Prestilol,10 mg+10 mg 30 pcs

Bisoprolol

Bisoprolol is a highly selective β1-adrenoreceptor blocker with no stimulating and corresponding membrane stabilizing effects. It has only a minor affinity for β2-adrenoceptors of bronchial and vascular smooth muscle as well as for β2-adrenoceptors involved in metabolic regulation. Thus, bisoprololol in general has no effect on airway resistance and metabolic processes in which β2-adrenoreceptors are involved. The selective effect of bisoprolol on β1-adrenoceptors is maintained beyond the therapeutic dose range.

Perindopril

Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (ACE inhibitor). ACE, or kinase II, is an exopeptidase that both converts angiotensin I into the vasoconstrictor angiotensin II and breaks down bradykinin, which has a vasodilator effect, into an inactive heptapeptide. ACE inhibition leads to a decrease in plasma angiotensin II concentration, which causes an increase in plasma renin activity (by a “negative feedback” mechanism) and a decrease in aldosterone secretion.

As ACE inactivates bradykinin, ACE suppression is accompanied by an increase in both circulating and tissue kallikrein-kinin system activity, while the prostaglandin system is also activated. It is possible that this effect is part of the mechanism of antihypertensive action of ACE inhibitors, as well as the mechanism of development of some side effects (e.g., cough).

Perindopril has a therapeutic effect due to the active metabolite perindoprilat. Other metabolites have no inhibitory effect on ACE in vitro.

Pharmacodynamic effects

Bisoprolol

Bisoprolol has no significant negative inotropic effects.

The maximal effect is noted 3-4 hours after taking the drug. Because T1/2 is 10-12 hours, bisoprololol has 24-hour action. The maximal antihypertensive effect of bisoprololol is usually reached after 2 weeks.

Bisoprolol decreases HR and stroke volume, which leads to a decrease in cardiac output and oxygen consumption when administered once in patients with CHF without chronic heart failure (CHF). With continuous use, initially increased peripheral vascular resistance decreases. Reduction of plasma renin activity is considered as one of the mechanisms of action underlying the antihypertensive effect of beta-adrenoblockers.

Bisoprolol reduces the sympathoadrenergic response by blocking the β-adrenoreceptors of the heart. This leads to a slower heart rate and myocardial contractility, resulting in reduced myocardial oxygen demand, which is a required effect in angina associated with CHD.

Perindopril

Arterial hypertension

Perindopril is a treatment for arterial hypertension of any severity. It has been shown to decrease both systolic and diastolic BP in the supine and standing position.

Perindopril decreases PPS, which leads to lower BP and improves peripheral blood flow without changing HR.

In general, perindopril administration increases renal blood flow, and FFR is usually unchanged.

Clinical efficacy and safety

Bisoprolol

In a study involving patients with NYHA class III and IV CHF with ejection fraction < 35% according to echocardiography, a decrease in overall mortality from 17.3% to 11.8% was shown. There was a decrease in cases of sudden death and a reduction in the number of episodes associated with heart failure requiring hospitalization. As a result, a significant improvement in the functional status of CHF according to the NYHA classification was shown.

Perindopril

The arterial hypertension

The maximum antihypertensive effect develops 4-6 h after a single oral dose and persists for at least 24 h: residual effects are observed, which are approximately 87-100% of the maximum effects. Decrease in BP is rapid. In responsive patients, BP normalization is achieved within a month and persists without the development of tachyphylaxis.

The discontinuation of therapy does not cause a “ricochet” effect.

Perindopril reduces left ventricular hypertrophy.

Perindopril has a vasodilator effect. It helps to restore elasticity of large arteries and reduce the wall thickness-lumen ratio for small arteries.

The adjuvant therapy with thiazide diuretics causes synergy by the type of summation of effects. The combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of hypokalemia associated with diuretic treatment.

Patients with stable CHD

The efficacy of perindopril in patients over 18 years of age with stable CHD without clinical symptoms of CHD was studied in a 4-year study. 90% of study participants had previously undergone myocardial infarction and/or revascularization procedure. Most patients received medications based on standard therapy, including platelet aggregation inhibitors, hypolipidemic agents, and beta-adrenoblockers. The primary efficacy criterion was a composite endpoint including cardiovascular mortality, nonfatal myocardial infarction and/or cardiac arrest with successful resuscitation.

