Concor® AM (Concor® AM)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceAmlodipine + BisoprololAmlodipine + Bisoprolol
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  • Amlodipine + Bisoprolol
    pills inwards 
    NORTH STAR, CJSC     Russia
  • Concor® AM
    pills inwards 
    Merck KGaA     Germany
  • Niperten® Combi
    pills inwards 
    KRKA-RUS, LLC     Russia
    • Dosage form: & nbspPills.
    Composition:

    Active substances in one tablet:

    5 mg of bisoprolol fumarate and 5 mg of amlodipine (as 6.95 mg of amlodipine besylate);

    5 mg of bisoprolol fumarate and 10 mg of amlodipine (in the form of 13.9 mg of amlodipine besylate);

    10 mg of bisoprolol fumarate and 5 mg of amlodipine (as 6.95 mg of amlodipine besylate);

    10 mg of bisoprolol and 10 mg of amlodipine (in the form of 13.9 mg of amlodipine besylate) fumarate.

    Excipients: cellulose microcrystalline 130.55 / 261.1 / 263.05 / 261.1 mg, sodium carboxymethyl starch (type A) 5/10/10/10 mg, magnesium stearate 1.5 / 3.0 / 3.0 / 3 , 0 mg, silicon dioxide colloidal anhydrous 1/2/2/2 mg.

    Description:

    Tablets 5 mg + 5 mg: white or almost white, oblong, slightly biconcave tablets, with a risk on one side and with engraving MS on the other side of the tablet, odorless.

    Tablets 5 mg + 10 mg: white or almost white, round, flat pills with a bevel, with a risk on one side of the tablet and with MS engraved on the other side of the tablet, odorless.

    Tablets 10 mg + 5 mg: white or almost white, oval, slightly biconvex tablets, with a risk on one side of the tablet and with MS engraved on the other side of the tablet, odorless.

    Tablets 10 mg + 10 mg: white or almost white, round, slightly biconcave tablets, with a risk on one side and with MS engraving on the other side of the tablet, odorless.

    Pharmacotherapeutic group:antihypertensive drug combined (beta-blocker + BCCC)
    ATX: & nbsp

    C.07.F.B   Selective beta-1 blockers in combination with other antihypertensive drugs

    Pharmacodynamics:

    This drug has pronounced antihypertensive and antianginal effects due to the complementary action of two active ingredients: BCCC-amlodipine and selective beta1adrenoblocker - bisoprolol.

    The mechanism of action of amlodipine:

    Amlodipine blocks the calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in the smooth muscle cells of the vessels than in the cardiomyocytes).

    The antihypertensive effect of amlodipine is due to a direct relaxing effect on the smooth muscle cells of the vessels, which leads to a decrease in the resistance of peripheral vessels.

    The mechanism of antianginal action is not fully understood, perhaps it is associated with the following two effects:

    1.Expansion of peripheral arterioles reduces the overall peripheral resistance, i.e. afterloading. Because the amlodipine does not cause reflex tachycardia, energy consumption and oxygen myocardium decreases.

    2. Expansion of large coronary arteries and coronary arterioles improves supply of oxygen to both normal and ischemic zones of the myocardium.

    Due to these effects, the supply of oxygen to the myocardium improves even with spasm of the coronary arteries (Prinzmetal angina or unstable angina).

    In patients with hypertension, taking the drug once a day causes clinically significant decrease in blood pressure in the "lying" and "standing" during the entire 24-hour interval between doses of the drug. Due to the slow development of the antihypertensive effect of amlodipine, it does not cause acute arterial hypotension.

    In patients with angina, taking the drug once a day increases the total time of exercise, the time until the onset of an attack of angina, and also the time to a significant decrease in the interval ST, and also reduces the frequency of angina attacks and the need for sublingual administration of nitroglycerin.

    There was no negative effect of amlodipine on the exchange of plasma lipids, blood glucose and serum uric acid.

    The mechanism of action of bisoprolol:

    Bisoprolol - selective beta1- adrenoblocker, without its own sympathomimetic activity, does not possess membrane-stabilizing action.

    He has only a slight affinity for the beta2-adrenergic receptors of the smooth muscles of the bronchi and vessels, and also to beta2adrenoreceptors involved in the regulation of metabolism. Consequently, bisoprolol in general, does not affect the resistance of the respiratory tract and the metabolic processes in which beta is involved2-adrenoceptors.

