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

Excipients: cellulose microcrystalline (21.10 / 20.00 mg), mannitol (148,50 / 144,60 mg), croscarmellose sodium (1.80 / 1.80 mg), magnesium stearate (3.60 / 3.60 mg) ;

film sheath: hypromellose 2.19 mg, titanium dioxide 0.88 mg, macrogol-6000 0.53 mg; it is allowed to use the finished shell "OPADRY^® 03F280038 white" (hypromellose 60,83%, titanium dioxide 24,45%, macrogol-6000 14,72%).

Description:

Round, biconvex tablets, covered with a film shell of white or almost white color, with engraving on one side: "BISOPROLOL 5" (dosage of 5 mg) or "BISOPROLOL 10" (dosage of 10 mg).

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.07 Bisoprolol

Pharmacodynamics:

Bisoprolol - selective beta₁-adrenoceptor without its own sympathomimetic activity, does not possess membrane-stabilizing action.

As for the other beta₁adrenoblockers, the mechanism of action for arterial hypertension is unclear. At the same time, it is known that 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 antianginal 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 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 arterial hypertension, the effect develops in 2-5 days, a 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 final diastolic pressure in the left ventricle 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, eating does not affect absorption. The effect of "first passage" through the liver is insignificant, 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. Permeability through the blood-brain barrier and the placental barrier is low.

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

Bisoprolol is excreted from the body in two ways, 50% of 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 intestines (with bile).

Since excretion takes place in the kidneys and in the liver equally, patients with a dysfunction of the liver or with renal insufficiency do not need to adjust the dose.The pharmacokinetics of bisoprolol is linear and does not depend on age.

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

Indications:

- Arterial hypertension;

- Ischemic heart disease: prevention of attacks stable angina pectoris.

Contraindications:

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

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

- cardiogenic shock;

- collapse;

- atrioventricular (AV) blockade II-III degree, without a pacemaker;

- sinoatrial blockade;

- syndrome of weakness of the sinus node;

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

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

- cardiomegaly (no signs of heart failure);

- severe forms of bronchial asthma and chronic obstructive disease lung (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) (with the exception of MAO type B inhibitors);

- concomitant use of floktaphenin and sultopride.

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

Carefully:

Psoriasis, depression (including history), diabetes mellitus (can mask symptoms of hypoglycemia), allergic reactions (in the anamnesis), bronchospasm (in the anamnesis), desensitizing therapy, prinzmetal angina, AV blockade of the I degree, expressed disturbances of kidney function (creatinine clearance (CC) less than 20 ml / min); severe liver dysfunction; thyrotoxicosis, advanced age.

Pregnancy and lactation:

Pregnancy

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-Teva 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 case when treatment with Bisoprolol-Teva 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 undesirable pregnancy and / or fetal events, alternative methods should be adopted therapy. You should carefully examine the newborn after delivery. Symptoms of hypoglycemia and bradycardia usually arise during the first 3 days of life.

Breastfeeding period

There is no data on the penetration of bisoprolol into breast milk. Therefore, taking Bisoprolol-Teva is not recommended for women during lactation.

If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The drug Bisoprolol-Teva is taken orally, 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 pectoris the maximum daily dose is 20 mg 1 time / day.

For patients with severe renal dysfunction (SC less than 20 ml / min) or with severe hepatic impairment the maximum daily dose is 10 mg once a day. Increasing the dose in such patients should be done with extreme caution.

Dose adjustment in elderly patients not required.

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 CHF); a feeling of palpitations; often marked decrease in blood pressure (especially in patients with CHF), manifestation of angiospasm (increased peripheral circulatory disorders, cold sensation in the extremities (paresthesia), infrequent - violation AV conduction (up to the development of complete transverse blockade and cardiac arrest), arrhythmias, orthostatic hypotension, aggravation of CHF with development of peripheral edema (swelling of the ankles, stop, shortness of breath), chest pain.

From the nervous system: often - dizziness headache, asthenia, fatigue, sleep disturbances, 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 - visual impairment, decrease 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, pain in the back.