Tert-butylamine perindopril therapy at a dose of 8 mg/day (equivalent to 10 mg perindopril arginine) resulted in a significant 1.9% reduction in absolute risk of complications (20% reduction in relative risk). In patients who had previously undergone a myocardial infarction or revascularization procedure, the absolute risk reduction was 2.2% (relative risk reduction – 22.4%) compared to the placebo group. When perindopril was added to patients receiving a beta-adrenoblocker, there was a significant reduction in absolute risk of cardiovascular mortality, nonfatal myocardial infarction and/or cardiac arrest with successful resuscitation of 2.2% (24% relative risk reduction) compared with beta-adrenoblocker therapy without perindopril addition.

Double RAAS blockade

There are data from clinical trials of combination therapy with an ACE inhibitor and an angiotensin II receptor antagonist (ARA II).

There have been clinical studies involving patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes with confirmed target organ damage, as well as studies involving patients with type 2 diabetes and diabetic nephropathy.

These studies found no significant positive effect of combination therapy on the occurrence of renal and/or cardiovascular events and on mortality rates, while the risk of hyperkalemia, acute renal failure, and/or arterial hypotension increased compared to monotherapy.

With consideration of the similar within-group pharmacodynamic properties of ACE inhibitors and ARA II, these results would be expected for interactions between any other drugs in the ACE inhibitor and ARA II classes.

Therefore, ACE inhibitors and ARA II should not be used concomitantly in patients with diabetic nephropathy.

There are data from a clinical trial investigating the effect of adding aliskiren to standard therapy with an ACE inhibitor or ARA II in patients with type 2 diabetes and chronic kidney disease or cardiovascular disease, or with a combination of these conditions. The study was terminated early due to an increased risk of adverse outcomes. Cardiovascular death and stroke occurred more frequently in the group of patients receiving aliskiren compared to the placebo group; also adverse events and serious adverse events of special interest (hyperkalemia, arterial hypotension and renal function disorders) were registered more frequently in the aliskiren group than in the placebo group.

Paediatric patients

There are no data on safety and efficacy of Prestilol® in children.

Indications

Active ingredient

Composition

Excipients:

Cellulose microcrystalline,

Calcium carbonate,

Pregelatinized starch,

Sodium carboxymethylstarch,

sodium croscarmellose,

anhydrous colloidal silica,

Magnesium stearate.

The composition of the film coating:

Glycerol, hypromellose, macrogol 6000, magnesium stearate, titanium dioxide, iron oxide yellow dye, iron oxide red dye.

How to take, the dosage

Pretilol tablets are taken orally, in the morning before meals, once a day.

The dose of the drug is determined by the physician on the basis of clinical indications, including consideration of the doses of bisoprolol and perindopril of prior monotherapy.

If 2.5 mg of bisoprolol and 2.5 mg of perindopril are indicated, then 1/2 tablet of Prestylol 5 mg + 5 mg once daily should be taken.

When 2.5 mg bisoprolol and 5 mg perindopril are prescribed, 1/2 tablet of 5 mg + 10 mg once daily should be taken.

In patients with impaired renal function, the single dose of Prestilol is prescribed taking into account the individual blood CK and may be as follows (bisoprolol + perindopril):

For treatment of elderly patients, doses should be prescribed according to recommendations for patients with impaired renal function, and doses should be titrated under close medical supervision.

Interaction

Interactions between bisoprolol and perindopril have not been observed in studies involving healthy volunteers. Information on interactions with other drugs is given below.

Drugs causing hyperkalemia. Certain medications and classes of drugs can increase the risk of hyperkalemia: aliskiren, potassium salts, potassium-saving diuretics, ACE inhibitors, angiotensin II receptor blockers, NSAIDs, heparins, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim. Combinations of these drugs increase the risk of developing hyperkalemia.

Concomitant administration is contraindicated (see section on Contraindications)

Aliskiren: Concomitant administration of Prestilol® and aliskiren is contraindicated in patients with diabetes or impaired renal function because of the risk of hyperkalemia, impaired renal function and increased cardiovascular morbidity and mortality.

