Epibloc

Pharmacologic Classification: Beta Blocking Agent, selective.
Pharmacology: Pharmacodynamics: Bisoprolol is a highly beta₁-selective-adrenoreceptor blocking agent, lacking intrinsic sympathomimetic and relevant membrane stabilizing activity. It only shows low affinity to the beta₂-receptor of the smooth muscles of the bronchi and vessels as well as to the beta₂-receptors concerned with metabolic regulation. Therefore, bisoprolol is generally not to be expected to influence the airway resistance and beta₂-mediated metabolic effects. Its beta₁-selectivity extends beyond the therapeutic dose range. Bisoprolol is used for the treatment of hypertension, angina pectoris and heart failure. As with other beta₁-blocking agents, the method of acting in hypertension is unclear. However, it is known that bisoprolol reduces plasma renin activity markedly.
Antianginal mechanism: Bisoprolol by inhibiting the cardiac beta receptors inhibits the response given to sympathetic activation. That results in the decrease of heart rate and contractility this way decreasing the oxygen demand of the cardiac muscle.
Pharmacokinetics: Absorption: Bisoprolol is absorbed and has a biological availability of about 90% after oral administration.
Distribution: The plasma protein binding of bisoprolol is about 30%. The distribution volume is 3.5 L/kg.
Biotransformation and elimination: Total clearance is approximately 15 L/h. The half-life in plasma of 10-12 hours gives a 24-hour effect after dosing once daily. Bisoprolol is excreted from the body by two routes, 50% is metabolized by the liver to inactive metabolites which are then excreted by the kidneys. The remaining 50% is excreted by the kidneys in metabolized form. Since the elimination takes place in the kidneys and the liver to the same extent a dosage adjustment is not required for patients with impaired liver function or renal insufficiency.
Linearity/non-linearity: The kinetics of bisoprolol are linear and independent of age.

Hypertension, Angina pectoris, Treatment of stable chronic heart failure with reduced systolic left ventricular function in addition to ACE inhibitors, and diuretics, and optionally cardiac glycosides.

Hypertension/Angina pectoris: Adults: The dosage should be individually adjusted, in particular according to the pulse rate and therapeutic success. It is recommended to start with 5 mg per day. The usual dose is 10 mg once daily with a maximum recommended dose of 20 mg once daily.
Elderly: It is recommended to start with the lowest possibe dose.
Renal or hepatic impairment: In patients with liver or kidney function disorders of mild to moderate severity, no dosage adjustment is normally required. In patients with severe renal impairment (creatinine clearance <20 mL/min) and in patients with severe liver function disorders it is recommended that a daily dose of 10 mg is not exceeded.
Experience with the use of bisoprolol in renal dialysis patients is limited. However, there is no evidence that the dosage regime needs to be altered.
Stable chronic heart failure: Standard treatment of CHF consists of an ACE inhibitor (or an angiotensin receptor blocker in case of intolerance of ACE inhibitors), a beta-blocking agent, diuretics, and when appropriate cardiac glycosides. Patients should be stable (without acute failure) when bisoprolol treatment is initiated. It is recommended that the treating physician should be experienced in the management of chronic heart failure.
Titration phase: The treatment of stable chronic heart failure with bisoprolol requires a titration phase.
The treatment with bisoprolol is to be started with a gradual uptitration 1.25 mg once daily for 1 week, if well tolerated increase to a maximum, recommended dose of 10 mg once daily.
Close monitoring of vital signs (heart rate, blood pressure) and symptoms of worsening heart failure is recommended during titration phase.
Duration of treatment: Treatment of stable chronic heart failure with bisoprolol is generally long-term treatment. The treatment with bisoprolol must not be stopped abruptly since this might lead to a transitory worsening condition. Especially in patients with ischaemic heart disease, treatment must not be discontinued suddenly. Gradual reduction of the daily dose is recommended.
Bisoprolol should be taken in the morning and can be taken with food. They should be swallowed with liquid and should not be chewed.
Pediatric population: There is no experience with bisoprolol in children and adolescents, therefore its use cannot be recommended.

Bisoprolol is contraindicated to patients having known hypersensitivity to the active substance or to any of the excipients. Acute heart failure or during episodes of heart failure decompensation requiring i.v. inotropic therapy. Cardiogenic shock, AV block of second and third degree, sick sinus syndrome, sinoatrial block, symptomatic bradycardia, symptomatic hypotension, severe bronchial asthma or severe chronic obstructive pulmonary disease, severe forms of peripheral arterial occlusive disease or severe forms of Reynaud's syndrome, untreated pheochromocytoma, metabolic acidosis.