    Selective action of the drug on beta1-adrenoceptors persists beyond the therapeutic range.

    Bisoprolol does not have a pronounced negative inotropic effect.

    The maximum effect of the drug is achieved 3-4 hours after ingestion. Even with the appointment of bisoprolol 1 time per day, its therapeutic effect persists for 24 hours due to a 10-12 hour half-life from the blood plasma.

    Usually,the maximum antihypertensive effect is achieved 2 weeks after the start of treatment.

    Bisoprolol reduces the activity of the sympathoadrenal system (CAS) by blocking beta1-adrenoceptors of the heart.

    With a single oral intake in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF) bisoprolol it reduces the heart rate (heart rate), reduces the stroke volume of the heart and, as a consequence, reduces the ejection fraction and the myocardial oxygen demand.

    With prolonged therapy, initially increased total peripheral vascular resistance (OPSS) is reduced. Reduction of renin activity in blood plasma is considered as one of the components of antihypertensive action of beta-blockers.

    Pharmacokinetics:

    Amlodipine:

    Suction

    Amlodipine is well absorbed after ingestion. The maximum concentration in the blood plasma is observed after 6-12 hours. Taking the drug along with the food does not affect its absorption. Absolute bioavailability is 64-80%.

    Distribution

    The apparent volume of distribution is 21 l / kg. The equilibrium concentration in the blood plasma (5-15 ng / ml) is achieved 7-8 days after the start of the drug.

    Research in vitro showed that circulating amlodipine approximately 93-98% is associated with blood plasma proteins.

    Metabolism and excretion

    Amlodipine undergoes intensive metabolism in the liver. Approximately 90% of the accepted dose is converted to inactive pyridine derivatives. Approximately 10% of the dose is excreted unchanged in the urine. Approximately 60% of the amount of inactive metabolites is excreted by the kidneys and 20-25% through the intestine. The decrease in plasma concentration is biphasic. The final half-life is approximately 35-50 hours, which allows the administration of the drug once a day. The total clearance is 7 ml / min / kg (25 l / h in a patient weighing 60 kg). In elderly patients it is 19 l / h.

    In elderly patients and patients with renal insufficiency There were no significant changes in the pharmacokinetics of amlodipine.

    Due to lower ground clearance patients with hepatic insufficiency lower initial doses should be given.

    Bisoprolol:

    Suction

    Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Its bioavailability, due to an insignificant metabolism "at the first passage" through the liver (at about 10%), is about 90% after ingestion. Eating does not affect bioavailability. Bisoprolol demonstrates linear kinetics, and its concentrations in the blood plasma are proportional to the dose taken in the range of 5 to 20 mg. The maximum concentration in the blood plasma is achieved in 2-3 hours.

    Distribution

    Bisoprolol is distributed quite widely. The volume of distribution is 3.5 l / kg. The connection with plasma proteins is approximately 30%.

    Metabolism

    Metabolized by the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and excreted by the kidneys. The main metabolites found in blood plasma and urine, do not show pharmacological activity.

    Data obtained as a result of experiments with microsomes of human liver in vitro, show that bisoprolol is metabolized primarily by isoenzyme CYP3A4 (about 95%), and isoenzyme CYP2D6 plays only an insignificant role.

    Excretion

    Bisoprolol clearance is determined by the balance between excretion by the kidneys in an unchanged form (about 50%) and metabolism in the liver (about 50%) to metabolites that are also excreted by the kidneys. The total ground clearance is 15 liters per hour. The half-life is 10-12 hours.

    Indications:

    Arterial hypertension: replacement therapy with monocomponent drugs amlodipine and bisoprolol in the same doses.

    Contraindications:

    For amlodipine:

    - unstable angina (with the exception of Prinzmetal angina);

    - Acute myocardial infarction (within the first 28 days);

    Clinically significant aortic stenosis.

