Expiration date: 09/2025
Registration number
The trade name of the drug: BISOPROLOL - PRANA
International nonproprietary name: bisoprolol
Dosage form: tablet, film coated
Composition:
1 tablet, film-coated, containing active substance:
hemifumarate bisoprolol (fumarate) is 5 or 10 mg,
excipients: corn starch, microcrystalline cellulose, magnesium stearate, crospovidone, silica colloidal anhydrous, calcium hydrogen phosphate anhydrous.
The composition of the shell:
for pills 5 mg:
macrogol-400, titanium dioxide, Dimethicone 100, iron oxide yellow,
for tablets of 10 mg:
macrogol-400, titanium dioxide, Dimethicone 100, iron oxide red.
Description
Round, biconvex tablets, film-coated, scored. Tablets with a dosage of 5 mg – light-yellow tablets with a dosage of 10 mg – light orange color. In the cross-section are visible two layers, the inner layer white or nearly white color.
Pharmacotherapeutic group: ?1 - blocker selective.
CODE ATX ?07??07.
Pharmacological action
Pharmacodynamics
Selective ?1–blocker without own sympathomimetic activity, has membrane stabilizing effect. Reduces renin activity of blood plasma, reduces the need of myocardium in oxygen, slows the heart rate (HR) (at rest and during exercise). It has hypotensive, antiarrhythmic and antianginal effects. Blocking in low doses of ?1-adrenergic receptors of the heart, reduces catecholamines stimulated the formation of cyclic adenosine monophosphate (camp) from adenosine triphosphate (ATP), reduces intracellular current of calcium ions (Ca2+), has a negative Chrono-, dromo-, batmo and inotropic effect, decreases atrioventricular conduction and excitability.
When exceeding the therapeutic dose having ?2-adrenoblokirtee action.
Total peripheral vascular resistance at the beginning of the drug in the first 24 h, increases (as a result of reciprocal increase in activity of ?-adrenergic receptors and eliminate stimulation of ?2-adrenoceptor), through 1-3 day returns to the original, and in long - term use is reduced.
Hypotensive effect is associated with a decrease in minute volume of blood, sympathetic stimulation of peripheral vessels, restoring sensitivity in response to reduction of blood pressure (BP) and the effect on the Central nervous system (CNS). In arterial hypertension effect occurs in 2-5 days, stable effect observed after 1-2 months.
Antianginal effect is due to reduction of requirement of a myocardium in oxygen as a result of deceleration in heart rate (heart rate) and reduction of myocardial contractility, lengthening of diastole, improved myocardial perfusion. By increasing end-diastolic pressure in the left ventricle and increase the tension of myshechnykh of the ventricles can increase oxygen demand, especially in patients with chronic heart failure (CHF).
When used in high therapeutic doses, unlike nonselective ?-blockers, has a less pronounced effect on bodies containing ?2-adrenergic receptors (pancreas, skeletal muscle, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause the delay of sodium ions (Na+) in the body, the severity of the atherogenic actions is not different from the action of propranolol.
Pharmacokinetics
Absorption is 80-90 %, eating does not affect the absorption. The maximum concentration in plasma is after 1-3 h, the relationship with blood plasma proteins - about 30 %. Permeability through the blood-brain barrier and placental barrier – low.
50 % of the dose is metabolized in the liver to form inactive metabolites, half-life (T1/2) for 10-12 hours. About 98% excreted by the kidneys, of which 50% is excreted unchanged, less than 2 % - through the intestines with the bile.
Indications for use
- hypertension,
- coronary heart disease: prevention of attacks of angina.
Contraindications
Hypersensitivity to the drug and other ?-blockers, shock (including cardiogenic), collapse, pulmonary edema, acute heart failure, congestive heart failure in the decompensation stage, the atrioventricular (AV) blockade II-III, sinoatrialnaya blockade, syndrome weakness of the sinus node, bradycardia, Prinzmetal's angina, cardiomegaly (with no signs of heart failure), hypotension (systolic BP less than 100 mm Hg.St., especially in myocardial infarction), severe forms of bronchial asthma and chronic obstructive pulmonary disease (COPD) in medical history, concomitant use of monoamine oxidase inhibitors (MAOIS) (with the exception of MAO-B), late stage of peripheral circulatory disorders, Raynaud's disease, pheochromocytoma (without the simultaneous use of ?-blockers), metabolic acidosis, age of 18 years (efficacy and safety not established).
With caution:hepatic insufficiency, chronic renal insufficiency, myasthenia gravis, thyrotoxicosis, diabetes mellitus, AV??????? I, depression (including in history), psoriasis, allergic reactions (in history), old age.
