Bisoprolol, 5 mg 50 pcs.

Pharmacotherapeutic group: selective beta1-adrenoblocker

ATX code: C07AB07

Pharmacological properties

Pharmacodynamics

A selective beta1-adrenoblocker with no sympathomimetic activity of its own, has no membrane-stabilizing action.

Bisoprolol in therapeutic doses has negligible affinity for beta2-adrenoreceptors of internal organs (pancreas, skeletal muscles, smooth muscle of peripheral arteries, bronchi and uterus) as well as for beta2-adrenoreceptors involved in metabolism regulation. Consequently, bisoprolol (unlike non-selective beta-adrenoblockers) in general does not affect the airway resistance, has a less pronounced effect on the organs containing beta2-adrenoreceptors and on carbohydrate metabolism, does not cause sodium ion retention in the body. The atherogenic effect of bisoprolol does not differ from that of propranolol. When increasing the dose above the therapeutic dose, bisoprololol loses selectivity and has beta2-adrenoblocking effect.

In therapeutic doses, bisoprololol blocks beta1-adrenoceptors of the heart, reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces intracellular calcium ions (Ca2+) flow, has negative chrono-, dromo-, batmo- and inotropic effects.

Bisoprolol reduces heart rate (HR) at rest and during exercise, slows atrioventricular (AV) conduction, reduces myocardial excitability. It reduces cardiac output, slightly reduces stroke volume, increases right atrial pressure and pulmonary artery congestion pressure at rest and during exercise.

Limits myocardial oxygen demand, reduces plasma renin activity. At the beginning of treatment in the first 24 hours after bisoprolol administration, total peripheral vascular resistance (TPRR) increases slightly (as a result of reciprocal increase of alpha-adrenoreceptor activity). After 1 to 3 days, OPPS returns to baseline.

In long-term therapy initially increased OPPS decreases.
The maximum hemodynamic effect is reached 3-4 hours after oral administration. When administered once daily therapeutic effect of bisoprololol is maintained for 24 hours due to 10-12 hour blood plasma elimination half-life.

Bisoprolol has the same electrophysiological effects as other beta-adrenoblockers. In electrophysiological studies, bisoprolol decreased HR, increased conduction time and refractory periods of sinoatrial and AV nodes. There was a prolongation of RR and PQ intervals as well as corrected QT interval (qtc) on ECG (within normal values).

Bisoprolol has antihypertensive, antianginal, and antiarrhythmic effects.
The mechanism of antihypertensive action of bisoprolol is not fully understood. Antihypertensive effect may be due to the decrease of the minute blood volume, sympathetic stimulation of peripheral vessels, decrease of plasma renin and renin-angiotensin system activity (important for patients with initial renin hypersecretion), restoration of aortic arch baroreceptors sensitivity in response to blood pressure (BP) decrease and the effect on the central nervous system (CNS). In arterial hypertension the effect comes in 2-5 days, the maximum BP decrease is usually reached in 2 weeks after the treatment start.

The antianginal effect is caused by decrease of myocardial oxygen demand as a result of HR shortening, slight decrease of contractility, prolongation of diastole, improvement of myocardial perfusion. When administered once in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF), bisoprolol decreases HR, cardiac stroke volume and, consequently, decreases ejection fraction and myocardial oxygen demand.

The antiarrhythmic effect is caused by the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased content of CAMF, arterial hypertension), decrease of spontaneous excitation rate of sinus and ectopic pacemakers and delay of AV conduction (mainly in antegrade and, to a lesser degree, in retrograde direction through AV node) and through additional pathways.

In clinical trials in patients with stable CHF of III-IV functional class according to NYHA classification (left ventricular ejection fraction < 35%) bisoprolol administration resulted in decrease of total mortality, sudden death and reduction of number of decompensation episodes of CHF requiring hospitalization. There was also a decrease in functional class of CHF by NYHA classification.

Pharmacokinetics

Intake. Bisoprolol is almost completely (> 90%) absorbed from the gastrointestinal tract. Its bioavailability due to insignificant metabolism during “primary passage” through the liver (at about 10-15%) is about 85-90% after oral administration. Food intake has no effect on the bioavailability of bisoprolol. Bisoprolol exhibits linear kinetics, with plasma concentrations proportional to the administered dose in the dose range of 5 to 20 mg. Maximum plasma concentrations are reached after 2-3 hours.

