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

Excipients: lactose monohydrate, microcrystalline cellulose, crospovidone, PB-22812 yellow (lactose monohydrate, iron oxide yellow oxide), magnesium stearate.

1 tablet of 10 mg contains:

active substance: bisoprolol fumarate (bisoprolol hemifumarate) 10 mg;

Excipients: lactose monohydrate, microcrystalline cellulose, crospovidone, PB-27215 dye beige (lactose monohydrate, iron oxide dye yellow, iron oxide oxide red), magnesium stearate.

Description:

Tablets 5 mg: pale yellow with impregnations, round, biconvex tablets with embossed "5" and risk on one side.

Tablets 10 mg: beige with splashes, round, biconvex tablets, embossed "10" and risk on one side.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.07 Bisoprolol

Pharmacodynamics:

Bisoprolol is a selective β₁- adrenoblocker, without its own sympathomimetic activity, does not possess membrane-stabilizing action. 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 β₁-adrenoceptors of the heart, reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic effect, reduces atrioventricular (AV) conductivity and excitability. If the therapeutic dose is exceeded, β₂-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 α-adrenergic receptor activity and elimination of stimulation of β₂-adrenoreceptors), after 1-3 days it returns to the initial level, and with prolonged use it decreases.

The hypotensive effect is associated with a decrease in the minute volume of blood, sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin-aldosterone system (important for patients with initial hypersecretion of renin);restoration of the sensitivity of the aortic arch baroreceptors 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 a decrease in heart rate and a decrease in myocardial contractility, diastole lengthening, and improvement in 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 nonselective β-adrenoceptor blockers, has a less pronounced effect on organs containing β₂-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 (more than 90%) 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%). The connection with blood plasma proteins is about 30%. The volume of distribution is 3.5 l / kg. The total ground clearance is about 15 l / h. The maximum concentration in blood plasma is determined after 1-3 hours. Permeability through the blood-brain barrier and placental barrier - low, secretion with breast milk - 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 (III functional class by classification NYHA) plasma concentrations of bisoprolol are higher, and the half-life is longer than in healthy volunteers. With daily intake of 10 mg of bisoprolol once a day, its maximum plasma concentration is 64 ± 21 ng / ml, and a half-life of 17 ± 5 hours.

Indications:

- Ahyperthermia;

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

Contraindications:

- Hypersensitivity to the components of the drug,

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

- shock (including cardiogenic),

- pulmonary edema,

- AV blockade of II-III degree, without an electrocardiostimulator,

- sinoatrial blockade,

- syndrome of weakness of the sinus node,

- bradycardia (heart rate less than 60 beats / min),

- Cardiomegaly (no signs of heart failure),

- severe arterial hypotension (systolic blood pressure 100 mmHg, especially with myocardial infarction),

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

- severe peripheral circulatory disorders, Raynaud's syndrome,

- metabolic acidosis,

- pheochromocytoma (without simultaneous use of α-blockers),

- simultaneous administration of monoamine oxidase inhibitors (MAO) (with the exception of MAO type B inhibitors),

- concomitant use of floktaphenin and sultopride,

- age under 18 years (effectiveness and safety not established),

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Carefully:

Psoriasis, depression (including in the anamnesis), diabetes mellitus (can mask symptoms of hypoglycemia), bronchospasm (in the anamnesis), conduction desensitizing therapy, AV blockade I extent, Prinzmetal angina, severe renal impairment (creatinine clearance less than 20 mL / min) expressed by human liver, thyrotoxicosis, adherence to a strict diet (with the exception of food of animal proteins), restrictive cardiomyopathy, congenital heart disease or heart disease valve hemodynamic disorders, CHF with myocardial infarction during the last 3 months.

Pregnancy and lactation:

Bisoprolol has pharmacological effects that can have harmful effects on the course of pregnancy and / or on the fetus or newborn.Usually, β-adrenoblockers reduce placental perfusion, which leads to a slowing of fetal growth, intrauterine fetal death, miscarriage, or premature birth. The fetus and newborn child may experience pathological reactions (eg, hypoglycemia, bradycardia, arterial hypotension).

Bisoprolol-ratiopharmum should not be used during pregnancy, it is possible to use it 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-ratopharm is considered necessary, monitoring of uteroplacental blood flow and intrauterine development of the fetus should be carried out. In case of adverse effects on pregnancy or fetus, alternative therapy should be considered. Symptoms of hypoglycemia and bradycardia usually occur within the first 3 days.

Data on the isolation of bisoprolol in breast milk are absent. Therefore, if you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The drug Bisoprolol-ratiofarm taken inside, in the morning on an empty stomach, once, without chewing,with a small amount of liquid.

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. It is possible to divide the daily dose into 2 doses.

If the liver or kidney function is mild or moderate there is usually no need for dose adjustment.

For patients with severe renal dysfunction (clearance of creatinine (CC) less than 20 ml / min) or with pronounced violations of liver function, the maximum daily dose is 10 mg.

Dose adjustment in elderly patients not required.

Side effects:

The frequency of adverse reactions listed below was determined in the following grades: very often (≥ 10%); often (from ≥ 1% up to <10%); infrequently ≥0,1% before < 1%); rarely (from ≥ 0.01% to <0.1%); very rarely (<0.01%, including individual messages).

