Expiration date: 03/2025

Release form and composition:

The tablets covered with a film cover of beige-yellow to beige, round, biconcave fracture on a white or nearly white.

1 tablet contains bisoprolol fumarate 5 or 10 mg

Excipients: Sodium croscarmellose (primelloza), povidone (polyvinylpyrrolidone medium weight), pre-gelatinized starch (starch 1500), colloidal silicon dioxide (Aerosil), talcum, microcrystalline cellulose, lactose (milk sugar), magnesium stearate.

Composition of film-coating: Opadry II (polyvinyl alcohol, partially hydrolyzed, titanium dioxide, talc, Macrogol (polyethylene glycol 3350), iron oxide, dye (II)).

Pharmachologic effect:

Selective beta1-blocker without its own sympathomimetic activity, has no membrane stabilizing action. It lowers blood plasma renin activity, reduces myocardial oxygen demand, reduces heart rate (at rest and during exercise).

It has antihypertensive, antiarrhythmic and antianginal effects. Blocking in low doses of beta1-adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cAMP from ATP, reduces intracellular calcium ion current, has a negative chrono-, Drome, BATM and inotropic effects, inhibits the conductivity and excitability of the myocardium reduces AV-conduction.

With increasing doses above the therapeutic has a beta2-adrenoceptor blocking action.

PR at the beginning of the drug in the first 24 hours, is increased (as a result of reciprocal increase in the activity of alpha-adrenoceptor stimulation and removal of beta2-adrenoceptor), which is 1-3 days returns to the original, but with long-term administration is reduced.

The hypotensive effect associated with a decrease in cardiac output, peripheral vascular sympathetic stimulation, decreased activity of the renin-angiotensin system (important for patients with initial hypersecretion of renin), restoration of sensitivity in response to the decrease in blood pressure and effect on the central nervous system. When hypertension effect occurs within 2-5 days, stable operation - through 1-2 months.

Antianginal effect is due to a decrease in myocardial oxygen demand by reducing heart rate and decrease contractility, lengthening of diastole, improving myocardial perfusion. By increasing end-diastolic pressure in the left ventricle and increase the tension of the muscle fibers of the ventricles can increase oxygen demand, especially in patients with chronic heart failure.

The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP levels, hypertension), decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers and slowing AV-holding (mainly in the antegrade and to a lesser extent, in a retrograde direction through AV-node) and on additional routes.

When used in high therapeutic doses, unlike non-selective beta-blocker, has a less pronounced effect on organs comprising a beta2-adrenoceptor (pancreas, skeletal muscle, smooth muscle of peripheral arteries, bronchial and uterine) and carbohydrate metabolism, does not cause delays sodium ions (Na +) in the body severity atherogenic action is different from that of propranolol.

Pharmacokinetics:

Absorption and distribution

Absorption - 80-90%, it does not affect food intake on absorption. Cmax in plasma observed after 1-3 h.

Communication with plasma proteins - about 30%. It passes through the placental barrier and the blood-brain barrier to a minor extent, in small amounts excreted in breast milk.

Metabolism and excretion

50% of the dose is metabolized in the liver to inactive metabolites.

T1 / 2 - 10-12. H About 98% is excreted in the urine - 50% unchanged, less than 2% - with bile.

Testimony:

• arterial hypertension
  
• Coronary heart disease: prevention of angina attacks.
  

Dosage and administration:

The drug is taken orally, in the morning, on an empty stomach, without chewing, the initial dose of 5 mg 1 time / day. If necessary, increase the dose to 10 mg 1 time / day. The maximum daily dose - 20 mg / day.

In patients with renal impairment with CC less than 20 ml / min, or with severe liver problems, the maximum daily dose should be 10 mg.

No dose adjustment in elderly patients is not required.

Side effects:

CNS: fatigue, weakness, dizziness, headache, sleep disorders, depression, anxiety, confusion, or momentary loss of memory, hallucinations, asthenia, myasthenia gravis, paresthesia in the extremities (in patients with intermittent claudication and syndrome Peyno), tremor.

