Instructions for use Bisoprolol-KV tablets 10 mg blister No. 30
Composition
active ingredient: bisoprolol;
5 mg: 1 tablet contains bisoprolol fumarate 5 mg;
excipients: lactose monohydrate, microcrystalline cellulose, crospovidone, magnesium stearate; iron oxide yellow dye (E 172);
10 mg: 1 tablet contains bisoprolol fumarate 10 mg;
Excipients: lactose monohydrate, microcrystalline cellulose, crospovidone, magnesium stearate; iron oxide yellow (E 172) and iron oxide red (E 172) dyes.
Dosage form
Pills.
Main physicochemical properties:
5 mg: round tablets with a biconvex surface, with a score, brownish-yellow color; inclusions are allowed on the surface of the tablets;
10 mg: round tablets with a biconvex surface, with a score, brownish-pink color; inclusions are allowed on the surface of the tablets.
Pharmacotherapeutic group
Selective β-adrenergic blockers. Bisoprolol. ATC code C07A B07.
Pharmacological properties
Pharmacodynamics.
Bisoprolol is a highly selective β1-adrenergic blocker. When used in therapeutic doses, it does not have intrinsic sympathomimetic activity and clinically pronounced membrane-stabilizing properties. It has antianginal and hypotensive effects. It reduces myocardial oxygen demand by reducing heart rate and cardiac output, as well as reducing blood pressure, and increases myocardial oxygen supply by reducing end-diastolic pressure and prolonging diastole. The drug has a very low affinity for β2-receptors of bronchial and vascular smooth muscle, as well as for β2-receptors of the endocrine system.
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. The maximum antihypertensive effect is achieved after 2 weeks of administration.
Pharmacokinetics.
Absorption. After oral administration, the drug is well absorbed from the gastrointestinal tract. Bioavailability is about 90% after oral administration and is independent of food intake. The pharmacokinetics of bisoprolol and plasma concentrations are linear in the dose range from 5 mg to 20 mg. The maximum plasma concentration (Cmax) is reached after 2-3 hours.
Distribution: The volume of distribution is 3.5 l/kg. Plasma protein binding is about 30%.
Metabolism and excretion. Bisoprolol is excreted from the body in two ways: 50% is biotransformed in the liver with the formation of inactive metabolites and excreted by the kidneys, 50% is excreted by the kidneys unchanged. In vitro studies using human liver microsomes have shown that bisoprolol is metabolized with the participation of CYP3A4 (95%), CYP2D6 plays only a minor role. The total clearance of bisoprolol is 15 l/h. The half-life is 10-12 hours.
Indication
– Arterial hypertension;
– ischemic heart disease (angina);
– chronic heart failure with left ventricular systolic dysfunction, in combination with ACE inhibitors, diuretics, and if necessary, with cardiac glycosides.
Contraindication
– Acute heart failure or heart failure in a state of decompensation requiring inotropic therapy;
– cardiogenic shock;
– atrioventricular block II and III degree (except in patients with an artificial pacemaker);
– sick sinus syndrome;
– pronounced sinoatrial block;
– symptomatic bradycardia;
– symptomatic arterial hypotension;
– severe bronchial asthma or severe chronic obstructive pulmonary disease;
– late stages of peripheral circulatory disorders or Raynaud's disease;
– untreated pheochromocytoma;
– metabolic acidosis;
– hypersensitivity to bisoprolol or other components of the drug.
Interaction with other medicinal products and other types of interactions
Combinations that are not recommended for use
Treatment of chronic heart failure
– Class I antiarrhythmics (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): negative effect on atrioventricular conduction and myocardial inotropic function.
All indications
– Calcium antagonists such as verapamil, and to a lesser extent diltiazem: negative effects on myocardial contractile function and atrioventricular conduction. Intravenous administration of verapamil may lead to severe hypotension and atrioventricular block in patients taking β-blockers.
– Centrally acting antihypertensives (clonidine, methyldopa, moxinidine, rilmenidine): may worsen heart failure. In combination therapy, abrupt withdrawal of these agents may increase the risk of reflex hypertension.
Combinations to be used with caution
Treatment of arterial hypertension or coronary heart disease (angina pectoris)
– Class I antiarrhythmics (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): may increase the negative effect on atrioventricular conduction and myocardial inotropic function.
– Dihydropyridine calcium antagonists (e.g. nifedipine, felodipine, amlodipine): may increase the risk of hypotension. The possibility of an increased negative effect on myocardial inotropic function in patients with heart failure cannot be excluded.
– Class III antiarrhythmic drugs (e.g. amiodarone): may increase the negative effect on atrioventricular conduction.
– Topical β-blockers (e.g. those contained in eye drops for the treatment of glaucoma): the effect of bisoprolol may be enhanced.
– Parasympathomimetics: atrioventricular conduction time may increase and the risk of bradycardia may increase.
– Insulin and oral hypoglycemic agents: the effect of these drugs is enhanced. Signs of hypoglycemia may be masked. Such an interaction is more likely when using non-selective β-blockers.
