Safety and tolerability of donepezil 23 mg in moderate to severe alzheimer's disease

Martin Farlow, Felix Veloso, Margaret Moline, Jane Yardley, Elimor Brand-Schieber, Francesco Bibbiani, Heng Zou, Timothy Hsu, Andrew Satlin

Research output: Contribution to journalArticle

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Abstract

Background: Donepezil 23 mg/d, recently approved in the United States for treatment of moderate to severe Alzheimer's disease (AD), was developed to address the need for an additional treatment option for patients with advanced AD. This report, based on a pivotal phase 3 study, presents a detailed analysis of the safety and tolerability of increasing donepezil to 23 mg/d compared with continuing 10 mg/d.Method: Safety analyses comprised examination of the incidence, severity, and timing of treatment-emergent adverse events (AEs) and their relationship to treatment initiation; changes in weight, electrocardiogram, vital signs, and laboratory parameters; and the incidence of premature study discontinuation. The analysis population (n = 1434) included all randomized patients who took at least 1 dose of study drug and had a postbaseline safety assessment. To further examine the effect of transition from a lower to a higher donepezil dose, a pooled analysis of safety data from 2 phase 3 trials of donepezil 5 mg/d and 10 mg/d was also performed.Results: The safety population comprised 1434 patients: donepezil 23 mg/d (n = 963); donepezil 10 mg/d (n = 471); completion rates were 71.1% and 84.7%, respectively. The most common AEs were nausea, vomiting, and diarrhea (donepezil 23 mg/d: 11.8%, 9.2%, 8.3%; donepezil 10 mg/d: 3.4%, 2.5%, 5.3%, respectively). AEs that contributed most to early discontinuations were vomiting (2.9% of patients in the 23 mg/d group and 0.4% in the 10 mg/d group), nausea (1.9% and 0.4%), diarrhea (1.7% and 0.4%), and dizziness (1.1% and 0.0%). The percentages of patients with AEs in the 23 mg/d group, as well as the timing, type, and severity of these AEs, were similar to those seen in previous donepezil trials with titration from 5 to 10 mg/d. Serious AEs were uncommon (23 mg/d, 8.3%; 10 mg/d, 9.6%).Discussion: The 23 mg/d dose of donepezil was associated with typical cholinergic AEs, particularly gastrointestinal-related AEs, similar to those observed in studies with a dose increase from 5 to 10 mg/d.Conclusion: The good safety and predictable tolerability profile for donepezil 23 mg/d supports its favorable risk/benefit ratio in patients with moderate to severe AD.Trial Registration: NCT00478205.

Original languageEnglish
Article number57
JournalBMC Neurology
Volume11
DOIs
StatePublished - May 25 2011

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Alzheimer Disease
Safety
Nausea
Vomiting
Diarrhea
donepezil
Vital Signs
Dizziness
Therapeutics
Cholinergic Agents
Population
Electrocardiography
Cohort Studies
Odds Ratio
Weights and Measures
Incidence
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Farlow, M., Veloso, F., Moline, M., Yardley, J., Brand-Schieber, E., Bibbiani, F., ... Satlin, A. (2011). Safety and tolerability of donepezil 23 mg in moderate to severe alzheimer's disease. BMC Neurology, 11, [57]. https://doi.org/10.1186/1471-2377-11-57

Safety and tolerability of donepezil 23 mg in moderate to severe alzheimer's disease. / Farlow, Martin; Veloso, Felix; Moline, Margaret; Yardley, Jane; Brand-Schieber, Elimor; Bibbiani, Francesco; Zou, Heng; Hsu, Timothy; Satlin, Andrew.

In: BMC Neurology, Vol. 11, 57, 25.05.2011.

Research output: Contribution to journalArticle

Farlow, M, Veloso, F, Moline, M, Yardley, J, Brand-Schieber, E, Bibbiani, F, Zou, H, Hsu, T & Satlin, A 2011, 'Safety and tolerability of donepezil 23 mg in moderate to severe alzheimer's disease', BMC Neurology, vol. 11, 57. https://doi.org/10.1186/1471-2377-11-57
Farlow, Martin ; Veloso, Felix ; Moline, Margaret ; Yardley, Jane ; Brand-Schieber, Elimor ; Bibbiani, Francesco ; Zou, Heng ; Hsu, Timothy ; Satlin, Andrew. / Safety and tolerability of donepezil 23 mg in moderate to severe alzheimer's disease. In: BMC Neurology. 2011 ; Vol. 11.
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abstract = "Background: Donepezil 23 mg/d, recently approved in the United States for treatment of moderate to severe Alzheimer's disease (AD), was developed to address the need for an additional treatment option for patients with advanced AD. This report, based on a pivotal phase 3 study, presents a detailed analysis of the safety and tolerability of increasing donepezil to 23 mg/d compared with continuing 10 mg/d.Method: Safety analyses comprised examination of the incidence, severity, and timing of treatment-emergent adverse events (AEs) and their relationship to treatment initiation; changes in weight, electrocardiogram, vital signs, and laboratory parameters; and the incidence of premature study discontinuation. The analysis population (n = 1434) included all randomized patients who took at least 1 dose of study drug and had a postbaseline safety assessment. To further examine the effect of transition from a lower to a higher donepezil dose, a pooled analysis of safety data from 2 phase 3 trials of donepezil 5 mg/d and 10 mg/d was also performed.Results: The safety population comprised 1434 patients: donepezil 23 mg/d (n = 963); donepezil 10 mg/d (n = 471); completion rates were 71.1{\%} and 84.7{\%}, respectively. The most common AEs were nausea, vomiting, and diarrhea (donepezil 23 mg/d: 11.8{\%}, 9.2{\%}, 8.3{\%}; donepezil 10 mg/d: 3.4{\%}, 2.5{\%}, 5.3{\%}, respectively). AEs that contributed most to early discontinuations were vomiting (2.9{\%} of patients in the 23 mg/d group and 0.4{\%} in the 10 mg/d group), nausea (1.9{\%} and 0.4{\%}), diarrhea (1.7{\%} and 0.4{\%}), and dizziness (1.1{\%} and 0.0{\%}). The percentages of patients with AEs in the 23 mg/d group, as well as the timing, type, and severity of these AEs, were similar to those seen in previous donepezil trials with titration from 5 to 10 mg/d. Serious AEs were uncommon (23 mg/d, 8.3{\%}; 10 mg/d, 9.6{\%}).Discussion: The 23 mg/d dose of donepezil was associated with typical cholinergic AEs, particularly gastrointestinal-related AEs, similar to those observed in studies with a dose increase from 5 to 10 mg/d.Conclusion: The good safety and predictable tolerability profile for donepezil 23 mg/d supports its favorable risk/benefit ratio in patients with moderate to severe AD.Trial Registration: NCT00478205.",
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AU - Veloso, Felix

