APO-BISOPROLOL

What it is

APO-BISOPROLOL contains bisoprolol fumarate and is available in tablets of 1.25 mg, 2.5 mg, 3.75 mg, 5 mg or 10 mg. Bisoprolol is a β1-selective-adrenoceptor blocking agent, lacking intrinsic stimulating and relevant membrane stabilising activity.

Approved indications

— Treatment of stable chronic moderate to severe heart failure in addition to ACE inhibitors, and diuretics, and optionally cardiac glycosides.

Dosing overview

Treatment with APO-BISOPROLOL is started with gradual uptitration: 1.25 mg once daily for 1 week, if well tolerated increase to 2.5 mg once daily for a further week, if well tolerated increase to 3.75 mg once daily for a further week, if well tolerated increase to 5 mg once daily for the 4 following weeks, if well tolerated increase to 7.5 mg once daily for the 4 following weeks, if well tolerated increase to 10 mg once daily for maintenance therapy. The maximum recommended dose is 10 mg once daily. Close monitoring of vital signs (heart rate, blood pressure), conduction disturbances and symptoms of worsening heart failure is recommended during the titration phase. APO-BISOPROLOL tablets should be taken in the morning and can be taken with food.

Key safety warnings

Transient worsening of heart failure, hypotension, or bradycardia may occur during the titration period and thereafter. In case of transient worsening of heart failure, hypotension, or bradycardia, reconsideration of the dosage of the concomitant medication is recommended. It may also be necessary to temporarily lower the dose of APO-BISOPROLOL or to consider discontinuation. The cessation of therapy with APO-BISOPROLOL should not be done abruptly unless clearly indicated. Care should be taken if β-blockers have to be discontinued abruptly in patients, particularly in patients with coronary artery disease. Severe exacerbation of angina and precipitation of myocardial infarction and ventricular arrhythmias have occurred following abrupt discontinuation of β-blockade in patients with ischaemic heart disease. Therefore, it is recommended that the dosage be reduced gradually over a period of about 8-14 days during which time the patient's progress should be assessed. APO-BISOPROLOL should be used with caution in patients with diabetes mellitus, especially those who are receiving insulin or oral hypoglycaemic agents. Diabetic patients should be warned that β-blockers affect glucose metabolism and may mask some important premonitory signs of acute hypoglycaemia, such as tachycardia. Although cardioselective (β1) beta-blockers may have less effect on lung function than non-selective beta-blockers, as with all beta-blockers, these should be avoided in patients with obstructive airway diseases, unless there are compelling clinical reasons for their use. Where such reasons exist APO-BISOPROLOL may be used with caution.

Contraindications

APO-BISOPROLOL is contraindicated in patients with: acute heart failure, episodes of heart failure decompensation requiring intravenous inotropic therapy, cardiogenic shock; AV block of second or third degree (without a pacemaker); sick sinus syndrome or sinoatrial block; bradycardia with less than 60 beats/min before the start of therapy; hypotension (systolic blood pressure less than 100 mm Hg); severe bronchial asthma or severe chronic obstructive pulmonary disease; late stages of peripheral arterial occlusive disease; Raynaud's syndrome; untreated phaeochromocytoma; metabolic acidosis; hypersensitivity to bisoprolol or to any of the excipients.

Regulatory history

APO-BISOPROLOL was first registered on the ARTG on 13 December 2011. The CIBIS II clinical trial included 2,647 ambulatory patients with chronic heart failure. In total 83% of patients were in NYHA class III and 17% were in NYHA class IV with stable symptomatic systolic heart failure. Total mortality was reduced from 17.3% to 11.8% (absolute reduction 5.5%; relative reduction 34%). A decrease in sudden death (3.6% vs. 6.3%, relative reduction 44%) and a reduced number of heart failure episodes requiring hospital admission (12% vs 17.6%, relative reduction 36%) was observed.