Bisoprolol-OBL - instructions for use, dose, side effects, contraindications

Active substance:
bisoprolol hemifumarate	2.5 mg	5 mg	10 mg
Excipients:
microcrystalline cellulose	32 mg	64 mg	128 mg
mannitol	55.5 mg	111 mg	222 mg
crospovidone	7 mg	14 mg	28 mg
silicon dioxide colloid (aerosil)	2 mg	4 mg	8 mg
magnesium stearate	1 mg	2 mg	4 mg
Average tablet weight	100 mg	200 mg	400 mg
Excipients for the shell:
hypromellose (hydroxypropylmethylcellulose)	2.1 mg	4.2 mg	8.4 mg
macrogol 6000 (polyethylene glycol 6000)	0.6 mg	1.2 mg	2.4 mg
titanium dioxide	0.3 mg	0.554 mg	0.96 mg
quinoline yellow dye	-	0.013 mg	-
dye Ponso 4R	-	-	0.24 mg
iron oxide yellow	-	6.033 mg
Average weight of coated tablet	103 mg	206 mg	412 mg

Description:

Dosage 2.5 mg: oblong, with rounded ends, biconvex tablets, covered with a film coat of white or almost white, with a risk.

Dosage of 5 mg: round, biconvex tablets, covered with a film coating of yellow color.

Dosage of 10 mg: oblong, with rounded ends, biconvex tablets, covered with a film shell of red color, with a risk.

On the cross-section of tablets of all dosages, the nucleus is white or almost white in color.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.07 Bisoprolol

Pharmacodynamics:

Bisoprolol - selective beta₁- adrenoblocker, without its own sympathomimetic activity, does not possess membrane-stabilizing action. As for the other beta₁adrenoblockers, the mechanism of action for arterial hypertension (AH) is unclear. At the same time bisoprolol reduces the activity of renin in the blood plasma, reduces the need for myocardium in oxygen, and reduces the heart rate (heart rate). Has antihypertensive, antiarrhythmic and anti-anginal action.

Blocking in low doses of beta₁-adrenoceptors of the heart, reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces the intracellular current of calcium ions, inhibits all cardiac functions, reduces atrioventricular (AV) conduction and excitability. If the therapeutic dose is exceeded, beta₂-adrenoblocking action. The total peripheral vascular resistance (OPSS) at the beginning of the drug application, in the first 24 hours, increases (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of beta stimulation₂-adrenoreceptors), returns to the initial value after 1-3 days, and decreases with prolonged use.

The antihypertensive effect is associated with a decrease in the minute volume of blood, sympathetic stimulation of the peripheral vessels, a decrease in the activity of the sympathetic adrenal system (CAS) (important for patients with initial hypersecretion of renin), restoration of sensitivity in response to lowering blood pressure (BP) and affecting the central nervous system (CNS). With AG, the effect develops after 2-5 days, stable effect is observed after 1-2 months.

The antianginal effect is due to a decrease in myocardial oxygen demand as a result of decreased contractility and other myocardial functions, diastole lengthening, and improved myocardial perfusion. By increasing the end diastolic pressure in the left ventricle (LV) and increasing the stretching of the ventricular muscle fibers, the need for oxygen may increase, especially in patients with chronic heart failure (CHF).

When used in average therapeutic doses, in contrast to non-selective beta-blockers, it exerts a less pronounced effect on organs containing beta₂-adrenoreceptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and carbohydrate metabolism; does not cause retention of sodium ions in the body; the severity of atherogenic action does not differ from that of propranolol.

Pharmacokinetics:

Bisoprolol is almost completely absorbed in the gastrointestinal tract (GIT), eating does not affect absorption. The effect of "primary transmission" through the liver is negligible, which leads to high bioavailability (90%).

Bisoprolol is metabolized along 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 microsomes of human liver in vitro, show that bisoprolol is metabolized primarily by isoenzyme CYP3A4 (about 95%), and isoenzyme CYP2D6 plays only a small role.

