for medical use
of BISOPROLOL medicine
the Trade name
Mezhdunarodnoye the unlicensed
name Bisoprolol Lekarstvennaya
the Tablet form, coated, 5 and 10 mg
One tablet contains
active agent: the bisoprolola fumarates – 5 mg or 10 mg,
excipients: magnesium stearate, silicon dioxide colloidal anhydrous, krospovidon, starch corn, cellulose microcrystalline
structure of a cover: Opadray the II yellow: talc, polyethyleneglycol, titan dioxide (E171), polyvinyl alcohol, iron oxide yellow (E172), quinolinic yellow (E104), orange yellow (E110).
Round tablets of a biconvex form, coated yellow color.
Beta blockers. Selection beta blockers.
The ATX C 07AB07 code
Pharmacokinetics Absorption properties – 80 – 90%, meal does not influence absorption. The maximum concentration in blood plasma is observed in 1-3 h, communication with proteins of blood plasma about 30%. Permeability through a blood-brain barrier and a placental barrier – low, secretion with breast milk – low.
The plasma elimination half-life equal to 10-12 hours provides the 24th hour efficiency at reception once a day. About 95% of medicine are removed through kidneys, a half of it in the form of not changed medicine.
In a human body active metabolites are not registered.
Bisoprolol – selection beta1-adrenoblocker without own sympathomimetic activity, (SMA) has hypotensive, antiarrhytmic and anti-anginal effect. Blocking in low doses a beta 1 adrenoceptors of heart, reduces stimulated catecholamines formation of tsAMF from ATP, reduces intracellular current of Sa2+, renders negative hrono-, dromo-, batmo- and inotropic action (urezhat ChSS, the conductivity and excitability oppresses, reduces contractility of a myocardium). At increase in a dose has beta2-adrenoceptor blocking effect. OPSS at the beginning of use of beta blockers, in the first 24 h, increases (as a result of reciprocal increase of activity of alpha adrenoceptors and elimination of stimulation of beta2-adrenoceptors) which in 1-3 days returns to initial, and at long appointment decreases. The hypotensive effect is connected with reduction of the IOC, sympathetic stimulation of peripheral vessels, decrease of the activity of RAAS (has bigger value for patients with initial hypersecretion of renin), recovery of sensitivity of baroreceptors of an aortic arch (there is no strengthening of their activity in response to decrease in the ABP) and influence on central nervous system. In arterial hypertension the effect occurs in 2-5 days, stable action – in 1-2 months. The anti-anginal effect is caused by reduction of need of a myocardium for oxygen as a result of an urezheniye of ChSS and decrease in contractility, lengthening of a diastole, improvement of perfusion of a myocardium. Due to increase in end diastolic pressure in a left ventricle and increases in stretching of muscle fibers of ventricles can increase oxygen requirement, especially at patients with HSN. The antiarrhytmic effect is caused by elimination of aritmogenny factors (tachycardias, superactivity of sympathetic nervous system, the increased maintenance of tsAMF, arterial hypertension), reduction of speed of spontaneous excitement of sinus and ectopic pacemakers and delay of AV of carrying out (mainly in antegrade and to a lesser extent in retrograde the directions through an AV node) and on additional ways. Unlike non-selective beta blockers, when assigning in average therapeutic doses has less significant impact on the bodies containing beta2-adrenoceptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchial tubes and a uterus) and on carbohydrate metabolism, does not cause Na delay + in an organism, the expressiveness of atherogenous action does not differ from effect of propranolol. At use in high doses renders the blocking effect on both subtypes of beta adrenoceptors.
Indications for use
– arterial hypertension
– coronary heart disease (stenocardia)
– chronic heart failure.
The route of administration and doses
of the Tablet should be accepted inside, washing down with a small amount of liquid in the morning till a breakfast, in time or after it. Tablets should not be chewed, broken or pounded in powder.
Treatment of arterial hypertension and coronary heart disease:
At all patients the dose is selected individually, first of all, taking into account ChSS and a condition of the patient.
