BICARD

APPROVED

Order of Ministry of Health Protection of Ukraine

01.09.2010 # 756

Certificate of State Registration

# UA 10921/01/02

INSTRUCTION

for Medical Use of Preparation

BICARD®

 

Remedy composition:

Acting substance: bisoprolol;

1 tablet contains bisoprolol fumarate (2:1) 5 mg or 10 mg respectively;

Supplementary substances: 5 mg tablets: microcrystal cellulose, colloid waterless silica dioxide, sodium starch glycollate (Type A), sodium crosscarmeloza, magnesium stearate, hypromeloza, talcum, ponceau 4R (E 124), polyethylene glycol 6000;

10 mg tablets:  microcrystal cellulose, colloid waterless silica dioxide, sodium starch glycollate (Type A), sodium crosscarmeloza, magnesium stearate, hypromeloza, talcum, titanium dioxide (E 171), polyethylene glycol 6000

 

Pharmaceutical form. Tablets covered by film coat.

 

Pharmacotherapeutic group. Selective blockers of beta-adrenoceptors.

Code ATC C07A B07.

 

Clinic characteristics.

Indications for use.

Arterial hypertension: ischemic heart disease (stenocardia); chronic cardiac insufficiency.

Contra indications.

Cardiac insufficiency in decompensation state; cardiogenic shock; atrioventicular block of II and III stage; sinus node weakness syndrome; frank sinoartial block; symptomatic bradycardia (cardiac rate (CR) is less than 50 beats per minute); symptomatic arterial hypertension (systolic arterial tension lower than 90 Hg mm); simultaneous intake of MAO inhibitors (except for MAO inhibitors of type B); obstructive wheezing illness of lungs, bronchial asthma; late stages of peripheral circulatory embarrassment, Raynaud’s disease; phaeochromocytoma that was not treated; metabolic acidosis; period of pregnancy and breast feeding; elevated sensitivity to the preparation’s components; child age.

Posology and method of administration.

The preparation dose is selected individually with taking into consideration therapy efficiency and pulse rate. The preparation should be taken in morning irrespective of meal, without chewing, washing down with small water quantity. In case of necessity to intake the preparation intake at the dose less than 5 mg, it is recommended to use other preparation of bisoprolol with possibility of this dosing.

 

Arterial hypertension.

The recommended dose is 5 mg (1 tablet of Bicard 5 mg) per day. At arterial hypertension of II stage (diastolic arterial tension is up to 105 Hg mm) at the beginning of the treatment the dose can be prescribed that is 2.5 mg of the preparation per day. In case of necessity the daily dose can be increased up to 10 mg per day.

Ischemic heart disease (stenocardia).

The recommended daily dose is 5 mg of bisoprolol fumarate once per day.

In case of necessity the dose can be increase up to 10 mg of bisoprolol fumarate once per day. The maximum daily dose is 10 mg.

Chronic cardiac insufficiency.

At chronic cardiac insufficiency the preparation is prescribed for a patient with moderate frank and severe cardiac insufficiency with reduced systolic function (ejection fraction ≤ 35 % according to echocardiography data) that are in stabilization state without aggravation during the last six weeks. The initial dose is 1.25 mg once per day during the first week (bisoprolol preparations are used with possibility of such dosing). During the 2nd week the preparation is prescribed 2.5 mg per day. During the 3rd week the therapeutic dose is 3.57 mg per day (bisoprolol preparations are used with possibility of such dosing).  Since 4th up to 8th week 5 mg dose is prescribed. Then the dose is increased up to 7.5 mg (since 8th up to 12th week). After the 12th week of therapy the maximum daily dose 10 mg is prescribed. The preparation dose increase is regulated by indices of heart rate, arterial tension, patient general state.

The maximum dose is 10 mg per day.

At treatment of patients with chronic cardiac insufficiency it is possible to combine bisoprolol with angiotensin converting enzyme inhibitor, diuretic and cardiac glycoside. After beginning of treatment with the preparation at the dose of 1.25 mg, patient with chronic cardiac insufficiency should be examined during 4 hours (arterial tension, cardiac rate, asequence, aggravation of cardiac insufficiency symptoms); in case of necessity the preparation is cancelled.

Patients with hepatic and renal insufficiency.

For patients with hepatic or renal malfunctions of light or average severity stage, usually dose selection is not necessary.

For patients with frank renal function reduction (creatinine clearance is less than 20 ml/minute) and patients with severe form of renal malfunction, the dose should not excess the daily dose 10 mg of Bicard.

