Bisoprolol pills 5mg, 60pcs

Composition

1 tablet contains:

Active ingredient:

bisoprolol fumarate 5 mg.

Auxiliary substances:

lactose monohydrate,

microcrystalline cellulose,

colloidal silicon dioxide,

crospovidone,

magnesium stearate.

Pharmacological action

Pharmacotherapy group

Beta-1-adrenoblocker selective

ATX code

C07AB

Pharmacodynamics :

Bisoprolol, a selective β1-adrenoblocker without its own sympathomimetic activity, does not have a membrane-stabilizing effect. As with other beta-1 blockers, the mechanism of action in arterial hypertension is unclear. At the same time, it is known that bisoprolol reduces the activity of renin in blood plasma reduces the need for myocardial oxygen and reduces the heart rate (HR). It has antihypertensive, antiarrhythmic and antianginal effects.

Blocking the beta-1-adrenergic receptors of the heart in low doses reduces the catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP) reduces the intracellular flow of calcium ions inhibits all heart functions reduces atrioventricular (AV) conduction and excitability. If the therapeutic dose is exceeded, it has a beta-2-adrenoblocking effect. The total peripheral vascular resistance at the beginning of the drug use increases in the first 24 hours (as a result of a reciprocal increase in the activity of α-adrenergic receptors and elimination of stimulation of β2-adrenergic receptors) after 1-3 days, it returns to its original value and decreases with prolonged use.

The antihypertensive effect is associated with a decrease in the minute volume of blood by sympathetic stimulation of peripheral vessels, a decrease in the activity of the sympathoadrenal system (SAS) (which is of great importance for patients with initial hypersecretion of renin), restoration of sensitivity in response to a decrease in blood pressure (BP) and an effect on the central nervous system. With arterial hypertension, the effect develops in 2-5 days, stable effect is noted in 1-2 months.

The antianginal effect is due to a decrease in myocardial oxygen demand as a result of reduced contractility and other myocardial functions, prolongation of diastole, and improvement of myocardial perfusion. By increasing the final diastolic pressure in the left ventricle and increasing the stretching of the muscle fibers of the ventricles, oxygen demand may increase, especially in patients with chronic heart failure (CHF).

When used in medium therapeutic doses, unlike non-selective beta-blockers, it has a less pronounced effect on the organs containing beta-2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of the peripheral arteries of the bronchi and uterus) and on carbohydrate metabolism; it does not cause sodium ion retention in the body; the severity of the atherogenic effect does not differ from that of propranolol.

Pharmacokinetics:

Bisoprolol is almost completely absorbed (more than 90%) in the gastrointestinal tract. Food intake does not affect absorption. The effect of “primary passage” through the liver is insignificant (at the level of 10-15%), which leads to high bioavailability (90%). Food intake does not affect the bioavailability of bisoprolol.

Bisoprolol is metabolized via the oxidative pathway without subsequent conjugation. All metabolites have a strong polarity and are excreted by the kidneys. The main metabolites found in blood plasma and urine do not show pharmacological activity. Data obtained as a result of experiments with human liver microsomes in vitro show that bisoprolol is primarily metabolized by the CYP3A4 isoenzyme (about 95%) and the CYP2D6 isoenzyme plays only a minor role.

Binding to plasma proteins is about 30%. The volume of distribution is 35 l / kg. Total ground clearance is approximately 15 l/h. The maximum concentration in the blood plasma is determined after 2-3 hours. Permeability through the blood-brain barrier and placental barrier is low.

The plasma half-life (10-12 hours) provides efficacy within 24 hours of a single daily dose.

Bisoprolol is eliminated from the body in two ways: 50% of the dose is metabolized in the liver to form inactive metabolites. About 98% is excreted by the kidneys, of which 50% is excreted unchanged; less than 2% – through the intestines (with bile).

Since renal and hepatic excretion occurs equally in patients with impaired liver function or renal insufficiency, no dose adjustment is required. The pharmacokinetics of bisoprolol are linear and independent of age.

In patients with CHF, plasma concentrations of bisoprolol are higher and the half-life is longer than in healthy volunteers.

There is no information on the pharmacokinetics of bisoprolol in patients with CHF and concomitant hepatic or renal impairment.

Indications

• Arterial hypertension,
• prevention of angina attacks,
• chronic heart failure.

Use during pregnancy and lactation

Bisoprolol has pharmacological effects that may have harmful effects on the course of pregnancy and/or on the fetus or newborn. Usually beta blockers reduce placental perfusion which leads to slower fetal growth intrauterine fetal death miscarriages or premature birth. The fetus and newborn baby may experience abnormal reactions (for example, hypoglycemia, bradycardia, hypotension).

