Instructions for use Bisoprolol-Teva tablets 5 mg blister No. 30
Composition
active ingredient: bisoprolol;
1 tablet contains bisoprolol hemifumarate 5 mg;
excipients: lactose monohydrate, microcrystalline cellulose, crospovidone, magnesium stearate;
for 5 mg tablets, yellow dye RV 22812 (which contains: lactose monohydrate, iron oxide yellow (E 172)).
Dosage form
Pills.
Main physicochemical properties:
5 mg tablets – pale yellow with specks, round, biconvex tablets with embossing “5” and a break line on one side.
Pharmacotherapeutic group
Selective β-adrenergic blockers.
ATX code C07A B07.
Pharmacological properties
Pharmacodynamics
Bisoprolol is a highly selective β1-adrenergic blocker. It has no intrinsic sympathomimetic activity and no clinically significant membrane-stabilizing properties. The drug has a very low affinity for β2-receptors of bronchial and vascular smooth muscle, as well as for β2-receptors involved in metabolic regulation. Thus, bisoprolol does not affect airway resistance and β2-mediated metabolic effects. The selectivity of bisoprolol for β1-adrenergic receptors extends beyond the therapeutic dose range.
Bisoprolol does not have a pronounced negative inotropic effect.
The maximum effect of bisoprolol occurs 3-4 hours after administration. The half-life from blood plasma is 10-12 hours, which results in 24-hour efficacy after a single dose of the drug. The maximum antihypertensive effect is achieved after 2 weeks of administration.
In intensive therapy in patients with coronary heart disease without chronic heart failure, bisoprolol reduces cardiac output and myocardial oxygen demand by reducing heart rate and stroke volume. With prolonged therapy, increased peripheral resistance decreases. The antihypertensive effect of β-blockers is also based on the mechanism of action of reducing plasma renin activity.
Bisoprolol inhibits the response to sympathoadrenergic activity by blocking cardiac β1 receptors. This leads to a slowdown in heart rate and a decrease in myocardial contractile function, which leads to a decrease in myocardial oxygen demand. This achieves the desired effect in patients with angina pectoris and ischemic heart disease.
Pharmacokinetics
After oral administration, more than 90% of bisoprolol is absorbed from the gastrointestinal tract. Absorption is independent of food intake. The first-pass effect is insignificant, which contributes to high bioavailability - approximately 90%. Binding to plasma proteins is approximately 30%. The volume of distribution is 3.5 l/kg.
Bisoprolol is eliminated from the body in two ways: approximately 50% is metabolized in the liver to form inactive metabolites and excreted by the kidneys, 50% is excreted by the kidneys unchanged. The total clearance of bisoprolol is 15 l/h. Due to the long half-life (10-12 hours), the drug retains its therapeutic effect for 24 hours when administered once a day.
The kinetics of bisoprolol are linear and independent of age.
Since the kidneys and liver are involved in the elimination of this drug approximately equally, no dose adjustment is required in patients with renal or hepatic insufficiency. In patients with chronic heart failure of the III functional class (according to the NYHA classification - New York Heart Association), the level of bisoprolol in the blood plasma is higher and the half-life is longer compared to healthy volunteers. The maximum plasma concentration in the equilibrium state is 64±21 ng/ml at a daily dose of 10 mg and a half-life of 17±5 hours.
Indication
Arterial hypertension; ischemic heart disease (angina pectoris); chronic heart failure with left ventricular systolic dysfunction in combination with ACE inhibitors, diuretics, and if necessary, cardiac glycosides.
Contraindication
Hypersensitivity to bisoprolol, other β-blockers or any of the components of the drug; acute heart failure or heart failure in a state of decompensation requiring intravenous inotropic therapy; cardiogenic shock; atrioventricular block of the second and third degree (except in patients with an artificial pacemaker); sick sinus syndrome; sinoatrial block; symptomatic bradycardia; symptomatic arterial hypotension; severe bronchial asthma or severe chronic obstructive pulmonary disease; severe forms of peripheral arterial occlusive disease or severe forms of Raynaud's syndrome; metabolic acidosis; untreated pheochromocytoma; simultaneous use with floctafenine and sultopride.