The therapy course is long. The therapy course duration depends on the disease character and flow.

The treatment should not be stopped urgently; the course should be stopped slowly, with gradual dose reduction.

Side reactions.

Unwished effects with occurrence frequency are classified pursuant to the following categories:

Very often (>1/10), often (≥ 1/100 and < 1/10), non-often (≥ 1/1000 and < 1/100), rarely (≥1/10000 and < 1/1000), very rarely (< 1/10000).

 

From nervous system side.

Often: dizziness, headache (especially: at the beginning of treatment, usually they are ill-defined and pass during 1-2 weeks).

Non-often: insomnia, depressions.

Rarely: hallucinations, paresthesia.

 

From vision organ side.

Rarely: lacrimation reduction (it should be taken into consideration at contact lens wear).

Very rarely: conjunctivitis, pain in eyes.

 

From acoustic organ side.

Rarely: impairment of hearing.

 

From cardio-vascular system side.

Very often: bradycardia (at patients with chronic cardiac insufficiency).

Often: feeling of cold or limb immobility, indications of cardiac insufficiency aggravation at the beginning of treatment (at patients with chronic cardiac insufficiency).

Sometimes: atrioventricular conduction abnormality (at patients with arterial hypertension and ischemic heart disease), orthostatic hypertension, increase of available intermittent limp.

From respiratory system side.

Sometimes: bronchospasm at patients with bronchial asthma in past medical history and chronic obstructive diseases of respiratory passages.

Rarely: allergic rhinitis.

 

From gastroenteric tract side:

Often: nausea, vomiting, diarrhea, constipation, abdominal pain.

 

From liver side.

Rarely: metabolism violation (increase of triglyceride level in blood), increase of hepatic enzyme activity in blood plasma (AST, ALT), hepatitis.

From skin and musculoskeletal system side.

Sometimes: muscular weakness, convulsions.

Rarely: hypersensitivity reactions – itch, hyperhidrosis, eruption.

Very rarely: hair shedding, at treatment with beta-receptor blockers state of patients with psoriasis the state impairment can occur in form of psoriatic eruption.

From urogenital system side.

Rarely: potency violation.

 

General abnormality.

Often: asthenia (at patients with chronic cardiac insufficiency), fatigability (especially at the beginning of treatment, usually ill-defined that pass during 1-3 weeks)

Sometimes: asthenia (at patients with arterial hypertension and ischemic heart disease).

Overdose.

Symptoms: bradycardia, arterial hypertension, cardiac insufficiency, bronchospasm, hypoglycemia.  

Treatment: the preparation cancellation, gastric lavage and activated carbon intake. In case of necessity symptomatic treatment should be used.

At bradycardia: intravenous injection of atropine.

At arterial hypertension: intake of vasoconstrictive preparations, intravenous injection of glucagon.

At atrioventricular block of II and III stage: infusive injection of orciprenaline; in case of necessity cardiostimulation therapy should be used.

Impairment of state at cardiac insufficiency: intravenous injection of diuretic remedies.

At bronchspasm: broncholithics (for example, orciprenaline), beta-adrenomimetics and/or aminophylline.

At hypoglycemia: intravenous injection of glucose.

Use during pregnancy and breast feeding.

During pregnancy the preparation intake is not recommended. It is possible to use it only when the supposed benefit for mother excesses potential risk for fetus. As a rule, beta-adrenoblockers reduce blood flow in placenta and can have influence on fetus development. It is necessary to control blood flow in placenta and womb. After act of delivery newborn should be under careful monitoring. Symptoms of hypoglycemia, respiration suppression and bradycardia can be supposed during the first days.

There are no data on Bicard discretion into breast milk or safety of influence on nursing infants.

Children.

There are no data as to efficiency and safety of the preparation use for children treatment. Therefore, Bicard is not used in pediatric practice.

Use pattern.

The treatment should not be stopped urgently, the course should be stopped slowly, with gradual dose decrease. At urgent cancellation of the preparation the withdrawal syndrome of development is possible, it results in disease recurrence. Therefore, the preparation cancellation and dose reduction should be carried out gradually, under doctor monitoring with taking into consideration individual reactions of patients.

The preparation should be used carefully at diabetes mellitus with sharp glycemic excursion in blood; glycemia symptoms can be concealed (for example, tachycardia, sense of heartbeats, hyperhidrosis); rigid diet; during desensibilization therapy; atrioventricular block of I stage; blood circulation failures (complaints can be increased, especially at the beginning of the therapy).