Extracorporeal therapies: Extracorporeal therapies that bring blood into contact with negatively charged surfaces, such as dialysis or hemofiltration using certain high-flow membranes (e.g., polyacrylonitrile membranes) and LDL apheresis using dextran sulfate, are contraindicated because of the increased risk of severe anaphylactoid reactions. If such treatment is necessary, another type of dialysis membrane or a different class of antihypertensive medication should be considered.

Sacubitril+valsartan: Concomitant use of perindopril with the combination of sacubitril+valsartan is contraindicated because suppression of neprilysin simultaneously with ACE inhibitor use may increase the risk of angioedema. The use of the combination of sacubitril + valsartan is possible not earlier than 36 hours after the last dose of perindopril. Perindopril may be used at least 36 hours after the last dose of sacubitril+valsartan combination.

Concomitant administration is not recommended

In conjunction with bisoprolol

Hypotensive agents of central action, such as clonidine and others (e.g., methyldopa, moxonidine, rilmenidine): concomitant administration of centrally acting hypotensive agents may worsen the course of heart failure by reducing central sympathetic tone (decreased HR and cardiac output, vasodilation). Abrupt discontinuation of therapy, especially prior to prior dose reduction of a beta-adrenoblocker, may increase the risk of ricochet arterial hypertension.

Class I antiarrhythmic drugs (e.g., quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): co-administration may affect AV conductivity and also increase the negative inotropic effect.

Slow calcium channel blockers (verapamil and, to a lesser extent, diltiazem): negative effects on contractility and AV conduction. IV administration of verapamil to patients receiving beta-adrenoblockers may lead to severe arterial hypotension and AV blockade.

In relation to perindopril

Aliskiren: In patients without diabetes mellitus or impaired renal function, there is also an increased risk of hyperkalemia, impaired renal function, increased incidence of cardiovascular adverse events and cardiovascular mortality.

Concomitant treatment with ACE inhibitors and angiotensin receptor blockers: Data from clinical studies have shown that dual blockade of the RAAS by combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is associated with a higher incidence of adverse events such as arterial hypotension, hyperkalemia, and reduced renal function (including acute renal failure) compared with use of the RAAS-acting drug alone.

. In patients with confirmed atherosclerosis, heart failure, or diabetes mellitus with target organ damage, concomitant use of an ACE inhibitor and angiotensin receptor blocker has been described in the literature as associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared to use of the RAAS-acting drug alone. Dual blockade (e.g., with a combination ACE inhibitor and angiotensin II receptor antagonist) should be limited to single cases with close monitoring of renal function, potassium and BP levels.

Estramustine: There is a risk of increased incidence of adverse events such as angioedema.

Concomitant use with co-trimoxazole (trimethoprim + sulfamethoxazole) may increase the risk of hyperkalemia.

Kalium-saving diuretics (e.g., triamterene, amiloride), potassium salts: hyperkalemia may occur (possibly fatal), especially when combined with renal failure (additional effects associated with hyperkalemia). Concomitant use of perindopril and the above mentioned drugs is not recommended. If concomitant use is necessary, they should be used with observance of caution and regular monitoring of serum potassium content.

Lithium preparations: Concomitant use of lithium preparations and ACE inhibitors has described a reversible increase in lithium concentration in blood and associated toxic effects. Concomitant use of perindopril with lithium preparations is not recommended, but if such a combination is deemed necessary, careful monitoring of serum lithium concentrations is required.

The concomitant use requires special caution

In connection with bisoprolol and perindopril

Hypoglycemic agents (insulin, oral hypoglycemic agents): Based on epidemiological studies, it can be assumed that the use of ACE inhibitors simultaneously with hypoglycemic agents (insulins, oral hypoglycemic agents) may increase the hypoglycemic effect with the risk of developing hypoglycemia. The development of this phenomenon seems to be more likely in the first weeks of combined therapy, as well as in patients with impaired renal function. Concomitant administration of bisoprolol with insulin and oral hypoglycemic agents may increase the hypoglycemic effect. Blockade of β-adrenoreceptors may mask the symptoms of hypoglycemia.

NSAIDs (including acetylsalicylic acid in doses ≥3 g/day): Administration of Prestilol® simultaneously with NSAIDs (i.e. acetylsalicylic acid in anti-inflammatory doses, COX-2 inhibitors and non-selective NSAIDs) may lead to a decrease in the hypotensive effect of bisoprolol and perindopril.

