PMID- 22681723
OWN - NLM
STAT- MEDLINE
DCOM- 20130212
LR  - 20220309
IS  - 1756-0500 (Electronic)
IS  - 1756-0500 (Linking)
VI  - 5
DP  - 2012 Jun 8
TI  - Long-term safety and tolerability of donepezil 23 mg in patients with moderate to 
      severe Alzheimer's disease.
PG  - 283
LID - 10.1186/1756-0500-5-283 [doi]
AB  - BACKGROUND: Donepezil (23 mg/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 10 mg/day and 
      randomized 2:1 to either increase their donepezil dose to 23 mg/day or continue 
      taking 10 mg/day. The objective of this study was to assess the long-term safety 
      and tolerability of donepezil 23 mg/day in patients with moderate to severe AD. 
      METHODS: Patients who completed the double-blind study and were eligible could 
      enroll into a 12-month extension study of open-label donepezil 23 mg/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. RESULTS: 
      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 +/- 3.5 months. 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 10 mg/day in the double-blind study to 23 mg/day in the 
      extension study had slightly higher rates of AEs and SAEs than patients who were 
      already receiving 23 mg (78.0% and 16.9% vs 72.8% and 14.0%, respectively). The 
      incidence of new AEs declined rapidly after the first 2 weeks and remained low 
      throughout the duration of the study. CONCLUSION: This study shows that long-term 
      treatment with donepezil 23 mg/day is associated with no new safety signals. The 
      elevated incidence of AEs in patients increasing the dose of donepezil from 10 
      mg/day to 23 mg/day was limited to the initial weeks of the study.
FAU - Tariot, Pierre
AU  - Tariot P
AD  - Banner Alzheimer's Institute, 901 E. Willetta Street, Third Floor, Phoenix, AZ 
      85006, USA.
FAU - Salloway, Steven
AU  - Salloway S
FAU - Yardley, Jane
AU  - Yardley J
FAU - Mackell, Joan
AU  - Mackell J
FAU - Moline, Margaret
AU  - Moline M
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120608
PL  - England
TA  - BMC Res Notes
JT  - BMC research notes
JID - 101462768
RN  - 0 (Biomarkers, Pharmacological)
RN  - 0 (Indans)
RN  - 0 (Nootropic Agents)
RN  - 0 (Piperidines)
RN  - 8SSC91326P (Donepezil)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*drug therapy/physiopathology
MH  - Ambulatory Care
MH  - Biomarkers, Pharmacological/metabolism
MH  - Cognition/drug effects
MH  - Donepezil
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Indans/*administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Neuropsychological Tests
MH  - Nootropic Agents/*administration & dosage/adverse effects
MH  - Piperidines/*administration & dosage/adverse effects
MH  - Treatment Outcome
PMC - PMC3493328
EDAT- 2012/06/12 06:00
MHDA- 2013/02/13 06:00
PMCR- 2012/06/08
CRDT- 2012/06/12 06:00
PHST- 2011/12/05 00:00 [received]
PHST- 2012/04/18 00:00 [accepted]
PHST- 2012/06/12 06:00 [entrez]
PHST- 2012/06/12 06:00 [pubmed]
PHST- 2013/02/13 06:00 [medline]
PHST- 2012/06/08 00:00 [pmc-release]
AID - 1756-0500-5-283 [pii]
AID - 10.1186/1756-0500-5-283 [doi]
PST - epublish
SO  - BMC Res Notes. 2012 Jun 8;5:283. doi: 10.1186/1756-0500-5-283.