Hypertension or Angina pectoris: Bisoprolol must be used with caution in patients with hypertension or angina pectoris and accompanying heart failure.
Chronic Heart Failure: The initiation and cessation of treatment of stable chronic heart failure with bisoprolol necessitates regular monitoring.
Bisoprolol must be used with caution in: Bronchospasm; Diabetes Mellitus with large fluctuations in blood glucose values; Strict fasting; Ongoing desensitization therapy (as with other Beta-blockers, bisoprolol may increase both sensitivity towards allergens and the severity of anaphylactic reactions); AV block of first degree; Prinzmetal's angina; Peripheral arterial occlusive disease; General anesthesia.

Pregnancy: Bisoprolol is not recommended during pregnancy unless clearly necessary. If treatment with bisoprolol is considered necessary, monitoring of the uteroplacental blood flow and the fetal growth is recommended. In case of harmful effects on pregnancy or the fetus, consideration of alternative treatment is recommended.
Breastfeeding: Breastfeeding is not recommended during administration of bisoprolol.

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Combinations not recommended: Chronic Heart Failure only: Class I antiarrhythmic medicinal products (e.g. quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone): Effect on atrio-ventricular conduction time may be potentiated and negative inotropic effect increased.
All indications: Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type: Negative influence on the contractility and atrio-ventricular conduction.
Intravenous administration of verapamil in patients on β-blocker treatment may lead to profound hypotension and atrioventricular block.
Centrally-acting antihypertensive medicinal products such as clonidine and others (e.g. methyldopa, moxonodine, rilmenidine): Concomitant use of centrally acting antihypertensive medicinal products may worsen heart failure by a decrease in the central sympathetic tonus (reduction of heart rate and cardiac output, vasodilation). Abrupt withdrawal, particularly if prior to beta-blocking agent discontinuation, may increase the risk of "rebound hypertension".
Combinations to be used with caution: Hypertension/Angina pectoris only: Class I antiarrhythmic medicinal products (e.g. quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone): Effect on atrio-ventricular conduction time may be potentiated and negative inotropic effect increased.
All indications: Calcium antagonists of dihydropyridine type such as felodipine and amlodipine: Concomitant use may increase the risk of hypotension, and an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.
Class III antiarrhythmic medicinal product (e.g. amiodarone): Effect on atrioventricular conduction time may be potentiated.
Topical beta-blocking agents (e.g. eye drops for glaucoma treatment) may add to the systemic effects of bisoprolol.
Parasympathomimetic medicinal products: Concomitant use may increase atrioventricular conduction time and the risk of bradycardia.
Insulin and oral antidiabetic medicinal products: Increase of blood sugar lowering effect. Blockade of beta-adrenoreceptors may mask symptoms of hypoglycemia.
Anesthetic agents: Attenuation of the reflex tachycardia and increase of the risk of hypotension.
Digitalis glycosides: Reduction of heart rate, increase of atrio-ventricular conduction time.
Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs may reduce the hypotensive effect of bisoprolol.
β-sympathomimetic agents (e.g. isoprenaline, dobutamine): Combination with bisoprolol may reduce the effect of both agents.
Sympathomimetic that activate both β- and α-adrenoreceptors (e.g. noradrenaline, adrenaline): Combination with bisoprolol may unmask the α-adrenoreceptor-mediated vasoconstrictor effects of these agents leading to a blood pressure increase and exacerbated intermittent claudication. Such interactions are considered to be more likely with non-selective β-blockers.
Concomitant use with antihypertensive agents as well as with other medicinal products with blood pressure lowering potential (e.g. tricyclic antidepressants, barbiturates, phenothiazines) may increase the risk of hypotension.
Combination to be considered: Mefloquine: Increased risk of bradycardia.
Monoamine oxidase inhibitors (except MAO-B inhibitors): Enhanced hypotensive effect of the beta-blocking agents, but also risk for hypertensive crisis.
Rifampicin: Slight reduction of the half-life of bisoprolol possible due to the induction of hepatic drug-metabolizing enzymes. Normally no dosage adjustment is necessary.
Ergotamine derivatives: Exacerbation of peripheral circulatory disturbances.

Store at temperatures not exceeding 30°C.

Beta-Blockers

C07AB07 - bisoprolol ; Belongs to the class of selective beta-blocking agents. Used in the treatment of cardiovascular diseases.

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