Adults: As a rule, the initial dose makes 5 mg of 1 times/days. If necessary, the dose can be increased up to 10 mg of 1 times/days. The maximum
daily dose makes 20 mg of 1 times/days.
For patients with serious violations of function of kidneys (clearance of creatinine & lt, 20 ml/min.) and patients with heavy abnormal liver functions the maximum daily dose should not exceed 10 mg a day.
Elderly people: Usually the dose decline is not required, as well as for other adults, the dose of 5 mg a day can be adequate for some patients and can be reduced in cases of serious violation of functions of a liver or kidneys.
Children: There is no experience of use of a bisoprolol by children therefore it is not recommended to be accepted to children.
Treatment of chronic heart failure:
The initiation of treatment of the chronic heart failure (CHF) the drug Bisoprolol demands obligatory carrying out a special phase of titration and regular medical control.
The tablets Bisoprolola have no risks for division into 2 parts (for division of a dose), in the period of an initial stage of titration the bisoprolola of the corresponding dosages is recommended to use other drugs.
Drug treatment begins according to the following scheme of titration. At the same time individual adaptation depending on that can be required, how well the patient transfers the appointed dose, i.e. the dose can be increased only if the previous dose was well transferred.
Week of therapy
the dosing Mode
of 1.25 mg of 1 time/days
the 2nd week
of 2.5 mg of 1 time/days
the 3rd week
of 3.75 mg of 1
time/days 4-7 weeks
of 5 mg of 1
time/days 8-11 weeks
of 7.5 mg of 1 time/days
the 12th week and further
10 mg of 1 time/days as maintenance therapy.
During a phase of titration and after it there can be a temporary deterioration in a course of heart failure, a liquid delay in an organism, arterial hypotension and bradycardia. In this case it is recommended to pay attention to selection of doses of the accompanying basic therapy (to optimize a dose of diuretic and/or APF inhibitor) before Bisoprolol dose decline.
Therapy by the drug Bisoprololom usually is long.
Do not interrupt sharply treatment and do not change the recommended dose without consultation with your doctor as it can lead to temporary aggravation of symptoms of heart. Especially it is not necessary to interrupt suddenly therapy at patients with coronary heart disease. If suspension of treatment is necessary, the daily dose has to decrease gradually.
is Very frequent
– deterioration in the available heart failure
– dizziness, a headache
– nausea, vomiting, diarrhea, a constipation
– cryesthesia or numbness in extremities, hypotonia
– an asthenia, fatigue
– disturbances of atrioventricular conductivity
– a bronchospasm at patients with bronchial asthma or with obstructive diseases of respiratory organs in the anamnesis
– muscle weakness, muscular spasms
– a depression, sleep disorders
– increase in level of triglycerides, increase in level of liver enzymes (ALT, nuclear heating plant)
– reduction of dacryagogue (it is necessary to consider when carrying contact lenses by the patient)
– a hearing disorder
– allergic rhinitis
– reactions of hypersensitivity, such as itching, reddening, rash
– disturbances of potency
– nightmares, hallucinations
Is very rare
– development of psoriasis or exacerbation of already existing disease or rash, like psoriasis
– an alopecia
In isolated cases
– a syncope
Inform your attending physician if you find in yourself any of the listed side effects, either any other undesirable or unexpected effects.
– hypersensitivity to a bisoprolol or to any of components of drug and to other beta blockers
– an acute heart failure, chronic heart failure in a decompensation stage
– the shock caused by disturbance of warm functions (cardiogenic shock), collapse
– atrioventricular block of II and III degree, without electrocardiostimulator
– a sick sinus syndrome
– sinuatrial blockade
– the slowed-down pulse rate causing symptoms (symptomatic
– the lowered blood pressure causing symptoms (symptomatic hypotension)
– severe forms of bronchial asthma and chronic obstructive pulmonary disease in the anamnesis
– late stages of disturbance of peripheric circulation, a Raynaud’s disease
– not treated tumors of adrenal glands (pheochromocytoma)
– a metabolic acidosis
– children’s age up to 18 years (the efficiency and safety are not established).
