Mega Lifesciences


Full Prescribing Info
Bisoprolol fumarate.
Each tablet contains: Bisoprolol Fumarate Ph. Eur 2.5 mg/5 mg/10 mg.
Excipients/Inactive Ingredients: Microcrystalline cellulose Ph. Eur., Silica colloidal anhydrous Ph. Eur., Croscarmellose Sodium Ph. Eur., Sodium Starch Glycolate (Type A) Ph. Eur., Magnesium stearate Ph. Eur.
Pharmacology: Pharmacodynamics: Bisoprolol is a beta1-selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing activity or intrinsic sympathomimetic activity in its therapeutic dosage range. Cardioselectivity is not absolute, however, and at higher doses (≥20 mg) bisoprolol fumarate also inhibits beta2-adrenoceptors, chiefly located in the bronchial and vascular musculature; to retain selectivity, it is therefore important to use the lowest effective dose.
Pharmacokinetics: Bisoprolol is absorbed almost completely from the gastrointestinal tract. Together with the very small first pass effect in the liver, this results in a high bioavailability of approximately 90%. The plasma protein binding of bisoprolol is about 30%. The distribution volume is 3.5 l/kg. The total clearance is approximately 15 l/h. The plasma elimination half-life (10-12 hours) provides 24 hours efficacy following a once daily dosage.
Bisoprolol is excreted from the body by two routes, 50% is metabolised by the liver to inactive metabolites which are then excreted by the kidneys. The remaining 50% is excreted by the kidneys in an unmetabolised form. Since 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.
The kinetics of bisoprolol are linear and independent of age.
In patients with chronic heart failure (NYHA stage III) the plasma levels of bisoprolol are higher and the half life is prolonged compared to healthy volunteers. Maximum plasma concentration at steady state is 64±21 ng/ml at a daily dose of 10 mg and the half life is 17±5 hours.
Management of hypertension. Management of angina pectoris.
Dosage/Direction for Use
This drug should be used under physician's prescription only.
For the management of hypertension in adults, the usual initial dosage of bisoprolol is 2.5-5 mg once daily. In patients whose blood pressure is not controlled adequately with the initial dosage, the dosage can be increased gradually as tolerated up to a maximum of 20 mg daily. For patients who received an initial dosage of 5 mg once daily, the dosage may be increased to 10 mg once daily and if needed to 20 mg once daily.
Modification of bisoprolol dosage generally is not necessary in geriatric patients with normal renal and hepatic function. The usual oral dose of bisoprolol in stable angina pectoris is 10 mg once daily with a maximum recommended dose of 20 mg/day. In some patients 5 mg/day may be adequate. Dosage adjustment of the drug is not normally required for elderly patients. However in patients with severely impaired renal function G.F.R < 20 > 5 ml/min and/or patients with advanced hepatic insufficiency, the daily dose of bisoprolol should not exceed 10 mg.
The most common signs expected with overdosage of a beta-blocker are bradycardia, hypotension, congestive heart failure, bronchospasm, and hypoglycemia. To date, a few cases of overdose (maximum: 2000 mg) with bisoprolol fumarate have been reported. Bradycardia and/or hypotension were noted. Sympathomimetic agents were given in some cases, and all patients recovered.
In general, if overdose occurs, Diopolol therapy should be stopped and supportive and symptomatic treatment should be provided. Limited data suggest that bisoprolol fumarate is not dialyzable. Based on the expected pharmacologic actions and recommendations for other beta-blockers, the following general measures should be considered when clinically warranted: Bradycardia: Administer IV atropine. If the response is inadequate, isoproterenol or another agent with positive chronotropic properties may be given cautiously. Under some circumstances, transvenous pacemaker insertion may be necessary.
Hypotension: IV fluids and vasopressors should be administered. Intravenous glucagon may be useful.
Heart Block (second or third degree): Patients should be carefully monitored and treated with isoproterenol infusion or transvenous cardiac pacemaker insertion, as appropriate.
Congestive Heart Failure: Initiate conventional therapy (ie, digitalis, diuretics, inotropic agents, vasodilating agents).
Bronchospasm: Administer bronchodilator therapy such as isoproterenol and/or aminophylline.
Hypoglycemia: Administer IV glucose.
Bisoprolol is contra-indicated in patients with: Acute heart failure or during episodes of heart failure decompensation requiring i.v. inotropic therapy; Cardiogenic shock; Second or third degree AV block (without a pacemaker); Sick sinus syndrome; Sinoatrial block; Bradycardia (heart rate less than 60 beats/min prior to start of therapy); Hypotension (systolic blood pressure <100 mmHg); Severe bronchial asthma or severe chronic obstructive pulmonary disease; Late stages of peripheral arterial occlusive disease and Raynaud's syndrome; Untreated phaeochromocytoma; Metabolic acidosis; Hypersensitivity to bisoprolol or to any of the excipients.
