Bikard-LF

General characteristics. Structure:

Active ingredient: 2,5 mg, 5 mg or 10 mg of a bisoprolol.

Excipients: magnesium stearate, aerosil, кросповидон, starch corn, cellulose microcrystallic, talc, polyethyleneglycol, titanium dioxide, polyvinyl alcohol, iron oxide yellow, quinolinic yellow E-104, orange yellow E-110.

Heart drug with unique properties. Its creation is achievement of clinical pharmacology and meets the need of medicine for drug, making the maximum therapeutic impact on cordial vascular system at the minimum negative impact on other bodies. In the beginning бисопролол it was used at coronary heart disease, then there were works on successful use in treatment of a hypertension, and in the 1990s results of an epoch-making research of a bisoprolol at heart failure were published. Efficiency and safety of use of a bisoprolol for cardiological patients with associated diseases of lungs, arrhythmias, the diabetes mellitus (DM), dislipidemiya, a renal and liver failure, at elderly, etc. is proved. Does not cause disturbances of sexual function in men.

Pharmacological properties:

Pharmacodynamics. Bisoprolol – the selection beta1-adrenoblocker without own SMA; has hypotensive, antiarrhytmic and anti-anginal effect. Blocking in low doses a beta 1 adrenoceptors of heart, reduces stimulated catecholamines formation of tsAMF from ATP, reduces intracellular current of Sa2+, renders negative hrono-, dromo-, batmo-and inotropic action (urezhat ChSS, ugnetayot conductivity and excitability, reduces contractility of a myocardium). At increase in a dose has beta2-adrenoceptor blocking effect. OPSS at the beginning of use of beta adrenoblockers, in the first 24 h, uveyolichivatsya (as a result of reciprocal increase of activity of alpha adrenoceptors and elimination of stimulation of beta2-adrenoceptors) which in 1-3 days is returned to initial, and at a long nayoznacheniye decreases.

The hypotensive effect is connected with reduction of the IOC, sympathetic stimulation of peripheral vessels, snizheyoniy activities of RAAS (has bigger value for patients with initial hypersecretion of a renin), recovery of sensitivity of baroreceptors of an aortic arch (there is no strengthening of their activity in response to decrease in the ABP) and influence on TsNS. At arterial hypertension the effect occurs in 2-5 days, stable action - in 1-2 months.

The anti-anginal effect is caused by reduction of a potrebyonost of a myocardium in oxygen as a result of an urezheniye of ChSS and decrease in contractility, lengthening of a diastole, improvement of perfusion of a miokaryod. Due to increase in end diastolic pressure in a left ventricle and increases in stretching of muscle fibers of ventricles can increase oxygen requirement, especially at patients with HSN. The antiarrhytmic effect is caused by elimination of aritmogenny factors (tachycardia, a superactivity of sympathetic nervyony system, the increased maintenance of tsAMF, arterial hypertension), reduction of speed of spontaneous excitement of sinus and ectopic pacemakers and delay of AV of carrying out (preyoimushchestvenno in antegrade and to a lesser extent in retrograde nayopravleniye through an AV node) and on additional ways. Unlike non-selective beta adrenoblockers, at appointment in average teyorapevtichesky doses exerts less expressed impact on the bodies containing beta2-adrenoceptors (a pancreas, skeletyony muscles, smooth muscles of peripheral arteries, bronchial tubes and a uterus) and on carbohydrate metabolism, does not cause Na delay + in an organism; expressiveness of atherogenous action does not differ from effect of propranolol. At use in high doses renders the blocking effect on both subtypes of beta adrenoceptors.

Pharmacokinetics. Absorption – 80 - 90%, meal does not influence absorption. The maximum concentration in a blood plasma is observed in 1-3 h, communication with proteins of a blood plasma about 30%. Permeability through a blood-brain barrier and a placental barrier – low, secretion with breast milk – low.

The plasma elimination half-life equal to 10-12 hours provides the 24th hour efficiency at reception once a day. About 95% of medicine are removed through kidneys, a half of it in the form of not changed medicine. In a human body active metabolites are not registered.

Indications to use:

- arterial hypertension;
- coronary heart disease (stenocardia);
- chronic heart failure.

Route of administration and doses:

Pill should be taken inside, washing down with a small amount of liquid in the morning till a breakfast, in time or after it. Tablets should not be chewed, broken or pounded in powder.

Treatment of arterial hypertension and coronary heart disease. At all patients the dose is selected individually, first of all, taking into account ChSS and a condition of the patient.

Adults: As a rule, the initial dose makes 5 mg of 1 times/days. If necessary, the dose can be increased to 10 mg of 1 times/days. The maximum daily dose makes 20 mg of 1 times/days.

For patients with serious violations of function of kidneys (clearance of creatinine <20 ml/min.) and patients with heavy abnormal liver functions the maximum daily dose should not exceed 10 mg a day.