Distribution. Bisoprolol is distributed quite widely. The volume of distribution is 3.5 l/kg. Bisoprolol binding to blood plasma proteins reaches approximately 35%; bisoprolol uptake by blood cells is not observed.
Metabolism. Bisoprolol is metabolized by the oxidative pathway without subsequent conjugation. All metabolites are strongly polar and are excreted by the kidneys.

The major metabolites found in plasma and urine have no pharmacological activity. The data obtained from in vitro experiments with human liver microsomes show that bisoprolol is metabolized primarily by the CYP3A4 isoenzyme (approximately 95%) and the CYP2D6 isoenzyme plays only a minor role.

Elimination. Bisoprolol clearance is determined by a balance between its excretion through the kidneys as unchanged substance (about 50%) and its oxidation in the liver (about 50%) to metabolites, which are then also excreted by the kidneys. Total clearance of bisoprololol is 15.6±3.2 L/h, with renal clearance of 9.6±1.6 L/h. The half-life (T1/2) of bisoprololol is 10-12 hours.

Since excretion occurs equally in the kidneys and the liver, patients with impaired hepatic function or with renal failure do not require dose adjustments. The pharmacokinetics of bisoprolol are linear and independent of age.

Pharmacokinetics in special patient groups

Renal dysfunction

. In a study in patients with renal impairment (mean creatinine clearance [CK] 28 mL/min), it was shown that a decrease in CK was accompanied by an increase in Cmax, AUC (area under the concentration-time curve), and T1/2 of bisoprololol. Since clearance of bisoprololol is equally handled by the kidneys and liver, there is no significant cumulation of bisoprolol in patients with severe renal impairment.

Hepatic disorders

In patients with cirrhosis, there is high variability and significant delayed elimination compared to healthy subjects (T1/2 of bisoprololol is 8.3 to 21.7 hours). No clinically significant differences in pharmacokinetics were found between patients with normal and impaired liver function.

Chronic Heart Failure

In patients with NYHA functional class III CHF, higher plasma bisoprolol levels and increased T1/2 were noted compared to healthy volunteers. Maximal bisoprolol plasma concentration at equilibrium is 64±21 ng/ml at a daily dose of 10 mg; T1/2 is 17±5 hours. The pharmacokinetics of bisoprololol in patients with CHF and concomitant hepatic or renal impairment have not been studied.

Elderly patients

In elderly patients a slight increase in some pharmacokinetic parameters (Tl/2, AUC, Cmaõ) of bisoprolol compared to younger patients has been noted, presumably due to age-related decrease in renal clearance. However, these differences are not clinically significant and do not require bisoprololol dose adjustment.

Indications

Active ingredient

Composition

How to take, the dosage

Bisoprolol is taken orally once daily with a little water, regardless of the time of meals. The tablets should not be chewed or crushed into a powder.

In all cases, the dosage and the regimen are individualized by the physician to each patient, especially based on the patient’s heart rate and their condition.

If arterial hypertension and CHD bisoprolol is indicated at 5 mg once daily. If necessary, the dose is increased to 10 mg once daily.

In the treatment of arterial hypertension and angina pectoris the maximum daily dose is 20 mg once daily.

Chronic heart failure

. The standard treatment regimen for CHF includes the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists (if ACE inhibitors are intolerant), beta-adrenoblockers, diuretics and, optionally, cardiac glycosides. Initiation of CHF treatment with biosoprolol requires mandatory special titration phase and regular physician monitoring.

The prerequisite for bisoprolol treatment is stable CHF without signs of exacerbation.

The treatment of CHF with bisoprololol begins according to the following titration scheme. Individual adaptation may be required depending on how well the patient tolerates the prescribed dose, which means that the dose may be increased only if the previous dose was well tolerated.

Bisoprolol tablets of 2.5 mg with a ricochet may be used to provide the following dosing regimen in CHF.

The recommended starting dose is 1.25 mg once daily. Depending on individual tolerance, the dose should be gradually increased to 2.5 mg, 3.75 mg (1½ 2.5 mg tablets), 7.5 mg (3 2.5 mg tablets), and 10 mg once daily. For 2.5 mg, 3.75 mg, and 10 mg doses, each subsequent dose increase should be at least 2 weeks later. For doses of 5 mg and 7.5 mg, each subsequent dose increase must be in 4 weeks at the earliest.

If the increased dose is not well tolerated by the patient, the dose may be reduced. The maximum recommended dose in CHF is 10 mg of the drug once daily.