From the senses: visual disturbances, reduced secretion of tear fluid, dryness and soreness of eyes, conjunctivitis.

Cardio-vascular system: sinus bradycardia, heart rate, conduction disturbances infarction, the AV -blokada (until the development of a complete transverse blockade and heart failure), arrhythmia, weakening of the myocardial contractility and development (worsening) of chronic heart failure (swelling of ankles, feet, dyspnea), reduced blood pressure, orthostatic hypotension, a manifestation of vasospasm (strengthening of peripheral blood circulation, cooling of the lower extremities, Raynaud's syndrome), pain in the chest.

From the digestive system: dryness of the oral mucosa, nausea, vomiting, abdominal pain, constipation or diarrhea, abnormal liver function (dark urine, yellow skin or sclera, cholestasis), changes in taste.

The respiratory system: nasal congestion, difficulty breathing when administered at high doses (loss of selectivity) and / or in predisposed patients - laryngo and bronchospasm.

From endocrine system: hyperglycemia (in patients insulinezavisimym diabetes), hypoglycemia (in patients receiving insulin), hypothyroid state.

Allergic reactions: itching, rash, urticaria.

Dermatological reactions: sweating, skin flushing, rash, psoriasiform skin reactions, exacerbation of psoriasis symptoms.

From the laboratory parameters: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, changes in the activity of liver enzymes (ALT increase, the ACT), bilirubin, triglycerides.

Effect on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia.

Other: back pain, arthralgia, weakening of libido, reduced potency, withdrawal syndrome (increased angina attacks, increased blood pressure).

Contraindications:

• Shock (including cardiogenic)
  
• collapse
  
• pulmonary edema
  
• Acute heart failure
  
• Chronic heart failure in a decompensation stage
  
• AV-block II and III degree
  
• Sinoatrial block
  
• SSS
  
• Expressed bradnkardiya
  
• Prinzmetal angina
  
• Cardiomegaly (without heart failure)
  
• Hypotension (systolic blood pressure less than 100 mmHg, especially myocardial infarction)
  
• Severe bronchial asthma and chronic obstructive pulmonary disease in history
  
• Simultaneous MAO inhibitors (except for MAO-B)
  
• Late stages of peripheral circulatory disorders, Raynaud's disease
  
• Pheochromocytoma (without simultaneous use of alpha-blockers)
  
• Metabolic acidosis
  
• The age of 18 years (effectiveness and safety have been established)
  
• Hypersensitivity to the drug and other beta-blockers.
  

Precautions should be prescribed the drug for liver failure, chronic renal failure, myasthenia gravis, thyrotoxicosis, diabetes mellitus, AV-blockade of I degree, depression (including history), psoriasis, as well as elderly patients.

Pregnancy and lactation:

Use in pregnancy and lactation is possible if the benefit to the mother outweighs the risk of side effects in the fetus and child.

Special instructions:

Monitoring of patients receiving bisoprolol should include measurement of heart rate and blood pressure (at the beginning of treatment - daily, then - 1 every 3-4 months) holding an electrocardiogram, determination of blood glucose levels 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 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.

At smoking patients the effectiveness of beta-blockers lower.

Patients who use contact lenses should bear in mind that during treatment may decrease the production of tear fluid.

When used in patients with pheochromocytoma have a risk of paradoxical hypertension (if not previously reached effective alpha adrenoblockade).

When thyrotoxicosis bisoprolol may mask certain clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because the symptoms can increase.

In diabetes may mask tachycardia caused by hypoglycemia. In contrast, non-selective beta-blockers is not practically increase insulin-induced hypoglycemia or 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 Bisoprolol.

