumen for small arteries.
Perindopril reduces the work of the heart by reducing the pre- and afterload on the heart: it reduces the filling pressure of the left and right ventricles, decreases the total peripheral vascular resistance, increases cardiac output and improves the cardiac index (according to studies).

Pharmacokinetics

The rate and extent of absorption of bisoprolol and perindopril in the composition of the preparation Prestilol do not significantly differ from the rate and extent of absorption of bisoprolol and perindopril when they are used separately as monotherapy.

bisoprolol

absorption
Bisoprolol is almost completely (> 90%) absorbed from the gastrointestinal tract. The effect of the first passage through the liver is insignificant (about 10%), which leads to a high bioavailability (about 90%) after oral administration.
distribution
The volume of distribution is 3.5 l / kg. Binding of bisoprolol to plasma proteins is about 30%.
Metabolism and excretion
Bisoprolol is eliminated from the body in two ways. 50% is metabolized in the liver to inactive metabolites, which are then excreted by the kidneys, and the remaining 50% are excreted by the kidneys unchanged. Total clearance is approximately 15 l / h. The half-life of plasma is 10-12 hours, which leads to a 24-hour effect after taking once a day.
Special patient groups
The kinetics of bisoprolol is linear and does not depend on age.
Since the removal of bisoprolol from the body is carried out equally by the kidneys and liver, dose adjustment is not required in patients with impaired liver function or renal failure. Pharmacokinetics in patients with chronic heart failure and with impaired liver or kidney function has not been studied. In patients with chronic heart failure (NYHA functional class III), plasma plasma bisoprolol is higher and the elimination half-life is longer compared with healthy volunteers. With a daily dose of 10 mg, the maximum plasma concentration in the equilibrium state is 64 ± 21 ng / ml, and the half-life is 17 ± 5:00.

perindopril

absorption
After taking perindopril is rapidly absorbed, the maximum concentration is reached after 1:00. The half-life of perindopril from blood plasma is 1:00.
distribution
The volume of distribution of unbound perindoprilat is approximately 0.2 l / kg. The binding of perindoprilat to plasma proteins is 20%, mainly from the angiotensin-converting enzyme, and is dose-dependent.
Metabolism
Perindopril refers to prodrugs. 27% of the dose of perindopril in the form of the active metabolite of perindoprilat enters the bloodstream. In addition to active perindoprilat, perindopril forms 5 more inactive metabolites. The maximum concentration of perindoprilat in the blood plasma is reached in 3-4 hours.
Since food intake reduces the conversion of perindopril to perindoprilat and, consequently, its bioavailability decreases, perindopril arginine is recommended to be taken orally in a single dose in the morning before a meal.
conclusion
Perindoprilat is excreted in the urine, the final half-life of the unbound fraction is approximately 17 hours. The state of equilibrium is reached after 4 days.
linearity
There is a linear relationship between the dose of perindopril and its concentration in the blood plasma.
Special patient groups
Withdrawal of perindoprilat is slowed down in elderly patients, as well as in patients with heart or kidney failure. It is recommended to select the dose for patients with renal insufficiency, taking into account the degree of renal failure (CC). The dialysis clearance of perindoprilat is 70 ml / min. The kinetics of perindopril changes in patients with cirrhosis of the liver, the hepatic clearance of the main molecule is halved. However, the amount of perindoprilat formed does not decrease. Therefore, such patients do not need to adjust the dose (see
Sections "Dosage and Administration" and "Features of the application").


Indications for Prestilol

Prestilol 5 mg / 10 mg and Prestilol 10 mg / 10 mg are indicated for the treatment of arterial hypertension and / or stable coronary heart disease (with a history of myocardial infarction and / or revascularization) in adult patients who require bisoprolol and perindopril in doses available in fixed combination.
Prestilol 5 mg / 5 mg and Prestilol 10 mg / 5 mg are indicated for the treatment of arterial hypertension and / or stable coronary heart disease (with a history of myocardial infarction and / or revascularization) and / or stable chronic heart failure with reduced systolic function left ventricular in adult patients who require therapy with bisoprolol and perindopril at a dose available in a fixed combination.