In addition, concomitant use of ACE inhibitors and NSAIDs may increase the risk of impaired renal function, including the possibility of acute renal failure, and increased serum potassium, especially in patients with baseline reduced renal function. Such a combination should be administered with caution, especially in elderly patients. Patients should receive adequate amount of fluids, it is recommended to monitor renal function both at the beginning of combined therapy and periodically during treatment.

Hypotensive and vasodilators: Concomitant use of hypotensive and vasodilators (such as nitroglycerin, other nitrates, or other vasodilators) or other medications that have the ability to lower BP (e.g., tricyclic antidepressants, barbiturates, phenothiazines) may increase the antihypertensive effects of perindopril and bisoprolol.

Tricyclic antidepressants/antipsychotics/general anesthetic agents: Concomitant administration of ACE inhibitors with some anesthetics, tricyclic antidepressants and antipsychotics may result in additional BP lowering.

The concomitant administration of bisoprolol and anesthetics may decrease reflex tachycardia and increase the risk of arterial hypotension.

Sympathomimetics: Concomitant administration of bisoprolol and beta-sympathomimetics (such as isoprenaline, dobutamine) may decrease the effects of both drugs.

Sympathomimetics that activate both β- and α-adrenoreceptors (e.g., noradrenaline, adrenaline): Combination with bisoprololol may reveal α-adrenoreceptor-mediated vasoconstrictor effects of these drugs, which may lead to higher BP and increased claudication. These interactions are more common with non-selective beta-adrenoblockers.

Sympathomimetics may decrease the antihypertensive effect of ACE inhibitors.

In connection with bisoprolol

Dihydropyridine-type slow calcium channel blockers such as felodipine and amlodipine: simultaneous use may increase the risk of hypotension, and further deterioration of ventricular pump function in patients with heart failure is not excluded.

Antirhythmic agents of class III (e.g., amiodarone): may increase the effect on AV conduction.

Parasympathomimetics: concomitant use may decrease AV conductivity and increase the risk of bradycardia.

Beta-adrenoblockers (e.g., eye drops prescribed to treat glaucoma): Concurrent use may increase the systemic effects of bisoprolol.

Foxglove preparations: decreased HR, slowed AV conduction.

In connection with perindopril

Baclofen: enhancement of antihypertensive effect. BP should be monitored carefully and the dose of hypotensive drug should be adjusted if necessary.

Potassium-bearing diuretics: In patients receiving diuretics, and especially in those with decreased BOD and/or saline, an excessive decrease in BP may be observed at the beginning of ACE inhibitor therapy. The likelihood of hypotensive effects may be reduced by discontinuing diuretic therapy, replenishing the RBC or increasing salt intake prior to initiating perindopril therapy, and by prescribing perindopril at a low dose with gradual increase in dose.

In arterial hypertension where prior diuretic therapy may have caused a decrease in RBC/salts, either the diuretic should be stopped before starting ACE inhibitor therapy (in which case the potassium-saving diuretic may be prescribed again later), or ACE inhibitor therapy should be started at a low dose with a subsequent gradual increase.

In patients with CHF treated with diuretics, ACE inhibitor therapy should be started at a very low dose and, if possible, after reducing the dose of a concomitantly used potassium-saving diuretic.

In all cases, renal function (creatinine level) monitoring is required during the first few weeks of ACE inhibitor therapy.

Potassium-saving diuretics (eplerenone, spironolactone): When taking eplerenone or spironolactone at doses from 12.5 mg to 50 mg daily and low-dose ACE inhibitors – when treating patients with NYHA class II-IV heart failure with ejection fraction < 40% and prior therapy with ACE inhibitors and “loop” diuretics there is a risk of hyperkalemia (with possible lethal outcome) especially if the recommendations regarding this drug combination are not followed.

Before initiating combined therapy, it is necessary to ensure that hyperkalemia and renal function abnormalities are absent. We recommend regular monitoring of creatinine and potassium concentrations in blood: weekly in the first month of treatment and monthly during treatment.

Racecadotril: Angioneurotic edema has been reported with ACE inhibitors (such as perindopril). The risk of angioedema may increase with concomitant use of racecadotril (antidiarrheal agent).

MTOR inhibitors (mammalian target of rapamycin) (e.g., sirolimus, everolimus, temsirolimus): The risk of angioedema may increase in patients receiving concomitant therapy with mTOR inhibitors.

