Biprolol

General characteristics. Structure:

International and chemical names: bisoprolol, 1-[4-[[2 (1-metiletoks) of an etoksa] marked] - fenoks]-3-[(1 methylethyl) - amine] - 2 propyl alcohols гемифуморат;
main physical and chemical properties: tablets of a round form, light yellow (5 mg) or from beige to beige with an orange shade (10 mg) of color with impregnations, with a biconvex surface, from risky; structure: 1 tablet contains 5 mg or 10 mg of a bisoprolol of a fumarat; excipients: microcrystallic cellulose, кросповидон, magnesium stearate, ferrous oxide yellow, ferrous oxide red (as a part of a tablet with a dosage of 10 mg), lactoses monohydrate.

Pharmacological properties:

Pharmacodynamics. Bisoprolol is the selection β the blocker operating preferential on _{β1-адренорецепторы}. Cardioselectivity makes 1:75 for a bisoprolol. Hemodynamic action consists in decrease in the heart rate (HR) at rest and at an exercise stress, in decrease in cordial emission and slight increase of the general peripheric resistance of vessels. Atrioventricular carrying out is slowed down and the refractory period of the AV-node is extended.

Pharmacokinetics. Bisoprolol treats lipophilic β-adrenoblockers.......... The main defining indicators of pharmacokinetics are: the high level of absorption in a digestive tract (> 90%) which is not depending on the use of food; practical lack of effect of "the first passing" through a liver (<10%); long elimination half-life (10 – 12 h); and, above all - the balanced clearance (50% of drug are removed in an invariable look by kidneys, and 50% - are metabolized in a liver). The maximum action develops in 1-3 hours after intake and continues within 24 hours. It gives the chance to accept drug of 1 times a day as before meal, and later, and to appoint him the patient with moderate hepatic and/or renal dysfunction. The balanced clearance and low level of linkng with serum proteins (about 30%) provides low variability of its concentration at patients and satisfactory portability at different age groups. In a human body active metabolites are not formed.

Indications to use:

Arterial hypertension, coronary heart disease (stenocardia), chronic heart failure.

Route of administration and doses:

Drug is accepted 1 time a day irrespective of meal. The maximum daily dose of Biprolol – 20 mg. For patients with the expressed renal failure (clearance of creatinine less than 20 ml/min.) and/or a heavy abnormal liver function the maximum daily dose makes 10 mg.
Arterial hypertension and coronary heart disease. The initial dose of Biprolol makes 2,5 mg/days. The average therapeutic dose makes 5 – 10 mg/days. The dosage is selected individually, taking into account efficiency of treatment, arterial pressure and pulse rate which are controlled on average each two weeks.
Chronic Heart Failure (CHF). The initial dose of Biprolol makes 1,25 mg/days. Within 4 hours after an initiation of treatment the patient with HSN has to be inspected (arterial pressure, ChSS, conductivity disturbance, progressing of symptoms of heart failure). Each two weeks increase a daily dose by 1,25 mg before achievement of the maximum daily dose – 10 mg (on condition of satisfactory portability) and inspect (arterial pressure, ChSS, conductivity disturbance, progressing of symptoms of heart failure). Emergence of side effects demands immediate correction of the dose appointed to patients. If necessary the reached dose can be gradually lowered. Treatment can be stopped if it is necessary, and then is resumed according to the same scheme. In case of development of intolerance or progressing of symptoms of heart failure during increase in a dose it is recommended to lower first of all Biprolol's dose or to immediately stop administration of drug (in case of the expressed hypotension, progressing of symptoms of heart failure which is followed by an acute fluid lungs).

Features of use:

Treatment by Biprolol, as a rule, is long and demands regular medical control. The course of treatment has to come to an end, as a rule, slowly, with a gradual dose decline. Drug cannot be cancelled suddenly in connection with possible development of a withdrawal. It should be considered especially at treatment of patients with a disease of coronary vessels, and also patients with chronic heart failure (at such patients the dose has to decrease twice weekly).
It is necessary to be careful at treatment of patients with a diabetes mellitus with considerable fluctuations of sugar in blood; treatment of patients with a metabolic acidosis; when performing the desensibilizing therapy; To AV blockade of the I degree; vasospastic stenocardia (Printsmetall stenocardia); at observance of a rigid diet. Before surgical intervention the doctor has to be informed on use by Biprolol's patient. Biprolol's appointment is allowed to patients with a pheochromocytoma only after reception of α-adrenoblockers.......... Biprolol's use at an aggravation of HSN is not recommended or during episodes of a decompensation of heart failure which demand intravenous administration of inotropic drugs. At the instruction in the anamnesis on existence at the patient or his relatives of psoriasis use of drug has to be made only after careful assessment of a ratio of advantage and risk. The maximum daily dose of Biprolol is 10 times less than the dose influencing on _{β2-адренорецепторы}. But irrespective of it reasonablly carefully to treat Biprolol's use for patients with tendency to bronchospasms (at an asthmatic bronchitis, bronchial asthma). Drug yields a positive take at anti-doping control, can also increase sensitivity to allergens and influence expressiveness of allergic reactions.
Due to the individual nature of mental reactions at administration of drug ability to manage the vehicle can be reduced.