Contraindications

    Hypersensitivity to the active substances or to any of the excipients or to any other ACE inhibitors;
    acute heart failure or heart failure in the decompensation stage, which requires intravenous inotropic therapy
    cardiogenic shock
    II or III degree blockade (without artificial pacemaker)
    sick sinus syndrome;
    sinoatrial blockade
    symptomatic bradycardia
    symptomatic hypotension
    severe bronchial asthma or severe chronic obstructive pulmonary disease;
    severe obliterating diseases of peripheral arteries or severe Raynaud syndrome
    untreated pheochromocytoma (see section “Peculiarities of use”);
    metabolic acidosis,
    history of angioedema associated with previous therapy with ACE inhibitors
    hereditary or idiopathic angioedema
    pregnancy or pregnancy planning (see section “Use during pregnancy or lactation”);
    simultaneous use with drugs containing aliskiren in patients with diabetes mellitus or renal failure (GFR

Interaction with other drugs and other types of interactions

In a study of the interaction conducted with the participation of healthy volunteers, the interaction between bisoprolol and perindopril was not found. Information about the interaction with other drugs of each of the active ingredients are listed below.
Drugs that cause hyperkalemia. Some drugs (therapeutic classes of drugs) may increase the risk of hyperkalemia, namely: aliskiren, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs (NSAIDs), heparin, immunosuppressants, such as cyclospheric pulses; trimethoprim. Simultaneous use of these drugs increases the risk of hyperkalemia.
Simultaneous use is contraindicated (see "Contraindications")
Aliskiren. The simultaneous use of the drug Prestilol and aliskiren in patients with diabetes mellitus or patients with impaired renal function is contraindicated because the risk of hyperkalemia and deterioration of renal function and cardiovascular morbidity and mortality increase.
Simultaneous use is not recommended.

Bisoprolol-related interactions

Centrally acting antihypertensive drugs such as clonidine and others (for example, methyldopa, moxonidine, rilmenidine). The simultaneous use of antihypertensive drugs with central action can lead to a worsening of the course of heart failure due to a decrease in central sympathetic tone (decrease in heart rate and cardiac output, vasodilation). The sudden discontinuation of therapy with β-blockers, in particular without prior dose reduction, may increase the risk of rebound hypertension.
Class I antiarrhythmic drugs (for example, quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone). It is possible to potentiate the effect on AV conduction time and enhance the negative inotropic effect.
Calcium antagonists of the verapamil group and, to a lesser extent, diltiazem. Negative effect on myocardial contractility and AV conduction. The introduction of verapamil to patients who use β-blockers can lead to significant arterial hypotension and AV blockade.

Interactions Associated with Perindopril

Aliskiren. In any other patients, as in diabetic patients or patients with impaired renal function, the risk of hyperkalemia, impaired renal function and cardiovascular morbidity and mortality increases.
The simultaneous use of ACE inhibitors and angiotensin receptor blockers. Data from clinical studies have shown that double blockade of renin-angiotensin- (RAAS) by the simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of adverse reactions such as hypotension, hyperkalemia and renal impairment (including acute renal failure) compared with with the use of a single drug that affects the RAAS (see
section "Contraindications"). Double blockade (i.e., a combination of an ACE inhibitor with angiotensin II receptor antagonists) can be applied in individual cases and under careful control of renal function, potassium levels, and blood pressure. The simultaneous use of ACE inhibitors and angiotensin II receptor blockers in patients with diabetic nephropathy is not recommended.
Estramustin. There is a risk of increased adverse reactions, in particular the occurrence of angioedema (angioedema).
Potassium-sparing diuretics (for example, triamterene, amiloride), potassium salts. The occurrence of hyperkalemia (possibly fatal), especially in patients with renal insufficiency (additive hyperkalemic effect). The aforementioned drugs are not recommended for simultaneous use with perindopril (see Section "Features of Use"). However, if the simultaneous administration of these substances is necessary, they should be used with caution and frequent monitoring of potassium in serum should be carried out. On the use of spironolactone in heart failure, see below.
Lithium. It was reported about a reversible increase in the concentration of lithium in the blood serum and an increase in its toxicity, while using it with ACE inhibitors. Simultaneous use of perindopril with lithium is not recommended. However, if such a combination is justified, the level of lithium concentration in blood serum should be carefully monitored (see Section “Peculiarities of Use”).