Bisoprolol should not be used during pregnancy use is possible if the benefit to the mother exceeds the risk of side effects in the fetus and / or child. In the case when treatment with Bisoprolol is considered necessary, it is necessary to monitor the uteroplacental blood flow and intrauterine fetal development. In case of negative effects on the pregnancy or fetus, alternative therapy should be considered. Symptoms of hypoglycemia and bradycardia usually occur within the first 3 days. The newborn should be carefully examined after delivery.

There are no data on the excretion of bisoprolol in breast milk. Therefore, if it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Contraindications

• Acute heart failure,
• chronic heart failure in the stage of decompensation,
• cardiogenic shock,
• collapse,
• AV-block II and III degree (without pacemaker),
• SSSU;
• sinoatrial block,
• bradycardia (heart rate
• Prinzmetal’s angina,
• marked reduction in blood pressure (systolic blood pressure
• , a severe form of bronchial asthma and COPD, a history of
• the later stages of peripheral circulatory disorders,
• Raynaud’s disease,
• pheochromocytoma (without the simultaneous use of alpha-blockers),
• metabolic acidosis,
• simultaneous reception of MAO inhibitors (except MAO inhibitors of type B),
• childhood and adolescence to 18 years,
• increased sensitivity to bisoprolol and to other beta-blockers.

Side effects

the Frequency of adverse reactions listed below were determined according to the following (classification of the world health organization): very often – at least 10%; often – not less than 1% but less than 10%; infrequently – not less than 01% but less than 1%; rarely – not less than 001% but less than 01%; very rarely – less than 001% including individual messages.

From the heart and blood vessels: very often – a decrease in heart rate (bradycardia especially in patients with CHF); palpitation sensation; often – a pronounced decrease in blood pressure (especially in patients with CHF) angiospasm manifestation (increased peripheral circulatory disorders cold sensation in the extremities (paresthesia); infrequently – violation of AV conduction (up to the development of complete transverse blockade and cardiac arrest) arrhythmias orthostatic hypotension worsening of the course of CHF with development of peripheral edema (swelling of the ankles, feet; shortness of breath) chest pain.

Nervous system disorders:  often – dizziness headache asthenia gravis increased fatigue sleep disorders depression anxiety; rarely-confusion or short-term memory loss “nightmarish” dreams hallucinations myasthenia gravis tremor muscle cramps. Usually, these phenomena are mild and usually disappear within 1-2 weeks after the start of treatment.

From the side of the senses:  rarely – visual impairment decreased tear production (should be considered when wearing contact lenses) tinnitus hearing loss ear pain; very rarely-dry and painful eyes conjunctivitis taste disorders.

Respiratory system disorders:  infrequently-bronchospasm in patients with bronchial asthma or obstructive airway diseases; rarely-allergic rhinitis; nasal congestion.

From the digestive system:  often – nausea vomiting diarrhea constipation dry oral mucosa abdominal pain; rarely-hepatitis increased activity of liver enzymes (alanine aminotransferase aspartate aminotransferase) increased bilirubin concentration changes in taste.

From the musculoskeletal system: infrequently-arthralgia back pain.

From the genitourinary system:  very rarely-violation of potency weakening of libido.

Laboratory parameters: rarely-an increase in the concentration of triglycerides in the blood; in some cases – thrombocytopenia agranulocytosis leukopenia.

Allergic reactions:  rarely – skin pruritus rash urticaria.

From the skin: rarely-increased sweating hyperemia of the skin exanthema psoriasis-like skin reactions; very rarely-alopecia beta-blockers can exacerbate the course of psoriasis.

Other services: withdrawal syndrome (increased frequency of angina attacks, increased blood pressure).

Interaction

Not recommended combinations

Class I antiarrhythmic agents (for example, quinidine disopyramide lidocaine phenytoin; flecainide propafenone), when used simultaneously with bisoprolol, can reduce AV conduction and contractility of the heart.

Slow calcium channel blockers (BCCs) such as verapamil and, to a lesser extent, diltiazem, when used concomitantly with bisoprolol, can lead to a decrease in myocardial contractility and impaired AV conduction. In particular, intravenous use of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV blockade.

Central antihypertensive agents (such as clonidine methyldopa moxonidine rilmenidine) can lead to a decrease in heart rate and cardiac output, as well as to vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal, especially before beta-blockers are discontinued, may increase the risk of developing “rebound” hypertension.

Combinations that require caution

Class III antiarrhythmic agents (such as amiodarone) may increase the violation of AV conduction.

The action of beta-blockers for topical use (for example, eye drops for the treatment of glaucoma) may increase the systemic effects of bisoprolol (lowering blood pressure and lowering heart rate).

Parasympathomimetics, when used concomitantly with bisoprolol, may increase the violation of AV conduction and increase the risk of bradycardia.