At the time of titration, regular monitoring of BP, HR and severity of CHF symptoms is recommended. Worsening of CHF symptoms is possible from the first day of using the drug.

If the patient is poorly tolerant of the maximum recommended dose, gradual dose reduction is possible.

A temporary worsening of CHF, arterial hypertension, or bradycardia may occur during or after the titration phase. In this case, first of all, dosage adjustment of concomitant therapy drugs is recommended. It may also be necessary to temporarily reduce the dose of bisoprolol or cancel it.

After the patient’s condition has stabilized, the dose should be titrated again, or treatment should continue.

Special patient groups Kidney or hepatic impairment

Elderly patients

Dose adjustment is not required.

To date, there are insufficient data regarding the use of bisoprololol in patients with CHF associated with type 1 diabetes mellitus, severe renal and/or hepatic dysfunction, restrictive cardiomyopathy, congenital heart defects or heart valve malformation with significant hemodynamic abnormalities. Also, there are still insufficient data regarding patients with CHF with myocardial infarction within the last 3 months.

Interaction

Unrecommended combinations
CRC treatment
Class I antiarrhythmic agents
Class I antiarrhythmic agents (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) when used simultaneously with bisoprolol may decrease AV conduction and heart contractility.
All indications for the use of bisoprolol:
Verapamil and diltiazem
Non-dihydropyridine “slow” calcium channel blockers (BMCCs), such as verapamil and, to a lesser extent, diltiazem, when used concomitantly with bisoprolol can lead to decreased myocardial contractility and impaired AV conduction, cardiac arrest, and heart failure. In particular, intravenous administration of verapamil to patients taking beta-adrenoblockers may lead to severe arterial hypotension and AV blockade.

Hypotensive agents of central action
Simultaneous use of bisoprolol with hypotensive agents of central action (such as clonidine, methyldopa, moxonidine, rilmenidine) may worsen the course of heart failure due to reduction of central sympathetic tone (slowed heart rate, reduced cardiac output, peripheral vasodilation).
Abrupt withdrawal of hypotensive drugs of central action, especially before withdrawal of beta-adrenoblockers may increase the risk of “ricochet” arterial hypertension (withdrawal syndrome). In patients simultaneously taking bisoprolol and clonidine, if it is necessary to discontinue therapy, bisoprolol should be discontinued several days before stopping clonidine. If replacement of clonidine with bisoprolol is expected, the beta-adrenoblocker should be administered several days after clonidine withdrawal.
Methyldopa increases the risk of bradycardia, AV block, cardiac arrest and heart failure development or aggravation.
Fingolimod
Fingolimod may increase the negative chronotropic effect of beta-adrenoblockers and lead to marked bradycardia. Concomitant use of fingolimod and bisoprolol is not recommended. In case of necessity of concomitant use of these drugs, close monitoring of the patient’s condition is required. It is recommended to start combined therapy in hospital and to monitor accordingly (prolonged HR control is indicated at least till the morning of the next day after the first simultaneous use of fingolimod and beta-adrenoblocker).
Combinations requiring special caution
Treatment of arterial hypertension and stable angina pectoris:
Class I antiarrhythmic agents
Class I antiarrhythmic agents (e.g., quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) when used simultaneously with bisoprolol may slow AV conduction and reduce cardiac contractility.
All indications for bisoprolol use:
Class III antiarrhythmic agents

Class III antiarrhythmic agents (e.g., amiodarone) may increase AV conduction impairment. Amiodarone and other antiarrhythmic agents increase the risk of development or worsening of bradycardia, cardiac arrest and heart failure.
Calcium channel blockers (CMBs) – dihydropyridine derivatives CMBs – dihydropyridine derivatives (eg, nifedipine, felodipine, amlodipine) in concurrent use with bisoprolol may increase the risk of hypotension. In patients with CHF, the risk of further deterioration of cardiac contractility cannot be excluded. Nifedipine may lead to a significant decrease of BP.
Drugs that reduce blood pressure
Hypotensive drugs (diuretics, clonidine, etc.) as well as other drugs.), as well as other drugs with possible antihypertensive effect (e.g., tricyclic antidepressants, barbiturates, phenothiazines) may increase the antihypertensive effect of bisoprolol and lead to excessive BP lowering.
Beta-adrenoblockers for topical use
The effects of beta-adrenoblockers for topical use (e.g. eye drops for glaucoma) may increase the systemic effects of bisoprolol (BP reduction, heart rate slowing).
Cholinomimetics
Cholinomimetics (parasympathomimetics) in concomitant use with bisoprolol may increase AV conduction disorders and increase the risk of bradycardia.
Hypoglycemic drugs
Hypoglycemic effects of insulin or hypoglycemic agents for oral administration may increase. Signs of hypoglycemia – in particular tachycardia – may be masked or suppressed. Such interactions are more likely when using non-selective beta-adrenoblockers.
Means for general anesthesia
Means for inhalation anesthesia may increase the risk of cardiodepressive action. There is a decrease in reflex tachycardia, increased risk of bradyarrhythmias and marked arterial hypotension.
Cardiac glycosides
Cardiac glycosides in concomitant use with bisoprolol may lead to an increase in pulse conduction time, and thus, to the development of bradycardia.