– Anesthesia agents: increased risk of myocardial depression and hypotension.
– Cardiac glycosides (digitalis preparations): can reduce heart rate, increase atrioventricular conduction time.
– Nonsteroidal anti-inflammatory drugs (NSAIDs): may weaken the hypotensive effect of bisoprolol.
– β-sympathomimetics (e.g. isoprenaline, dobutamine): use in combination with bisoprolol may lead to a decrease in the therapeutic effect of both agents.
– Sympathomimetics that activate α- and β-adrenergic receptors (e.g. adrenaline, noradrenaline): increase blood pressure. This interaction is more likely with non-selective β-blockers.
– Antihypertensive agents (e.g. tricyclic antidepressants, barbiturates, phenothiazines): increase the risk of arterial hypotension.
Combinations that require special attention
– Mefloquine: may increase the risk of bradycardia.
– MAO inhibitors (except MAO inhibitors type B): increase the hypotensive effect of β-blockers. There is a risk of developing hypertensive crisis.
Application features
The drug should be used with caution in patients with the following conditions:
– diabetes mellitus with sharp fluctuations in blood glucose levels, while symptoms of hypoglycemia (tachycardia, palpitations, sweating) may be hidden;
– strict diet;
– conducting desensitization therapy;
– atrioventricular block I degree;
– Prinzmetal's angina;
– peripheral circulatory disorders (at the beginning of therapy, complaints may increase);
– general anesthesia.
It is necessary to warn the anesthesiologist about taking β-adrenergic blockers. In patients who are scheduled for general anesthesia, the use of β-blockers reduces the incidence of arrhythmias and myocardial ischemia during anesthesia, intubation and the postoperative period. It is recommended to continue using β-blockers during the intraoperative period. The anesthesiologist should 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 a decrease in pressure. 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.
Currently, there is insufficient therapeutic experience in the treatment of chronic heart failure in patients with the following diseases and pathological conditions: type 1 diabetes mellitus, severe renal dysfunction, severe hepatic dysfunction, restrictive cardiomyopathy, congenital heart disease, hemodynamically significant acquired valvular heart disease, myocardial infarction within the last 3 months.
Combinations of bisoprolol with calcium antagonists such as verapamil or diltiazem, with class 1 antiarrhythmic drugs and with centrally acting antihypertensive agents are not recommended (see section "Interaction with other medicinal products and other types of interactions").
In bronchial asthma or other chronic obstructive pulmonary diseases, concomitant therapy with bronchodilators is indicated. In some cases, while taking the drug, patients with bronchial asthma may require higher doses of β2-sympathomimetics due to increased airway tone.
Like other β-blockers, bisoprolol may increase sensitivity to allergens and increase the incidence of anaphylactic reactions. In such cases, treatment with adrenaline does not always have a positive therapeutic effect.
Patients with psoriasis (including a history of psoriasis) should use β-blockers (e.g. bisoprolol) after careful benefit/risk assessment.
Patients with pheochromocytoma should be prescribed the drug only against the background of previous therapy with α-adrenoblockers. Symptoms of thyrotoxicosis may be masked against the background of taking the drug. When using the drug Bisoprolol-KV, a positive result may be noted during doping control.
At the beginning of treatment with the drug, regular monitoring of blood pressure is necessary.
If necessary, drug therapy should be terminated slowly, gradually reducing the dose.
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.
Use during pregnancy or breastfeeding
During pregnancy, the drug should be used only if the expected benefit to the mother outweighs the potential risk to the fetus. As a rule, β-blockers reduce placental blood flow and may affect fetal development. If treatment with a β-blocker is necessary, it is preferable that it be a β1-selective β-blocker. It is necessary to monitor uteroplacental blood flow and fetal growth.
After delivery, the newborn should be closely monitored. Symptoms of hypoglycemia and bradycardia can be expected during the first 3 days.
There is no data on the excretion of bisoprolol into breast milk or the safety of effects on breastfed infants, therefore the use of the drug during breastfeeding is not recommended.
Ability to influence reaction speed when driving vehicles or other mechanisms
In some cases, the drug may affect the ability to drive or operate complex mechanisms. Particular attention should be paid at the beginning of treatment, when changing the dose of the drug or when interacting with alcohol.
Method of administration and doses
The tablets should be taken without chewing, in the morning, on an empty stomach or during breakfast, with a small amount of liquid.
Arterial hypertension; coronary heart disease (angina pectoris)
The recommended dose is 5 mg (1 tablet of Bisoprolol-KV 5 mg) per day. In case of moderate hypertension (diastolic blood pressure up to 105 mm Hg), a dosage of 2.5 mg (½ tablet of 5 mg) is acceptable.
If necessary, the daily dose can be increased to 10 mg (1 tablet of Bisoprolol-KV 10 mg) per day. The maximum recommended dose is 20 mg per day.
