BISOGAMMA

Active material: Bisoprolol
When ATH: C07AB07
CCF: Beta₁-adrenoblokator
ICD-10 codes (testimony): I10, i20
When CSF: 01.01.01.02
Manufacturer: WÖRWAG PHARMA GmbH & Co. KG (Germany)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, Film-coated light yellow, round, convex on one side, with the mark on the other side, chamfered surface of the tablet to the risk.

Excipients: krospovydon, pre-gelatinized starch, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, macrogol 6000, Titanium dioxide (E171), talc, dye iron (III) oxide yellow (E172), gipromelloza (HPMC).

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.

Pills, Film-coated from yellow to orange, round, convex on one side, with the mark on the other side, chamfered surface of the tablet to the risk.

Excipients: krospovydon, pre-gelatinized starch, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, macrogol 6000, polysorbate 20, Titanium dioxide (E171), calcium carbonate (E170), talc, dye iron (III) oxide yellow (E172), gipromelloza (HPMC 5), gipromelloza (HPMC 50).

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.

Pharmacological action

Selective beta₁-blocker without intrinsic sympathomimetic activity, It does not have the membrane-stabilizing action. It reduces plasma renin activity, reducing myocardial oxygen demand, reduces heart rate (at rest and during exercise).

It has hypotensive, antiarrhythmic and antianginal. Blocking in low doses β₁-adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cAMP from ATP, reduces intracellular calcium ion current, It has a negative chrono, dromo-, ʙatmo- and inotropic effect.

With increasing doses of the above therapeutic exerts beta₂-adrenoceptor blocking action.

At the beginning of the drug, first 24 no, PR increases (as a result of reciprocal increase in the activity of alpha-adrenoceptor stimulation and removal of β₂-adrenoreceptorov) and by 1-3 d returns to the original, and chronic administration decreases.

The hypotensive effect is associated with a decrease in cardiac output, sympathetic stimulation of peripheral vessels, decreased activity of the renin-angiotensin system (It is of great importance for patients with initial hypersecretion of renin), restoration of sensitivity in response to a decrease in blood pressure and the influence of the central nervous system.

When hypertension effect after 2-5 days, stable operation – through 1-2 of the month.

Antianginal effect is due to a decrease in myocardial oxygen demand as a result of deceleration in heart rate and decrease contractility, lengthening of diastole, improving myocardial perfusion. At the expense of increasing end-diastolic pressure in the left ventricle and increased tensile ventricular muscle fibers 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, hypertension), decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers and slowing of AV (mainly in the antegrade and, less, in retrograde direction through the AV-node) and on additional routes.

When used in high therapeutic doses, Unlike non-selective beta-blockers, Bisogamma^® It has a less pronounced effect on the organs, содержащие b₂-adrenoreceptory (pancreas, skeletal muscle, smooth muscle peripheral arteries, bronchial and uterine) and carbohydrate metabolism, It does not cause a delay of sodium ions in the body; in the expression atherogenic action does not differ from propranolol.

Pharmacokinetics

Absorption and distribution

After oral administration absorption is 80- 90% bisoprolol. Receiving simultaneously with food did not affect the absorption.

C_max plasma levels achieved after 1-3 no. The binding to plasma proteins – about 30%.

Metabolism and excretion

To 10% dose undergoes effect “first pass”. Report the news: 50% – active metabolites, 50% – in unchanged form. T_1/2 is 10-12 no.

Testimony

- Arterial hypertension;

- Prevention of angina attacks.

Dosage regimen

The drug is administered orally at a dose 5 mg 1 time / day, morning, fasting. If necessary, increase the dose to 10 mg 1 time / day. The maximum dose – 20 mg / day.

For elderly patients dose adjustment is required.

In patients with impaired renal function in QA < 20 ml / min or severe hepatic impairment the maximum daily dose – 10 mg.

The tablets are not liquid.

Side effect

From the central and peripheral nervous system: fatigue, weakness, dizziness, headache, sleep disorders, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenia, myasthenia, paresthesias in extremities (in patients with intermittent claudication and Raynaud's syndrome), tremor, convulsions.