Cardiac glycosides increase the risk of AV block, cardiac arrest and heart failure.
Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs may decrease the antihypertensive effect of bisoprolol (through sodium ion retention and kidney blockade of prostaglandin synthesis).
Sympathomimetics
Concomitant use of bisoprolol with beta-adrenomimetics (such as isoprenaline or dobutamine) may reduce the effect of both drugs.
Concomitant use of bisoprolol with adrenomimetics affecting beta- and alpha-adrenoreceptors (such as epinephrine [adrenaline]) may increase vasoconstrictor effects resulting from alpha-adrenoreceptor stimulation and may result in arterial hypertension or worsening of claudication. Such interactions are more likely when using non-selective beta-adrenoblockers.
There have been described cases of pronounced arterial hypertension when concomitant use of beta-adrenoblockers with alpha-adrenomimetics, including drugs for topical use (such as anticongestive agents in the form of nasal drops).
Combinations to be considered Mefloquine
Mefloquine concomitantly used with bisoprolol may increase the risk of bradycardia.
Monoamine oxidase inhibitors (MAO)
MAO inhibitors (except MAO B inhibitors) may increase the antihypertensive effect of beta-adrenoblockers. Concomitant use may also lead to the development of a hypertensive crisis. A break in treatment between withdrawal of MAO inhibitors and administration of bisoprolol should be at least 14 days. Ergot alkaloids
Unhydrogenated ergot alkaloids increase the risk of peripheral circulatory disturbances when taking beta-adrenoblockers. Ergotamine increases the risk of peripheral circulatory disorders.
Pharmacokinetic interactions
Rifampicin increases metabolic clearance and shortens the T1/2 of bisoprolol. Dosage adjustment is usually not required.

Caution should be exercised when using bisoprololol concomitantly with inducers of isoenzymes of microsomal hepatic oxidation.
Increased concentration of bisoprolol in plasma when used with CYP3A4 inhibitors and its decrease when used with CYP3A4 inducers may occur. Bisoprolol may increase plasma concentrations of drugs metabolized with the participation of CYP3A4 isoenzyme and, possibly, CYP2D6.
No interaction of bisoprolol with thiazide diuretics, digoxin and cimetidine was found in pharmacokinetic studies. Bisoprololol has no effect on prothrombin time in patients receiving stable dose warfarin.

Special Instructions

Cessation of therapy and “withdrawal”

Bisoprolol treatment should not be abruptly discontinued or the recommended dose changed without first consulting a physician, as this may lead to a temporary worsening of heart function. Treatment should not be interrupted suddenly, especially in patients with CHD (aggravation of angina attacks, myocardial infarction and ventricular arrhythmias have been reported in patients with CHD when beta-adrenal blockers are stopped suddenly). If discontinuation of treatment is necessary, the dose of bisoprolol should be reduced gradually. In case of significant aggravation of angina or development of acute coronary syndrome, bisoprolol should be temporarily resumed.

Diseases in which caution should be exercised Bisoprololol should be used with caution in the following cases: severe forms of COPD and nonsevere forms of bronchial asthma; diabetes with significant fluctuations in blood glucose concentration: bisoprolol may mask symptoms of hypoglycemia (marked decrease in blood glucose concentration), such as tachycardia, palpitations or increased sweating; strict diet; conducting desensitization therapy; 1st degree AV blockade; vasospastic angina (Prinzmetal angina); mild to moderate peripheral arterial circulatory disorders (worsening of symptoms may occur at the beginning of therapy); psoriasis (includingincluding history of psoriasis).

Cardiovascular disease

Beta-adrenoblockers should not be used in decompensated CHF until the patient has been stabilized.