    By bisoprolol:

    - acute heart failure or chronic heart failure (CHF) in the stage of decompensation, requiring inotropic therapy;

    - atrioventricular (AV) blockade of II and III degree, without an electrocardiostimulator;

    - syndrome of weakness of the sinus node (SSSU);

    - Sinoatrial blockade;

    - pronounced bradycardia (heart rate less than 60 beats / min);

    - severe forms of bronchial asthma or chronic obstructive pulmonary disease (COPD);

    - marked violations of peripheral arterial blood circulation or syndrome Reynaud;

    - pheochromocytoma (without simultaneous use of alpha-blockers);

    metabolic acidosis;

    By combination of amlodipine / bisoprolol:

    - hypersensitivity to amlodipine, other dihydropyridine derivatives, bisoprolol and / or any of the excipients;

    - severe arterial hypotension (systolic blood pressure less than 100 mm Hg);

    - shock (including cardiogenic);

    - Children under 18 years of age (efficacy and safety not established).

    Carefully:

    CHF (including non-ischemic etiology III-IV functional class by classification NYHA), hepatic insufficiency, renal failure, hyperthyroidism, diabetes mellitus with significant fluctuations in the concentration of glucose in the blood, AV blockade of I degree, angina of Prinzmetal, occlusive diseases of peripheral arteries, psoriasis (including anamnesis), fasting (strict diet), pheochromocytoma (with simultaneous use of alpha-blockers), bronchial asthma and COPD, concomitant desensitizing therapy, general anesthesia, elderly age, arterial hypotension, diabetes mellitus Type 1, aortic stenosis, mitral stenosis, acute myocardial infarction (after the first 28 days).

    Pregnancy and lactation:

    For amlodipine:

    In experimental studies fetotoxic and embryotoxic effects of the drug have not been established, but use in pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus.

    There is no evidence of excretion of amlodipine in breast milk.However, it is known that other BCCC - dihydropyridine derivatives are excreted in breast milk. In this connection, if it is necessary to prescribe amlodipine during lactation, the question of stopping breastfeeding should be resolved.

    By bisoprolol:

    The use of bisoprolol in pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus. Beta-adrenoblockers reduce blood flow in the placenta and can affect the development of the fetus. Blood flow in the placenta and uterus should be monitored, and the growth and development of the unborn child should be monitored, and in the event that undesirable events occur pregnancy and / or fetus to take alternative therapies.

    You should carefully examine the newborn after delivery. In the first three days of life symptoms of bradycardia and hypoglycemia may occur.

    There is no data on the isolation of bisoprolol in breast milk. Therefore, its administration is not recommended for women during lactation. If bisoprolol is required during lactation, breastfeeding should be discontinued.

    Dosing and Administration:

    Tablets for oral administration.Tablets should be taken in the morning, regardless of food intake, without chewing.

    The recommended daily dose is 1 tablet per day of a certain dosage.

    Selection and titration of the dose individually for each patient is performed by the doctor during the appointment of monocomponent drugs containing the active ingredients contained in the preparation Concor® AM.

    Duration of treatment

    Treatment with Concor® AM is usually a long-term therapy.

    Impaired liver function

    In patients with impaired liver function, excretion of amlodipine can be slowed down. A special dosing regimen for this group of patients is not defined, but the drug should be given with caution in this case.

    For patients with severe impairment of liver function, the maximum daily dose of bisoprolol is 10 mg.

    Impaired renal function

    Patients with impaired renal function of mild or moderate severity of dosing regimen are generally not required. Amlodipine not output by dialysis. Patients undergoing dialysis should be prescribed amlodipine with extreme caution.

    For patients with severe renal impairment (creatinine clearance less than 20 ml / min), the maximum daily dose of bisoprolol is 10 mg.

    Elderly patients

    Elderly patients may be given regular doses of the drug. Caution is required only when the dose is increased.

    Children

    The drug is not recommended for use in children under the age of 18 due to lack of data on efficacy and safety. Treatment should not be stopped abruptly, as this may lead to a temporary deterioration in the clinical condition. Especially, treatment should not be abruptly discontinued in patients with ischemic heart disease. A gradual dose reduction is recommended.

    Side effects:

    Unwanted adverse reactions observed with the use of active ingredients separately are presented in accordance with the following frequency grouping criteria: Very frequent> 1/10; frequent> 1/100 - <1/10; infrequent> 1/1 000 - <1/100; rare> 1/10 000 - <1/1 000; very rare (<1/10 000), unknown (estimate based on available data can not be performed)

    For amlodipine:

    Violations of the blood and lymphatic system: very rarely: leukopenia, thrombocytopenia.

    Immune system disorders: very rarely: allergic reactions.

    Disorders from the metabolism and nutrition: very rarely: hyperglycemia.