– diabetes with considerable fluctuations of level of glucose in blood: symptoms of obviously reduced level of glucose (hypoglycemia) such as tachycardia, heartbeat or perspiration can mask
– a rigid diet
– the continuing desensibilizing therapy
– moderate disturbances of atrioventricular conductivity (first extent of AV blockade)
– disturbances of a blood-groove in coronary vessels because of a vascular spasm (Printsmetal’s stenocardia)
– peripheral occlusal damages of arteries (after the beginning of therapy there can be strengthening of symptoms)
– the patients having psoriasis, or having psoriasis in the anamnesis.
Bisoprolol enhances effect of other hypotensive drugs. At a concomitant use with reserpine, α-metildopy and a clonidine bradycardia probability increases. Cardiac glycosides, Methyldopum, reserpine and guanfatsin, BMKK (verapamil, diltiazem), Amiodaronum, etc. antiarrhytmic medicines increase risk of development or aggravation of bradycardia, AV of blockade, cardiac arrest and SN. Nifedipine can lead to considerable decrease in the ABP. Diuretics, a clonidine, sympatholytics, gidralazin, etc. can lead hypotensive medicines to excessive decrease in the ABP. The allergens used for an immunotherapy or extracts
of allergens for skin tests increase risk of emergence of heavy system allergic reactions or an anaphylaxis at the patients receiving bisoprolol.
Iodinated X-ray contrast medicines for in/in introductions increase risk of development of anaphylactic reactions.
Phenytoinum at in in introduction, medicines for inhalation general anesthesia (derivatives of hydrocarbons) increase expressiveness of cardiodepressive action and probability of decrease in the ABP.
Bisoprolol changes efficiency of insulin and oral hypoglycemic medicines, masks symptoms of the developing hypoglycemia (tachycardia, increase in the ABP). Bisoprolol reduces clearance of lidocaine and xanthines, and increases their concentration in plasma, especially at patients with initially increased clearance of theophylline under the influence of smoking.
NPVP weaken hypotensive effect (Na delay + and blockade of synthesis of prostaglandins kidneys).
Bisoprolol extends action of not depolarizing muscle relaxants and anticoagulating effect of coumarins.
Rub – and tetracyclic antidepressants, antipsychotic HP (neuroleptics), ethanol, sedative and HP hypnotic drugs strengthen oppression of central nervous system.
Simultaneous use with MAO inhibitors owing to considerable strengthening of hypotensive action is not recommended, having rummaged in treatment between intake of MAO inhibitors and a bisoprolola has to make not less than 14 days.
Not hydrogenated alkaloids of an ergot increase risk of development of disturbances of peripheric circulation. Ergotamine increases risk of development of disturbance of peripheric circulation, Sulfasalazinum increases concentration of a bisoprolol in plasma, rifampicin reduces elimination half-life of a bisoprolol.
Intravenous administration of antagonists of calcium and antiarrhytmic means is not recommended during use of a bisoprolol.
Respiratory system: In bronchial asthma or other symptomatic chronic obstructive diseases of lungs the accompanying bronchodilatory therapy is shown. Patients to asthma can sometimes have an increase in resistance of airways that demands higher dosage of beta2-sympathomimetics.
Allergic reactions: Beta-blockers, including Bisoprolol, can increase sensitivity to allergens and weight of anaphylactic reactions because of weakening of adrenergic return regulation under the influence of beta-blockers. Treatment by adrenaline not always gives the expected therapeutic effect.
General anesthesia: The anesthesiologist has to apply with care beta-blockers at the patients who are exposed to the general anesthesia. If the patient Bisoprolol needs to appoint before operation, it should be done gradually, and full 48 hours prior to anesthesia.
Pheochromocytoma: At patients with a tumor of adrenal glands (pheochromocytoma) Bisoprolol can be appointed only after the previous blockade of alpha receptors.
Thyrotoxicosis: at drug treatment Bisoprolol symptoms of hyperfunction of a thyroid gland (thyrotoxicosis) can mask.