Drug combinations requiring attention

In connection with bisoprolol

Mefloquine: increased risk of bradycardia.

MAO inhibitors (except MAO type B inhibitors): increased antihypertensive effect of beta-adrenoblockers, but there is also a risk of hypertensive crisis.

In connection with perindopril

Glyptins (linagliptin, saxagliptin, sitagliptin, vildagliptin): increased risk of angioedema due to reduction of dipeptidyl peptidase IV (DPP-IV) activity by glyptin in patients receiving ACE inhibitor treatment.

Gold preparations: In patients receiving injectable gold preparations (sodium aurothiomalate) concomitantly with ACE inhibitor, including perindopril, development of nitrite reactions (flushing of the face, nausea, vomiting and hypotension) has been described in rare cases.

Special Instructions

All the special instructions and precautions for each component apply to Prestilol®.

Serious arterial hypotension

The ACE inhibitors may cause a sharp decrease in BP. Severe arterial hypotension rarely develops in patients with an uncomplicated course of arterial hypertension. The risk of excessive BP decrease is increased in patients with decreased BOD, e.g., against the background of diuretic therapy, with strict salt-free diet, during hemodialysis, diarrhea or vomiting, and in patients with severe arterial hypertension with high renin activity.

Developed arterial hypotension may occur in patients with clinical manifestations of heart failure with or without renal impairment. This risk is more likely in patients with severe heart failure as a reaction to administration of “loop” diuretics, hyponatremia or functional renal failure.

Patients at increased risk of symptomatic arterial hypotension should be closely monitored by medical personnel during initiation of therapy and dose adjustment. A similar approach applies to patients with CHD or cerebrovascular disease, in whom an excessive decrease in BP may result in myocardial infarction or acute cerebrovascular events.

If arterial hypotension develops, the patient should be placed in the supine position and, if necessary, a 9 mg/ml (0.9%) sodium chloride solution should be infused intravenously. Transient arterial hypotension is not a contraindication for further drug administration. As a rule, the drug may be continued after refill of the blood circulation and increase in blood pressure.

In some patients with CHF who have normal or decreased BP, there may be an additional decrease in BP as a result of perindopril. This effect is predictable and usually does not require discontinuation of therapy. If symptoms of arterial hypotension develop, dose reduction or gradual withdrawal of the drug, or use of its individual components as monotherapy may be required.

Hypersensitivity/angioneurotic edema

Rare cases of angioedema of the face, extremities, lips, mucous membranes, tongue, vocal cleft and/or larynx have been reported in patients treated with ACE inhibitors, including perindopril. These phenomena may develop at any time during treatment. In such cases, treatment with Prestilol® should be discontinued immediately.

The therapy with beta-adrenoblockers should be continued. The patient should be monitored until the signs of edema have resolved. In cases where only the face and lips are affected, the condition usually resolves without treatment, although antihistamines may be used to relieve symptoms.

Contraindications

– acute heart failure or episodes of decompensation of heart failure when IV administration of inotropic drugs is required;

p> – cardiogenic shock;

– AV blockade of degree II or III (without pacemaker);

p> – SSRI;

– sinoatrial block;

– marked bradycardia (HR less than 60 bpm.

– severe arterial hypotension (systolic BP less than 100 mm Hg).

– severe bronchial asthma or severe COPD;

– severe peripheral arterial circulatory disorders or severe Raynaud’s syndrome;

– untreated pheochromocytoma;

– metabolic acidosis;

– history of angioedema (Quincke’s edema) with other ACE inhibitors;

– hereditary or idiopathic angioedema;

p> – collapse;

– concomitant use with drugs containing aliskiren in patients with diabetes mellitus or impaired renal function (GFR < 60 ml/min/1.73 m2 of body surface area);

– concomitant use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy;

– concomitant use with sacubitril+valsartan combination;

– extracorporeal therapy leading to blood contact with negatively charged surfaces;

– Severe bilateral stenosis of the renal arteries or stenosis of the artery of the only functioning kidney;

Pregnancy;

Breastfeeding;

Above 18 years of age.