Interaction with other medicinal products and other types of interactions
Contraindicated combinations
Floctafenine: β-blockers may interfere with compensatory cardiovascular reactions associated with hypotension or shock that may be caused by floctafenine.
Sultopride: bisoprolol should not be used concomitantly with sultopride due to an increased risk of ventricular arrhythmia.
Not recommended combinations
Class I antiarrhythmics (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): possible potentiation of the effect on atrioventricular conduction and increased negative inotropic effect (careful clinical and ECG monitoring is necessary).
All indications
Calcium antagonists (verapamil group, to a lesser extent diltiazem): negative effect on myocardial inotropic function and atrioventricular conduction. Intravenous administration of verapamil in patients taking β-blockers can lead to severe hypotension and atrioventricular block. Centrally acting antihypertensive drugs (clonidine, methyldopa, guanfacine, moxonidine, rilmenidine): possible worsening of heart failure due to decreased central sympathetic tone (decreased heart rate and cardiac output, vasodilation). Abrupt withdrawal of the drug, especially if it is preceded by withdrawal of β-adrenoreceptor blockers, may increase the risk of rebound hypertension. Monoamine oxidase inhibitors (MAO) (except MAO inhibitors type B): increased hypotensive effect of β-blockers, there is a risk of developing hypertensive crisis.
Combinations to be used with caution
Treatment of arterial hypertension or coronary heart disease (angina pectoris)
Class I antiarrhythmic drugs (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): possible potentiation of the effect on atrioventricular conduction and increased negative inotropic effect.
All indications
Calcium antagonists (dihydropyridine derivatives, e.g. nifedipine, felodipine, amlodipine): possible increased risk of arterial hypotension. The possibility of increased negative effects on myocardial inotropic function in patients with heart failure cannot be excluded. Class III antiarrhythmics (e.g. amiodarone): possible potentiation of effects on atrioventricular conduction. Other β-blockers, including topical β-blockers (e.g. those contained in eye drops for the treatment of glaucoma): possible enhancement of the systemic effects of bisoprolol. Parasympathomimetics: possible increase in atrioventricular conduction time and increased risk of bradycardia. Insulin and oral antidiabetic agents: increased hypoglycemic effect. β-adrenoceptor blockade may mask symptoms of hypoglycemia.
Anesthetics: attenuation of reflex tachycardia, increased risk of myocardial depression and hypotension (see section "Special warnings and precautions for use").
Cardiac glycosides: decrease in heart rate, increase in atrioventricular conduction time. Nonsteroidal anti-inflammatory drugs (NSAIDs): possible weakening of the hypotensive effect of bisoprolol. Ergotamine derivatives: increased peripheral circulatory disorders. β-sympathomimetics (e.g. isoprenaline, orciprenaline, dobutamine): use in combination with bisoprolol may lead to a decrease in the therapeutic effect of both drugs. Higher doses of adrenaline may be required for the treatment of allergic reactions. Sympathomimetics that activate α- and β-adrenoceptors (e.g. adrenaline, noradrenaline), a possible manifestation of α-adrenoceptor-mediated vasoconstrictor effect, which leads to an increase in blood pressure and an increase in the phenomenon of intermittent claudication. Such an interaction is more likely when using non-selective β-blockers.
When used concomitantly with antihypertensive agents and agents with hypotensive effects (e.g. tricyclic antidepressants, barbiturates, phenothiazines), the risk of arterial hypotension may increase.
Baclofen: increased hypotensive effect.
Amifostine: increased hypotensive effect.
In case of simultaneous use, consider
Mefloquine: possible increased risk of bradycardia.
Corticosteroids: decreased hypotensive effect due to water and sodium retention in the body.
Rifampicin: A slight reduction in the half-life of bisoprolol may occur due to induction of hepatic drug-metabolizing enzymes. No dose adjustment is usually required.
Application features
Treatment of stable chronic heart failure with bisoprolol should begin with a titration phase.
In patients with coronary heart disease, treatment should not be stopped abruptly without urgent need, as this may lead to a transient deterioration of the condition. In patients with coronary heart disease, there is a risk of myocardial infarction or sudden death in the event of abrupt discontinuation of treatment (for more details see section "Method of administration and dosage"). Initiation and discontinuation of bisoprolol treatment requires regular monitoring.