Special groups of patients
At the moment patients have no sufficient therapeutic experience of use of drug Bisoprolol with heart failure and the accompanying achrestic diabetes of the I type, heavy renal failures, heavy abnormal liver functions, a restrictive cardiomyopathy, congenital heart diseases or organic defects of valves of heart breaking a hemodynamics. Also patients have no sufficient therapeutic experience of use of drug Bisoprolol with heart failure and a myocardial infarction for the last 3 months.
Special groups of patients
Renal failure or liver:
Treatment of arterial hypertension or stenocardia:
In an abnormal liver function or kidneys of easy or moderate degree usually does not demand correction of a dose.
In the profound renal failures (clearance of creatinine less than 20 ml/min.) and at patients with a serious illness of a liver the maximum daily dose makes 10 mg.
Pregnancy and the period of a lactation
during pregnancy Bisoprolol should be recommended only if the advantage for mother exceeds risk of development of side effects at a fruit. As a rule, beta blockers reduce a blood stream in a placenta and can influence fetation. It is necessary to trace attentively a blood stream in a placenta and a uterus and also to monitor growth and development of future child, and in case of dangerous manifestations concerning pregnancy or a fruit, to take alternative therapeutic measures.
It is necessary to examine carefully the newborn after the delivery. In the first three days of life there can be symptoms of decrease in level of glucose in blood and ChSS.
There are no data on excretion of a bisoprolol in breast milk or safety of impact of a bisoprolol on babies. Therefore administration of drug Bisoprolol is not recommended to women during feeding by a breast.
Features of influence of medicine on ability to run the vehicle or potentially dangerous
Bisoprolol mechanisms did not affect ability to drive the car at a research of the patients having diseases of coronary vessels of heart. However owing to individual reactions the ability to drive the car or work with technically difficult mechanisms can be broken. On it it is necessary to pay special attention in an initiation of treatment, after change of a dose and also at simultaneous alcohol intake.
Symptoms: arrhythmia, ventricular premature ventricular contraction, profound bradycardia, AV blockade, decrease in the ABP, HSN, cyanosis of nails of fingers or palms, breath difficulty, bronchospasm, dizziness, unconscious states, spasms.
Treatment: gastric lavage and prescribing of the adsorbing medicines, symptomatic therapy: at the developed AV to blockade – in/in introduction of 1-2 mg of atropine, epinephrine or statement of a temporary pacemaker, in ventricular premature ventricular contraction – lidocaine (drugs 1a of a class are not used), at decrease in the ABP – the patient has to be in position of Trendelenburg if there are no symptoms of a fluid lungs, – in/in plasma substituting solutions, at inefficiency – administration of epinephrine, a dopamine, Dobutaminum (for maintenance of chronotropic and inotropic action and elimination of the significant decrease in the ABP), at SN – cardiac glycosides, diuretics, a glucagon, in spasms – in/in diazepam, at a bronchospasm – β2-адреностимуляторы is inhalation.
The form of release and packing
On 10 or 15 tablets place in blister strip packaging from a film of polyvinylchloride and aluminum foil.
On two, three or five blister strip packagings on 10 tablets together with the instruction for medical use on state and Russian in a pack from cardboard.
On two blister strip packagings on 15 tablets together with the instruction for medical use on state and Russian in a pack from cardboard.
To Store storage conditions in the place protected from moisture and light at a temperature not above 25 °C.
To store out of children’s reach!
not to use a period of storage after the expiration date specified on packing.
According to the prescription
Producer SOOO “Lekfarm”, Republic of Belarus, 223110, Logoysk, Minskaya St., 2a Ph./fax: (01774)-53801 e-mail: firstname.lastname@example.org
the Owner of the registration certificate
of SOOO “Lekfarm”, Republic of Belarus
the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods) of TsentrAziyaFarm LLP, 050030, Republic of Kazakhstan Almaty, Suyunbaya Ave., 258 V ph. 727 232 90 50, 727 385 04 00