Concomitant use of Bisoprolol with beta-adrenomimetics (for example, isoprenaline dobutamine) may lead to a decrease in the effect of both drugs. The combination of bisoprolol with adrenomimetics that affect beta-and alpha-adrenergic receptors (for example, norepinephrine epinephrine) can increase the vasoconstrictor effects of these drugs that occur with the participation of alpha-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely to occur with non-selective beta-blockers.

Mefloquine, when co-administered with bisoprolol, may increase the risk of developing bradycardia.

Allergens used for immunotherapy or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving bisoprolol.

Iodine-containing radiopaque diagnostic agents for intravenous use increase the risk of anaphylactic reactions.

Phenytoin when administered intravenously means for inhalation anesthesia (derivatives of hydrocarbons) increase the severity of cardiodepressive effects and the likelihood of lowering blood pressure.

The effectiveness of insulin and hypoglycemic agents for oral use may change during treatment with bisoprolol (masks the symptoms of developing hypoglycemia: tachycardia, increased blood pressure).

Clearance of lidocaine and xanthines (other than theophylline) may decrease due to a possible increase in their concentration in blood plasma, especially in patients with an initially increased clearance of theophylline under the influence of smoking.

The antihypertensive effect is weakened by nonsteroidal anti-inflammatory drugs (NSAIDs) (sodium ion retention and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (sodium ion retention).

Cardiac glycosides methyldopa reserpine and guanfacine slow calcium channel blockers (verapamil diltiazem) amiodarone and other antiarrhythmic agents increase the risk of developing or exacerbating bradycardia AV block of cardiac arrest and heart failure.

Nifedipine can lead to a significant decrease in blood pressure.

Diuretics clonidine sympatholytics hydralazine and other antihypertensive agents can lead to an excessive decrease in blood pressure.

The effect of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins may be prolonged during treatment with bisoprolol.

Tricyclic and tetracyclic antidepressants antipsychotics (neuroleptics) ethanol sedatives and hypnotics increase central nervous system depression.

Concomitant use with MAO inhibitors (with the exception of MAO B inhibitors) is not recommended due to a significant increase in the antihypertensive effect. Simultaneous use can also lead to the development of a hypertensive crisis. A break in treatment between taking MAO inhibitors and bisoprolol should be at least 14 days.

Non-hydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders.

Ergotamine increases the risk of developing peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol in the blood plasma.

Rifampicin shortens the half-life of bisoprolol.

How to take, course of use and dosage

The drug Bisoprolol is taken orally in the morning on an empty stomach once without chewing with a small amount of liquid. Tablets should not be chewed or ground into powder.

Treatment of arterial hypertension and angina pectoris

In all cases, the treatment regimen and dosage are selected by the doctor for each patient individually, in particular, taking into account the heart rate and therapeutic response.

In patients with arterial hypertension and coronary heart disease, the initial dose is usually 5 mg once a day. If necessary, the dose is increased to 10 mg once a day.

In the treatment of arterial hypertension and angina pectoris, the maximum daily dose is 20 mg 1 time/day. It is possible to divide the daily dose into 2 doses.

Treatment of stable chronic heart failure

The standard treatment regimen for CHF includes the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists (in case of intolerance to ACE inhibitors), beta-blockers, diuretics, and optionally cardiac glycosides. Initiation of treatment with Bisoprolol for CHF requires a special titration phase and regular medical monitoring.

A prerequisite for treatment with Bisoprolol is stable chronic heart failure without signs of exacerbation.

Treatment of CHF with Bisoprolol begins according to the following titration schedule. This may require individual adjustment depending on how well the patient tolerates the prescribed dose, i. e. the dose can only be increased if the previous dose was well tolerated. The recommended starting dose is 125 mg (1/2 tablet of 25 mg) once daily. Depending on individual tolerance, the dose should be gradually increased to 25 mg 375 mg (11/2 tablets of 25 mg) 75 mg (3 tablets of 25 mg) and 10 mg once a day. Each subsequent increase in the dose should be carried out at least two weeks later.

If an increase in the dose of the drug is poorly tolerated by the patient, it is possible to reduce the dose. The maximum recommended dose for CHF is 10 mg of Bisoprolol once a day.

During titration, regular monitoring of blood pressure, heart rate, and the severity of CHF symptoms is recommended. Worsening of the symptoms of CHF is possible from the first day of use of the drug.

If the patient does not tolerate the maximum recommended dose of the drug, a gradual dose reduction is possible.

During or after the titration phase, there may be a temporary deterioration in the course of CHF, hypotension, or bradycardia. In this case, it is recommended first of all to adjust the doses of concomitant therapy. You may also need to temporarily reduce the dose of Bisoprolol or cancel it.

After the patient’s condition stabilizes, the dose should be re-titrated or the treatment should be continued.