In the initial stages of bisoprolol use, patients require continuous monitoring.

Beta-adrenoblockers can cause bradycardia. If the resting HR is less than 50 to 55 bpm, the dose should be reduced or bisoprololol should be discontinued.

In common with other beta-adrenoblockers, bisoprololol may cause prolongation of the PQ interval on ECG. Bisoprololol should be used with caution in patients with grade I AV blockade.

Nonselective beta-adrenoblockers may increase the frequency and duration of angina attacks in patients with vasospastic angina (Prinzmetal angina) due to alpha-receptor-mediated coronary artery vasoconstriction. Cardioselective beta1-adrenoblockers (including bisoprolol) should be used with caution in vasospastic angina.

To date, there are insufficient data regarding the use of bisoprololol in patients with CHF in combination with type 1 diabetes mellitus, severe renal and/or hepatic dysfunction, restrictive cardiomyopathy, congenital heart disease or heart valve malformation with severe hemodynamic abnormalities. There are also still insufficient data regarding patients with CHF with myocardial infarction within the last 3 months.

The respiratory system

. Although selective beta1-adrenoblockers have less effect on respiratory function than non-selective beta-adrenoblockers, bisoprolol should be prescribed with extreme caution in patients with COPD and nonsevere bronchial asthma and only if the possible benefits exceed the potential risks. In bronchial asthma or COPD concomitant use of bronchodilators is indicated. Patients with bronchial asthma may have increased airway resistance, requiring a higher dose of beta2-adrenomimetics.

In patients with COPD, bisoprolol prescribed in combination therapy to treat heart failure should be started at the lowest possible dose, and patients should be closely monitored for the appearance of new symptoms (e.g., dyspnea, exercise intolerance, cough).

Extensive surgical interventions and general anesthesia

. If surgical interventions are necessary, the anesthesiologist should be advised that the patient is taking beta-adrenoblockers (risk of drug interactions with development of severe bradyarrhythmias, decreased reflex tachycardia, and arterial hypotension). It is recommended not to discontinue bisoprolol in the perioperative period without an obvious need (because beta-adrenoreceptor blockade reduces the risk of arrhythmias and myocardial ischemia during the induction of anesthesia and tracheal intubation). If bisoprolol treatment must be interrupted prior to surgery, the drug should be discontinued at least 48 hours before surgery.

Pheochromocytoma

In patients with pheochromocytoma, bisoprololol may only be prescribed with the use of alpha-adrenoblockers.

Thyrotoxicosis

In thyroid hyperfunction, beta-adrenoblockers (including bisoprolol) may mask tachycardia and reduce the severity of thyrotoxicosis symptoms. Abrupt withdrawal of the drug may cause exacerbation of symptoms of the disease and development of thyrotoxic crisis.

Hypersensitivity reactions

Beta-adrenoblockers, including bisoprolol, may increase sensitivity to allergens and the severity of anaphylactic/hypersensitivity reactions due to impaired adrenergic compensatory regulation by beta-adrenoblockers. The use of conventional therapeutic doses of epinephrine (adrenaline) against the background of beta-adrenoblockers does not always lead to the desired clinical effect. Caution should be exercised when prescribing bisoprolol for patients with a history of severe hypersensitivity reactions or undergoing desensitization.

Psoriasis

In deciding whether to use bisoprolol in patients with psoriasis, the anticipated benefit of the drug must be carefully weighed against the possible risk of exacerbation of the psoriasis course.

Contact lenses

Patients who wear contact lenses should be aware that the use of beta-adrenoblockers may decrease tear fluid production.

Influence on ability to drive vehicles, mechanisms According to the results of the study, in patients with CHD, bisoprolol does not affect the ability to drive vehicles. However, due to individual reactions, the ability to drive or operate technically complex mechanisms may be impaired. Special attention should be paid to this at the beginning of treatment and after changing the bisoprololol dose.

Synopsis

Contraindications

Side effects

The frequency of side effects is classified according to the recommendations of the World Health Organization: Very common (≥ 1/10), common (≥ 1/100 to

< 1/10), infrequent (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), frequency unknown (cannot be estimated from available data).

Mental disorders: infrequent – sleep disturbance, depression; rare – hallucinations, nightmares.

Nervous system disorders: often – dizziness, headache (in patients with hypertension or angina pectoris these symptoms are especially common at the beginning of treatment. Usually these phenomena are mild and usually go away within 1-2 weeks after the start of treatment); rarely – loss of consciousness.