AU - Moline, Margaret

AU - Yardley, Jane

AU - Brand-Schieber, Elimor

AU - Bibbiani, Francesco

AU - Zou, Heng

AU - Hsu, Timothy

AU - Satlin, Andrew

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N2 - Background: Donepezil 23 mg/d, recently approved in the United States for treatment of moderate to severe Alzheimer's disease (AD), was developed to address the need for an additional treatment option for patients with advanced AD. This report, based on a pivotal phase 3 study, presents a detailed analysis of the safety and tolerability of increasing donepezil to 23 mg/d compared with continuing 10 mg/d.Method: Safety analyses comprised examination of the incidence, severity, and timing of treatment-emergent adverse events (AEs) and their relationship to treatment initiation; changes in weight, electrocardiogram, vital signs, and laboratory parameters; and the incidence of premature study discontinuation. The analysis population (n = 1434) included all randomized patients who took at least 1 dose of study drug and had a postbaseline safety assessment. To further examine the effect of transition from a lower to a higher donepezil dose, a pooled analysis of safety data from 2 phase 3 trials of donepezil 5 mg/d and 10 mg/d was also performed.Results: The safety population comprised 1434 patients: donepezil 23 mg/d (n = 963); donepezil 10 mg/d (n = 471); completion rates were 71.1% and 84.7%, respectively. The most common AEs were nausea, vomiting, and diarrhea (donepezil 23 mg/d: 11.8%, 9.2%, 8.3%; donepezil 10 mg/d: 3.4%, 2.5%, 5.3%, respectively). AEs that contributed most to early discontinuations were vomiting (2.9% of patients in the 23 mg/d group and 0.4% in the 10 mg/d group), nausea (1.9% and 0.4%), diarrhea (1.7% and 0.4%), and dizziness (1.1% and 0.0%). The percentages of patients with AEs in the 23 mg/d group, as well as the timing, type, and severity of these AEs, were similar to those seen in previous donepezil trials with titration from 5 to 10 mg/d. Serious AEs were uncommon (23 mg/d, 8.3%; 10 mg/d, 9.6%).Discussion: The 23 mg/d dose of donepezil was associated with typical cholinergic AEs, particularly gastrointestinal-related AEs, similar to those observed in studies with a dose increase from 5 to 10 mg/d.Conclusion: The good safety and predictable tolerability profile for donepezil 23 mg/d supports its favorable risk/benefit ratio in patients with moderate to severe AD.Trial Registration: NCT00478205.

AB - Background: Donepezil 23 mg/d, recently approved in the United States for treatment of moderate to severe Alzheimer's disease (AD), was developed to address the need for an additional treatment option for patients with advanced AD. This report, based on a pivotal phase 3 study, presents a detailed analysis of the safety and tolerability of increasing donepezil to 23 mg/d compared with continuing 10 mg/d.Method: Safety analyses comprised examination of the incidence, severity, and timing of treatment-emergent adverse events (AEs) and their relationship to treatment initiation; changes in weight, electrocardiogram, vital signs, and laboratory parameters; and the incidence of premature study discontinuation. The analysis population (n = 1434) included all randomized patients who took at least 1 dose of study drug and had a postbaseline safety assessment. To further examine the effect of transition from a lower to a higher donepezil dose, a pooled analysis of safety data from 2 phase 3 trials of donepezil 5 mg/d and 10 mg/d was also performed.Results: The safety population comprised 1434 patients: donepezil 23 mg/d (n = 963); donepezil 10 mg/d (n = 471); completion rates were 71.1% and 84.7%, respectively. The most common AEs were nausea, vomiting, and diarrhea (donepezil 23 mg/d: 11.8%, 9.2%, 8.3%; donepezil 10 mg/d: 3.4%, 2.5%, 5.3%, respectively). AEs that contributed most to early discontinuations were vomiting (2.9% of patients in the 23 mg/d group and 0.4% in the 10 mg/d group), nausea (1.9% and 0.4%), diarrhea (1.7% and 0.4%), and dizziness (1.1% and 0.0%). The percentages of patients with AEs in the 23 mg/d group, as well as the timing, type, and severity of these AEs, were similar to those seen in previous donepezil trials with titration from 5 to 10 mg/d. Serious AEs were uncommon (23 mg/d, 8.3%; 10 mg/d, 9.6%).Discussion: The 23 mg/d dose of donepezil was associated with typical cholinergic AEs, particularly gastrointestinal-related AEs, similar to those observed in studies with a dose increase from 5 to 10 mg/d.Conclusion: The good safety and predictable tolerability profile for donepezil 23 mg/d supports its favorable risk/benefit ratio in patients with moderate to severe AD.Trial Registration: NCT00478205.

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