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.
5 mg and 10 mg tablets
Approved indication: Alzheimer's disease
AMH Section 16.5
The concentration of acetylcholine is reduced in the brains of patients with Alzheimer's disease. This abnormality has led to trials of anticholinesterases such as tacrine (see `Tacrine in the treatment of Alzheimer's disease' Aust Prescr 1996;19:14-7). Donepezil is also an inhibitor of acetylcholinesterase, but has less peripheral activity than tacrine.
Clinical trials of donepezil have studied patients with mild to moderately severe Alzheimer's disease. Rating scales and subjective assessments have been used to evaluate its effects. The drug has been more efficacious than placebo in studies of 12-24 weeks' duration. While these responses may have statistical significance, their clinical significance is unclear.
Donepezil is given once a day. It takes 3 weeks to reach a steady state as the half-life is approximately 70 hours. While some donepezil is excreted unchanged in the urine, it is also metabolised. As the metabolic pathways include cytochromeP450 2D6 and 3A4, there is a potential for drug interactions, but donepezil is said to have no significant interaction with theophylline, cimetidine, warfarin or digoxin.
The increase in cholinergic activity contributes to some of the adverse effects of donepezil. The most common adverse effects are nausea, vomiting and diarrhoea. The clinical trials on which marketing approval is based were only of up to6 months' duration, so long-term safety data are limited.
There appear to have been no trials comparing donepezil and tacrine. Donepezil is better tolerated with only 5-13% of patients stopping treatment because of adverse effects. (Approximately 17% of the patients who received tacrine in clinical trials had to stop treatment.) Patients taking donepezil do not require the frequent monitoring of liver function which is required when starting tacrine. While donepezil may have some advantages over tacrine, both drugs only have modest therapeutic effects. Neither drug halts the progression of the disease, nor are they approved for use by severely affected patients.