Before beginning of the treatment it is recommended to carry out examination of external respiration functions at patients with bronchial asthma in past medical history.

General anesthesia. It is necessary to warm anesthesiologist about intake of beta-adrenoreceptors blockers. It is not recommended to use beta-adrenoreceptors blockers during surgical interferences. It can increase risk of arrhythmias and myocardial ischemia occurrence. The dose should be gradually reduced and the preparation intake should be stopped approximately 48 hours before general anesthesia.

Patients with psoriasis (including those in family past medical history) beta-adrenoblockers are prescribed after the sound judgment of benefit/risk relation.

Do not use the preparation at patients with pheochromocytoma, if previously efficient alpha-adrenoblock is not achieved.

Thyreotoxicosis symptoms can be masked on the background of the preparation intake.

Beta-adrenoblockers can provoke appearance, increase quantity and continue attacks of vasospastic stenocardia / Prinzmetal’s angina, that it necessary to take into consideration at prescription of bisoprolol.

As a rule, patients with chronic obstructive diseases of respiratory tract should not use beta-blockers, or in case of necessity they should intake them in minimum doses (initial dose is 2.5 mg per day) in combination with bronchodilatators.

In case of hepatic and renal function severe abnormality, the dose should not be more than 10 mg per day, clinic state of such patients requires adequate medical control.

The preparation can increase sensibility to allergens and evidence to allergic reactions. At patients of elderly age correction of dosing is not necessary, however, patients of this category can have elevated sensibility even for usual doses of the preparation.

Ability to influence on quick reaction capability at driving motor transport or work with other mechanisms.

Taking into consideration possibility of influence on arterial tension and cardiac rhythm with appearance of corresponding clinic symptomatology, ability to drive car or work with complex mechanisms can be reduced. Therefore, it is recommended to prescribe carefully bisoprolol to persons who drive motor transport facilities and potentially dangerous mechanisms.

Interaction with other remedies and other kinds of interaction.

Combinations with floctafenine, sultopride, monoaminoxidaze inhibitors (except for MAO-B inhibitors) are contraindicative.

Allergens used for immunotherapy / allergen extracts for skin tests in combination with beta-adrenoblockers can provoke severe systemic allergic reactions.

Combinations of bisoprolol with calcium antagonists (verapamil, diltazem, bepridil) are not recommended / requires special care due to increase of negative influence on inotropic myocardium function, AV-conductibility and arterial tension.

Preparations containing clondine, reserpine, alpha-methyldopa should not be used together with bisoprolol, because considerable slowdown of cardiac rate can occur. Clondine, guanfacine can suppress AV-conductibility, reduce cardiac rate.

If after use of combined therapy with clondine it is cancelled, after termination of beta-adrenoblocker intake, the treatment with clondine should last during several days ensuring adequate medical control pursuant to patient state.

Combinations that should be used with care: antiarythmic preparations of class I (for example, disopyramide, quinidin, lidocain, diphenylhydantoin, propafenone).

Antiarythmic preparations of class III (amiodarone, sotalol).

Calcium antagonists (derivatives of dihydropiridine) – increase of arterial hypertension risk and cardiac insufficiency development risk.

Action of insulin and peroral antidiabetic preparations can change at simultaneous use with bisoprololol that can mask hypoglycemia features.

Cardiac glycosides – reduction of cardiac rate, continuation of atrioventricular conductibility.

Baclofen – increase of anti-hypertensive activity.

Contrast products containing iodine – beta-blockers can increase risk of development of anaphilactic reactions that are obstinate to treatment.

Preparations blocking synthesis of prostaglandins (in particular, non-steroid anti-inflammatory remedies) – reduction of anti-hypertension effect.

Ergotamine derivates – aggravation of peripheral blood circulation failure.

Sympathomimetic agents – combination with bisoprolol can reduce effects of the both preparations. Sympathomimetics activating alpha- and beta-adrenoblockers (adrenalin, noradrenalin) increase arterial tension and enhance intermittent claudication phenomena.

Three-cyclic antidepressants, barbiturates, phenothiazines, as well as other anti-hypertensive agents – enhancement of arterial tension effect decrease.

Anti-hypertensive remedies (diuretics, APF inhibitors, alpha-adrenoblockers) and nitrates potentiate anti-hypertensive action of bisoprolol.

Corticosteroids – decrease of anti-hypertensive effect is possible due to water and nitrates retention.

Cimetidine can decrease clearance of beta-adrenoblockers that are metabolized in liver and respectively – increase their bioavailability.