Dose changes and adjustments are determined by the doctor individually, depending on the patient's condition.
Bisoprolol-KV must be used with caution in patients with arterial hypertension or ischemic heart disease accompanied by heart failure.
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-KV is prescribed for the treatment of patients with chronic heart failure without signs of exacerbation.
Treatment of chronic heart failure with Bisoprolol-KV should be initiated according to the titration scheme below and may be adjusted depending on individual body responses.
– 1.25 mg** of bisoprolol fumarate once daily for 1 week, increasing to
– 2.5 mg* bisoprolol fumarate (½ 5 mg tablet) once daily for the next 1 week, increasing to
– 3.75 mg** bisoprolol fumarate once daily for the next 1 week, increasing to
– 5 mg of bisoprolol fumarate once daily for the next 4 weeks, increasing to
– 7.5 mg of bisoprolol fumarate (1 ½ tablets of 5 mg) once a day for the next 4 weeks, increasing to
– 10 mg of bisoprolol fumarate (1 tablet of 10 mg or 2 tablets of 5 mg) once a day as maintenance therapy.
* At the beginning of therapy for chronic heart failure, it is recommended to use the drug at a dosage of 2.5 mg;
** Use in appropriate dosage.
The maximum recommended dose of bisoprolol fumarate is 10 mg once daily.
Regular monitoring is necessary at the beginning of treatment for persistent chronic heart failure. During the titration phase, vital signs (blood pressure, heart rate) and symptoms of progression of heart failure should be monitored.
Treatment modification
If worsening of heart failure, hypotension or bradycardia occurs during or after the titration phase, dose adjustment is recommended, which may require a temporary reduction in the dose of bisoprolol or possibly discontinuation of treatment. Treatment can be continued once the patient's condition has stabilized.
The course of treatment with Bisoprolol-KV is long.
Do not stop treatment suddenly or change the recommended dose without consulting your doctor, as this may worsen the patient's condition. If necessary, treatment with the drug should be discontinued slowly, gradually reducing the dose.
Patients with hepatic and renal insufficiency
Arterial hypertension; ischemic heart disease. For patients with mild to moderate hepatic or renal impairment, dose adjustment is usually not required. For patients with severe renal impairment (creatinine clearance less than 20 ml/min) and patients with severe hepatic impairment, the daily dose should not exceed 10 mg bisoprolol.
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.
Elderly patients do not require dose adjustment.
Children
There are no clinical data on the efficacy and safety of the drug for the treatment of children.
Overdose
Symptoms: bradycardia, hypotension, acute heart failure, hypoglycemia, bronchospasm. 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.
Treatment. In case of overdose, consult a doctor immediately. Depending on the degree 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.
For bradycardia: intravenous atropine. If there is no reaction, isoprenaline or another drug with a positive chronotropic effect is administered with caution. In exceptional cases, an artificial pacemaker is administered.
For arterial hypotension: taking vasoconstrictor drugs, intravenous administration of glucagon.
In case of atrioventricular block of the II and III degree: infusion of isoprenaline; if necessary, cardiac pacing.
In case of exacerbation of chronic heart failure: intravenous administration of diuretics and vasodilators.
For bronchospasm: bronchodilators (e.g. isoprenaline), β2-adrenomimetics and/or aminophylline.
For hypoglycemia: intravenous glucose administration.
Adverse reactions
Cardiovascular system: bradycardia (in patients with chronic heart failure, arterial hypertension or ischemic heart disease), signs of worsening heart failure (in patients with chronic heart failure, arterial hypertension or ischemic heart disease), atrioventricular conduction disorders, feeling of coldness or numbness in the extremities, arterial hypotension (especially in patients with heart failure).
Nervous system: dizziness*, headache*, syncope.
On the part of the organs of vision: decreased tear secretion (should be taken into account when wearing contact lenses), conjunctivitis.
On the part of the auditory organs: hearing impairment.
On the part of the respiratory system: bronchospasm in patients with a history of bronchial asthma and chronic obstructive airway diseases, allergic rhinitis.
Gastrointestinal: nausea, vomiting, diarrhea, constipation.
Skin and connective tissue disorders: hypersensitivity reactions – itching, redness, rash; alopecia. When treated with β-blockers, worsening of the condition of patients with psoriasis in the form of psoriatic rash may be observed.
Musculoskeletal system: muscle weakness, cramps.
From the hepatobiliary system: hepatitis.
From the reproductive system: impaired potency.
Psychiatric: depression, sleep disorders, nightmares, hallucinations.
Laboratory indicators: increased triglyceride levels in the blood, increased activity of liver enzymes in blood plasma (AST, ALT).
General disorders: asthenia (in patients with chronic heart failure, arterial hypertension or ischemic heart disease), fatigue*.
* 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
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister; 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Kyiv Vitamin Plant".
Location of the manufacturer and address of its place of business
04073, Ukraine, Kyiv, Kopylivska St., 38.
Website: www.vitamin.com.ua.
