{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T17:53:05Z","timestamp":1794419585002,"version":"4.9.1"},"reference-count":73,"publisher":"Wiley","issue":"s1","license":[{"start":{"date-parts":[[2004,10,20]],"date-time":"2004-10-20T00:00:00Z","timestamp":1098230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:p>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\u2010effects and general tolerability concerns, including hepatotoxicity. Side\u2010effects associated with increased cholinergic activity, particularly in the gastrointestinal (GI) system, can prevent patients from achieving effective doses of drug. In addition, the advanced age and frail nature of patients with AD mean that poor tolerability is a serious concern. The potential for drug\u2013drug interactions is also an important consideration, due to the high prevalence of comorbid disease in these patients.<\/jats:p><jats:p>Data both from clinical trials and studies in routine clinical practice have shown that donepezil is associated with a low incidence of GI adverse events (AEs) that is comparable with placebo. Donepezil is a potent, selective inhibitor of acetylcholinesterase, and selective inhibition of central as opposed to peripheral ChEs might be expected to reduce the incidence of AEs, thus this may explain the lower incidence of cholinergic AEs observed following treatment with donepezil, compared with nonselective ChE inhibitors.<\/jats:p><jats:p>There are no differences in cardiovascular AEs, including bradycardia, between placebo and donepezil groups in the clinical trials published to date, even in a very sick vascular dementia population with high rates of comorbidity and concomitant medication use.<\/jats:p><jats:p>Data from single\u2010 and multiple\u2010dose studies of donepezil in patients with hepatic impairment and with moderately to severely impaired renal function indicate that donepezil is safe and well tolerated in these groups. Furthermore, both <jats:italic>in vitro<\/jats:italic> and clinical studies have shown that donepezil is not associated with drug\u2013drug interactions.<\/jats:p><jats:p>The incidence of weight loss is very similar between donepezil\u2010 and placebo\u2010treated 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\u2003mg\u2003day<jats:sup>\u22121<\/jats:sup> or switching to morning dosing can reduce these events to the levels of placebo\u2010treated patients.<\/jats:p><jats:p>Over 770 million days of patient use and an extensive publication database demonstrate that donepezil has a good tolerability and safety profile.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2004.01848.x","type":"journal-article","created":{"date-parts":[[2004,10,20]],"date-time":"2004-10-20T08:51:46Z","timestamp":1098262306000},"page":"1-8","source":"Crossref","is-referenced-by-count":108,"title":["The safety and tolerability of donepezil in patients with Alzheimer's 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