APO-CARVEDILOL

What it is

APO-CARVEDILOL contains carvedilol, available in tablet strengths of 3.125 mg, 6.25 mg, 12.5 mg and 25 mg. Carvedilol is a dual action cardiovascular agent that is a vasodilating, non-selective beta-blocking agent with antioxidant properties. Vasodilation is mediated primarily by selective blockade of alpha1-adrenoreceptors.

Approved indications

— Treatment of hypertension. — Treatment of patients with symptomatic mild to severe (NYHA class II to IV) congestive heart failure as an adjunct to conventional treatments such as diuretics, digoxin, ACE inhibitors and vasodilators.

Dosing overview

Dosing differs between the two approved indications.

APO-CARVEDILOL should be taken with food to slow the rate of absorption and reduce the risk of orthostatic effects.

Key safety warnings

Beta-blockers can cause worsening heart failure. Since carvedilol has beta-blocking properties, care must be taken during initiation and up-titration in heart failure patients, where worsening heart failure has been observed. It is critical to carefully follow the recommended dosing for carvedilol in congestive heart failure patients to minimise this risk. In patients with heart failure, ischaemic heart disease or angina pectoris, abrupt cessation of therapy may lead to deterioration. There have been reports of severe exacerbation of angina, myocardial infarction and ventricular arrhythmias following abrupt discontinuation of beta-blocker therapy. When discontinuing carvedilol in patients with angina pectoris, the dosage should be gradually reduced over about two weeks. Hypotension and postural hypotension occurred in 9.7% and syncope in 3.4% of congestive heart failure patients receiving carvedilol compared to 3.6% and 2.5% of placebo patients. The risk was highest during the first 30 days of dosing, corresponding to the up-titration period. Mild hepatocellular injury has occurred rarely with carvedilol therapy. At the first symptom or sign of liver dysfunction such as pruritus, dark urine, persistent anorexia, jaundice, right upper quadrant tenderness or unexplained flu-like symptoms, laboratory testing should be performed. If the patient has laboratory evidence of liver injury or jaundice, carvedilol should be stopped and not restarted. Very rare cases of severe cutaneous adverse reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported during treatment with carvedilol. Carvedilol should be permanently discontinued in patients who experience severe cutaneous adverse reactions possibly attributable to carvedilol.

Contraindications

APO-CARVEDILOL must not be used in patients with NYHA Class IV decompensated heart failure requiring intravenous inotropic support. It is contraindicated in bronchial asthma or related bronchospastic conditions including COPD with a bronchospastic component, and in allergic disorders including asthma and allergic rhinitis which may suggest a predisposition to bronchospasm. Carvedilol must not be used in severe sinus bradycardia of less than 45 to 50 beats per minute or sick sinus syndrome unless a permanent pacemaker is in place. It is contraindicated in shock, including cardiogenic and hypovolaemic shock, and in second and third degree atrioventricular block. Carvedilol is contraindicated in patients with clinically manifest liver dysfunction and in severe hypotension with systolic blood pressure below 85 mmHg.

PBS listing

APO-CARVEDILOL is registered on the ARTG in four tablet strengths: 3.125 mg, 6.25 mg, 12.5 mg and 25 mg, in both blister pack and bottle presentations, first listed on 15 November 2006. The documents provided do not contain information about PBS listing, restriction type or ex-manufacturer price.

Regulatory history

APO-CARVEDILOL was registered on the ARTG on 15 November 2006 in four tablet strengths across eight product registrations sponsored by Arrotex Pharmaceuticals. The documents provided do not contain information about PBAC outcomes, AusPAR status or Black Triangle designation.