Expiration date: 05/2025
Structure and Composition:
Tablets, film-coated. One tablet contains active substance:
bisoprolol fumarate 5 or 10 mg
Excipients: potato starch - 24/36 mg colloidal silicon dioxide (Aerosil) - 1.8 / 2.7 mg of magnesium stearate - 0.6 / 0.9 mg of lactose monohydrate (milk sugar) - 63.1 / 91.7 mg povidone - 4.5 / 6.7 mg MCC - 21/32 mg
shell film: selekoat AQ-02140 - 6/9 mg, including Hypromellose (hydroxypropyl) - 3.3 / 4.95 mg macrogol 400 (polyethylene glycol 400) - 0.54 / 0.81 mg of macrogol 6000 (polyethylene glycol 6000) - 0.84 / 1.26 mg titanium dioxide - 1,278 / 1,917 mg dye "sunset" yellow - 0.042 / 0.063 mg
in blisters 7, 10, 28 or 30 pieces. a stack of cardboard 2 or 4 of the package (7 Table.) and 3, 5 or 10 packs (10 tab.), or 1 or 2 of the package (28 tab.), or 1, 2 or 3 packs (30 in Table )..
Description pharmaceutical form:
Tablets, film-coated light orange color, round, biconcave. The cross section shows two layers: an inner layer - almost white.
Pharmacokinetics:
Suction. Bisoprolol is almost completely (90%) absorbed from the gastrointestinal tract. Due to its low bioavailability metabolization at the first passage through the liver (at about 10%) is approximately 90% after oral administration. Food does not affect the bioavailability. Bisoprolol demonstrates linear kinetics, and its plasma concentration is proportional to the dose in the dose range of 5 to 20 mg. Cmax plasma levels achieved in 2-3 hours.
Distribution. Bisoprolol is distributed widely enough. Vd is 3.5 L / kg. Communication plasma protein reaches about 30%.
Metabolism. It is metabolized by oxidative way without subsequent conjugation. All metabolites are polar (water soluble) and the kidneys. Major metabolites detected in plasma and urine did not exhibit pharmacological activity. Data obtained from experiments with microsomes in vitro human liver demonstrate that bisoprolol is metabolized mainly via isoenzyme CYP3A4 (about 95%) and CYP2D6 isozyme plays only a minor role.
Withdrawal. The clearance of bisoprolol is determined by the equilibrium between the renal excretion as unchanged (about 50%) and metabolism in the liver (approximately 50%) to metabolites, which are also excreted by the kidneys. The total clearance is 15 l / h. T1 / 2 - 10-12 h.
There is no information on the pharmacokinetics of bisoprolol in patients with chronic heart failure and simultaneous impaired liver or kidney function.
Description of the pharmacological actions:
Of selective &, beta1-blocker without its own sympathomimetic activity, has no membrane stabilizing action. It has only a slight affinity for &, beta2-adrenoceptor airway smooth muscle and blood vessels, as well as &, beta2-adrenoceptor involved in the regulation of metabolism. Therefore, bisoprolol generally does not affect the airway resistance and metabolic processes that are involved in &, beta2-adrenoretsetseptory.
As a rule, the maximum reduction in blood pressure is achieved within 2 weeks after initiation of therapy.
Bisoprolol reduces the activity simpatoadrenalovoj system, blocking &, beta1-adrenergic receptors of the heart.
For a single ingestion in patients with coronary artery disease with no evidence of chronic heart failure (CHF), bisoprolol slows heart rate, reduces the stroke volume and, as a consequence, reduces the ejection fraction and myocardial oxygen demand. When long-term therapy initially elevated peripheral vascular resistance is reduced. Reducing the activity of renin in blood plasma is considered as one of the components of the antihypertensive action of &, beta-blockers.
Indications:
- Chronic heart failure
- arterial hypertension
- Coronary heart disease: prevention of attacks of stable angina.
Contraindications:
- hypersensitivity to bisoprolol or to any of the excipients and other &, beta-blockers
- lactase deficiency, lactose intolerance, glucose-galactose malabsorption
- cardiogenic shock, collapse
- acute heart failure
- Heart failure decompensation requiring of inotropic therapy
- AV block II and III degree sinoatrial block without pacemaker syndrome sick sinus bradycardia (heart rate less than 50 bpm. / Min)
- severe bronchial asthma or COPD
- marked reduction of blood pressure (SBP less than 90 mm Hg)
- The expressed disturbances of peripheral circulation or Raynaud's syndrome
- pheochromocytoma (without simultaneous application &, alpha-blockers)
- metabolic acidosis
- lactation
- simultaneous reception of MAO inhibitors (except MAO-B inhibitors)
- simultaneous use with floctafenine and sultopride
- age of 18 years (effectiveness and safety have been established).