Simultaneous use that requires special attention

Interactions Associated with Bisoprolol and Perindopril
Antidiabetic agents (insulin, oral hypoglycemic agents). The results of epidemiological studies suggest that the simultaneous use of ACE inhibitors and antidiabetic agents (insulin, oral hypoglycemic agents) may lead to increased glucose-lowering effect with the risk of hypoglycemia. Most likely this phenomenon can occur in the first weeks of combined treatment and in the presence of renal failure. The simultaneous use of bisoprolol with insulin and oral hypoglycemic agents can lead to increased glucose-lowering effect. A blockade of β-adrenoreceptors may mask the symptoms of hypoglycemia.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin at a dose of ≥ 3 g / day. With simultaneous use of Prestilol with NSAIDs (such as acetylsalicylic acid in anti-inflammatory doses, inhibitors of COX-2 cyclooxygenase and non-selective NSAIDs), the antihypertensive effect of bisoprolol and perindopril may be reduced. In addition, the simultaneous use of ACE inhibitors and NSAIDs increases the risk of impaired renal function, including possible acute renal failure, and increases the level of potassium in the blood, especially in patients with a pre-established renal dysfunction. This combination should be prescribed with caution, especially in elderly patients. Patients need to restore the water balance and consider the control of renal function after the start of combination therapy and with further treatment.
Antihypertensive drugs and vasodilators. Concurrent use with antihypertensive drugs, vasodilators (for example, nitroglycerin, other nitrates, or other vasodilators) or with other drugs that can lower blood pressure (for example, tricyclic antidepressants, barbiturates, phenothiazines) may increase the risk of hypotensive effects of the adrenitis.
Tricyclic antidepressants / antipsychotics / anesthetics. The simultaneous use of ACE inhibitors and some anesthetics, tricyclic antidepressants and antipsychotics can lead to a further reduction in blood pressure. The simultaneous use of bisoprolol with anesthetics can lead to a weakened reflex tachycardia and an increased risk of arterial hypotension.
Sympathomimetics. β-sympathomimetics (for example, isoprenaline, dobutamine): simultaneous use with bisoprolol can reduce the effects of both drugs. Sympathomimetics that activate α- and β-adrenergic receptors (for example, norepinephrine, epinephrine): a combination with bisoprolol may reveal the vasoconstrictor effects mediated through α-adrenergic receptors of these drugs, will increase blood pressure and exacerbate intermittent claudication. Such interactions are more likely with non-selective β-blockers. Sympathomimetics can reduce the antihypertensive effects of ACE inhibitors.

Bisoprolol-related interactions

Calcium antagonists of the dihydropyridine type, such as felodipine and amlodipine. Simultaneous use may increase the risk of hypotension; An increased risk of further deterioration of the pumping function of the ventricles in patients with heart failure cannot be ruled out.
Class III antiarrhythmic drugs (for example, amiodarone). Possible to increase the effect on the time of AV conduction.
Parasympathomimetic drugs. Simultaneous use may increase AV conduction time and the risk of bradycardia.
ß-blockers of local action (for example, eye drops for the treatment of glaucoma). Simultaneous use may enhance the systemic effects of bisoprolol.
Digitalis glycosides. Decrease in heart rate, increase in AV conduction time.

Interactions Associated with Perindopril

Baclofen Enhances antihypertensive effect. Blood pressure should be monitored and dose adjustment should be performed if necessary.
Diuretics. In patients taking diuretics, and especially in the case of impaired water-electrolyte metabolism, an excessive decrease in blood pressure after the start of treatment with ACE inhibitors is possible. The likelihood of the development of a hypotensive effect is reduced if diuretic is canceled, an increase in circulating blood volume or salt intake before the start of therapy, which should be started with low doses with a gradual increase in doses of perindopril. In hypertension, when a pre-prescribed diuretic could cause water / electrolyte deficiency, it must be canceled before starting treatment with an ACE inhibitor (in such cases, diuretic therapy can be resumed over time) or treatment with an ACE inhibitor should start at low doses with a gradual increase in dose. In case of congestive heart failure in the presence of a diuretic, the use of an ACE inhibitor should be started with a low dose, probably after a dose reduction of a concomitant diuretic. In all cases, it is necessary to monitor kidney function (creatinine level) during the first weeks of treatment with an ACE inhibitor.
Potassium-sparing diuretics (eplerenone, spironolactone). The simultaneous use of eplerenone or spironolactone in doses of 12.5 mg to 50 mg per day with low doses of ACE inhibitors in the case of non-compliance with recommendations for the appointment of this combination there is a risk of hyperkalemia (possibly fatal) in the treatment of patients with heart failure II-IV class NYHA and an ejection fraction of <40% that were previously treated with ACE inhibitors and a loop diuretic. Before the appointment of such a combination, you should ensure that there is no hyperkalemia and renal failure. It is recommended to conduct thorough monitoring of kalemia and creatininemia weekly during the first month of treatment and monthly in the future.

