Bisoprolol-Ratiofarm 5 mg tablet number 50

Bisoprolol-Ratiofarm (BISOPROLOL-RATIOPHARM) user manual

Composition

active ingredient: bisoprolol; 1 tablet contains 5 mg or 10 mg of bisoprolol hemifumarate;
auxiliary substances: lactose, microcrystalline cellulose, crospovidone, magnesium stearate for tablets of 5 mg color yellow PO 22812 (which contains: lactose, iron oxide yellow (E172))
for tablets of 10 mg beige dye RO 27215 (which contains: lactose, iron oxide yellow (E172), iron oxide red (E172)).

Dosage form

Pills.

Basic physical and chemical properties:

pills of 5 mg - pale yellow with interspersed, round, biconvex with embossed "5" and a fault line on one side;
tablets of 10 mg - beige color with impregnations, round, biconvex with an embossed "10" and a fault line on one side.

Pharmacological group

Selective blockers of ß-adrenergic receptors. Code АТХС07А В07.

Pharmacological properties

Pharmacodynamics.

Bisoprolol is an active, highly selective blocker of ß 1 -adrenoceptors, without BCA. Has hypotensive and antianginal action. The mechanism of antihypertensive action is a decrease in the minute volume of the heart, a decrease in sympathetic stimulation of peripheral vessels, and inhibition of renin release by the kidneys. The antianginal action is associated with blockade of β 1 -adrenoceptors. Bisoprolol reduces the need for myocardium in oxygen by reducing heart rate and cardiac output and lowering blood pressure, increasing oxygen supply to the myocardium by decreasing the end diastolic pressure and extending the diastole. Bisoprolol has a very low affinity for the ß 2 receptors of the smooth muscles of the bronchi and vessels, as well as for the ß2 receptors of the endocrine system.

The maximum effect of bisoprolol occurs 3-4 hours after admission. The half-life of the plasma is 10-12 hours, which leads to a 24-hour effectiveness after a single dose. The maximum antihypertensive effect is achieved after 2 weeks of admission.

Pharmacokinetics.

After ingestion, the drug is well absorbed from the gastrointestinal tract. The effect of the first passage through the liver is negligible, which contributes to high bioavailability - approximately 90%. Binding to plasma proteins is approximately 30%. The volume of distribution is 3.5 l / kg. The total clearance of bisoprolol is 15 l / h.

Bisoprolol is excreted from the body in two ways. Approximately 50% is metabolized in the liver with the formation of inactive metabolites, which are excreted by the kidneys. The remaining 50% is excreted by the kidneys unchanged.After approximately the same involvement of the kidneys and liver in the induction of this drug, patients with renal or hepatic insufficiency do not need to adjust the dose. The kinetics of bisoprolol is linear and does not depend on age.

Indications

• Arterial hypertension;
• ischemic heart disease (angina)
• chronic heart failure with systolic dysfunction of the left ventricle in combination with ACE inhibitors, diuretics, if necessary - cardiac glycosides.

Contraindications

• Hypersensitivity to bisoprolol or other components of the drug
• acute heart failure or heart failure in a state of decompensation, requiring inotropic therapy;
• cardiogenic shock
• blockade of II and III degree;
• syndrome of weakness of the sinus node;
• pronounced sinoatrial block
• Bradycardia with a heart rate of less than 60 beats per minute before the start of therapy;
• arterial hypotension (systolic blood pressure below 100 mm Hg);
• severe form of bronchial asthma or severe chronic obstructive pulmonary disease,
• late stages of peripheral circulation and Raynaud's syndrome
• metabolic acidosis,
• pheochromocytoma, was not treated;
• a combination of floktaphenin and sultopride.

Interaction with other drugs and other interactions

Contraindications are combinations.

Floktaphenin: b-blockers can aggravate compensatory cardiovascular reactions due to arterial hypotension and shock, which may result in the use of floktaphenin.
Sultopride: Bisoprolol should not be used concomitantly with sultopride because of the increased risk of ventricular arrhythmia.
Unsupported combinations.

Treatment of chronic heart failure.

Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): a negative effect on AV conduction and inotropic myocardial function.

All indications.

Calcium antagonists (verapamil, diltiazem, bepridil): a negative effect on the inotropic function of the myocardium, AV-conduction, blood pressure. The administration of verapamil may result in severe arterial hypotension and AV blockade in patients taking ß-blockers.
Hypotensive drugs central action (clonidine, methyldopa, guanfacine, moxinidine, rilmenidine): increased risk of reflex hypertension, as well as a significant slowdown in the heart rate, possibly suppressing AV conduction, worsening heart failure. With combined therapy, sudden withdrawal of these drugs can increase the risk of reflex hypertension.