Perhaps the increased severity of hypersensitivity reactions and the lack of effect of conventional doses zpinefrina with aggravated allergologicheekogo history. If necessary, an elective surgical treatment is performed for the cancellation of the drug 48 hours before general anesthesia. If the patient has taken the drug before surgery, he should choose the drug for general anesthesia with minimal negative inotropic effect.

Reciprocal activation of the vagus nerve can be removed in / atropine (1-2 mg).

Drugs that reduce the reserves of catecholamines (including reserpine), may enhance the effect of beta-blockers, so patients taking such drug combinations should be under constant medical supervision in order to identify pronounced lowering of blood pressure and bradycardia.

Patients with diseases bronhospasticheskimi can assign cardioselective blocker in case of intolerance and / or ineffectiveness of other antihypertensive drugs. Overdosing is dangerous development of bronchospasm.

In the case of elderly patients increasing bradycardia (less than 50 u. / Min.), Pronounced reduction in blood pressure (systolic blood pressure below 100 mm Hg), AV -blokady, reduce the dose or discontinue treatment.

It is recommended to discontinue therapy in the development of depression.

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 vanilinmindalnoy acid, antinuclear antibody titers.

Effects on ability to drive vehicles and management mechanisms

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.

Overdose:

Symptoms: arrhythmia, ventricular premature beats, bradycardia, AV-blockade, marked reduction in blood pressure, chronic heart failure, cyanosis of nails of fingers or palms, shortness of breath, bronchospasm, dizziness, fainting, seizures.

Treatment: gastric lavage and the appointment of adsorbents symptomatic therapy: AV blockade under which developed - in / in a 1-2 mg of atropine, epinephrine or staging a temporary pacemaker with ventricular arrhythmia - lidocaine (IA class of drugs are not used) with a decrease in blood pressure - the patient must be in Trendelenburg position if there are no signs of pulmonary edema - in / plasma substituting solutions, with inefficiency - the introduction of epinephrine, dopamine, dobutamine (to maintain the chronotropic and inotropic effects and elimination of significant decrease in blood pressure), heart failure - cardiac glycosides, diuretics, glucagon in convulsions - in / diazepam with bronchospasm in beta adrenostimulyatorov inhalation.

Drug Interactions:

The allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reaction or anaphylaxis in patients receiving bisoprolol.

Iodine radiopaque drugs for the on / in the increase the risk of anaphylactic reactions.

Phenytoin at / in the introduction, drugs for inhalation general anesthesia (derivatives of hydrocarbons) increase the intensity of cardiodepressive action and the likelihood of blood pressure lowering.

Changes the effectiveness of insulin and oral hypoglycemic drugs, masking the symptoms of developing hypoglycemia (tachycardia, increased blood pressure).

Reduces clearance of lidocaine and xanthine (except dyphylline) and increases their concentration in plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking.

Antihypertensive effect of weakening the NSAID (delay Na + and the blockade of prostaglandin synthesis by the kidneys), corticosteroids, and estrogens (delay of Na + ions).

Cardiac glycosides, methyldopa, reserpine, guanfacine and blockers, slow calcium channel blockers (verapamil, diltiazem) and amiodoron other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV-blockade, heart failure and heart failure.

Nifedipine can lead to a significant reduction in blood pressure.

Diuretics, clonidine, sympatholytic, hydralazine, and other antihypertensive drugs may cause an excessive decrease of blood pressure.

Extends the action of non-depolarizing muscle relaxants and anticoagulant effect of coumarin.

Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and hypnotic drugs increase CNS depression.

Not recommended simultaneous application with MAO inhibitors due to the significant increase in the hypotensive action, a break in treatment between receiving MAO inhibitors and bisoprolol must not be less than 14 days.

Non-hydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders.

Ergotamine increases the risk of peripheral circulatory disorders sulfasalazine increases the concentration of bisoprolol in the plasma half-life of rifampin shortens.

Conditions and terms:

List B. The drug should be stored in a dry, dark, place inaccessible to children at temperature not above 25 ° C. Shelf life - 3 years.