Simultaneous use that requires attention

Bisoprolol-related interactions
Meflokhin. Increased risk of developing bradycardia.
MAO inhibitors (with the exception of MAO-B inhibitors). Strengthening the hypotensive effect of β-blockers and the risk of developing a hypertensive crisis.

Interactions Associated with Perindopril

Glyptin (linagliptin, saxagliptin, sitagliptin, vildagliptin). In patients who are destined to a combination of glyptin and an ACE inhibitor, the risk of an angioedema may increase due to the fact that gliptin reduces the activity of dipeptilpeptidase-IV (DPP-IV).
Gold. The simultaneous use of ACE inhibitors, including perindopril, and injectable preparations of gold (sodium aurothiomalate) can rarely cause reactions similar to those that occur with the use of nitrates (symptoms: facial flushing (tides), nausea, vomiting and hypotension).


Application features

All the warnings associated with each of the components of Prestilol relate to the drug Prestilol.
Hypotension. ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension is rarely observed in patients with uncomplicated hypertension and more likely in patients with hypovolemia, such as those taking diuretics, following a salt-restricted diet, in patients on dialysis, in patients with diarrhea or vomiting, or in patients with severe renino-hypertensive (see sections "Interaction with other drugs and other types of interactions" and "Adverse reactions"). Symptomatic arterial hypotension is more likely in patients with symptomatic heart failure, with or without concomitant renal failure. The occurrence of symptomatic hypotension is most likely in patients with more severe heart failure who take large doses of loop diuretics, have hyponatremia or renal insufficiency of a functional nature. Patients with an increased risk of developing symptomatic arterial hypotension at the beginning of therapy and at the dose selection stage should be closely monitored by a physician. These warnings also apply to patients with coronary heart disease or cerebrovascular diseases, in whom excessive lowering of blood pressure can lead to myocardial infarction or stroke. If arterial hypotension develops, the patient should be transferred to a horizontal position and, if necessary, intravenous sodium chloride solution 9 mg / ml (0.9%) should be administered intravenously. Transient hypotension is not a contraindication for the further use of Prestilol, which can usually be used without any obstacles after the restoration of circulating blood volume and an increase in blood pressure. In some patients with congestive heart failure with normal or low blood pressure, perindopril may cause an additional reduction in systemic blood pressure. This effect is expected and usually does not require cessation of treatment. If symptomatic arterial hypotension, it may be necessary to reduce the dose or to gradually discontinue treatment with the use of individual components.
Hypersensitivity / angioedema. In patients taking ACE inhibitors, including perindopril, rare cases of angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and / or larynx have been reported (see Section "Adverse reactions").
This can occur at any time during treatment. In such cases, you must immediately stop using the drug Prestilol. Therapy with β-blockers should be continued. It is necessary to establish proper supervision of the patient until the symptoms disappear. In cases where the swelling has spread only to the face and lips, the patient’s condition has usually improved without treatment, but the administration of antihistamines may be helpful in reducing symptoms. Angioedema associated with laryngeal edema can be fatal. If the swelling spreads to the tongue, glottis or larynx, which can lead to airway obstruction, emergency treatment is urgently needed, which may include administering adrenaline and / or maintaining the airway. The patient must be under constant medical supervision until the symptoms disappear completely and permanently. Patients with a history of angioedema, who was not associated with therapy with ACE inhibitors, have an increased risk of developing angioedema (see the “Contraindications” section). Patients during treatment with ACE inhibitors reported rare cases of intestinal angioedema. These patients had abdominal pain (with or without nausea and vomiting); in some cases, no previous angioedema of the face was observed, and C-1 esterase was normal. Diagnosis of intestinal angioedema was established during computed tomography or ultrasound or during surgery. After discontinuation of the ACE inhibitor, the symptoms of angioedema disappeared. When conducting a differential diagnosis of abdominal pain that occurs in patients while taking ACE inhibitors, it is necessary to consider the possibility of intestinal angioedema.
Liver dysfunction. Rarely, the use of ACE inhibitors has been associated with a syndrome that begins with cholestatic jaundice and turns into transient liver necrosis, sometimes with a fatal outcome. The mechanism of occurrence of this syndrome is unknown. Patients who develop jaundice in the presence of ACE inhibitors or significantly increase liver enzymes should stop taking the ACE inhibitor and receive appropriate medical examination and treatment (see Section "Adverse reactions").