Combinations should be used with caution.

Treatment of arterial hypertension or coronary heart disease (angina pectoris).

Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): a negative effect on AV conduction and inotropic myocardial function.

All indications.

Antiarrhythmic drugs of the III class (for example amiodarone): a negative effect on AV-conduction.
Calcium antagonists (dihydropyridine derivatives, eg nifedipine, felodipine, amlodipine): may increase the risk of arterial hypotension and the risk of developing heart failure. The possibility of an increase in the negative effect on the inotropic function of the myocardium in patients with heart failure is not ruled out.
Anticholinesterase drugs (including tacrine): increased AV-conduction and increased risk of bradycardia.
β-blockers of local action (in particular, contained in eye drops for the treatment of glaucoma): can enhance the action of bisoprolol.
Insulin and oral antidiabetics: the effect of these drugs is enhanced. Bisoprolol may mask symptoms of hypoglycemia.Such an interaction is more likely when using non-selective ß-blockers.
Cardiac glycosides (digitalis preparations): reduce the heart rate, increase the AV conduction time.
Means for anesthesia: increase the risk of oppression of myocardial function and development of arterial hypotension.
Nonsteroidal anti-inflammatory drugs (NSAIDs): reduce the hypotensive effect of bisoprolol.
Derivatives of ergotamine: exacerbation of peripheral circulatory disorders.
β-sympathomimetics (eg isoprenaline, dobutamine): a combination with bisoprolol may reduce the therapeutic effect of both drugs.
Sympathomimetics, which activate α- and β-adrenergic receptors (epinephrine, norepinephrine), increase blood pressure and enhance the phenomenon of intermittent claudication. Such an interaction is more likely when using non-selective ß-blockers.
Tricyclic antidepressants, barbiturates, phenothiazines and other antihypertensive drugs: increase the risk of hypotension.
Baclofen: increased antihypertensive activity.
Amifostin: increased hypotensive activity.
Parasympathomimetics: AV conduction time may increase and the risk of bradycardia may increase.
Antihypertensive drugs (eg tricyclic antidepressants, barbiturates, phenothiazine): increase the risk of hypotension.

Combinations are allowed.

Mefloquine: increased risk of bradycardia. Corticosteroids: it is possible to reduce the antihypertensive effect due to delay in water and sodium in the body.
MAO inhibitors (except for MAO type B inhibitors): increase the antihypertensive effect of ß-blockers. There is a risk of developing a hypertensive crisis.

Application features

The drug should be used with caution to patients under such conditions:

• bronchospasm (bronchial asthma, chronic obstructive pulmonary disease) requires concomitant therapy with bronchodilators. In patients with bronchial asthma, airway tone may increase, which may require an increase in the dose of b 2 -sympathomimetics. Before the start of treatment, it is recommended to perform a study of the function of external respiration in patients with bronchial asthma in an anamnesis
• general anesthesia. It is necessary to warn an anesthesiologist about admission of ß-adrenergic blockers. In patients who are scheduled for general anesthesia, the use of ß-blockers reduces the incidence of arrhythmia and myocardial ischemia during anesthesia, intubation and postoperative period. It is recommended to continue the use of ß-blockers during the intraoperative period. An anesthesiologist must take into account the potential interaction with other drugs that can lead to bradyarrhythmia, reflex tachycardia, and a reduction in the ability of the reflex mechanism to compensate for lowering blood pressure. The dose should be gradually reduced and discontinuation of the drug approximately 48 hours before general anesthesia
• use of contrast products containing iodine: ß-blockers may increase the risk of developing anaphylactic reactions refractory to treatment;
• diabetes mellitus with sharp fluctuations in blood glucose levels due to the possibility of masking the symptoms of hypoglycemia;
• thyrotoxicosis because of the possibility of masking adrenergic symptoms (tachycardia, palpitation, increased sweating)
• strict diet;
• during desensitization. Like other b-blockers, bisoprolol may increase sensitivity to allergens and increase anaphylactic reactions. Treatment with epinephrine does not always provide the expected therapeutic effect;
• blockade of the 1st degree;
• angina of prinzmetal. β-adrenoblockers can provoke the appearance, increase the number and lengthen the attacks of vasospastic angina / angina Prinzmetal;
• violations of peripheral circulation, including with Raynaud's disease or intermittent claudication: it is possible to increase complaints, especially at the beginning of therapy,
• patients with pheochromocytoma bisoprolol can be prescribed exclusively after therapy with a-adrenoblockers;
• patients with psoriasis (including family history), bisoprolol should be prescribed only after a thorough assessment of the benefit / risk ratio;
• simultaneous treatment with anticholinesterase drugs (including tacrine): this may increase the time of atrioventricular conduction and / or enhance bradycardia;
• current desensitizing therapy.