Impaired nervous system:

often - increased fatigue, asthenia, dizziness, headache. Usually, these phenomena are of an easy nature and usually take place within 1-2 weeks after the start of treatment;

infrequently - sleep disorders, depression; rarely - nightmares, hallucinations.

Heart Disease:

very often bradycardia;

infrequently infringement AV conduction (up to the development of complete transverse blockade and cardiac arrest), arrhythmias, worsening of CHF flow with the development of peripheral edema (swelling of the ankles, feet), dyspnea.

Vascular disorders:

often marked decrease in blood pressure (especially in patients with CHF), manifestation of angiospasm (increased peripheral circulatory disturbances, sensation of coldness in the extremities (paresthesia));

infrequently - orthostatic hypotension.

Disorders from the gastrointestinal tract:

often - nausea, vomiting, diarrhea, abdominal pain, constipation, dryness of the oral mucosa;

rarely - a change in taste.

Disorders from the liver and bile ducts:

rarely - hepatitis, increased activity of liver enzymes (alanine aminotransferase, aspartate aminotransferase), increased bilirubin concentration.

Disturbances from the respiratory system, chest and mediastinal organs:

infrequently - laryngo- and bronchospasm in patients with bronchial asthma or obstructive airway disease;

rarely - allergic rhinitis, nasal congestion.

Disturbances from the musculoskeletal and connective tissue:

infrequently - muscle weakness, cramps in the calf muscles, arthralgia.

Disorders from the side of the organ of vision:

rarely - impaired vision, reduced tearing (should be absorbed when wearing contact lenses);

very rarely - dryness and soreness of the eyes, conjunctivitis.

Hearing disorders and labyrinthine disturbances:

rarely - hearing impairment.

Disturbances from the skin and subcutaneous tissues:

rarely - increased sweating, allergic reactions (skin hyperemia, skin itching, skin rash, urticaria), psoriasis-like skin reactions;

very rarely - alopecia, exacerbation of psoriasis.

Disorders from the endocrine system:

rarely - an increase in the concentration of triglycerides in the blood, hypoglycemia.

Disorders from the genitourinary system:

rarely - a violation of potency, a weakening of the libido.

Immune system disorders:

rarely - the emergence of antinuclear antibodies with unusual clinical symptoms of lupus-like syndrome, which disappear with the end of treatment.

Laboratory and instrumental data:

rarely - an increase in the concentration of triglycerides in the blood;

very rarely - thrombocytopenia, agranulocytosis, leukopenia.

General disorders and disorders at the site of administration:

very rarely - withdrawal syndrome (increased 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: gastric lavage, intake of adsorptive agents, symptomatic therapy.

With developed AV blockade - intravenous injection of 1-2 mg of atropine, epinephrine or the establishment of a temporary pacemaker.

With ventricular extrasystole - lidocaine (preparations IA class do not apply).

If there is a marked decrease in blood pressure, the patient should be in the Trendelenburg position; if there are no signs of pulmonary edema - intravenous injection of plasma-substituting solutions, if they are ineffective - epinephrine, dopamine, dobutamine (to maintain chronotropic and inotropic action and to eliminate the pronounced decrease in blood pressure).

With heart failure - cardiac glycosides, diuretics, glucagon.

With convulsions - in / in diazepam.

With bronchospasm - inhalation β₂-adrenomimetics.

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 doctor should be informed about the use of other medicines, even if the application is carried out without a doctor's order.

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.

Combinations, the use of which is contraindicated:

Floktaphenin

In the case of shock or arterial hypotension caused by the use of floktaphenin, β-adrenoblockers cause a decrease in compensatory cardiovascular reactions.

Sulphoprid

Bisoprolol should not be used concurrently with sultopride, since there is a high risk of ventricular arrhythmias.

Combinations not recommended:

Blocks of "slow" calcium channels (BCC): verapamil, diltiazem

Increase the negative effect on myocardial contractility and atrioventricular conductivity.

Hypotensive drugs of central action (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine)

With the simultaneous administration of anti-hypertensive drugs, central action may develop decompensation of heart failure due to a decrease in the tone of the sympathetic nervous system (decrease in heart rate and strength, vasodilation).

Sudden abolition of the drug may lead to a sharp increase in blood pressure (withdrawal syndrome), especially when this occurs before the abolition of the β-blocker.

MAO inhibitors

MAO type A inhibitors should not be taken concomitantly with bisoprolol, since there is a risk of developing a hypertensive crisis.

Combinations requiring caution:

Antiarrhythmic drugs I class (quinidine, disopyramide)

Possible increase of negative inotropic action and lengthening of time AV (requires strict clinical and electrocardiographic monitoring).

Antiarrhythmic drugs of III class (amiodarone)

Possible amplification of a negative effect on AV conductivity.

BCCC (dihydropyridine derivatives)

Increase the risk of developing arterial hypotension with simultaneous application. In patients with latent congestive heart failure, simultaneous use of β-blockers can lead to decompensation of heart failure.

