Donepezil (23mg/day) is approved by the US Food and Drug Administration for the treatment of patients with moderate to severe Alzheimer’s disease (AD). Approval was based on results from a 24-week, randomized, double-blind study of patients who were stable on donepezil 10mg/day and randomized 2:1 to either increase their donepezil dose to 23mg/day or continue taking 10mg/day. The objective of this study was to assess the long-term safety and tolerability of donepezil 23mg/day in patients with moderate to severe AD.
Patients who completed the double-blind study and were eligible could enroll into a 12-month extension study of open-label donepezil 23mg/day. Clinic visits took place at open-label baseline and at months 3, 6, 9, and 12. Safety analyses comprised examination of the incidence, severity, and timing of treatment-emergent adverse events (AEs); changes in weight, electrocardiogram, vital signs, and laboratory parameters; and discontinuation due to AEs.
915 double-blind study completers were enrolled in the open-label extension study and 902 comprised the safety population. Mean treatment duration in this study was 10.3±3.5months. In total, 674 patients (74.7%) reported at least one AE; in 320 of these patients (47.5%) at least one AE was considered to be possibly or probably study drug related. The majority of patients reporting AEs (81.9%) had AEs of mild or moderate severity. There were 268 patients (29.7%) who discontinued early, of which 123 (13.6%) were due to AEs.
Patients increasing donepezil dose from 10mg/day in the double-blind study to 23mg/day in the extension study had slightly higher rates of AEs and SAEs than patients who were already receiving 23mg (78.0% and 16.9% vs 72.8% and 14.0%, respectively). The incidence of new AEs declined rapidly after the first 2weeks and remained low throughout the duration of the study.
This study shows that long-term treatment with donepezil 23mg/day is associated with no new safety signals. The elevated incidence of AEs in patients increasing the dose of donepezil from 10mg/day to 23mg/day was limited to the initial weeks of the study.
Keywords: Donepezil 23mg, Donepezil, Safety, Tolerability, Clinical trial