At the beginning of the treatment, patients should be monitored, especially for elderly patients. Treatment should not be stopped suddenly if there is no clear indication for this. If patients with ischemic heart disease suddenly stop treatment, there is a risk of myocardial infarction and sudden death. If necessary, therapy with the drug should be completed slowly, gradually reducing the dose.

At present, there is no sufficient therapeutic experience in the treatment of chronic heart failure in patients with such diseases and pathological conditions: type I diabetes mellitus, severe renal dysfunction, severe liver function, restrictive cardiomyopathy, congenital heart disease, hemodynamically significant valvular heart disease acquired, myocardial infarction myocardium for the last 3 months.

Combination with amiodarone is not recommended, given the risk of automatic contractility and cardiac conduction disorders (suppression of compensatory sympathetic reactions).

In general, combinations of bisoprolol with calcium antagonists such as verapamil or diltiazem, with class I antiarrhythmic drugs and with central-action antihypertensives are not recommended (see Section "Interaction with Other Drugs and Other Interactions").

When bisoprolol is used, a positive result can be noted in doping control.

If necessary, therapy with the drug should be completed slowly, gradually reducing the dose.

Like other ß-blockers, bisoprolol can increase both the sensitivity to allergens and the severity of anaphylactic reactions.Treatment with epinephrine may not always lead to the expected therapeutic effect.

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 lactation

The use of bisoprolol in pregnant women is possible only if absolutely necessary after assessing the relationship between benefit and risk to the mother and fetus. As a rule, β-adrenoblockers reduce blood flow in the placenta and can affect fetal development. If treatment with ß-blockers is necessary, it is desirable that this is a ß 1 -selective ß-blocker. It is necessary to control blood flow in the placenta and uterus. After delivery, the newborn should be carefully monitored.Symptoms of hypoglycemia and bradycardia can be expected within the first 3 days. There is no data on the penetration of bisoprolol into breast milk. Therefore, the drug is not recommended during breastfeeding.

The ability to influence the reaction rate when driving vehicles or other mechanisms

In some cases, the ability to drive a car and other mechanisms can be reduced at the start of treatment, when a drug is substituted, or when interacting with alcohol.

Dosing and Administration

Tablets are for oral use.

Arterial hypertension; ischemic heart disease (angina).

The recommended dose is 5 mg per day. In the case of moderate hypertension (diastolic pressure up to 105 mmHg) a dose of 2.5 mg is appropriate.

If necessary, the dose can be increased to 10 mg per day. The maximum recommended dose is 20 mg per day.

The change and adjustment of the dose are set individually, depending on the patient's condition.

Bisoprolol must be used with caution in patients with arterial hypertension or coronary heart disease, accompanied by heart failure.

Chronic heart failure with systolic dysfunction of the left ventricle in combination with ACE inhibitors, diuretics, if necessary - cardiac glycosides.

Standard therapy for chronic heart failure: ACE inhibitors (or angiotensin receptor blockers in case of intolerance to ACE inhibitors), ß-adrenergic blockers, diuretics and, if necessary, cardiac glycosides.

Bisoprolol is prescribed for the treatment of patients with chronic heart failure without signs of exacerbation.

Treatment of chronic heart failure with bisoprolol begins in accordance with the titration scheme presented below and can be adjusted depending on the individual reactions of the body.

1,25 mg * of bisoprolol fumarate 1 time per day for 1 week, increasing to
2.5 mg * of bisoprolol fumarate 1 time per day for the next 1 week, increasing to
3.75 mg * of bisoprolol fumarate 1 time per day for the next 1 week, increasing to
5 mg of bisoprolol fumarate once a day for the next 4 weeks, increasing to
7.5 mg of bisoprolol fumarate once a day for the next 4 weeks, increasing to
10 mg of bisoprolol fumarate once a day as maintenance therapy.
* Use bisoprolol in the appropriate dosage.

The maximum recommended dose of bisoprolol fumarate is 10 mg 1 time per day.