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

Cardio-vascular system: sinusovaya bradycardia, heartbeat, conduction disturbances infarction, AV блокада (until the development of a full cross-blockade and heart failure), weakening of myocardial contractility, development (aggravation) chronic heart failure (swelling of the ankles, stop; breathlessness), decrease in blood pressure, orthostatic hypotension, manifestation of vasospasm (increased peripheral circulatory disorders, coldness of the lower extremities, Raynaud's syndrome), chest pain.

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 liver enzymes (ALT increase, ACT) and bilirubin, changes in taste.

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

On the part of the endocrine system: giperglikemiâ (in patients with non-insulin dependent diabetes mellitus), gipoglikemiâ (patients, receiving insulin), hypothyroid state.

From the hematopoietic system: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia.

On the part of the musculoskeletal system: backache, arthralgia, cramps in the calf muscles.

On the part of the reproductive system: the weakening of the libido, reduced potency.

Allergic reactions : itching, rash, hives.

Dermatological reactions: increased sweating, dermahemia, rash, psoriasiform skin reactions, exacerbation of psoriasis symptoms, alopecia.

Effect on the fetus: intrauterine growth, gipoglikemiâ, bradycardia.

Other: withdrawal (increasing angina attacks, increased blood pressure), elevated levels of triglycerides.

Contraindications

- Shock (incl. cardiogenic);

- Collapse;

- Pulmonary edema;

- Acute heart failure;

- Chronic heart failure decompensation;

— AV-blockade II and III degrees;

- SSS;

- Sinoatrialynaya blockade;

- Vыrazhennaya bradycardia;

- Prinzmetal angina;

- Kardiomegalija (without signs of heart failure);

- Hypotension (systolic blood pressure <100 mmHg., especially in myocardial infarction);

- Severe bronchial asthma and other obstructive airway disease;

- Late stages of peripheral circulatory disorders, Raynaud's disease;

- Pheochromocytoma (without the simultaneous use of alpha-blockers);

- Metabolic acidosis;

- Depression;

- Co-administration of MAO inhibitors (except the MAO-B inhibitor);

- Childhood and adolescence up 18 years;

- Hypersensitivity to the drug;

- Hypersensitivity to other beta-blockers.

Precautions should be prescribed to patients with hepatic insufficiency, chronic renal failure, myasthenia, thyrotoxicosis, diabetes, AV block I degrees, psoriaze; When specifying a history of depression, allergic reactions; elderly patients.

Pregnancy and lactation

The appointment of the drug during pregnancy and may lakattsii only, when the intended benefits to the mother outweighs the potential risk to the fetus or infant.

Cautions

Monitoring of patients, taking the drug Bisogamma^®, It involves the measurement of the heart rate and blood pressure (at the beginning of treatment – daily, then 1 once every 3-4 of the month), conduct an electrocardiogram, determination of blood glucose levels with concomitant diabetes mellitus (1 once every 4-5 Months). Elderly patients is recommended to monitor renal function (1 once every 4-5 Months). It should teach the patient methods of calculating heart rate and instruct on the need of medical advice in heart rate less than 50 u. / min. Before treatment is recommended study of respiratory function in patients with a history of bronchopulmonary history.

Approximately 20% patients with angina Beta-blockers are ineffective. Main reasons – severe coronary atherosclerosis with a low threshold of ischemia (HR less 100 beats / min.) and increased end-diastolic volume of the left ventricle, which violates the subendocardial blood flow.

In the case of elderly patients increasing bradycardia (less 50 u. / min.), pronounced reduction in blood pressure (systolic BP below 100 mmHg.), AV-blockade is necessary to reduce the dose or stop treatment.

Do not abruptly discontinue the treatment because of the risk of severe arrhythmias and myocardial infarction. The abolition of a gradually, reducing the dose for 2 weeks or more (reduce the dose by 25% in 3-4 day).

In applying the drug in patients with pheochromocytoma has the paradoxical risk of hypertension (if not previously achieved effective blockade of α-adrenergic receptors).

When thyrotoxicosis bisoprolol may mask certain clinical signs of hyperthyroidism (eg, taxikardiju). Abrupt withdrawal of the drug Bisogamma^® in patsientov with tireotoksikozom contraindicated, as able to exacerbate symptoms.

