Donepezil use in Alzheimer disease

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug-drug interactions, and the therapeutic issues concerning the use of donepezil in patients with Alzheimer disease. DATA SOURCES: Published articles and abstracts in English were identified by MEDLINE (January 1985-July 1997) searches using the search terms donepezil, E2020, treatment of Alzheimer's disease, and cholinesterase inhibitors. Additional articles were identified from the bibliographies of the retrieved articles. Data were also obtained from approved product labeling. DATA EXTRACTION: The literature was assessed for adequate description of patients, methodology, and outcomes. DATA SYNTHESIS: Donepezil is a cholinesterase inhibitor that is selective and specific for acetylcholinesterase. It is metabolized by hepatic isoenzymes CYP2D6 and CYP3A4 and undergoes glucuronidation, Information about drug interactions is limited, but a potential for drug-drug interactions does exist, given the route of elimination. Donepezil has a relative bioavailability of 100%, following oral administration and is not affected by the presence of food. In 15-and 30-week trials, donepezil was effective in patients with mild-to-moderate Alzheimer disease as shown by improvements on standard assessment instruments (i.e., the Alzheimer's Disease Assessment Scale-Cognitive Subscale, the Clinical Interview-Based Impression of Change with Caregiver Input). Adverse effects were comparable with those of placebo, and monitoring of liver function tests is not required. CONCLUSIONS: Donepezil is an effective symptomatic treatment for some patients with mild-to-moderate Alzheimer disease. Although no comparative trials have been reported, donepezil appears to be a safe alternative for tacrine, given its convenient once-daily dosing, minimal adverse effects, and lower total cost.