Racial features. ACE inhibitors are more likely to cause angioedema in patients of the Negroid race than in patients of other races. Like other ACE inhibitors, perindopril less effectively reduces blood pressure in patients of the Negroid race with hypertension than in patients of other races, which may be explained by the low level of renin in the blood of these patients.
Cough It was reported about the occurrence of cough while taking ACE inhibitors. This cough is unproductive, persistent and stops after discontinuation of Prestilol. A cough provoked by an ACE inhibitor should be part of the differential diagnosis of cough.
Hyperkalemia. In some patients, while taking ACE inhibitors, including perindopril, an increase in serum potassium concentration was noted. Risk factors for hyperkalemia include renal failure, impaired kidney function, age> 70 years, diabetes, intercurrent conditions such as dehydration, acute cardiac decompensation, metabolic acidosis, and simultaneous use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, or amiloride) potassium supplements or potassium salts thereof; or taking other drugs that increase the concentration of potassium in the blood serum (in particular heparin). The use of dietary supplements containing potassium, potassium-sparing diuretics, or potassium salt substitutes, especially for patients with impaired renal function, can lead to a significant increase in serum potassium. Hyperkalemia can cause serious, sometimes fatal arrhythmias. If the simultaneous use of perindopril and any of the above substances is considered appropriate, such use requires caution and frequent monitoring of the level of potassium in the blood serum (see Section "Interaction with other drugs and other types of interactions").
Combinations with lithium. Simultaneous use of lithium and perindopril is usually not recommended (see
Section "Interaction with other drugs and other types of interactions").
Combinations with potassium-sparing preparations, food supplements containing potassium or potassium salt substitutes. The simultaneous use of perindopril with potassium-sparing drugs or nutritional supplements containing potassium, or salt substitutes with potassium is usually not recommended (see the Section "Interaction with other drugs and other types of interactions").
Combinations with calcium antagonists, class I antiarrhythmic drugs and antihypertensive agents with central action. Simultaneous use of bisoprolol with calcium antagonists such as verapamil or diltiazem, with class I antiarrhythmic drugs and centrally acting antihypertensive drugs is usually not recommended (see the section "Interaction with other drugs and other types of interactions").
Termination of treatment. It is necessary to avoid abrupt withdrawal of treatment with β-blockers, especially in patients with coronary heart disease, as this can lead to a transient deterioration of heart function. The dosage should be reduced gradually, with the use of individual components, preferably within two weeks and, if necessary, initiate replacement therapy.
Bradycardia. If during treatment, the resting heart rate decreases to
Blockade I degree. Given the negative dromotropic effect of β-blockers, they should be administered with caution to patients with AV-blockade grade I.
Aortic and mitral stenosis / hypertrophic cardiomyopathy. Like other ACE inhibitors, perindopril should be administered with caution to patients with mitral stenosis and obstruction of exit from the left ventricle (aortic stenosis or hypertrophic cardiomyopathy).
Angina Prinzmetala. The use of β-blockers may increase the number and duration of attacks in patients with Prinzmetal angina pectoris. The use of selective β 1 -adrenoreceptor blockers is possible in milder forms of the disease and only in combination with vasodilators.
Impaired renal function. In case of impaired renal function, the daily dose of Prestilol should be based on QA (see the section “Dosage and administration”). Routine medical observation of such patients should include control of creatinine and potassium levels (see the “Adverse Reactions” section). In patients with symptomatic heart failure, hypotension that occurs at the beginning of treatment with ACE inhibitors can lead to a further deterioration in renal function. It has been reported about acute renal failure, which is usually reversible. In some patients with bilateral renal artery stenosis or single kidney artery stenosis, when using ACE inhibitors, there was an increase in blood urea and creatinine in the blood serum, usually returning to normal after stopping treatment. This is more common in patients with renal insufficiency. The presence of renovascular hypertension increases the risk of severe hypotension and renal failure. The treatment of such patients should be started under close medical supervision, with small doses and with careful dose titration. Considering the above, diuretics can contribute to the occurrence of arterial hypotension, so they need to be canceled and the kidney function should be monitored during the first weeks of Prestilol treatment.

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