The connection with blood plasma proteins is about 30%. The volume of distribution is 3.5 l / kg. The total ground clearance is approximately 15 l / h. The maximum concentration in the blood plasma is determined after 2-3 hours. The permeability through the blood-brain barrier (BBB) and the placental barrier is low.

The half-life of blood plasma (T_1/2) (10-12 hours) provides efficacy within 24 hours after taking a single daily dose.

Bisoprolol is excreted from the body in two ways, 50% The dose is metabolized in the liver with the formation of inactive metabolites. About 98% is excreted by the kidneys, 50 of them% output in unmodified form; less than 2% - through the intestine (with bile).

Patients with impaired hepatic function or with renal insufficiency do not need dose adjustment. The pharmacokinetics of bisoprolol is linear and does not depend on age.

In patients with CHF, plasma concentrations of bisoprolol are higher, and T_1/2longer than in healthy volunteers.

Indications:

- Arterial hypertension;

- ischemic heart disease: prevention of attacks of stable angina pectoris;

chronic heart failure.

Contraindications:

- Hypersensitivity to the components of the drug and other beta-blockers;

- acute heart failure and chronic heart failure in the stage of decompensation, requiring inotropic therapy;

- cardiogenic shock;

- collapse;

- atrioventricular block II-III degree, without a pacemaker;

- sinoatrial blockade;

- syndrome of weakness of the sinus node (SSSU);

- bradycardia (heart rate before treatment less than 60 beats per minute);

- severe arterial hypotension (systolic blood pressure less than 100 mm Hg);

- severe forms of bronchial asthma and chronic obstructive pulmonary disease (COPD) in history;

- severe peripheral circulatory disturbances;

- Raynaud's syndrome;

- metabolic acidosis;

- pheochromocytoma (without simultaneous use of alpha-blockers);

- simultaneous administration of monoamine oxidase inhibitors (MAO), except for MAO type B inhibitors);

- concomitant use of floktaphenin and sultopride;

- age to 18 years (efficacy and safety not established).

Carefully:Use with caution Bisoprolol in the following cases: desensitizing therapy, prinzmetal angina, hyperthyroidism, type 1 diabetes mellitus and diabetes mellitus with significant fluctuations in blood glucose concentration, AV blockade of I degree, severe renal failure (creatinine clearance less than 20 ml / min), severe liver dysfunction, psoriasis, restrictive cardiomyopathy,congenital heart disease or heart valve disease with severe hemodynamic disorders, chronic heart failure with myocardial infarction during the last 3 months, severe allergic reactions (in the anamnesis), depression (including in the anamnesis), pregnancy, the period of breastfeeding, severe diet.

Pregnancy and lactation:

Bisoprolol does not have direct cytotoxic, mutagenic and teratogenic effects, but it has pharmacological effects that can have harmful effects on the course of pregnancy and / or on the fetus or newborn. Usually beta-adrenoblockers reduce placental perfusion, which leads to a slowing of fetal growth, fetal death, miscarriage or premature birth. The fetus and the newborn child may experience pathological reactions, such as intrauterine growth retardation, hypoglycemia, bradycardia.

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 the child. In the event that the drug treatment Bisoprolol is considered necessary, blood flow in the placenta and uterus should be monitored, and the growth and development of the unborn child should be monitored and, in the event of undesired pregnancy and / or fetal events, alternative therapies. You should carefully examine the newborn after delivery. Symptoms of hypoglycemia and bradycardia usually arise during the first 3 days of life.

There is no data on the isolation of bisoprolol in breast milk. Therefore, taking the drug bisoprolol is not recommended for women during lactation. If it is necessary to use the drug during the period of breastfeeding, breastfeeding should be discontinued.

