ARX-METOPROLOL

What it is

ARX-METOPROLOL is metoprolol succinate tablets available in strengths of 23.75 mg, 47.5 mg, 95 mg or 190 mg. Metoprolol is a β1-selective β-blocker that blocks β1-receptors at doses lower than those needed to block β2-receptors. ARX-METOPROLOL consists of several hundred beads of metoprolol succinate, each coated with a polymeric membrane which controls the rate of metoprolol release. After rapid disintegration within the gastrointestinal tract, metoprolol is continuously released for approximately 20 hours, and a stable metoprolol plasma concentration is achieved over a dosage interval of 24 hours.

Approved indications

— Stable, chronic heart failure as an adjunct to other heart failure therapy.

Dosing overview

ARX-METOPROLOL is recommended for once daily treatment and is preferably taken together with the morning meal. Tablets should be swallowed with liquid and should not be chewed or crushed. The dose should be individually adjusted in patients with chronic heart failure stabilised on other heart failure treatment. It is recommended that patients be titrated from an initial low dose: starting with 23.75 mg once daily for two weeks, then 47.5 mg once daily for two weeks, then 95 mg once daily for two weeks, and continuing to 190 mg or the highest tolerated dose. Patients with moderate to severe heart failure (NYHA III–IV) should start with half a 23.75 mg tablet once daily for one week, then take a full 23.75 mg tablet once daily for the second week. During long-term treatment the aim should be to reach 190 mg once daily (or the highest tolerated dose).

Key safety warnings

ARX-METOPROLOL should not be ceased abruptly due to the risk of rebound hypertension and tachycardia. If treatment is to be discontinued, it should be reduced gradually. Some patients may experience an initial, usually transient, worsening of the symptoms and signs of heart failure when starting treatment. If this occurs, the patient should be monitored very closely and the dose should be reduced if symptoms continue to worsen. Where ARX-METOPROLOL is prescribed for patients known to be suffering from asthma, an inhaled β2-agonist should be administered. The dosage of β2-agonists may require adjustment, however the risk of ARX-METOPROLOL interfering with β2-receptors is less than with conventional tablet formulations. ARX-METOPROLOL should be used with caution in patients with diabetes mellitus, especially those 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. In patients with insulin or non-insulin dependent diabetes, especially labile diabetes, or with a history of spontaneous hypoglycaemia, β-blockade may result in the loss of diabetic control and delayed recovery from hypoglycaemia.

Contraindications

ARX-METOPROLOL is contraindicated in patients with predisposition to bronchospasm, as β-adrenergic blockade of the smooth muscle of bronchi and bronchioles may result in an increased airways resistance. β-blockers are contraindicated in any patient with a history of airways obstruction or a tendency to bronchospasm. Contraindications also include right ventricular failure secondary to pulmonary hypertension, significant right ventricular hypertrophy, second and third degree atrioventricular block, shock (including cardiogenic and hypovolaemic shock), and unstable decompensated congestive heart failure (pulmonary oedema, hypoperfusion or hypotension). Additional contraindications include continuous or intermittent inotropic therapy acting through β-receptor agonism, clinically relevant sinus bradycardia (less than 45–50 beats per minute), non-compensated congestive heart failure, sick-sinus syndrome (unless a permanent appropriately functioning pacemaker is in place), severe peripheral arterial circulatory disorders, suspected acute myocardial infarction with specific haemodynamic parameters, hypotension, and untreated phaeochromocytoma. ARX-METOPROLOL is also contraindicated in patients with hypersensitivity to any component and related β-blocker derivatives.

Regulatory history

ARX-METOPROLOL XL modified release tablets in strengths of 23.75 mg, 47.5 mg, 95 mg and 190 mg were first listed on the Australian Register of Therapeutic Goods on 18 October 2011.