Special Precautions
Bisoprolol must be used with caution in: Heart failure (the treatment of stable chronic heart failure with bisoprolol has to be initiated with a special titration phase). Bronchospasm (bronchial asthma, obstructive airways diseases). Concomitant treatment with inhalation anaesthetics. Diabetes mellitus with large fluctuations in blood glucose values; symptoms of hypoglycaemia can be masked. Strict fasting. Ongoing desensitisation therapy. AV block of first degree. Prinzmetal's angina. Peripheral arterial occlusive disease (intensification of complaints may occur particularly during the start of therapy).
In bronchial asthma or other chronic obstructive lung diseases, which may cause symptoms, bronchodilating therapy should be given concomitantly. Occasionally an increase of the airway resistance may occur in patients with asthma, therefore the dose of β2-stimulants may have to be increased.
As with other β-blockers, bisoprolol may increase both the sensitivity towards allergens and the severity of anaphylactic reactions. Adrenaline treatment does not always give the expected therapeutic effect.
Patients with psoriasis or with a history of psoriasis should only be given β-blockers (e.g. bisoprolol) alter carefully balancing the benefits against the risks.
In patients with phaeochromocytoma bisoprolol must not be administered until after alpha-receptor blockade.
Under treatment with bisoprolol the symptoms of a thyrotoxicosis may be masked.
In patients with ischaemic heart disease, treatment should not be withdrawn abruptly.
Combination with calcium antagonists, clonidine or monoamine oxidase inhibitors (except MAO-B inhibitors) is not recommended.
Effects on ability to drive and operate machine: Patients should know how they react to Bisoprolol before they drive or use machines because occasionally, dizziness or fatigue may occur.
Pregnancy: There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing mothers: It is not known whether this drug is excreted in human milk. Therefore, breastfeeding is not recommended during administration of bisoprolol.
Use In Pregnancy & Lactation
Pregnancy: There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing mothers: It is not known whether this drug is excreted in human milk. Therefore, breastfeeding is not recommended during administration of bisoprolol.
Adverse Reactions
Potential Adverse Reactions: A variety of adverse reactions not listed (see Side Effects) have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to bisoprolol extended release tablets.
Central Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics.
Cardiovascular: Intensification of AV block.
Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.
Heart Failure: In the MERIT-HF study, serious adverse events and adverse events leading to discontinuation of study medication were systematically collected. Following are the adverse events in the MERIT-HF study that occurred at an incidence of equal to or greater than 1% in the bisoprolol extended release tablets group and greater than placebo by more than 0.5%, regardless of the assessment of causality: Dizziness/vertigo, bradycardia, accident and/or injury.
Other adverse events with an incidence of >1% on bisoprolol extended release tablets and as common on placebo (within 0.5%) included myocardial infarction, pneumonia, cerebrovascular disorder, chest pain, dyspnea/dyspnea aggravated, syncope, coronary artery disorder, ventricular tachycardia/arrhythmia aggravated, hypotension, diabetes mellitus/diabetes mellitus aggravated, abdominal pain, and fatigue.
It is advised to inform to doctor of any adverse reaction suffered from using this drug.
Side Effects
Hypertension and Angina: Most adverse effects have been mild and transient. The following adverse reactions have been reported for bisoprolol.
Central Nervous System: Tiredness and dizziness have occurred in about 10 of 100 patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, somnolence, nightmares, and insomnia have also been reported.
Cardiovascular: Shortness of breath and bradycardia have occurred in approximately 3 of 100 patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; congestive heart failure; peripheral edema; syncope; chest pain; and hypotension have been reported in about 1 of 100 patients.
Respiratory: Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients.
Gastrointestinal: Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, digestive tract disorders, and heartburn have been reported in about 1 of 100 patients.
Hypersensitive Reactions: Pruritus or rash has occurred in about 5 of 100 patients. Worsening of psoriasis has also been reported.
Fever combined with aching and sore throat, laryngospasm, and respiratory distress.
Miscellaneous: Peyronie's disease has been reported in fewer than 1 of 100,000 patients. Musculoskeletal pain, blurred vision, decreased libido and tinnitus have also been reported.
There have been rare reports of reversible alopecia, agranulocytosis, and dry eyes.
Discontinuation of the drug should be considered if any such reaction is not otherwise explicable.
Drug Interactions
Diopolol should not be combined with other beta-blocking agents. Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored, because the added beta-adrenergic blocking action of Bisoprolol may produce excessive reduction of sympathetic activity. In patients receiving concurrent therapy with clonidine, if therapy is to be discontinued, it is suggested that Bisoprolol be discontinued for several days before the withdrawal of clonidine.
Diopolol should be used with care when myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes), or antiarrhythmic agents, such as disopyramide, are used concurrently.
Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
Concurrent use of rifampin increases the metabolic clearance of Diopolol, resulting in a shortened elimination half-life of Diopolol. However, initial dose modification is generally not necessary.
Risk of Anaphylactic Reaction: While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.
Protect from light and moisture.
Store below 30°C in a dry place.
Shelf Life: 3 years from manufacturing date.
MIMS Class
ATC Classification
C07AB07 - bisoprolol ; Belongs to the class of selective beta-blocking agents. Used in the treatment of cardiovascular diseases.
Tab (white to off-white, round, biconvex with a breakline on one side) 2.5 mg x 2 x 14's. 5 mg x 2 x 14's. 10 mg x 2 x 14's.
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