Dosing and Administration:

A drug Bisoprolol taken in the morning on an empty stomach, once a day with a small amount of liquid, in the morning before breakfast, during or after it. Tablets should not be chewed or ground into a powder. In all cases, the regimen and dosage are selected by the doctor for each patient individually, in particular taking into account the heart rate and the patient's condition. With arterial hypertension and ischemic heart disease, the drug is prescribed 5 mg once a day.If necessary, increase the dose to 10 mg once a day.

In the treatment of hypertension and angina, the maximum daily dose is 20 mg 1 time / day.

Treatment with bisoprolol of chronic heart failure

The beginning of treatment of chronic heart failure drug Bisoprolol requires mandatory conduct of a special phase of titration and regular medical supervision.

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

Treatment of chronic heart failure drug Bisoprolol starts according to the following titration scheme. Individual adaptation may be required depending on how well the patient tolerates the prescribed dose, i. E. The dose can be increased only if the previous dose is well tolerated.

To ensure the appropriate titration process at the initial stages of treatment, it is recommended to use the drug in smaller doses.

The recommended initial dose is 1.25 mg (1/2 tablets of 2.5 mg) once a day.Depending on the individual tolerability, the dose should be gradually increased to 2.5 mg, 3.75 mg (1.5 tablets of the drug bisoprolol 2.5 mg), 5 mg, 7.5 mg (1 tablet of 5 mg and 1/2 tablets of 2.5 mg), and 10 mg once a day with an interval of not less than 2 or more weeks.

If the increase in the dose of the drug is poorly tolerated by the patient, a dose reduction is possible.

The maximum daily dose for the treatment of chronic heart failure is 10 mg 1 time per day.

During titration, regular monitoring of blood pressure, heart rate and symptoms of chronic heart failure is recommended. The worsening of symptoms of chronic heart failure is possible from the first day of application of the drug.

During or after the titration phase, temporary deterioration in the course of chronic heart failure, arterial hypotension, or bradycardia may occur. In this case, it is recommended first of all to pay attention to the choice of a dose of concomitant standard therapy. It may also be necessary to temporarily reduce the dose of the drug Bisoprolol or cancellation of its reception. After stabilization of the patient's condition, a repeated titration of the dose should be performed, or the treatment should be continued.

Treatment with bisoprolol in case of impaired renal or hepatic function

If the liver or kidney function is mild or moderate, usually no dose adjustment is required.

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

Treatment with bisoprolol in elderly patients

Correction of the dose is not required.

To date, there is insufficient data on the use of the drug Bisoprolol in patients with chronic heart failure associated with type 1 diabetes mellitus, severe impairment of kidney and / or liver function, restrictive cardiomyopathy, congenital heart disease or hemodynamically caused heart disease.

Also, sufficient data have not yet been obtained regarding patients with chronic heart failure with myocardial infarction (MI) during the last 3 months.

Side effects:

The frequency of adverse reactions listed below was determined according to the following (classification of the World Health Organization): very often - not less than 10%; often - not less than 1%,but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0,01%; but less than 0.1%; very rarely - less than 0.01%, including individual reports.

From the side of the heart and blood vessels: very often - a decrease in heart rate (bradycardia, especially in patients with heart failure), a feeling of heartbeat; often a marked decrease in blood pressure (especially in patients with CHF), manifestation of angiospasm (increased peripheral circulatory disorders, cold sensation in the extremities (paresthesia), infrequent AV conduction (up to the development of complete transverse blockage and cardiac arrest), arrhythmias, orthostatic hypotension , aggravation of the course of CHF with the development of peripheral edema (swelling of the ankles, feet, dyspnea), chest pain.

From the nervous system: often - dizziness, headache, asthenia, fatigue, insomnia, depression, anxiety; rarely - confusion or short-term memory loss, "nightmarish" dreams, hallucinations, myasthenia gravis; tremor, muscle cramps. Usually, these phenomena are of an easy nature and usually pass within 1-2 weeks after the start of treatment.

From the sense organs: rarely - impaired vision,reduction in tearing (should be considered when wearing contact lenses), tinnitus, hearing loss, ear pain; very rarely - dryness and soreness of the eyes, conjunctivitis, taste disorders.