Use in pregnancy and lactation
Application of pregnancy is possible if the benefit to the mother outweighs the risk of side effects in the fetus and child.
Data on the allocation of bisoprolol in the breast milk is not. So if you need to use of the drug BISOPROLOL-PRANA during lactation, breastfeeding should be discontinued.
Method of application and doses
Inside, in the morning on an empty stomach, without chewing, once.
Arterial hypertension and ischemic heart disease: prevention of attacks of angina:
It is recommended to take 5 mg once. If necessary, increase the dose to 10 mg 1 time per day. The maximum daily dose of 20 mg.
In all cases the mode of reception and dose selects the physician for each patient individually, in particular, given the value of heart rate and therapeutic response.
In patients with impaired renal function in creatinine clearance (CC) less than 20 ml/min or with acute human liver the maximum daily dose – 10 mg.
Dose adjustment in elderly patients is not required.
Side effects
In the Central and peripheral nervous system: fatigue, weakness, dizziness, headache, sleep disorders, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenia, myasthenia, paresthesia in the extremities (in patients with "intermittent" claudication and Raynaud's syndrome), tremor, seizures (including calf muscles).
On the part of the organ of vision: visual disturbances, reduced secretion of tear fluid, dryness and soreness of eyes, conjunctivitis.
From the side of cardiovascular system:sinus bradycardia, heartbeat, impaired conduction of the myocardium, AV??????? (until the development of a complete transverse blockade and heart failure), arrhythmia, weakening of myocardial contractility, the development (worsening) of CHF (swollen ankles, feet, shortness of breath), reducing AD, orthostatic hypotension, manifestation of angiospasm (increased peripheral circulatory disorders, cold lower extremities, Raynaud's syndrome), chest pain.
From the digestive system:dry mucous membranes of the mouth, nausea, vomiting, abdominal pain, constipation or diarrhea, the human liver (dark urine, yellowness of the sclera or skin, cholestasis), changing taste.
The respiratory system:nasal congestion, difficulty breathing in the appointment of high doses (loss of selectivity) and/or prone patients – laringo - and bronchospasm.
From the endocrine system: hyperglycemia (in patients with non-insulin dependent diabetes), hypoglycemia (in patients, receiving insulin), hypothyroidism.
Allergic reactions: skin itching, rash, hives.
With the skin:increased sweating, hyperemia of skin, exanthema, psoriasiform skin reactions, exacerbation of psoriasis, alopecia.
The laboratory parameters:thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, change of enzyme activity of the liver (increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, triglycerides.
Effect on fetus:intrauterine growth retardation, hypoglycemia, bradycardia.
Other:pain in the back, artralgia, reduced libido, reduced potency syndrome "cancel" (increasing angina attacks, increased blood pressure).
Overdose
Symptoms: arrhythmia, ventricular arrythmia, expressed aetiology, AV???????, marked reduction in blood pressure, congestive heart failure, cyanosis of nails of fingers or palms, difficulty in breathing, bronchospasm, dizziness, fainting, seizures.
Treatment: gastric lavage and the appointment of absorbent material, symptomatic therapy: when developed AV??????? – intravenous injection of 1-2 mg of atropine, epinephrine or staging a temporary pacemaker with ventricular arrhythmia – lidocaine (class IA drugs do not apply), the decline in AD – the patient should be in Trendelenburg position if there are no signs of pulmonary edema – intravenous administration of plasma-substituting solutions in case of its ineffectiveness – introduction epinephrine, dopamine, dobutamine (for maintaining chronotropic and inotropic actions and resolve expressed lower AD), heart failure – cardiac glycosides, diuretics, glucagon, in convulsions – diazepam intravenously, with bronchospasm – ?2-agonists inhalation.
Interaction with other drugs
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-containing radiopaque sredstva intravenous administration increases the risk of anaphylactic reactions.
Fenitoina intravenous, means for inhalation anesthesia (derivatives of hydrocarbons) increase the intensity of cardiodepressive actions and reduce the likelihood of AD.
Changes the effectiveness of insulin and hypoglycemic agents for oral administration, masking the symptoms of developing hypoglycemia (tachycardia, the AD).
Reduces the clearance of lidocaine and xantinov (except theophylline) and increases their concentration in plasma, especially in patients with initially increased clearance of theophylline under the influence of Smoking.
Weaken hypotensive effect nonsteroidal anti-inflammatory drugs (NSAIDs) (delay of sodium ions (Na+) and blockade of prostaglandin synthesis by the kidneys), glucocorticoids and estrogens (delay of Na+ions).
Cardiac glycosides, methyldopa, reserpine, and guanfacine, blockers "slow" calcium channels (verapamil, diltiazem), amiodarone and other antiarrhythmic sredstava the risk of developing or exacerbating bradycardia, AV???????, cardiac arrest and heart failure.
