Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Kredex (SmithKline Beecham)
3.125 mg, 6.25 mg, 12.5 mg and 25 mg tablets
Dilatrend (Boehringer Mannheim)
6.25 mg, 12.5 mg and 25 mg tablets
Indication: hypertension, heart failure
Catecholamine neurotransmitters may act at either alpha orbeta adrenoceptors. The alpha receptor mediates vasoconstriction, whereas stimulation of the beta receptor results in increased cardiac contractility, vasodilatation and increased heart rate. Certain adverse effects may be anticipated during treatment with a beta blocker e.g. impaired peripheral circulation. However, carvedilol has both alpha and beta blocking actions, so the problem of cold extremities may be reduced. This dual action is due to the fact that carvedilolis a racemic compound whose enantiomers have different effects.
Carvedilol is a lipophilic, non-selective antagonist with no intrinsic sympathomimetic activity. It is absorbed rapidly from the gutand undergoes first-pass metabolism. Bioavailability is approximately 25% and is increased by liver impairment as the drug undergoes hepatic clearance.
Carvedilol is effective in reducing blood pressure, and has recently been investigated for the treatment of heart failure. In severe heart failure, catecholamine concentrations rise so sympathetic antagonists may counter some of the adverse haemodynamic effects.
In one trial, 696 patients with chronic heart failure were given carvedilol and 398 were given placebo.1 It is important to note that only patients who could tolerate carvedilol for an initial test period were randomised. This study was stopped early because there was a clear difference in mortality. Approximately 8% of the placebo group died compared with 3% of the carvedilol group. The risk of hospitalization was reduced by 27% in the carvedilol group. As the patients were also taking digoxin, diuretics and an ACE inhibitor, carvedilol has only been approved for use as an adjunct to these treatments.
Approximately 5% of the patients with heart failure had to withdraw from clinical trials because of adverse events. Patients may complain of dizziness, blurred vision or diarrhoea. They may also develop bradycardia, hypotension or worsening heart failure.
- U.S. Carvedilol Heart Failure Study Group. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996;334:1349-55.