In diabetes Bisogamma^® may mask tachycardia, induced hypoglycemia. In contrast, non-selective beta blockers hardly increase insulin-induced hypoglycemia or delay recovery of the concentration of glucose in the blood to normal levels.

Perhaps the increased severity of hypersensitivity reactions and the lack of effect of conventional doses of epinephrine with aggravated allergic history.

If necessary, an elective surgical treatment drug Bisogamma^® should be abolished for 48 h before general anesthesia. If the patient has taken the drug before surgery, he should choose a drug for general anesthesia with minimal negative inotropic effects.

Reciprocal activation of the vagus nerve can eliminate I / atropine (1-2 mg).

Drugs, reducing stocks catecholamines (incl. reserpine), may enhance the action of beta-blockers, so patients, taking such drug combinations, We should be under constant medical supervision for timely monitoring pronounced reduction in blood pressure or bradycardia.

Patients with diseases bronhospasticheskimi can assign cardioselective blocker in case of intolerance and / or ineffectiveness of other antihypertensive drugs. Overdose danger of developing bronchospasm.

When used in combination with clonidine its reception can be terminated only after a few days after discontinuation of bisoprolol.

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

At smoking patients the effectiveness of beta-blockers lower.

Patients, use contact lenses, We should take into account, that during treatment Bisogamma^® may decrease the production of tear fluid.

The drug should be discontinued prior to the study content in the blood and urine kateholamiiov, normetanephrine and vanilinmindalnoy acid, antinuclear antibodies.

Effects on ability to drive vehicles and management mechanisms

During treatment, patients should be careful when driving and occupation of other potentially hazardous activities, require high concentration and speed of psychomotor reactions.

Overdose

Symptoms: ventricular premature beats, vыrazhennaya bradycardia, AV блокада, marked reduction in blood pressure, congestive heart failure, cyanosis of nails of fingers or hands, difficulty breathing, bronchospasm, dizziness, fainting, convulsions.

Treatment: gastric lavage and appointment of adsorbing drugs. Symptomatic therapy: which developed in the AV-blockade - in / in a 1-2 mg atropine, epinephrine, or staging a temporary pacemaker; when ventricular arrhythmia – lidokain (drugs IA class shall not apply). By reducing blood pressure patient should be in the Trendelenburg position; if there are no signs of pulmonary edema – I / O solutions plazmozameschayuschie, the ineffectiveness – administration of epinephrine, dopamine, doʙutamina (to maintain chronotropic and inotropic effects and eliminate significant decrease in blood pressure); Heart failure – cardiac glycosides, Diuretic, glucagon; with cramps – in / diazepam; with bronchospasm – beta₂-adrenostimulyatorov inhalation.

Drug Interactions

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

Iodine radiopaque drugs for i / v administration increase the risk of anaphylactic reactions in patients, receiving bisoprolol.

Phenytoin in in / in the introduction, drugs for inhalation general anesthesia (hydrocarbon derivatives) cardiodepressive increase the severity of the action and the likelihood of blood pressure lowering in patients, receiving bisoprolol.

Bisoprolol alter the effectiveness of insulin and oral hypoglycemic drugs, masking the symptoms of developing hypoglycemia (taxikardiju, increased blood pressure).

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

The hypotensive effect of bisoprolol reduce NSAID (delay of sodium ions and the blockade of prostaglandin synthesis by the kidneys), SCS and estrogens (delay of sodium ions).

Cardiac glycosides, methyldopa, reserpine and guanfacine, blockers slow calcium channels (verapamil, diltiazem), amiodarone and other antiarrhythmics while the use of bisoprolol increase the risk of developing or worsening of bradycardia, AV-blockade, heart failure and congestive heart failure.

When applied simultaneously with nifedipine may be a significant reduction in blood pressure.

In an application with bisoprolol diuretics, klonidin, simpatolitiki, hydralazine, and other antihypertensive drugs may cause an excessive decrease of blood pressure.

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

Three- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and hypnotics drugs increase the depressant effect of bisoprolol on the CNS.

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

Negidrirovannыe alkaloidы sporыnьi (incl. ergotamin) while the use of bisoprolol increase the risk of peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol in blood plasma.

Rifampicin reduces T_1/2 bisoprolol.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or above 25 ° C. Shelf life - 3 year.