Precautions: conducting desensitizing therapy Prinzmetal angina hyperthyroidism, diabetes mellitus type 1 and diabetes mellitus with significant fluctuations in the degree of concentration in the blood glucose AV block I expressed renal insufficiency (Cl creatinine less than 20 mL / min), expressed human liver psoriasis restrictive cardiomyopathy congenital heart defects or Valvular heart Disease with severe hemodynamic impairment of CHF with myocardial infarction within the last 3 months pheochromocytoma (with concomitant use &, alpha-blockers) strict diet.
Application of pregnancy and breastfeeding:
During pregnancy, the drug Aritel should be advised to use only if the benefit to the mother outweighs the risk of side effects in the fetus. Typically, &, beta-blockers reduce blood flow to the placenta and affect fetal development. It is necessary to monitor blood flow in the placenta and uterus, as well as to observe the growth and development of the child, in case of occurrence of adverse events in relation to pregnancy and / or fetus - the use of alternative therapies. It is necessary to carefully examine the newborn after delivery. In the first three days of life may experience symptoms of hypoglycemia and bradycardia.
Data on the allocation of bisoprolol into breast milk is not. Therefore, the drug Aritel not recommended for women during lactation. If necessary Aritel intake during lactation, breast-feeding should be discontinued.
Side effect:
The frequency of adverse reactions listed below is defined as follows: very common (&, ge 1/10) often (&, ge 1/100, <, 1/10) infrequently (&, ge 1/1000, <, 1/100 ) rarely (&, ge 1/10 000, <1/1000), very rare (<1/10 000), including isolated reports.
CNS: often - dizziness *, headache * rarely - fatigue rare - loss of consciousness.
General disorders: often - asthenia (patients with chronic heart failure), fatigue * infrequently - asthenia (patients with arterial hypertension or angina).
Mental disorders: rarely - depression, insomnia, rarely - hallucinations, nightmares.
For the skin: rarely - hypersensitivity reactions, such as itching, rash, redness of the skin is very rare - alopecia. &, Beta-blockers may exacerbate the symptoms of psoriasis flow or induce psoriasis-like rash.
From the urogenital system: rarely - a violation of potency, the weakening of the libido, Peyronie's disease, cystitis, renal colic, polyuria.
From the musculoskeletal system: rarely - muscle weakness, muscle cramps.
From the digestive system: often - nausea, vomiting, diarrhea, constipation, rarely - hepatitis.
From the side of hematopoiesis: in some cases - thrombocytopenia, agranulocytosis.
With the respiratory system: rarely - bronchospasm in patients with asthma or airway obstruction in the history of rare - allergic rhinitis.
From a sight organ: seldom - a decrease in lacrimation (to consider when wearing contact lenses) rarely - conjunctivitis.
On the part of the organ of hearing: rarely - hearing impairment.
From the CCC: very often - bradycardia (in patients with heart failure) often - worsening CHF current symptoms (in patients with heart failure), the sensation of cooling and numbness in the extremities, marked reduction in blood pressure, especially in patients with chronic heart failure rarely - a violation of AV conduction, bradycardia (in patients with hypertension or angina), worsening of heart failure symptoms flow (in patients with hypertension or angina), orthostatic hypotension.
Effect on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia.
From the reproductive system: rarely - a violation of potency.
Laboratory findings: rarely - increased triglyceride concentration and liver transaminases (ACT, ALT) in blood.
* In patients with hypertension or angina, these symptoms usually appear at the beginning of treatment, softly pronounced and disappear within 1-2 weeks after starting treatment.
Drug Interactions:
Not recommended combinations
In the treatment of heart failure. Class I antiarrhythmics (eg quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), while the use of bisoprolol may reduce AV conduction and contractile ability of the heart.
In the treatment of heart failure, arterial hypertension, stable angina. CCB verapamil type and to a lesser extent diltiazem while the use of bisoprolol may lead to a decrease in myocardial contractility and AV conduction disorders. In particular, in / with the introduction of verapamil in patients receiving &, beta-blockers, may cause severe hypotension and AV blockade.
Antihypertensive drugs central action (such as clonidine, methyldopa, moxonidine, rilmenidine) may lead to a slowing of the heart rate and reducing cardiac output and to vasodilatation due to the reduction of the central sympathetic tone. Abrupt withdrawal, particularly to the cancellation &, beta-blockers may increase the risk of rebound hypertension.
Combinations requiring special care
In the treatment of hypertension, stable angina. Class I antiarrhythmics (eg quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), while the use of bisoprolol may reduce AV conduction and myocardial contractility.
In the treatment of heart failure, arterial hypertension, stable angina. BPC-dihydropyridine derivatives (eg, nifedipine, felodipine, amlodipine), while the use of bisoprolol may increase the risk of hypotension. In patients with heart failure can not exclude the risk of further deterioration of the contractile function of the heart.