Visual disorders: rare – decreased tear production (should be considered when wearing contact lenses); very rare – conjunctivitis.

Hearing organ and labyrinth disorders: rare – hearing impairment. Cardiac disorders: very common – bradycardia (in patients with CHF); common – aggravation of CHF symptoms (in patients with CHF); infrequent – AV

Conduction disorders, aggravation of CHF symptoms (in patients with hypertension or angina pectoris), bradycardia (in patients with hypertension or angina pectoris).

Vascular disorders: frequently – sensation of cold or numbness in the extremities, arterial hypotension, especially in patients with heart failure; infrequently – orthostatic hypotension.

Disorders of the respiratory system, thorax and mediastinum: infrequently – bronchospasm in patients with bronchial asthma or obstructive airway disease in the anamnesis; rarely – allergic rhinitis.

Gastrointestinal tract disorders: frequently – nausea, vomiting, diarrhea, constipation.

Liver and biliary tract disorders: rarely – hepatitis.

Dermatological and subcutaneous tissue disorders: rare – hypersensitivity reactions (such as skin itching, skin hyperemia, skin rash); very rare: alopecia. Beta-adrenoblockers may cause exacerbation or worsening of the course of psoriasis, or cause psoriasis-like rashes.

Muscular and connective tissue disorders: infrequent – muscle weakness, seizures.

Disorders of the genitals and mammary gland: rarely – impaired potency.

General disorders and disorders at the site of administration: Frequent – asthenia (in patients with CHF), increased fatigue; infrequent – asthenia (in patients with hypertension or angina pectoris).

Laboratory and instrumental data: rare – increased activity of

“hepatic” transaminases: aspartate aminotransferase (ACT), alanine aminotransferase (ALT) in blood, increased concentration of triglycerides in blood.

Overdose

Symptoms: arrhythmia, ventricular extrasystole, marked bradycardia, AV blockade, marked BP decrease, acute heart failure, hypoglycemia, acrocyanosis, difficulty breathing, bronchospasm, dizziness, syncope, seizures.

The sensitivity to single high-dose bisoprolol administration varies widely among individual patients and is likely to be highly sensitive in patients with CHF.

Treatment: if an overdose occurs, the first step is to stop taking the drug, perform gastric lavage, prescribe adsorptive agents, and administer symptomatic therapy.

In case of marked bradycardia – intravenous injection of atropine. If the effect is insufficient, a drug with a positive chronotropic effect may be administered with caution. Sometimes temporary placement of a pacemaker may be necessary.

In case of a significant decrease in BP – intravenous administration of plasma replacement solutions and vasopressors. Intravenous administration of glucagon may be effective.

In case of hypoglycemia, intravenous administration of dextrose (glucose) may be indicated. In AV blockade: patients should be constantly monitored and treated with beta-adrenomimetics such as epinephrine. Placement of a pacemaker, if necessary.

In exacerbation of CHF, intravenous diuretics, drugs with positive inotropic effect, and vasodilators.

In case of bronchospasm – administration of bronchodilators, including beta2-adrenomimetics and/or aminophylline.

Pregnancy use

Pregnancy

The pharmacological effects of bisoprolol may have adverse effects on pregnancy and the fetus/newborn. In general, beta-adrenoblockers decrease blood flow in the placenta, which may lead to fetal growth retardation, intrauterine fetal death or premature delivery. The fetus and the newborn may develop adverse events (e.g., hypoglycemia and bradycardia). If treatment with beta-adrenoblockers is necessary, selective beta1-adrenoblockers should be preferred.

In pregnancy, bisoprolol should be used only if absolutely necessary, if the expected benefits to the mother exceed the possible risk of side effects in the fetus and/or newborn. Blood flow in the placenta and uterus should be monitored, as well as the growth and development of the unborn child. In case of adverse events in relation to pregnancy and/or fetus, the use of alternative therapies is recommended.

The newborn should be carefully examined after delivery. In the first three days of life, the newborn may have symptoms of bradycardia and hypoglycemia.

Breastfeeding period

According to preclinical studies, bisoprolol and/or its metabolites penetrate the milk of lactating rats. There are no data on the excretion of bisoprolol into breast milk. Therefore, bisoprolol administration is not recommended for women during breastfeeding. If bisoprolol administration during lactation is necessary, breastfeeding should be stopped. .

Similarities