With caution

Patients with increased risk of developing severe arterial hypotension, hypovolemia and hyponatremia (due to salt-free diet and/or prior therapy with diuretics, dialysis, vomiting, diarrhea), cerebrovascular diseases (including cerebrovascular insufficiency), coronary insufficiency, history of angioneurotic edema, patients of non-Hispanic race, risk factors for hyperkalemia, combination with lithium drugs, concomitant use with potassium-saving diuretics, drugs containing potassium salts, angiotensin receptor blockers, concomitant use with aliskiren-containing drugs, Combination with slow calcium channel blockers, class I antiarrhythmic agents or centrally acting hypotensive agents, abrupt discontinuation of therapy, bradycardia, grade I AV blockade, mitral stenosis, aortic stenosis, hypertrophic cardiomyopathy, Prinzmetal angina, impaired renal function (GFR< 90 ml/min), renovascular hypertension, bilateral renal artery stenosis, artery stenosis of the single kidney (risk of severe arterial hypotension and renal failure), patients after renal transplantation, hemodialysis using high flow membranes (risk of anaphylactoid reactions), patients during LDL apheresis procedure, patients during desensitization treatment, neutropenia/agranulocytosis/thrombocytopenia/anemia, bronchospasm (bronchial asthma, obstructive airway disease), diabetes mellitus type 1 and diabetes mellitus type 2 with significant fluctuations in blood glucose concentration, strict diet, peripheral artery occlusive disease, surgery/general anesthesia (risk of developing excessive BP reduction), psoriasis, pheochromocytoma, hyperthyroidism, severe liver function disorders Restrictive cardiomyopathy, congenital heart disease, hemodynamically significant organic lesions of heart valves, myocardial infarction within last 3 months, congenital glucose-6-phosphate dehydrogenase deficiency (single cases of hemolytic anemia), connective tissue diseases (incl.including systemic lupus erythematosus, scleroderma), depression (including in anamnesis).

Side effects

Unwanted reactions detected on bisoprolol monotherapy during clinical trials and/or in the post-registration period:

Added reactions detected on perindopril monotherapy during clinical studies and/or in the post-registration period:

Overdose

There are no data on overdose of Prestylol® in humans.

Bisoprolol

Symptoms: The most common signs to be expected with beta-adrenal blocker overdose are bradycardia, arterial hypotension, bronchospasm, acute heart failure, and hypoglycemia.

To date only a few cases of bisoprolol overdose (maximum dose 2000 mg) have been described in patients with arterial hypertension and/or CHD, with development of bradycardia and/or arterial hypotension. All described patients recovered. The degree of individual sensitivity to bisoprololol at a single high dose varies widely, and it is likely that patients with heart failure are more sensitive.

Treatment: In case of overdose, treatment should be discontinued and supportive symptomatic therapy should be given. There is limited evidence that bisoprolol is poorly excreted by dialysis. Based on expected pharmacological effects and recommendations for other beta-adrenoblockers, the following should be considered:

– Bradycardia – IV administration of atropine. If the effect is insufficient, isoprenaline or another agent with a positive chronotropic effect may be administered with caution. Occasionally transvenous placement of an artificial pacemaker may be necessary.

– Severe arterial hypotension – IV fluids and vasoconstrictors should be given. IV administration of glucagon may be effective.

– AV blockade (grade II or III) – close monitoring of the patient’s condition and infusion of isoprenaline or transvenous placement of an artificial pacemaker is required.

– Acute worsening of the course of heart failure – IV administration of diuretics, inotropic agents, vasodilators.

– Bronchospasm – administration of bronchodilators such as isoprenaline, beta2-sympathomimetics and/or aminophylline.

Hypoglycemia – IV administration of glucose.

Perindopril

Symptoms: There are limited data on overdose in humans. Symptoms associated with ACE inhibitor overdose may include arterial hypotension, circulatory shock, water-electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, and cough.

Treatment: for treatment of overdose, an intravenous infusion of sodium chloride solution at a concentration of 9 mg/ml (0.9%) is recommended. In case of severe arterial hypotension the patient should be placed in a supine position with elevated legs.

If necessary, angiotensin II and/or catecholamine solution may be administered intravenously. Perindopril may be eliminated from the systemic blood stream by hemodialysis. If bradycardia resistant to therapy develops, an artificial pacemaker may be required. Indices of basic vital functions, serum electrolyte and creatinine concentrations should be constantly monitored.