    Disorders of the psyche: infrequently: insomnia, mood changes (including anxiety), depression; rarely: confusion.

    Disturbances from the nervous system: often: headache, dizziness, drowsiness (especially at the beginning of treatment); infrequently: fainting, hypoesthesia, paresthesia, dysgeusia, tremor; very rarely: muscle hypertension, peripheral neuropathy.

    Disturbances on the part of the organ of sight: infrequently: impaired vision (including diplopia).

    Hearing disorders and labyrinthine disorders: infrequently: noise in the ears.

    Disorders from the gastrointestinal tract: often: nausea, abdominal pain; infrequent: vomiting, changing the mode of defecation (including constipation or diarrhea), dyspepsia, dryness of the oral mucosa; very rarely - gastritis, gingival hyperplasia, pancreatitis.

    Disturbances from the liver and bile ducts: very rarely: hepatitis *, jaundice *.

    Heart Disease: often: a feeling of heartbeat; very rarely: myocardial infarction, arrhythmia (bradycardia, ventricular tachycardia, atrial fibrillation).

    Vascular disorders: often: "flushes" of blood to the face, infrequently: marked decrease in blood pressure; very rarely: vasculitis.

    Disturbances from the respiratory system, chest and mediastinal organs: infrequently: shortness of breath, rhinitis; very rarely: cough.

    Disorders from the kidneys and urinary tract: infrequently: pollakiuria, painful urge to urinate, nocturia.

    Violations of the genitals and mammary gland: infrequently: impotence, gynecomastia.

    General disorders and disorders at the site of administration: often: peripheral edema, increased fatigue; infrequently: chest pain, asthenia, pain, general malaise.

    Disturbances from musculoskeletal and connective tissue: often: swelling of the ankles; infrequently: arthralgia, myalgia, muscle cramps, back pain.

    Disturbances from the skin and subcutaneous tissue: infrequently: alopecia, purpura, discoloration, increased sweating, itching, rash, exanthema; very rarely: angioedema, erythema multiforme exudative, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, Quincke's edema, photosensitivity.

    Laboratory and instrumental data: infrequently: weight gain, weight loss; very rarely: an increase in the activity of "liver" enzymes *.

    * In most cases with cholestasis

    By bisoprolol:

    Disorders from the metabolism and nutrition: rarely: increased concentration of triglycerides.

    Disorders of the psyche: infrequently: depression; rarely: hallucinations, nightmares.

    Disturbances from the nervous system: often: headache **, dizziness **; infrequently: insomnia; rarely: faint.

    Disturbances on the part of the organ of sight: rarely: a decrease in lacrimation (should be considered when wearing contact lenses); very rarely: conjunctivitis.

    Hearing disorders and labyrinthine disorders: rarely: hearing impairment.

    Heart Disease: infrequent: violation of AV conduction, bradycardia, aggravation of symptoms of CHF.

    Vascular disorders: often: sensation of cooling or numbness in the extremities, pronounced decrease in blood pressure; infrequently: orthostatic hypotension.

    Disturbances from the respiratory system, chest and mediastinal organs: infrequently: bronchospasm in patients with bronchial asthma or airway obstruction in anamnesis; rarely: allergic rhinitis.

    Disorders from the gastrointestinal tract: often: nausea, vomiting, diarrhea, constipation.

    Disturbances from the liver and bile ducts: rarely: hepatitis.

    Disturbances from the skin and subcutaneous tissue: rarely: hypersensitivity reactions, such as pruritus, rash, hyperemia of the skin; very rarely: alopecia. Beta-blockers can exacerbate the symptoms of psoriasis or cause a psoriasis-like rash.

    Disturbances from musculoskeletal and connective tissue: infrequently: muscle weakness, muscle cramps.

    Violations of the genitals and mammary gland: rarely: impotence.

    General disorders and disorders at the site of administration: often: increased fatigue **; infrequently: exhaustion **.

    Laboratory and instrumental data: rarely: increased activity of "hepatic" transaminases in the blood (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)).

    ** Especially often these symptoms appear at the beginning of the course of treatment. Usually, these phenomena are of an easy nature and usually pass within 1-2 weeks after the start of treatment.

    Overdose:

    For amlodipine:

    Symptoms: marked decrease in blood pressure with possible development of reflex tachycardia and excessive peripheral vasodilation (risk of development of severe and persistent arterial hypotension, incl.with the development of shock and death).

