British journal of clinical pharmacology
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Br J Clin Pharmacol · Nov 2004
ReviewThe safety and tolerability of donepezil in patients with Alzheimer's disease.
Cholinesterase (ChE) inhibitors, which prevent the hydrolysis of acetylcholine, have been approved for the symptomatic treatment of Alzheimer's disease (AD) for over a decade. However, the first ChE inhibitors were associated with a high incidence of side-effects and general tolerability concerns, including hepatotoxicity. Side-effects associated with increased cholinergic activity, particularly in the gastrointestinal (GI) system, can prevent patients from achieving effective doses of drug. ⋯ The incidence of weight loss is very similar between donepezil- and placebo-treated patients. Although insomnia and other sleep disorders have been reported following administration of donepezil, lengthening the time period before increasing the dose of donepezil from 5 to 10 mg day(-1) or switching to morning dosing can reduce these events to the levels of placebo-treated patients. Over 770 million days of patient use and an extensive publication database demonstrate that donepezil has a good tolerability and safety profile.