Class III antiarrhythmics (eg amiodarone) may increase the violation of AV conduction.
Action &, beta-blockers for topical application (eg eye drops for glaucoma treatment) may enhance the systemic effects of bisoprolol (lowering blood pressure, slowing of the heart rate).
Parasympathomimetics while the use of bisoprolol may increase the violation of AV conduction and increase the risk of bradycardia.
Hypoglycemic effect of insulin or hypoglycemic agents for oral administration can be enhanced. Symptoms of hypoglycaemia - particularly tachycardia - may be masked or suppressed. Such interactions are more likely when using a nonselective &, beta-blockers.
Funds for general anesthesia may increase the risk cardiodepressive action, resulting in hypotension (see. "Special Instructions").
Cardiac glycosides while the use of bisoprolol may lead to an increase of the pulse of time and thus to the development of bradycardia.
NSAIDs may reduce the antihypertensive effect of bisoprolol.
The simultaneous use of the drug with &, beta-agonists (eg isoprenaline, dobutamine) may reduce the effect of both drugs.
Combination of bisoprolol with agonists that affect &, beta- and &, alpha-adrenergic receptors (eg norepinephrine, epinephrine), may enhance the vasoconstrictor effects of these agents arising from participation &, alpha-adrenergic receptors, resulting in increased blood pressure. Such interactions are more likely when using a nonselective &, beta-blockers.
Antihypertensives, as well as with other possible means antihypertensive effect (e.g. tricyclic antidepressants, barbiturates, phenothiazines), may enhance the antihypertensive effect of bisoprolol.
Mefloquine while the use of bisoprolol may increase the risk of bradycardia.
MAO inhibitors (except MAO-B inhibitors) may increase the antihypertensive effect of &, beta-blockers. Concomitant use can also lead to the development of hypertensive crisis.
contraindicated combinations
Floctafenine: Blockers &, beta-adrenergic receptors may interfere with the compensatory cardiovascular reactions with hypotension caused by floctafenine.
Sultopride there exists the risk of ventricular arrhythmias.
Dosage and administration:
Inside, in the morning before breakfast, during, or after, 1 time a day with plenty of fluids. Tablets should not be chewed or triturate.
CHF. Home treatment of CHF requires a mandatory drug Aritel the special titration phase and regular medical supervision.
A prerequisite for treatment with Aritel is stable chronic heart failure without acute symptoms.
CHF Aritel drug treatment is started in accordance with the following titration scheme. This may require individual adaptation depending on how well the patient carries the prescribed dose, i.e. the dose can be increased only if the previous dose was well tolerated.
To ensure proper titration process in the initial stages of treatment is recommended to use the drug in smaller doses.
The recommended starting dose is 1.25 mg (Table 0.5., 2.5 mg) once a day. Depending on individual tolerability, the dose should be gradually increased to 2.5 3.75 (Tables 1.5. 2.5 mg) 7.5 5 (Table 1. 5 mg and 1 tablet. 2.5 mg) 1 and 10 mg once a day with an interval of at least two weeks.
If an increase in the dose of the drug is poorly tolerated by the patient, the dose may be reduced.
The maximum daily dose for the treatment of chronic heart failure is 10 mg 1 time a day.
During titration we recommend regular monitoring of blood pressure, heart rate and increase the severity of symptoms of CHF. Worsening heart failure symptoms may already be on the first day of the drug.
During the titration phase, or it can occur after a temporary deterioration in the flow of CHF, hypotension or bradycardia. In this case, it is recommended first of all to carry out a correction dose of concomitant therapy drugs. It may also require temporary dose reduction or withdrawal of treatment Aritel.
After stabilization, the patient should undertake a re-titration of the dose or continue the treatment.
Arterial hypertension and coronary heart disease (prevention of attacks of stable angina). When hypertension and coronary heart disease the drug is prescribed 5 mg 1 time per day. If necessary to increase the dose of 10 mg 1 time per day.
In the treatment of hypertension and angina maximum daily dose is 20 mg once a day one.
Bisoprolol formulation can be applied in other dosage forms (tablets with 2.5 mg Valium).
In all cases, the reception mode, and selects the dose the doctor for each patient individually, in particular taking into account the individual characteristics and the patient's condition.
Special patient groups
Impaired renal or hepatic function. In violation of mild or moderate hepatic or renal function Dosage adjustment is not usually required. When expressed violations kidney (Cl creatinine less than 20 mL / min) and in patients with severe liver disease, the maximum daily dose is 10 mg. Increasing the dose in such patients should be administered with extreme caution.
Elderly patients. Dose adjustment is not required.