    Treatment: gastric lavage, the appointment of activated carbon to maintain the function of the cardiovascular system, the control performance of the heart and lungs, an elevated position of the limbs, control of blood volume and diuresis. Intensive symptomatic therapy. To restore the vascular tone - the use of vasoconstrictive drugs (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade - intravenous calcium gluconate. Hemodialysis is ineffective.

    By bisoprolol:

    Symptoms: AV blockade, pronounced bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia.

    The sensitivity to a single dose of a high dose of bisoprolol varies greatly among individual patients and, probably, patients with CHF are highly sensitive.

    Treatment: In case of an overdose, first of all, it is necessary to stop taking the drug and begin supporting symptomatic therapy.

    With severe bradycardia: intravenous administration of atropine.If the effect is insufficient, with caution, you can enter a drug that has a positive chronotropic effect. Sometimes it may be necessary to temporarily set up an artificial pacemaker.

    With a pronounced decrease in blood pressure: intravenous injection of plasma-substituting solutions and vasopressor preparations. Intravenous administration of glucagon may also be indicated.

    With the AV block: patients should be under constant observation and receive treatment with beta-adrenomimetics, such as epinephrine. If necessary - staging an artificial pacemaker.

    With exacerbation of CHF flow: intravenous injection of diuretics, drugs with a positive inotropic effect, as well as vasodilators.

    When bronhospazme: the appointment of bronchodilators, including beta2adrenomimetics and / or aminophylline.

    When hypoglycemia: intravenous dextrose (glucose).

    Bisoprolol practically does not give in to dialysis.

    Interaction:

    For amlodipine:

    The simultaneous use of amlodipine with thiazide diuretics, beta-blockers, nitrates long-acting, sublingual preparations nitroglycerin, non-steroidal anti-inflammatory drugs, antibiotics and hypoglycemic agents for oral intake is considered safe.

    Inhibitors CYP3A4: Use with caution amlodipine concomitantly with inhibitors CYP3A4.

    Strong and moderate inhibitors CYP3A4 (eg, protease inhibitors, antifungal agents of the azole group, macrolides of the type erythromycin or clarithromycin, verapamil or diltiazem) can increase the concentration of amlodipine in the blood plasma to clinically significant values.

    Inductors CYP3A4: Simultaneous application with inducers CYP3A4 (incl. rifampicin, St. John's wort perforated) can lead to a decrease in the concentration of amlodipine in the blood plasma. Use with caution amlodipine simultaneously with inductors CYP3A4.

    Simvastatin: Simultaneous use with amlodipine may lead to an increase in the concentration of simvastatin in blood plasma. Patients receiving amlodipine, the use of simvastatin in a dose exceeding 20 mg per day is not recommended.

    Grapefruit juice, cimetidine, aluminum / magnesium (as part of antacids) and sildenafil do not affect the pharmacokinetics of amlodipine.

    Amlodipine may enhance the antihypertensive effect of other antihypertensive drugs.

    Amlodipine does not affect the pharmacokinetics atorvastatin, digoxin, ethanol (beverages containing alcohol), warfarin or cyclosporine.

    Amlodipine has no effect on laboratory performance.

    By bisoprolol:

    Unrecommended combinations

    Blocks of "slow" calcium channels (BCCI) type verapamil, and to a lesser extent, diltiazem, with simultaneous application with bisoprolol may lead to a decrease in myocardial contractility, pronounced blood pressure lowering and disruption AV conductivity. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV blockade.

    Hypotensive means of central action (such as clonidine, methyldopa, moxonidine, rilmenidine) with simultaneous application with bisoprolol may lead to a decrease in heart rate and a decrease in cardiac output, as well as to vasodilation due to a decrease in the central sympathetic tone.Abrupt cancellation, especially before the abolition of beta-blockers may increase the risk of developing "ricochet" hypertension.

    Combinations that require caution

    BCCC derivatives of dihydropyridine (eg, nifedipine) with simultaneous application with bisoprolol may increase the risk of developing arterial hypotension. In patients with heart failure, the risk of subsequent deterioration of the contractile function of the heart can not be ruled out.

    Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) with simultaneous application with bisoprolol may reduce AV conduction and contractility of the myocardium.

    Antiarrhythmic drugs of III class (eg, amiodarone) can increase the violation AV conductivity.