From the respiratory system: infrequently bronchospasm in patients with bronchial asthma or obstructive airway disease; rarely - allergic rhinitis, nasal congestion.

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

From the side of the musculoskeletal system: infrequently - arthralgia, back pain.

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

Laboratory indicators: rarely - an increase in the concentration of triglycerides in the blood; in some cases - thrombocytopenia, agranulocytosis, and leukopenia.

Allergic reactions: rarely - skin itching, rash, hives.

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

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

If any of the side effects indicated in the instructions are aggravated, or if you notice any other side effects not listed in the instructions, inform your doctor.

Overdose:

Symptoms: arrhythmia, ventricular extrasystole, pronounced bradycardia, AV blockade, marked decrease in blood pressure, acute heart failure, hypoglycemia, acrocyanosis, difficulty breathing, bronchospasm, dizziness, fainting, seizures.

Treatment: In case of an overdose, first of all, stop taking the drug, rinse the stomach, prescribe adsorbing agents, and conduct symptomatic therapy.

With severe bradycardia intravenous atropine. If the effect is insufficient, with caution, you can enter a drug that has a positive chronotropic effect. Sometimes it may be necessary to temporarily set up an artificial pacemaker.

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

In hypoglycemia, intravenous administration of glucagon or intravenous dextrose (glucose) may be indicated.

With AV blockade: patients should be under constant observation and receive treatment with beta-adrenomimetics, such as epinephrine (adrenalin). If necessary, staging an artificial pacemaker.

With an exacerbation of the course of CHF - intravenous injection of diuretics, drugs with a positive inotropic effect, as well as vasodilators.

When bronhospazme - the appointment of bronchodilators, including beta₂adrenomimetics and / or aminophylline.

Interaction:

Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin; flecainide propafenone) with simultaneous application with bisoprolol may reduce AV conduction and contractility of the myocardium.

Antiarrhythmic drugs of III class (eg, amiodarone) can enhance the disturbance of AV conduction.

Act beta-blockers for topical application (eg, eye drops for the treatment of glaucoma) can enhance the systemic effects of bisoprolol (lowering blood pressure, decreasing heart rate).

Parasympathomimetics with simultaneous application with bisoprolol may increase the disturbance of AV conduction and increase the risk of developing bradycardia.

Simultaneous use of the drug Bisoprolol from beta-adrenomimetics (e.g., isoprenaline, dobutamine) can lead to a decrease in the effect of both drugs.

The combination of bisoprolol with adrenomimetics, affecting the beta and alpha-adrenoreceptors (for example; norepinephrine, epinephrine (epinephrine), may enhance the vasoconstrictor effects of these agents that occur with alpha-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using nonselective beta-blockers.

Mefloquine with simultaneous application 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 administration increase the risk of anaphylactic reactions.

Phenytoin with intravenous injections, means for inhalation anesthesia (derivatives of hydrocarbons) increase the severity of cardiodepressive action and the likelihood of reducing blood pressure.

Efficiency insulin and hypoglycemic agents for oral administration may vary with treatment with bisoprolol (masks the symptoms of developing hypoglycemia: tachycardia, increased blood pressure).

Clearance lidocaine and xanthine (except theophylline) may decrease due to a possible increase in their concentration in the blood plasma, especially in patients with initially elevated clearance of theophylline under the influence of smoking.

Antihypertensive effect weaken Non-steroidal anti-inflammatory drugs (NSAIDs) (retention of sodium ions and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (sodium ion retention).

Cardiac glycosides, methyldopa, reserpine and guanfacine, blockers of "slow" calcium channels (verapamil, diltiazem), amiodarone and other antiarrhythmics increase the risk of developing or worsening bradycardia, AV blockade, cardiac arrest and heart failure.

Simultaneous use with the drug Nifedipine may lead to a risk of enhancing the antihypertensive effect of bisoprolol.

Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs may lead to an excessive decrease in blood pressure.

Act Nondepolarizing muscle relaxants and anticoagulant effect coumarins during the treatment with bisoprolol may be prolonged.

Tricyclic and tetracyclic antidepressants, antipsychotics (antipsychotics), ethanol, sedatives and hypnotics increase the inhibition of the central nervous system.

Not recommended simultaneous PChanging the with MAO inhibitors due to a significant increase in antihypertensive action. A break in treatment between taking MAO inhibitors and bisoprolol should be at least 14 days.

Unhydrated alkaloids of ergot increase the risk of peripheral circulatory disorders.

Ergotamine increases the risk of peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol in the blood plasma.

Rifampicin shortens T_1/2bisoprolol.

Special instructions:

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

It is necessary to teach the patient how to calculate the heart rate and instruct him about the need for medical consultation at a heart rate of less than 60 beats per minute.

Before the start of treatment, it is recommended to perform an external respiration function in patients with a history of bronchopulmonary anamnesis.

Patients who use contact lenses should take into account that against the background of drug treatment, a decrease in the production of tear fluid is possible.

When using the drug Bisoprolol In patients with pheochromocytoma, there is a risk of developing paradoxical hypertension (unless an effective blockade of alpha-adrenergic receptors is previously achieved).

With thyrotoxicosis bisoprolol can mask certain clinical signs of thyrotoxicosis (eg, tachycardia). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated, since it can strengthen symptoms.

In diabetes mellitus can mask tachycardia caused by hypoglycemia. In contrast to nonselective beta-blockers, it does not substantially increase insulin-induced hypoglycemia and does not delay the restoration of glucose concentration in the blood to a normal value.

With the simultaneous use of clonidine, his reception may be discontinued only a few days after drug withdrawal Bisoprolol.

It is possible to increase the severity of the reaction of hypersensitivity and the lack of effect from the usual doses of epinephrine (adrenaline) against the background of a weighed allergic anamnesis. If it is necessary to conduct routine surgical treatment, the drug should be discontinued 48 hours before the general anesthesia. If the patient has taken the drug before surgery, he should choose a drug for general anesthesia with a minimum negative inotropic effect.

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

Medicines that deplete the catecholamine depot (incl. reserpine), can enhance the action of beta-blockers, so patients who take such combinations of drugs should be under constant medical supervision to detect a marked decrease in blood pressure or bradycardia.

Patients with bronchospastic diseases can be cautiously prescribed cardioselective beta-blockers in the 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 can increase. If the dose is exceeded Bisoprolol in such patients there is a risk of developing bronchospasm.

If patients develop an increasing bradycardia (heart rate less than 60 beats per minute), a marked decrease in blood pressure (systolic blood pressure less than 100 mm Hg), AV blockade, it is necessary to reduce the dose or stop treatment.

It is recommended to stop drug therapy Bisoprolol with the development of depression.

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

It is necessary to cancel the drug before the study of the concentration in the blood and urine of catecholamines, normetanefrin, vanillylmandelic acid, antinuclear antibody titers.

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

Effect on the ability to drive transp. cf. and fur:

Application of the drug Bisoprolol does not affect the ability to drive vehicles according to the results of the study in patients with IHD.However, due to individual reactions, the ability to drive vehicles or work with technically complex mechanisms can be disrupted. This should be paid special attention at the beginning of treatment, after changing the dose, as well as with the simultaneous use of alcohol.

Form release / dosage:

Film coated tablets, 2.5 mg, 5 mg and 10 mg.

Packaging:

By 10, 15, 20 or, 30 tablets into a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 1, 2, 3, 5, 10 contour squares with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000903

Date of registration:18.10.2011 / 10.06.2013

Expiration Date:18.10.2016

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Representation: & nbspOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCRussia

Information update date: & nbsp14.02.2017

Illustrated instructions

Instructions

Bisoprolol-OBL (Bisoprolol-OBL)