Rifampicine also accelerates bisoprolol metabolism, however, as a rule, it does not require the correction of the latter.

Xanthine (aminophylline, theophylline) – mutual weakening of therapeutic effects at combination with beta-adrenoblockers is possible.

Bicard effect can be enhanced at simultaneous prescription with hydralazine and alcohol.

Anesthesia. Before surgical interferences it is necessary to warm anesthesiologist about bisoprolol intake. Remedies for inhalation narcosis, derivatives of hydrocarbons (chloroform, cyclopropane, halothane, methoxyflurane) at simultaneous prescription with beta-blockers increase risk of myocardium function suppression and development of hypotension reactions.

At simultaneous use with anti-arrhythmic remedies (phenytoin, disopyramide, lidocaine, flecainide, amiodarone) conductibility and negative inotropic effect can occur.

At simultaneous use with parasympathomimetric preparations atrioventricular conductibility hour can increase and risk of bradycardia elevates.

At simultaneous use of Bicard and beta-blockers (those containing in eye drops  for glaucoma treatment) bisoprolol action can be enhanced.

At simultaneous use with insulin and anti-diabetic preparations for peroral use hypoglycemic effect can occur.

At simultaneous use with beta-adrenoblockers hypoglycemia symptoms can be concealed.

At simultaneous use with anesthetic remedies risk of arrhythmia and myocardium ischemia can increase.

Simultaneous use with cardiac glycosides (foxglove preparation) can result in CR reduction, atrioventricular conductibility can be violated.

At simultaneous use with beta-sympathomimetics (dobutamine, orciprenaline) the effect of the both remedies is reduced.

Sympathomimetics that activating alpha- and beta adrenoreceptors (adrenalin, noradrenalin) increase arterial tension and enhance intermittent claudication phenomena.

At simultaneous use with MAO inhibitors (except for MAO inhibitors of type B) hypotensive effect of beta-adrenoblockers increases.

Pharmacological properties.

Pharmacodynamics.

Bicard is selective beta-adrenoblocker. At use in therapeutic doses it has no internal sympathomimetic activity and clinically frank membrane-stabilizing properties. It has anti-anginal action: decreases need of myocard in oxygen due to CR reduction and cardiac output decrease and arterial tension, increases myocard supply with oxygen  at the expense of end-diastolic pressure and diastole protraction.

It has hypotensive action due to cardiac output decrease, retardation of rennin secretion by kidneys, as well as influence to baroreceptors of aortic arch and carotid bulb. At long use of the preparation first of all elevated peripheral vascular resistance decreases. At chronic cardiac insufficiency the preparation suppresses activated sympathoadrenal and rennin-angiotensin-aldosterone system. Bicard has very low cognation with beta-receptors of smooth muscles of bronchi and vessels, as well as with beta-receptors of endocrine system. The preparation only in single cases can have influence on smooth muscles of bronchi and peripheral arteries, as well on glucose metabolism. At single use Bicard action is preserved during 24 hours.

Pharmacokynetics.

Absorption. After internal intake the preparation is absorbed well from gastrointestinal tract. Bioavailability is about 90 % and does not depend on meal. The maximum concentration in blood plasma (Cmax) is achieved after 1-3 hours after meal. Binding with blood plasma albumins is about 30 %.

Metabolism and excretion.

Effect of “the first passage” through liver is expressed negligibly (less than 10 %). About 50 % of dose is bio-transformed in liver with formation of non-active metabolites.  About 98 % is excreted from organism by kidneys, 50 % – in unchanged form, the rest – in form of about 2 % of dose of metabolites – through intestinal tract. The time of semi-excretion is 10-12 hours.

Pharmacokynetics in special clinic cases.

Pharmacokyneetics of bisoprolol is linear, its indices do not depend on age.

Dose correction with patients with hepatic or renal functions of light and average severity stage is not necessary.

Pharmaceutical characteristics.

Basic physical and chemical properties: round, two-bulbaceous tablets covered with film coat;

By 5 mg – of rose color, by 10 mg – of white color.

Shelf life.

2 years.

Recommendations on storage.

It should be stored in original package in childproof places at temperature maximum 25 °C.

Package.

10 tablets in blister, 3 blisters in cardboard box.

Category of supply.

With prescription.

Manufacturer.

Bioveeta Laboratories Pvt. Ltd.

Location.

India, B705, Vardhaman vatika, G.B. Road, Manpada, Thane (W).

Date of the last revision.

Stamp: It is coordinated with registration dossier materials and authentically true data as to this preparation use.