Special patient groups

Impaired kidney or liver function:

– with mild or moderate hepatic or renal impairment, no dose adjustment is usually required;

– with severe renal impairment (creatinine clearance less than 20 ml / min) and in patients with severe liver disease, the maximum daily dose is 10 mg. Increasing the dose in such patients should be carried out with extreme caution.

Currently there are insufficient data on the use of Bisoprolol in patients with CHF associated with type 1 diabetes mellitus severe renal and/or liver dysfunction restrictive cardiomyopathy congenital heart defects or heart valve disease with severe hemodynamic disorders.

Also, until now, insufficient data have been obtained on patients with CHF with myocardial infarction in the last 3 months.

Overdose

Symptoms: arrhythmia ventricular extrasystole severe bradycardia AV block severe decrease in blood pressure acute heart failure hypoglycemia acrocyanosis difficulty breathing bronchospasm dizziness syncope convulsions.

Treatment: if an overdose occurs first of all it is necessary to stop taking the drug conduct gastric lavage prescribe adsorbents conduct symptomatic therapy.

With severe bradycardia-intravenous use of atropine. If the effect is insufficient, a remedy with a positive chronotropic effect can be administered with caution. Sometimes it may be necessary to temporarily install an artificial pacemaker.

With a pronounced decrease in blood pressure – intravenous use of plasma-substituting solutions and vasopressors.

For hypoglycemia, intravenous dextrose (glucose) may be indicated.

In case of AV block: patients should be constantly monitored and treated with P-adrenomimetics such as epinephrine. If necessary, an artificial pacemaker can be installed.

In case of exacerbation of the course of CHF, intravenous use of diuretics, drugs with positive inotropic effects, as well as vasodilators.

In case of bronchospasm-the appointment of bronchodilators, including beta-2-adrenomimetics and / or aminophylline.

Special instructions

Monitoring of the condition of patients taking Bisoprolol should include heart rate and blood pressure measurement ECG measurement of blood glucose concentration in patients with diabetes mellitus (1 time in 4-5 months). In elderly patients, it is recommended to monitor renal function (1 time in 4-5 months).

The patient should be trained in the method of calculating heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min.

Before starting treatment, it is recommended to conduct a study of the function of external respiration in patients with a burdened bronchopulmonary history.

Patients who use contact lenses should take into account that during treatment with the drug, it is possible to reduce the production of tear fluid.

When using the drug Bisoprolol in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (if an effective blockade of alpha-adrenergic receptors is not achieved beforehand).

In thyrotoxicosis, bisoprolol may mask certain clinical signs of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated because it can increase symptoms.

In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentration to normal values.

With simultaneous use of clonidine, its use can be stopped only a few days after the withdrawal of Bisoprolol.

It is possible to increase the severity of the hypersensitivity reaction and the lack of effect from conventional doses of epinephrine (epinephrine) against the background of a burdened allergic history.

If elective surgical treatment is necessary, the drug should be discontinued 48 hours before general anesthesia. If the patient has taken the drug before surgery, he should choose a general anesthesia drug with a minimal negative inotropic effect.

Reciprocal activation of the vagus nerve can be eliminated by intravenous use of atropine (1-2 mg).

Medications that deplete the catecholamine depot (including reserpine) can increase the effect of beta-blockers, so patients taking such combinations of medications should be constantly monitored by a doctor for a pronounced decrease in blood pressure or bradycardia.

Patients with bronchospastic diseases may be cautiously prescribed cardioselective beta-blockers in case of intolerance and/or ineffectiveness of other antihypertensive agents. Against the background of taking beta-blockers in patients with concomitant bronchial asthma, airway resistance may increase. If the dose of Bisoprolol is exceeded, such patients are at risk of developing bronchospasm.

If patients with increasing bradycardia (heart rate less than 60 beats/min) show a marked decrease in blood pressure (systolic blood pressure less than 100 mm Hg) AV blockade, the dose should be reduced or treatment should be discontinued.

It is recommended to stop therapy with Bisoprolol if depression develops.

Do not abruptly interrupt treatment due to the risk of developing severe arrhythmias and myocardial infarction. Discontinuation of the drug is carried out gradually reducing the dose for 2 weeks or more (reduce the dose by 25% in 3-4 days).

The drug should be discontinued before testing the blood and urine concentrations of catecholamines normetanephrine vanillinmindal acid and antinuclear antibody titers.

In smokers, the effectiveness of beta-blockers is lower.

Influence on the ability to drive vehicles and mechanisms:

The use of Bisoprolol does not affect the ability to drive vehicles according to the study results in patients with CHD. However, due to individual reactions, the ability to drive vehicles or work with technically complex mechanisms may be impaired. This should be paid special attention at the beginning of treatment after changing the dose, as well as when drinking alcohol at the same time.

Storage conditions

Store in a dark place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 3 years.

Do not use after the expiration date.

Active ingredient

Bisoprolol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Arrhythmia, Hypertension, Heart Failure