Cholinesterase inhibitors (including tacrine)

Possible time lengthening AV conduction and (or) increased bradycardia.

Other beta-blockers, including those contained in eye drops

Potentiation of hypotensive effect of bisoprolol.

Insulin and hypoglycemic agents for oral administration

The hypoglycemic effect of insulin or hypoglycemic agents for oral ingestion may be enhanced. Symptoms of hypoglycemia - in particular, tachycardia - can be masked or suppressed. Similar interactions are more likely when using non-selective β-blockers.

Means for anesthesia

Simultaneous reception of bisoprolol and funds for general anesthesia can cause a weakening of reflex tachycardia and an increased risk of developing arterial hypotension.

Cardiac glycosides (digitalis preparations)

Increase the risk of bradycardia, lengthen the time AV conductivity.

Non-steroidal anti-inflammatory drugs (NSAIDs)

Reduce the antihypertensive effect of bisoprolol.

Derivatives of ergotamine

Increase the risk of peripheral circulatory disorders.

β-adrenomimetics (isoprenaline, dobutamine)

Simultaneous reception leads to a weakening effect of both drugs.

Tricyclic antidepressants, barbiturates, phenothiazine and other antihypertensives

Risk of increased hypotensive effect.

Baclofen

Strengthening of hypotensive action. It is necessary to control blood pressure and dose correction of an antihypertensive drug.

Amifostine

Strengthening of hypotensive action.

Special instructions:

In bronchial asthma or other chronic obstructive airway diseases, which are the cause of characteristic symptoms, additional bronchodilator therapy is needed.Periodically in patients with concomitant bronchial asthma, respiratory tract resistance may increase with the use of β-blockers, which requires an increase in the dose of β₂-adrenomimetics. Before the start of treatment, it is recommended to perform an external respiration function in patients with a history of bronchopulmonary anamnesis.

β-adrenoblockers can increase the number and duration of angina attacks in patients with Prinzmetal angina pectoris. The use of selective β₁-adrenoconjugators is possible in patients with mild forms of manifestation and only in combination with vasodilating drugs.

In cases of peripheral circulatory disorders, such as Raynaud's syndrome and "intermittent claudication," there may be an increase in symptoms, especially at the beginning of treatment with Bisoprolol-ratopharm.

Patients using 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-ratopharm in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (unless an effective blockade of α-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 non-selective β-adrenoblockers, it does not substantially increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose to normal levels.

With the simultaneous use of clonidine, his reception can be stopped only a few days after the discontinuation of the drug Bisoprolol-ratiofarm.

In some cases, the use of P-blockers can cause the development or deterioration of the course of psoriasis, or lead to the appearance of psoriatic rashes on the skin.

Bisoprolol-ratiopharm should be administered only after careful weighing of the expected benefit and possible risk.

The control of the condition of patients taking the drug Bisoprolol-ratopharm must include a measurement of heart rate and blood pressure (at the beginning of treatment - every day, then once in 3-4 months), ECG, blood glucose 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 heart rate and instruct about the need for medical consultation at heart rate less than 50 beats per minute. 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 carry out a planned surgical intervention, 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 β-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 prescribed cardioselective β-blockers in case of intolerance and / or ineffectiveness of other antihypertensive agents. When the dose of Bisoprolol-ratopharm is exceeded, there is a danger of developing bronchospasm. If older bradycardia is detected in elderly patients (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-ratiofarm when depression develops.

At the beginning of treatment, the drug should be monitored regularly, especially if the course of therapy is performed by elderly patients. Treatment should not be interrupted suddenly, especially in patients with ischemic heart disease. If discontinuation of treatment is necessary, then the dose should be reduced gradually.

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 (by 25% in 3-4 days).

Bisoprolol-ratiopharm gives a positive result in doping control.

Currently, there is insufficient therapeutic experience of the drug in patients with chronic heart failure in the presence of concomitant diseases:

- chronic heart failure II functional class by classification NYHA,

- diabetes 1 type,

- renal impairment (serum creatinine ≥ 300 μmol / L or ≥ 3.4 mg / dL),

- violations of the liver,

- in patients older than 80 years,

- restrictive cardiomyopathy,

- congenital heart diseases,

- organic heart disease with hemodynamic disorders,

- the first 3 months after myocardial infarction.

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

The intake of the drug does not affect the ability to drive vehicles. However, due to individual reactions, the ability to drive vehicles or work with technically dangerous mechanisms can be disrupted. Especially it should be considered at the beginning of the course of therapy and in case of an increase in the dose.

Form release / dosage:

Tablets, 5 mg and 10 mg.

Packaging:

10 tablets per blister PVC / Al-Folga.

By 3, 5 or 10 blisters with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-007275/10

Date of registration:28.07.2010

Expiration Date:Unlimited

The owner of the registration certificate:ratiofarm GmbHratiofarm GmbH Germany

Manufacturer: & nbsp

MERCKLE, GmbH Germany

Representation: & nbspratiofarm РУС ООО ratiofarm РУС ООО Russia

Information update date: & nbsp14.02.2017

Illustrated instructions

Instructions

Bisoprolol-ratopharm (Bisoprolol-ratiopharm)