At the beginning of the treatment of chronic chronic insufficiency, regular monitoring is necessary. During the titration phase, monitoring of the following vital signs (blood pressure, heart rate) and symptoms of progression of heart failure is necessary.

Modification of treatment.

If arterial hypotension or bradycardia worsens during the titration phase or after it, cardiac insufficiency worsens, a dose adjustment is recommended, which may require a temporary reduction in the dose of bisoprolol or, possibly, suspension of treatment. After stabilization of the patient's condition, treatment should be continued.

The course of treatment is long.

Do not stop treatment suddenly and change the recommended dose without consulting a doctor, as this can lead to a worsening of the patient's condition. If necessary, the treatment should be completed slowly, gradually reducing the dose.

Patients with impaired renal and hepatic function

Arterial hypertension; cardiac ischemia.

For patients with impaired hepatic function or kidneys of mild and moderate severity, dosing is usually not necessary.Patients with severe renal disorders (creatinine clearance <20 mL / min) and patients with severe hepatic dysfunction are advised not to exceed 10 mg daily dose bisoprolol fumarate.

Chronic heart failure.

Unknown pharmacokinetics of bisoprolol in patients with chronic heart failure simultaneously with impaired liver function and / or renal, however increasing the dose must be carefully.

bisoprolol dose adjustment is not required for elderly patients. However, the drug is recommended to start with the lowest possible dose.

Children

Experience in the use of the drug in children is not available, so its use is not recommended.

Overdose

Symptoms: bradycardia, hypotension, congestive heart failure, bronchospasm, hypoglycemia. There is wide variation in individual sensitivity to a single high dose of bisoprolol in heart failure patients may be more sensitive to the drug.

In case of overdose, you should immediately consult a doctor.

In case of overdose also cases of AV-blockade III, and dizziness were reported.

Treatment: stop taking the drug and conduct supportive and symptomatic treatment. There are limited data bisoprolol difficult to dialysis.

If necessary to monitor the respiratory function; It may be indicated artificial respiration.

When bronchospasm: bronchodilators (e.g., isoprenaline) or β 2 agonists and / or aminophylline.

In atrioventricular block II and III degree: administering isoprenaline infusion; if necessary - pacing.

Deterioration in heart failure: administering diuretics, vasodilators.

When bradycardia: atropine. If no reaction, caution should be given another drug or isoprenaline positive chronotropic effect. In exceptional cases, introduce an artificial pacemaker.

If hypotension: receiving vasoconstrictors and plasma substitutes, administration of glucagon.

When hypoglycemia: intravenous glucose.

Adverse reactions

Immune system: the appearance of antinuclear antibodies with such specific clinical symptoms of lupus-like syndrome, disappear after cessation of treatment.

On the part of the psyche: sleep disturbance, depression, nightmares, hallucinations.

Violation of metabolism: increased blood triglycerides, hypoglycemia.

From the nervous system: fatigue, exhaustion, dizziness * headache * loss of consciousness.

On the part of the organs of vision: reduced lacrimation (to consider when wearing contact lenses), conjunctivitis.

On the part of hearing: hearing impairment.

Of the heart: bradycardia, disturbance of AV conduction, the appearance / intensification signs of heart failure.

From the vessels a sensation of cold or numb extremities, hypotension (especially in patients with heart failure), worsening of Raynaud's disease, intermittent claudication gain available, orthostatic hypotension.

The respiratory system: bronchospasm in patients with asthma or chronic obstructive pulmonary disease in the history of allergic rhinitis.

On the part of the gastrointestinal tract: nausea, vomiting, diarrhea, abdominal pain, constipation.

Liver: increased liver enzymes (ALT, AST) in blood plasma of hepatitis.

Skin and subcutaneous tissue disorders: hypersensitivity reactions, including itching, redness, rash, flushing, increased sweating, hair loss, ß-blockers may induce or aggravate psoriasis, psoriatic lesions.

On the part of the musculoskeletal system: muscle weakness, cramps, arthropathy.

Reproductive system: violation of potency.

General disorders: Fatigue *, asthenia.

Laboratory studies: elevated triglycerides, liver enzymes (ALT, AST) *.

* Applies only to patients with hypertension or ischemic heart disease. These symptoms usually occur early in treatment, are mild and disappear within the first 1-2 weeks.

In case of any side effects or adverse reactions should inform your doctor immediately.

Shelf life

3 years.

Storage conditions

Store at a temperature not higher than 25 ° C in the reach of children.

Packaging

10 tablets in a blister, 3 or 5 blisters per box.

Category of leave

On prescription.