Currently, there is insufficient therapeutic experience in the treatment of heart failure in patients with the following diseases and pathological conditions: type 1 diabetes mellitus (insulin-dependent), severe renal impairment, severe hepatic impairment, restrictive cardiomyopathy, congenital heart disease, hemodynamically significant acquired valvular heart disease, myocardial infarction within the last 3 months.
bronchospasm (bronchial asthma, obstructive airways diseases); simultaneous treatment with cholinesterase inhibitors (including tacrine): possible increase in atrioventricular conduction time or increased bradycardia; use of iodine-containing contrast agents: b-blockers can interfere with compensatory cardiovascular reactions in case of arterial hypotension or shock caused by the use of iodine-containing contrast agents; diabetes mellitus with significant fluctuations in blood glucose levels - due to the possibility of masking symptoms of hypoglycemia (tachycardia, palpitations, increased sweating). When treated with bisoprolol, it is necessary to monitor blood glucose levels; strict diet; desensitization therapy. Like other β-blockers, bisoprolol can increase sensitivity to allergens and increase the severity of anaphylactic reactions. In such cases, treatment with adrenaline does not always give a positive therapeutic effect; atrioventricular block of the 1st degree; Prinzmetal's angina; obliterating peripheral arterial diseases (at the beginning of therapy, complaints may worsen); general anesthesia.
It is necessary to inform the anesthesiologist about the use of β-adrenergic blockers. In patients who are scheduled for general anesthesia, the use of β-blockers reduces the incidence of arrhythmia and myocardial ischemia during induction of anesthesia, intubation and the postoperative period. It is recommended to continue the use of β-blockers during the perioperative period. It is necessary to inform the anesthesiologist about the use of β-adrenergic blockers, since the doctor must take into account the potential interaction with other drugs, which can lead to bradyarrhythmia, reflex tachycardia and a decrease in the ability of the reflex mechanism to compensate for blood loss. In case of discontinuation of bisoprolol before surgery, the dose should be gradually reduced and the drug should be discontinued 48 hours before general anesthesia.
Combinations of bisoprolol with calcium antagonists of the verapamil or diltiazem group, with class I antiarrhythmic drugs and with centrally acting antihypertensive agents are not recommended (see section "Interaction with other medicinal products and other types of interactions").
Although cardioselective β-blockers (β1) have less effect on lung function than non-selective β-blockers, their use, like all β-blockers, should be avoided in obstructive airways disease unless there is a compelling reason for treatment. If necessary, bisoprolol should be used with caution. In patients with obstructive airways disease, treatment with bisoprolol should be initiated at the lowest possible dose and patients should be monitored for new symptoms (such as dyspnea, exercise intolerance, cough).
In bronchial asthma or other chronic obstructive pulmonary diseases that may cause symptoms, concomitant therapy with bronchodilators is indicated. In some cases, patients with bronchial asthma may require higher doses of β2-sympathomimetics due to increased airway resistance while taking the drug.
Patients with psoriasis (including those with a history of psoriasis) are prescribed β-blockers (e.g. bisoprolol) after a careful assessment of the benefit/risk ratio.
Patients with pheochromocytoma are prescribed bisoprolol only after treatment with α-blockers.
Symptoms of thyrotoxicosis may be masked while taking the drug.
When using bisoprolol, a positive result may be observed during doping control.
The drug contains lactose, so it should not be prescribed to patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
Ability to influence reaction speed when driving vehicles or other mechanisms
It has been reported that in patients with coronary heart disease, the drug did not affect the ability to drive. However, in individual cases, the drug may affect the ability to drive or operate complex mechanisms. Special caution is required at the beginning of treatment, when changing the dose of the drug or when interacting with alcohol.
Use during pregnancy or breastfeeding
Pregnancy. Bisoprolol has pharmacological properties that may cause harmful effects on the course of pregnancy and/or the development of the fetus/newborn. As a rule, β-blockers reduce placental blood flow, which may cause intrauterine growth retardation, intrauterine death, spontaneous abortion or premature birth. Adverse effects in the fetus and newborn (e.g. hypoglycemia, bradycardia) may develop. If treatment with a β-blocker is necessary, it is preferable that it be a β1-selective adrenoblocker.