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, urticaria

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).

Overdose:

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

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.

When AV blockade: patients should be under constant supervision, and receive treatment with beta-adrenomimetics, such as epinephrine. If necessary - staging an artificial pacemaker.

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

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

Interaction:

The effectiveness and tolerability of drugs can be affected by the simultaneous use of other drugs. This interaction can also occur when two drugs are taken in a short time. The physician should be informed about the use of other medicines, even if the application is carried out without a prescription.

Antiarrhythmic drugs of the first class (for example, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone) with simultaneous application with bisoprolol may reduce AV conduction and contractility of the myocardium.

Antiarrhythmic drugs of the III class (for example, amiodarone) can increase the violation AV conductivity.

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

Parasympatomimetics with simultaneous use with bisoprolol may increase the disruption AV conductivity and increase the risk of developing a bradycardia.

The simultaneous use of Bisoprolol-Teva with beta-adrenomimetics (eg, isoprenaline, dobutamine) can lead to a decrease in the effect of both drugs.

The combination of bisoprolol with adrenomimetics, affecting beta and alpha-adrenergic receptors (for example, norepinephrine, 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 tools for intravenous administration increase the risk of anaphylactic reactions.

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

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

The clearance of lidocaine and xanthines (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.

The hypotensive effect weakens non-steroidal anti-inflammatory drugs (NSAIDs) (sodium ion delay and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (sodium ion delay).

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

Nifedipine can lead to a significant reduction in blood pressure.

Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensives can lead to excessive blood pressure lowering.

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

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

It is not recommended simultaneous use with MAO inhibitors due to a significant increase in antihypertensive effect. A break in treatment between taking MAO inhibitors and bisoprolol should be at least 14 days.

Unhydrated ergot alkaloids 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 the half-life of bisoprolol.

Special instructions:

Monitoring the condition of patients taking the drug Bisoprolol-Teva, should include measurement of heart rate and blood pressure, ECG, determination of blood glucose in patients with diabetes (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 heart rate and instruct about the need for medical consultation at heart rate less than 50 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-Teva in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (if not previously achieved effective blockade of alpha-adrenergic receptors).

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 non-selective 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, its administration can be stopped only a few days after the discontinuation of Bisoprolol-Teva.

It is possible to increase the severity of the reaction of hypersensitivity and the lack of effect from the usual doses of epinephrine against the background of a burdened allergological 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. When the dose of Bisoprolol-Teva is exceeded in such patients, there is a danger of developing bronchospasm.

If patients develop an increasing bradycardia (heart rate less than 50 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 therapy with Bisoprolol-Teva 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 examining the concentration in the blood and urine of catecholamines, normetanephrine, vanillin-mandelic acid, antinuclear antibody titers.

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

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

The use of bisoprolol-Teva does not affect the ability to drive vehicles according to the results of the study in patients with ischemic heart disease.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:Tablets, film-coated, 5 mg and 10 mg.

Packaging:

10 tablets in a blister of PVC / PVDC film and aluminum foil. 3 or 5 blisters together with instructions for use in a cardboard pack.

When produced at OOO Teva, Russia

10 tablets in the blister of PVC / PVDC film according to GOST 25250-88 or Eur.Ph. current edition and aluminum foil in accordance with GOST 745-2014 or TU 9570-001-63543701-11.

3 or 5 blisters together with instructions for use in a pack of cardboard in accordance with GOST 12303-80 from cardboard type chrome or chrome-ersatz according to GOST 7933-89 or other similar quality.

Storage conditions:

Store at a temperature not 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:LSR-007326/10

Date of registration:29.07.2010 / 26.07.2016

Expiration Date:Unlimited

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Works Private, Ltd. Co. Hungary

Teva, Open Company Russia

Representation: & nbspTeva Teva Israel

Information update date: & nbsp07.04.2017

Illustrated instructions

Instructions

Bisoprolol-Teva (Bisoprolol-Teva)