    Parasympathomimetics with simultaneous use with bisoprolol may increase the violation AV conductivity and increase the risk of developing a bradycardia.

    Action of beta-blockers for topical application (eg, eye drops for the treatment of glaucoma) can enhance the systemic effects of bisoprolol (lowering blood pressure, decreasing heart rate).

    Hypoglycemic action of insulin or hypoglycemic agents for oral administration may be enhanced. Symptoms of hypoglycemia - in particular tachycardia - can be masked. Such interactions are more likely when using nonselective beta-blockers.

    Means for general anesthesia can weaken reflex tachycardia and increase the risk of developing arterial hypotension (see section "Special instructions").

    Cardiac glycosides with simultaneous application with bisoprolol may lead to an increase in the timing of the impulse and to the development of bradycardia.

    Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the antihypertensive effect of bisoprolol.

    The simultaneous use of bisoprolol with beta-adrenomimetics (e.g., isoprenaline, dobutamine) can lead to a decrease in the effect of both drugs.

    The combination of bisoprolol with adrenomimetics that affect beta and alpha-adrenergic receptors (eg, norepinephrine, epinephrine) may enhance the vasoconstrictor effects of these agents that occur with the participation of alpha-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely to occur when applying nonselective beta-blockers.

    Hypotensive drugs as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines), can enhance the antihypertensive effect of bisoprolol.

    Combinations that are necessary consider

    Meflokhin with simultaneous use with bisoprolol may increase the risk of developing bradycardia.

    MAO inhibitors (except for MAO B inhibitors) can enhance the antihypertensive effect of beta adrenoblockers. Simultaneous application can also lead to the development of hypertensive crisis.

    Rifampicin slightly shortens the half-life (T1/2) of bisoprolol. As a rule, dose adjustment is not required.

    Derivatives of ergotamine with simultaneous application with bisoprolol increase the risk of peripheral circulatory disorders.

    Special instructions:

    For amlodipine:

    Patients with heart failure should take amlodipine carefully. In patients with heart failure III-IV stages by classification NYHA Amlodipine increases the risk of pulmonary edema, which is not associated with worsening symptoms of CHF.

    By bisoprolol:

    Discontinuation of bisoprolol treatment should not be sudden, especially in patients with ischemic heart disease, unless there are clear indications for withdrawal. Sudden abolition of bisoprolol may lead to a temporary worsening of cardiac pathology.

    Bisoprolol should be administered with extreme caution to patients with hypertension or angina pectoris, in combination with heart failure.

    As in the case of other beta-blockers, bisoprolol can cause an increase in sensitivity to allergens and increase anaphylactic reactions, so care must be taken with simultaneous desensitizing therapy. The use of epinephrine can not always produce the expected therapeutic effect.

    When bisoprolol is used, the symptoms of hyperthyroidism may be masked.

    In patients with pheochromocytoma bisoprolol should be appointed only after blockade of alpha-adrenergic receptors.

    Before conducting a general anesthesia, the anesthetist should be informed of the patient's admission of beta-blockers. If it is necessary to cancel the beta-blocker before surgery,this should be done gradually and completed approximately 48 hours before anesthesia.

    With bronchial asthma or COPD simultaneous application is shown bronchodilating agents. In patients with bronchial asthma, an increase in airway resistance may be required, which requires a higher dose beta2-adrenomimetics.

    Effect on the ability to drive transp. cf. and fur:During the period of drug treatment, care should be taken in the management of vehicles and work with technically complex mechanisms.
    Form release / dosage:

    Tablets, 5 mg + 5 mg, 5 mg + 10 mg, 10 mg + 5 mg and 10 mg + 10 mg.

    Packaging:10 tablets in blisters from the combined film "cold" (polyamide / aluminum foil / PVC) // aluminum foil.
    3 blisters of 10 tablets are packed in a cardboard box together with instructions for use.
    Storage conditions:

    Store at a temperature not exceeding 30 ° C.

    Keep the drug out of the reach of children.
    Shelf life:

    3 years.

    Do not use after the expiration date indicated on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-001137
    Date of registration:03.11.2011 / 06.08.2014
    The owner of the registration certificate:Merck KGaAMerck KGaA Germany
    Manufacturer: & nbsp
    Representation: & nbspTakeda Pharmaceuticals Ltd.Takeda Pharmaceuticals Ltd.
    Information update date: & nbsp01.11.2016
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