After delivery, the newborn should be closely monitored. Symptoms of hypoglycemia and bradycardia can be expected during the first 3 days.
Breastfeeding. There is no data on the excretion of bisoprolol into breast milk. Therefore, taking the drug is not recommended during breastfeeding.
Method of administration and doses
The tablets are intended for oral administration. Bisoprolol-Teva tablets should be taken in the morning on an empty stomach, during or after breakfast, swallowed without chewing, with a small amount of liquid. The tablet can be divided into equal doses.
Arterial hypertension; coronary heart disease (angina pectoris)
Treatment should be started gradually with low doses and then increased. The recommended dose is 5 mg per day. In case of moderate hypertension (diastolic blood pressure up to 105 mm Hg), a dose of 2.5 mg is suitable.
If necessary, the daily dose can be increased to 10 mg per day. Further dose increases are justified only in exceptional cases. The maximum recommended dose is 20 mg per day.
Dose adjustments are determined by the physician individually depending on pulse rate and therapeutic benefit.
Chronic heart failure with left ventricular systolic dysfunction in combination with ACE inhibitors, diuretics, and if necessary, cardiac glycosides
Standard therapy for chronic heart failure: ACE inhibitors (or angiotensin receptor blockers in case of intolerance to ACE inhibitors), β-adrenergic blockers, diuretics and, if necessary, cardiac glycosides.
Bisoprolol is prescribed for the treatment of patients with chronic heart failure without signs of exacerbation.
Therapy should be carried out by a doctor with experience in the treatment of chronic heart failure.
Treatment of chronic heart failure with bisoprolol is initiated according to the titration schedule below and may be adjusted depending on individual body responses.
1.25 mg* bisoprolol hemifumarate once daily for 1 week, increasing to 2.5 mg* bisoprolol hemifumarate once daily for the next 1 week, increasing to 3.75 mg* bisoprolol hemifumarate once daily for the next 1 week, increasing to 5 mg bisoprolol hemifumarate once daily for the next 4 weeks, increasing to 7.5 mg bisoprolol hemifumarate once daily for the next 4 weeks, increasing to 10 mg bisoprolol hemifumarate once daily as maintenance therapy.
* Use bisoprolol in the appropriate dosage.
Bisoprolol at a dose of 2.5 mg is recommended for use at the beginning of therapy for chronic heart failure.
The maximum recommended dose is 10 mg once a day.
During the titration phase, the following vital signs (blood pressure, heart rate) and symptoms of heart failure progression should be monitored. Symptoms may develop from the first day after starting treatment.
Treatment modification
If the maximum recommended dose is not tolerated, a gradual dose reduction may be considered. If during or after the titration phase there is a gradual worsening of heart failure, hypotension or bradycardia, dose adjustment is recommended, which may require a temporary reduction in the bisoprolol dose or possibly discontinuation of treatment. After the patient's condition has stabilized, the possibility of reinitiating bisoprolol treatment should always be considered.
Treatment with the drug should not be stopped suddenly, especially in patients with ischemic heart disease, as this may lead to a deterioration in the patient's condition. If necessary, treatment with the drug is recommended to be discontinued slowly, gradually reducing the dose (for example, reducing the dose by half every week).
Treatment of stable chronic heart failure is usually long-term.
The course of treatment with bisoprolol is long and depends on the nature and severity of the disease.
Patients with impaired renal and hepatic function
Arterial hypertension; ischemic heart disease
For patients with mild to moderate hepatic or renal impairment, dose adjustment is usually not required. In patients with severe renal impairment (creatinine clearance <20 ml/min) and in patients with severe hepatic impairment, a daily dose of 10 mg is not recommended. There are limited data on the use of bisoprolol in patients on dialysis. There is no need to change the dosage regimen.
Chronic heart failure
There are no data on the pharmacokinetics of bisoprolol in patients with chronic heart failure concomitant with impaired liver and/or kidney function, therefore, increasing the dose should be done with caution.
For elderly patients, dosage adjustment of bisoprolol is not required.
Children
There is no clinical data on the efficacy and safety of the drug for the treatment of children, therefore the drug should not be used in this category of patients.
