CARVIDOL

What it is

Carvedilol is the active ingredient in CARVIDOL tablets. Each tablet contains 3.125 mg, 6.25 mg, 12.5 mg or 25 mg of carvedilol. Carvedilol is a dual action cardiovascular agent that is a vasodilating, non-selective beta-blocking agent with antioxidant properties.

Approved indications

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

Dosing overview

Dosing is individualised according to indication and patient factors.

**Hypertension:** Once daily dosing is recommended. The recommended dose for initiation of therapy is 12.5 mg once a day for the first two days, thereafter the recommended dosage is 25 mg once a day. If necessary, the dosage may subsequently be increased at intervals of at least two weeks up to the recommended maximum daily dose of 50 mg given once a day or twice daily. **Symptomatic congestive heart failure:** The recommended starting dose is 3.125 mg twice daily for two weeks. If this dose is tolerated, the dosage may subsequently be increased, at intervals of not less than two weeks, to 6.25 mg twice daily, followed by 12.5 mg twice daily, then 25 mg twice daily. The recommended maximum daily dose is 25 mg twice daily in patients with mild or moderate CHF weighing less than 85 kg. In patients with mild or moderate CHF weighing more than 85 kg, the recommended maximum daily dose is 50 mg twice daily. For all patients with severe CHF the recommended maximum daily dose is 25 mg twice daily.

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 of the drug in heart failure patients, since worsening heart failure has been observed in this phase of treatment. In order to minimise the risk of these events, it is critical to carefully follow the recommended dosing for carvedilol in patients with congestive heart failure. 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, and of myocardial infarction or ventricular arrhythmias occurring in patients with angina pectoris, following abrupt discontinuation of beta-blocker therapy. Therefore, when discontinuing carvedilol in patients with angina pectoris the dosage should be gradually reduced over a period of about two weeks and the patient should be carefully observed. 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, respectively. The risk for these events was highest during the first 30 days of dosing, corresponding to the up-titration period. Mild hepatocellular injury, confirmed by rechallenge, has occurred rarely with carvedilol therapy. In controlled studies of congestive heart failure, the incidence of liver function abnormalities reported as adverse experiences was 5.0% (38 of 765 patients) in patients receiving carvedilol and 4.6% (20 of 437 patients) in those receiving placebo.

Contraindications

Carvedilol must not be used in patients with: NYHA Class IV decompensated heart failure requiring intravenous inotropic support; bronchial asthma or related bronchospastic conditions including chronic obstructive pulmonary disease (COPD) with a bronchospastic component; allergic disorders (including asthma and allergic rhinitis) which may suggest a predisposition to bronchospasm; severe sinus bradycardia (less than 45 to 50 beats per minute) or sick sinus syndrome (unless a permanent pacemaker is in place); shock (including cardiogenic and hypovolaemic shock); second and third degree atrioventricular block; known hypersensitivity to carvedilol; clinically manifest liver dysfunction; or severe hypotension (systolic blood pressure < 85 mmHg).

Regulatory history

Carvedilol tablets in strengths of 3.125 mg, 6.25 mg, 12.5 mg and 25 mg were first listed on the Australian Register of Therapeutic Goods on 21 April 2020 under ARTG entries 332856, 332855, 332854 and 332853 respectively, sponsored by Arrotex Pharmaceuticals.