APO-NEBIVOLOL

What it is

APO-NEBIVOLOL contains nebivolol hydrochloride and is available in tablet strengths of 1.25 mg, 5 mg and 10 mg. Nebivolol is a selective β1-receptor antagonist in extensive metabolisers at doses less than or equal to 10 mg. The d-enantiomer is largely responsible for the β-receptor antagonist activity while the l-enantiomer has mild vasodilating properties attributable to an interaction with the L-arginine/nitric oxide pathway.

Approved indications

— Treatment of essential hypertension. — Treatment of stable chronic heart failure as an adjunct to standard therapies in patients 70 years or older.

Dosing overview

The blood pressure lowering effect becomes evident after 2 weeks of treatment, with optimal effect sometimes reached only after 4 weeks. In patients with renal insufficiency for hypertension, the recommended starting dose is 2.5 mg daily, with the daily dose potentially increased to 5 mg if needed. In patients over 65 years for hypertension, the recommended starting dose is 2.5 mg daily, with the daily dose potentially increased to 5 mg if needed.

Key safety warnings

Cessation of therapy with APO-NEBIVOLOL should not be done abruptly unless clearly indicated. Care should be taken if β-blockers have to be discontinued abruptly in patients with coronary artery disease, as 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. It is recommended that the dosage be reduced gradually over a period of about 1–2 weeks. β-adrenergic antagonists may induce bradycardia; if the pulse rate drops below 50–55 bpm at rest and/or the patient experiences symptoms suggestive of bradycardia, the dosage should be reduced or treatment gradually withdrawn. Nebivolol may mask certain symptoms of hypoglycaemia (tachycardia, palpitations) in diabetic patients. β-blockers could further increase the risk of severe hypoglycaemia when used concurrently with sulfonylureas. In patients with chronic obstructive pulmonary disorders, β-adrenergic antagonists should be used with caution as airway constriction may be aggravated.

Contraindications

Hypersensitivity to nebivolol hydrochloride or to any of the excipients. Liver insufficiency or liver function impairment. Acute heart failure, cardiogenic shock or episodes of heart failure decompensation requiring intravenous inotropic therapy. Sick sinus syndrome, including sino-atrial block. Second and third degree heart block without a pacemaker. History of bronchospasm (including that in chronic obstructive pulmonary disease) and/or asthma. Untreated phaeochromocytoma. Metabolic acidosis. Bradycardia (heart rate less than 60 bpm prior to starting therapy). Hypotension (systolic blood pressure less than 100 mmHg). Severe peripheral circulatory disturbances.

PBS listing

APO-NEBIVOLOL 5 mg tablet is listed on the PBS with 2 items and restricted authority required, with an ex-manufacturer price of A$21.44. APO-NEBIVOLOL 10 mg tablet is listed on the PBS with 2 items and restricted authority required, with an ex-manufacturer price of A$24.24.

Regulatory history

APO-NEBIVOLOL 5 mg and 10 mg tablet formulations were first registered on the ARTG on 21 February 2018, with the 1.25 mg tablet also registered on the same date.