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.
Aropax 20 (Smith Kline Beecham)
20 mg tablets
Paroxetine is a serotonin re-uptake inhibitor. It is well absorbed from the gut, but undergoes first pass liver metabolism. This first pass metabolism can become partially saturated resulting in non-linear pharmacokinetics in some patients. The lipophilic molecule is extensively distributed through the body with only 1% remaining in the plasma. Excretion occurs by metabolism, with the metabolites being excreted in the faeces and urine. Increased plasma concentrations may occur in patients with renal or hepatic impairment. A lower maximum dose is recommended in elderly patients. Unlike fluoxetine, another serotonin re-uptake inhibitor, the metabolites of paroxetine are relatively inactive. The elimination half-life is approximately 24 hours.
In comparative studies, the drug was more effective than placebo and of similar efficacy to the tricyclic antidepressants. As paroxetine has a low affinity for adrenoceptors and muscarinic cholinergic receptors, cardiovascular and anticholinergic adverse effects are less common than with the tricyclics. The more common adverse effects of paroxetine during clinical trials were nausea, somnolence and sweating.
As paroxetine is metabolised by the liver and inhibits cytochrome P450, practitioners should be aware of potential interactions. There is an interaction with cimetidine, phenytoin and probably warfarin. There are no studies on the concomitant use of paroxetine with neuroleptics or tricyclic antidepressants. A gap of at least two weeks is recommended between paroxetine and monoamine oxidase inhibitor therapy.
Paroxetine has been approved as a once a day treatment for major depressive illness. More data are required to determine the long-term safety and efficacy of paroxetine and whether it is more effective in certain types of depression than in others.