Overdose
In case of overdose (for example, using a daily dose of 15 mg instead of 7.5 mg), cases of third-degree atrioventricular block, bradycardia and dizziness have been recorded. The most common signs of overdose with β-blockers are bradycardia, arterial hypotension, acute heart failure, bronchospasm, hypoglycemia. There is a wide variability in individual sensitivity to a single high dose of bisoprolol, patients with heart failure may be more sensitive to the drug. Therefore, treatment should be started with a gradual increase in dosage (see section "Method of administration and dosage").
Treatment
In case of overdose, treatment with the drug is discontinued and supportive and symptomatic therapy is carried out. There is limited evidence that bisoprolol is difficult to dialyze. In case of suspected overdose, in accordance with the expected pharmacological action and based on recommendations for other β-blockers, the following general measures should be considered.
For bradycardia: intravenous atropine. If there is no response, isoprenaline or another drug with a positive chronotropic effect is administered with caution. In exceptional cases, transvenous administration of an artificial pacemaker may be necessary.
For hypotension: intravenous fluids and vasoconstrictors. Intravenous glucagon may be useful.
In case of second and third degree atrioventricular block: careful observation and infusion of isoprenaline or transvenous pacemaker.
In case of exacerbation of chronic heart failure: intravenous administration of diuretics, inotropic drugs, vasodilators.
For bronchospasm: bronchodilators (e.g. isoprenaline), β2-adrenomimetics and/or aminophylline.
For hypoglycemia: intravenous glucose administration.
Adverse reactions
Adverse reactions are classified according to frequency as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); frequency unknown (cannot be estimated from the available data).
On the part of the immune system
Rare: appearance of antinuclear antibodies with specific clinical symptoms such as lupus-like syndrome, which disappears after discontinuation of treatment.
Metabolism and nutrition
Rare: hypoglycemia.
From the psyche
Uncommon: sleep disorders, depression.
Rare: nightmares, hallucinations.
From the nervous system
Common: fatigue, exhaustion, dizziness*, headache*.
Rare: loss of consciousness.
From the organs of vision
Rare: decreased tear production (should be taken into account when wearing contact lenses).
Very rare: conjunctivitis.
From the hearing organs
Rare: hearing impairment.
From the heart
Very common: bradycardia (in patients with chronic heart failure).
Common: signs of worsening of pre-existing heart failure (in patients with chronic heart failure).
Uncommon: bradycardia (in patients with arterial hypertension or ischemic heart disease), atrioventricular conduction disorders, signs of worsening of pre-existing heart failure (in patients with arterial hypertension or ischemic heart disease).
From the vascular side
Common: feeling of coldness or numbness of the extremities, worsening of pre-existing intermittent claudication, hypotension (especially in patients with heart failure).
Uncommon: orthostatic hypotension.
Respiratory system
Uncommon: bronchospasm in patients with a history of bronchial asthma or obstructive airways disease.
Rare: allergic rhinitis.
Gastrointestinal tract
Common: gastrointestinal complaints such as nausea, vomiting, diarrhea, abdominal pain, constipation.
Liver
Rare: hepatitis.
Skin and subcutaneous tissue disorders
Rare: hypersensitivity reactions including itching, redness, rash.
Very rare: β-blockers may cause or exacerbate psoriasis, psoriatic rashes, hair loss.
Musculoskeletal system
Uncommon: muscle weakness, cramps, arthropathy.
From the reproductive system
Rare: impotence.
General disorders
Common: asthenia (in patients with chronic heart failure), fatigue*.
Uncommon: asthenia (in patients with arterial hypertension or ischemic heart disease).
Laboratory studies
Rare: increased triglyceride levels in the blood, increased activity of liver enzymes in the blood plasma (AST, ALT).
* Applies only to patients with arterial hypertension or coronary heart disease. These symptoms usually occur at the beginning of therapy, are mild and disappear within the first 1-2 weeks.
In case of side effects or adverse reactions, you should immediately inform your doctor.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 ° C in the original packaging in order to protect from moisture. Keep out of the reach of children.
Packaging
10 tablets in a blister, 3 blisters in a box.
Vacation category
According to the recipe.
Producer
Merkle GmbH.
Location of the manufacturer and its business address
Ludwig-Merkle-Strasse 3, 89143 Blaubeuren, Germany.