Elderly people: Usually the dose decline is not required, as well as for other adults, the dose of 5 mg a day can be adequate for some patients and can be lowered in cases of serious violation of functions of a liver or kidneys.

Children: There is no experience of use of a bisoprolol by children therefore it is not recommended to be accepted to children.

Treatment of chronic heart failure. An initiation of treatment of the chronic heart failure (CHF) drug Bikard-LF demands obligatory carrying out a special phase of titration and regular medical control.

Since tablets Bikard-LF have no risks for division into 2 parts (for division of a dose), in the period of an initial stage of titration the bisoprolola of the corresponding dosages is recommended to use other drugs.

Treatment by drug begins according to the following scheme of titration. At the same time individual adaptation depending on that can be required, how well the patient transfers the appointed dose. I.e. the dose can be increased only if the previous dose was well transferred.

Week of therapy	Dosing mode
1 week	1,25 mg of 1 times/days.
2 week	2,5 mg of 1 times/days.
3 week	3,75 mg of 1 times/days.
4-7 week	5 mg of 1 times/days.
8-11 week	7,5 mg of 1 times/days.
12 week and further	10 mg of 1 time/days as a maintenance therapy.

During a phase of titration and after it there can be a temporary deterioration in a course of heart failure, a liquid delay in an organism, arterial hypotension and bradycardia. In this case Bikarda-LF is recommended to pay attention to selection of doses of the accompanying basic therapy (to optimize a dose of diuretic and/or APF inhibitor) before a dose decline. Treatment Bikardom-LF should be interrupted only in urgent cases. After stabilization of a condition of the patient it is necessary to carry out repeated titration, or to continue treatment.

Features of use:

It is necessary to be careful at:

- Treatment of patients with a diabetes mellitus with considerable fluctuations of sugar in blood. Symptoms of a hypoglycemia can be disguised.
- To a rigid diet.
- Treatment of patients with a metabolic acidosis.
- Treatment of patients with heavy hypersensitivity reaction in the anamnesis.
- Performing the desensibilizing therapy.
- To an atrioventricular block of the I degree.
- Vasospastic stenocardia (Printsmetal's stenocardia)
- Use during pregnancy and feeding by a breast.

It is not necessary to apply Bikard-LF at pregnancy and during feeding by a breast, and also to treatment of children as for these cases there is no sufficient experience yet. If Bikard-LF is in exceptional cases applied during pregnancy, then treatment has to be stopped by him in 72 hours prior to the expected term of childbirth because of a possibility of emergence of the slowed-down pulse, reduction of content of sugar in blood and respiratory depressions of the newborn. If it is impossible, then after delivery the newborn has to be under careful medical observation. Symptoms of a hypoglycemia can usually be expected within the first 3 days.

Medicine Bikard-LF is produced in the form of round biconvex tablets without risks. Tablets are indivisible. In need of reception of smaller doses it is necessary to use other drugs of a bisoprolol of the corresponding dosages (in coordination with the doctor).

Side effects:

Determination of frequency of side reactions: very often (≥1/10); often (≥1/100, <1/10); infrequently (≥1/1000, <1/100); seldom (≥1/10 000, <1/1000); very seldom (<1/10 000, including separate messages).

From a nervous system: often - fatigue, dizziness, a headache, numbness and cold in extremities; infrequently - sleeplessness, a depression, an adynamy; seldom - drowsiness, hallucinations, dryness in a mouth.

From sense bodys: seldom - a vision disorder, a hearing disorder, reduction of secretion of the lacrimal liquid, dryness and morbidity of eyes; very seldom - conjunctivitis.

From cardiovascular system: very often - a sinus bradycardia; often - decrease in the ABP, manifestation of a vasomotor spasm (strengthening of disturbance of peripheric circulation, a cold snap of the lower extremities, paresthesias); infrequently - AV conductivity disturbance, orthostatic hypotension, a decompensation of chronic heart failure, peripheral hypostases.

From the alimentary system: often - dryness of a mucous membrane of an oral cavity, nausea, vomiting, diarrhea, a lock; seldom - hepatitis.

From respiratory system: infrequently - difficulty of breath at appointment in high doses (selectivity loss) and/or at predisposed patients - laringo-and a bronchospasm; seldom - a nose congestion.

From endocrine system: a hyperglycemia (at patients with a non-insulin-dependent diabetes mellitus), a hypoglycemia (at the patients receiving insulin).

Allergic reactions: seldom - an itch, rash, urticaria.

From integuments: seldom - sweating strengthening, a dermahemia; very seldom - psoriazopodobny skin reactions, an aggravation of symptoms of psoriasis, an alopecia.

From a musculoskeletal system: infrequently - muscular weakness, spasms in gastrocnemius muscles, an arthralgia.