Side effects:

Cardiovascular system. Orthostatic hypotension, bradycardia, AV conductivity disturbance, attacks of vasospastic stenocardia, as a rule, in an initiation of treatment. Symptoms of disturbance of peripheric circulation (paresthesia) can sometimes be observed. At patients with the alternating lameness, Reynaud's syndrome strengthening of the main displays of a disease is possible.
Nervous system. At the beginning of a course of treatment temporary frustration – increased fatigue, dizziness, a headache, sleep disorders are possible. Possible reduction in the rate of motor and mental reactions, developing of a depression, is very rare - hallucinations.
Respiratory system. Nose congestion, rhinitis. The patients predisposed to a bronchospasm (at an asthmatic bronchitis, bronchial asthma), can have an otdyshka.
Digestive tract. In some cases  diarrhea, locks, nausea, abdominal pains. Isolated cases of a hepatotoxic of a bisoprolol are described.
Musculoskeletal system. In some cases  muscular weakness, spasms.
Dermatological reactions. Sometimes – an itch.  Erubescence, perspiration, allergic rashes is rare. At patients with psoriasis the exacerbation of a disease is possible.
Organs of sight. Reduction of secretion of the lacrimal liquid (it is necessary to consider when carrying contact lenses), is rare  a vision disorder, conjunctivitis.
Urinogenital bodies. Seldom - disturbance of a potentiality.
At the accompanying (latent) diabetes mellitus tolerance to glucose can decrease (very seldom).

Interaction with other medicines:

MAO inhibitors. At simultaneous use of Biprolol with MAO inhibitors the risk of development of disturbances of conductivity, a collapse or arterial hypertension increases. Therefore Biprolol's use is admissible only in 15 days after cancellation of MAO inhibitors.
Nitrates. Biprolol exponentiates anti-anginal effect of nitrates, at the same time side effect of each of drugs decreases (a heart consciousness and a headache – nitrates; bradycardia and a cryesthesia in extremities  Biprolol).
Clonidine (clonidine). At Biprolol and Klonidin's simultaneous use its influence on conductivity and ChSS is exponentiated (negative hrono-and dromotropic action). At simultaneous treatment by Biprolol and the Clonidine it is impossible to cancel both drugs at the same time because of risk of development of hypertensive crisis: in such cases the Clonidine is cancelled in several days after Biprolol's cancellation.
Theophylline. At Biprolol and Teofillin's simultaneous use decrease in bronkhodilyatiruyushchy effect of the last is possible.
Rifampicin, Cimetidinum practically do not influence Biprolol's pharmacokinetics.
Baclofenum. Use of Baclofenum against the background of treatment by Biprolol can strengthen hypotensive effect of the last.
Corticosteroids. At simultaneous use of Biprolol and corticosteroids decrease in hypotensive effect of Biprolol is possible.
Nonsteroid protivospalitelny means. Against the background of treatment by Biprolol use of NPVS (very seldom) can slightly reduce hypotensive effect of Biprolol.
The contrast agents containing iodine; the allergens used for immunotherapy/diagnosis. To treat reasonablly more carefully simultaneous use of Biprolol and contrasts/allergens because of a nonexcluded possibility of strengthening of allergic effect of the used drugs, especially at predisposed patients.
Anesthesia. When carrying out the general anesthesia against the background of treatment by Biprolol strengthening of hypotensive effect is possible.

Contraindications:

Hypersensitivity to drug components. Cardiogenic shock, AV blockade of II and III degrees, a sick sinus syndrome, the expressed sinuatrial blockade, bradycardia (less than 50 beats/min), the expressed hypotension (systolic pressure is lower than 90 mm of mercury.), the expressed disturbances of peripheric circulation, at a concomitant use of MAO inhibitors (for an exception of MAO-B inhibitors).
Biprolol's use is contraindicated to sick HSN if ChSS less than 60 beats/min and/or systolic pressure is lower than 100 mm of mercury.
It is not necessary to apply Biprolol at pregnancy, during feeding by a breast, and also to treatment of children up to 12 years.

Overdose:

Bradycardia, arterial hypotension, heart failure, bronchospasm, Crocq's disease, spasms, hypoglycemia. In this case Biprolol's reception should be stopped immediately, in hard cases to carry out a gastric lavage, to enter sorbents (absorbent carbon). It is also necessary to provide breath monitoring, in the presence of indications to transfer to an artificial respiration. Cardiovascular complications are treated symptomatic. At the expressed bradycardia administration of atropine is possible. Action of β-blockers is counteracted by introduction of an izoprenalin which can be combined with dopamine.

Storage conditions:

To store in dry, protected from light, the place, unavailable to children, at a temperature not above 25 °C.
Period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging, on 3 blister strip packagings in a pack.