There are currently insufficient data on the use of the drug Aritel in patients with CHF, conjugated with type 1 diabetes, severe impaired renal function and / or liver disease, restrictive cardiomyopathy, congenital heart defects or hemodynamically caused by heart disease. Also still not sufficient data has been obtained relative to CHF patients with myocardial infarction within the past 3 months.
Overdose:
Symptoms: AV block, bradycardia, decreased blood pressure, bronchospasm, acute cardiac insufficiency and hypoglycaemia.
Treatment: First of all you need to stop taking the drug and start supporting symptomatic therapy.
In severe bradycardia: in / atropine. If the effect is insufficient, you can enter with caution agent with positive chronotropic effect. Sometimes it may require temporary staging an artificial pacemaker.
In marked decrease in blood pressure: in / in a plasma-purpose solutions and vasopressors.
When AV blockade: patients should be under constant supervision and receive treatment &, beta-agonists such as epinephrine. If necessary - setting an artificial pacemaker.
When exacerbation of chronic heart failure: in / with the introduction of diuretics, drugs with positive inotropic effect and vasodilators.
When bronchospasm: the use of bronchodilators, including &, Beta2-sympathomimetic and / or aminophylline.
When hypoglycemia: in / with the introduction of dextrose (glucose).
Special instructions:
Patients should not discontinue medication abruptly and modify the recommended dose without first consulting your doctor, because this may lead to a temporary worsening of cardiac activity.
Treatment should not be interrupted suddenly, especially in patients with CAD. If discontinuation is necessary, the dose should be reduced gradually.
Control patients taking bisoprolol should include monitoring of heart rate and blood pressure (at the beginning of treatment - daily, then 1 every 3-4 months), ECG, blood glucose concentration in diabetic patients (1 every 4-5 months). In elderly patients, it is recommended to monitor renal function (1 every 4-5 months). It is necessary to train the patient's heart rate calculation method and instruct on the need of medical advice in heart rate less than 50 bpm. / Min.
Before treatment is recommended to study of respiratory function in patients with a history of bronchopulmonary history.
Approximately 20% of patients with angina pectoris &, beta-blockers are ineffective. The main reason - severe coronary atherosclerosis with a low threshold of ischemia (heart rate less than 100 beats / min.) And increased end-diastolic volume of the left ventricle, which violates the subendocardial blood flow.
Smokers efficiency &, beta-blockers lower.
Patients who use contact lenses should bear in mind that during treatment may decrease the production of tear fluid.
When applied in patients with pheochromocytoma are at risk of paradoxical hypertension (if not previously achieved effective &, alpha-adrenoblockade).
In hyperthyroidism drug may mask certain clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of the drug in patients with hyperthyroidism is contraindicated because the symptoms can increase.
In diabetes may mask tachycardia caused by hypoglycemia. Unlike nonselective &, beta-blockers practically no increase insulin-induced hypoglycemia and delay recovery of blood glucose to normal levels.
At the same time taking clonidine its reception can be terminated only after a few days after discontinuation of the drug Aritel.
Perhaps the increased severity of hypersensitivity reactions and the lack of effect of conventional doses of epinephrine (adrenaline) with aggravated allergic history.
If necessary, an elective surgical treatment drug cancellation performed for 48 hours prior to general anesthesia. If the patient has taken the drug before surgery, he should choose the drug for general anesthesia with minimal negative inotropic effect. It is necessary to warn the anesthetist that the patient is taking the drug Aritel.
Reciprocal activation of the vagus nerve can be removed in / atropine (1-2 mg).
Drugs that reduce stocks of catecholamines (including reserpine), may enhance the action of &, beta-blockers, so patients taking these combinations of drugs should be under constant medical supervision in order to identify arterial hypotension or bradycardia. Patients with diseases bronhospasticheskimi can assign cardioselective blocker in case of intolerance and / or ineffectiveness of other antihypertensive drugs, but should strictly follow the dosage. Overdosing is dangerous development of bronchospasm.
In the case of elderly patients increasing bradycardia (less than 50 u. / Min), hypotension (Sad below 100 mm Hg), AV blockade bronchospasm, ventricular arrhythmias, severe liver and renal function is necessary to reduce the dose or stop treatment.
It is recommended to discontinue therapy in the development of depression caused by the reception &, beta-blockers.
Do not abruptly discontinue the treatment because of the risk of severe arrhythmias and myocardial infarction. Abolition are gradually reducing the dose for 2 weeks or more (reduce dose by 25% in 3-4 days).
It is necessary to cancel prior to the study in blood and urine catecholamines and Normetanephrine vanillylmandelic acid titers of antinuclear antibodies.
Effects on ability to drive or to perform work requiring higher rate of physical and mental reactions. During the period of treatment must be careful when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions.