From a reproductive system: seldom - erectile dysfunction.

Laboratory indicators: seldom - increase in activity of hepatic transaminases, increase in level of triglycerides, in some cases - thrombocytopenia, an agranulocytosis.

Others: withdrawal (strengthening of attacks of stenocardia, increase in the ABP).

Interaction with other medicines:

Bisoprolol strengthens effect of other hypotensive drugs. At a concomitant use with Reserpinum, α-metildopy and a clonidine the probability of bradycardia increases. Cardiac glycosides, Methyldopum, Reserpinum and гуанфацин, BMKK (verapamil, diltiazem), Amiodaronum, etc. antiarrhytmic medicines increase risk of development or aggravation of bradycardia, AV of blockade, a cardiac standstill and SN. Nifedipine can lead to considerable decrease in the ABP. Diuretics, a clonidine, sympatholytics, гидралазин, etc. can lead hypotensive medicines to excessive decrease in the ABP. The allergens used for an immunotherapy or extracts of allergens for skin tests increase risk of emergence of heavy system allergic reactions or an anaphylaxis at the patients receiving бисопролол.

Iodinated X-ray contrast medicines for in/in introductions increase risk of development of anaphylactic reactions.

Phenytoinum at in introduction, medicines for inhalation general anesthesia (derivatives of hydrocarbons) increase expressiveness of cardiodepressive action and probability of decrease in the ABP.

Bisoprolol changes efficiency of insulin and peroral hypoglycemic medicines, masks symptoms of the developing hypoglycemia (tachycardia, increase in the ABP). Bisoprolol reduces clearance of lidocaine and xanthines, and increases their concentration in plasma, especially at patients with initially increased clearance of theophylline under the influence of smoking.

NPVP weaken hypotensive effect (Na delay + and blockade of synthesis of prostaglandins kidneys).

Bisoprolol extends action of not depolarizing muscle relaxants and anticoagulating effect of coumarins.

Rub - and tetracyclic antidepressants, antipsychotic HP (neuroleptics), ethanol, sedative and HP hypnotic drugs strengthen oppression of TsNS.

Simultaneous use with MAO inhibitors owing to considerable strengthening of hypotensive action is not recommended, having rummaged in treatment between reception of MAO inhibitors and a bisoprolola has to make not less than 14 days.

Not hydrogenated alkaloids of an ergot increase risk of development of disturbances of peripheric circulation. Ergotamine increases risk of development of disturbance of peripheric circulation; Sulfasalazinum increases concentration of a bisoprolol in plasma, rifampicin reduces an elimination half-life of a bisoprolol.

Intravenous administration of antagonists of calcium and antiarrhytmic means is not recommended during use of a bisoprolol.

Contraindications:

Hypersensitivity, acute SN or dekompensirovanny HSN, cardiogenic shock, AV blockade of II-Sh of the Art., SA blockade, SSSU, bradycardia (ChSS less than 60 beats/min - at treatment of HSN, less than 50/mines - according to other indications), a cardiomegaly (without SN signs), aryoterialny hypotension (systolic the ABP less than 100 mm Hg - at treatment of HSN and 90 mm hg - according to other indications), HOBL (including bronkhiyoalny asthma), disturbance of peripheric circulation (late stages); pregnancy, the lactation period, a concomitant use of ingiyobitor of MAO (except for MAO-B inhibitors).

Overdose:

Symptoms: arrhythmia, ventricular premature ventricular contraction, the expressed bradycardia, AV blockade, decrease in the ABP, HSN, cyanosis of nails of fingers or palms, breath difficulty, a bronchospasm, dizziness, unconscious states, spasms.

Treatment: a gastric lavage and purpose of the adsorbing medicines; symptomatic therapy: at the developed AV to blockade – in/in introduction of 1-2 mg of atropine, Epinephrinum or statement of a temporary pacemaker; at ventricular premature ventricular contraction – lidocaine (drugs 1a of a class are not used); at decrease in the ABP – the patient has to be in the provision of Trendelenburga; if there are no fluid lungs signs, – in/in plasma substituting solutions, at inefficiency – introduction of Epinephrinum, dopamine, Dobutaminum (for maintenance of chronotropic and inotropic action and elimination of the expressed decrease in the ABP); at – cardiac glycosides, diuretics, a glucagon; at spasms – in/in diazepam; at a bronchospasm – β2-адреностимуляторы it is inhalation.

Storage conditions:

In the place protected from moisture and light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

10 or 15 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil. On 3, 5 or 6 blister strip packagings on 10 tablets together with the application instruction in a pack from a cardboard; on two blister strip packagings on 15 tablets together with the application instruction in a pack from a cardboard; on four blister strip packagings on the 15th a dosage of 2,5 mg together with the application instruction in a pack from a cardboard.