Nifedipinom to lead to a significant decrease in blood pressure.
Diuretics, clonidine, sympatholytic, hydralazine, and other antihypertensive sredstvami lead to excessive reduction of HELL.
Prolongs the action of non-depolarizing muscle relaxants and increases anticoagulant effectcomparison.
Three - and tetracyclic antidepressants, antipsychotic means (neuroleptics), ethanol, sedatives and hypnotics srestaurnat CNS depression.
Not recommended simultaneous application with MAO inhibitors, due to significant increase gipotenzivnogo actions, break in treatment between receiving MAO inhibitors and bisoprolol must be not less than 14 days.
Non-hydrogenated alkaloids storagepower the risk of peripheral circulatory disorders.
Ergotamine increases risk of peripheral circulation,sulfasalazine bisoprolol improves concentration in plasma, rifampicin reduces T1/2.
Special instructions
Control patients receiving the drug BISOPROLOL-PRANA should include measurement of HR and AD (at the beginning of treatment – daily, then 1 once in 3-4 months), ECG, determination of the concentration of blood glucose in patients with diabetes mellitus (1 once in 4-5 months). In elderly patients it is recommended to monitor kidney function (1 once in 4-5 months).
Should teach the patient methods of calculating heart rate and instruct on the need of medical advice in the heart rate less than 50 beats/min.
Before treatment is recommended study of respiratory function in patients with a history of bronchopulmonary history.
About 20% of patients with angina, ?-blockers are ineffective. Main causes: severe coronary atherosclerosis with the low threshold of ischemia (heart rate less than 100 beats/min) and increased end-diastolic volume of the left ventricle that violate the upper subendocardialnah blood flow.
In smokers the effectiveness of ?-blockers below.
Patients using contact lenses should take into account that the treatment may decrease the production of tear fluid.
When used in patients with pheochromocytoma there is a risk of paradoxical hypertension (if not previously achieved the effective ?-adrenoblokada).
Thyrotoxicosis bisoprolol can mask certain clinical signs of hyperthyroidism (eg, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, because it can reinforce the symptoms.
At diabetes can mask the tachycardia, caused by hypoglycemia. Unlike nonselective ?-blockers hardly enhances insulin-induced hypoglycemia and delay recovery of the glucose concentration in the blood to normal levels.
At the same time taking clonidine its reception can be terminated only a few days after discontinuation of the drug BISOPROLOL-PRANA.
Perhaps the increased severity of hypersensitivity reactions and lack of effect of conventional doses of epinephrine with aggravated allergic anamnesis.
In case of the need for planned surgical treatment elimination of the drug is carried out for 48 h before General anesthesia. If the patient has taken the drug before surgery, he should choose drug for General anesthesia with minimal negative inotropic effects.
Reciprocal activation of the vagus nerve can eliminate intravenous atropine (1-2 mg).
Medicines, reducing stocks of catecholamines (including reserpine), may enhance the action of ?-blockers, therefore, patients, accepting such combination drugs, should be under constant supervision of a doctor to identify expressed lower HELL or bradycardia.
Patients with bronchospastic diseases you can assign a cardioselective ?-blockers in case of intolerance and /or ineffectiveness of other antihypertensive agents. Overdose is dangerous development of bronchospasm.
In the case of elderly patients increasing bradycardia (less 50 beats/min), expressed lower AD (systolic BP below 100 mm Hg.St.), AV???????, it is necessary to reduce the dose or stop the treatment.
It is recommended to discontinue therapy in the development of depression.
Do not abruptly discontinue the treatment because of the risk of developing the syndrome "cancel" (severe arrhythmias and myocardial infarction). Lifting a gradually reducing the dose over 2 weeks or more (reduce the dose 25% in 3-4 day). Should be lifted before the examination of blood and urine catecholamines, normetanephrine and vanillylmandelic acid, titles of antinuclear antibodies.
Effects on ability to drive and other mechanical means: the possibility of engaging in potentially hazardous activities, require increased attention and psychomotor speed reactions, should be addressed only after the evaluation of individual patient response to the drug (especially in the beginning of treatment, in connection with the possibility of dizziness).
Release form
Tablets, film-coated, 5 and 10 mg., 10 tablets in a contour cell package. 50, 60, 70, 80, 90, 100 tablets in plastic jar. Each Bank or 1, 2, 3, 4 contour packaging along with instructions for use is placed in cardboard pack.
Storage conditions
List B.
Store in a dry, protected from light place at temperature not exceeding 25 OC.
Store in places inaccessible to children.
Shelf life
3 years.
Do not use after the expiry date printed on the package.
