scholarly journals Efficacy, Safety, and Tolerability of Switching from Oral Cholinesterase Inhibitors to Rivastigmine Transdermal Patch with 1-Step Titration in Patients with Mild to Moderate Alzheimer’s Disease: A 24-Week, Open-Label, Multicenter Study in Japan

2019 ◽  
Vol 9 (2) ◽  
pp. 302-318 ◽  
Author(s):  
Kengo Ueda ◽  
Sadao Katayama ◽  
Tetsuaki Arai ◽  
Nobuo Furuta ◽  
Shinichiro Ikebe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Poor Response ◽  
Delivery Rate ◽  
Application Site ◽  
Transdermal Patch ◽  
Maintenance Period ◽  
Open Label ◽  
Titration Period

Background: Few studies have investigated treatment options for patients with Alzheimer’s disease (AD) showing a poor response to oral cholinesterase inhibitors (ChEIs) in Japan. Objective: To investigate the efficacy and safety of switching from oral ChEIs to rivastigmine transdermal patch in patients with AD. Methods: In this multicenter, open-label, phase IV study in outpatient clinics in Japan, patients with mild-moderate AD who had a poor response to or experienced difficulty in continuing donepezil or galantamine were switched to rivastigmine transdermal patch (5 cm2; loaded dose 9 mg, delivery rate 4.6 mg/24 h) with a 1-step titration in week 4 (10 cm2; loaded dose 18 mg, delivery rate 9.5 mg/24 h), which was continued for 4 weeks in the titration period and 16 weeks in a maintenance period. The primary endpoint was the change in Mini-Mental State Examination (MMSE) total score from baseline to week 24. Results: A total of 118 patients were enrolled and switched to rivastigmine, of which 102 completed the 24-week study. The MMSE total score was essentially unchanged during the study, with a least-square mean change (SD) of −0.35 (2.64) at week 24 (p = 0.1750). Exploratory analysis with a mixed-effect model comparing changes in MMSE between the pre- and post-switch periods suggested that switching to rivastigmine prevented a worsening of MMSE. Application site skin reactions/irritations occurred in 30.5% of patients overall, in 22.0% in the 8-week titration period, and in 10.2% in the 16-week maintenance period. Conclusion: Within-class switching from an oral ChEI to rivastigmine transdermal patch might be an efficacious and tolerable option for AD patients showing a poor or limited response to a prior oral ChEI.

Rivastigmine and Concomitant Memantine in Alzheimer's Disease: Safety and Tolerability

CNS Spectrums ◽  
2010 ◽  
Vol 15 (9) ◽  
pp. 594-598 ◽  
Author(s):  
Beth Safirstein ◽  
Xiangyi Meng ◽  
Jason T. Olin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Safety Data ◽  
Gastrointestinal Symptoms ◽  
Application Site ◽  
Transdermal Patch ◽  
Open Label ◽  
Rivastigmine Patch ◽  
Multicenter Trials ◽  
Memantine Treatment

ABSTRACTBackground: Investigate the safety and tolerability of rivastigmine capsules and transdermal patch in patients with moderate Alzheimer's disease receiving concomitant memantine.Methods: Safety data from two prospective, open-label, multicenter trials were analyzed. Study US32: patients received rivastigmine capsules (3–12 mg/day) plus memantine (20 mg/day). Study US38: patients switched from donepezil to rivastigmine patches (4.6 mg/24 hours) immediately or following 7 days' withdrawal; ∼50% received concomitant memantine (20 mg/day).Results: The rivastigmine patch demonstrated more favorable tolerability than rivastigmine capsules, being associated with fewer adverse events (AEs) (73% versus 83%), serious AEs (10% versus 23%) and gastrointestinal symptoms (4% versus 26% for nausea; 4% versus 11% for vomiting). Application site reactions occurred in 17% of patients.Conclusion: Concomitant memantine treatment with rivastigmine patch and capsule is generally well tolerated. The favorable tolerability and safety profile of rivastigmine transdermal patch is not further improved with concomitant memantine. Recommendations to minimize application site reactions are provided.

scholarly journals Good rate of clinical response to cholinesterase inhibitors in mild and moderate Alzheimer's disease after three months of treatment: An open-label study

2013 ◽  
Vol 7 (2) ◽  
pp. 190-196 ◽  
Author(s):  
Luis Felipe José Ravic de Miranda ◽  
Marilourdes do Amaral Barbosa ◽  
Patrícia Regina Henrique Peles ◽  
Patrícia Hilar Pôças ◽  
Pedro Augusto Lopes Tito ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrovascular Disease ◽  
Clinical Response ◽  
Cholinesterase Inhibitors ◽  
Rating Scale ◽  
The Elderly ◽  
Open Label ◽  
Age Related ◽  
Moderate Dementia

ABSTRACT Life expectancy in Brazil has increased markedly over the last 30 years. Hence, age-related disorders, such as Alzheimer's disease (AD), warrant special attention due to their high prevalence in the elderly. Pharmacologic treatment of AD is based on cholinesterase inhibitors (ChEI) and memantine, leading to modest clinical benefits both in the short and long-term. However, clinical response is heterogeneous and needs further investigation. Objective: To investigate the rate of response to ChEI in AD after three months of treatment. Methods: Patients with mild or moderate dementia due to probable AD or to AD associated with cerebrovascular disease were included in the study. The subjects were assessed at baseline and again after three months of ChEI treatment. Subjects were submitted to the Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale, Katz Basic Activities of Daily Living, Pfeffer Functional Activities Questionnaire, Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia. Good response was defined by a gain of ≥2 points on the MMSE after three months of treatment in relation to baseline. Results: Seventy-one patients, 66 (93%) with probable AD and five (7%) with AD associated with cerebrovascular disease, were evaluated. The good response rate at three months was 31.0%, being 37.2% and 21.4% in mild and moderate dementia, respectively. There were no significant differences on most tests, except for improvement in hallucinations, agitation and dysphoria in moderate dementia patients. Conclusion: The rate of good clinical response to ChEI was higher than usually reported. Specific behavioral features significantly improved in the subgroup of moderate dementia.

scholarly journals Apathy in Alzheimer’s Disease: Any Effective Treatment?

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Raffaele Rea ◽  
Anna Carotenuto ◽  
Angiola M. Fasanaro ◽  
Enea Traini ◽  
Francesco Amenta
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pharmacological Treatment ◽  
Literature Search ◽  
Cholinesterase Inhibitors ◽  
Significant Activity ◽  
Systematic Literature Search ◽  
Egb 761 ◽  
Open Label ◽  
Randomized Controlled

Objective. This review has evaluated the effectiveness of pharmacological treatment of apathy in patients with Alzheimer’s disease (AD).Methods. A systematic literature search was conducted on published clinical trials assessing the effects of pharmacological treatment on apathy in AD over the last 10 years.Results. Fourteen studies considered of good quality were included in the analysis (4 randomized controlled trials, 9 open-label studies, and 1 retrospective analysis). Cholinesterase inhibitors were investigated in 9 studies, monoaminergic compounds such as methylphenidate and modafinil in two trials and one trial, respectively, andGinkgo biloba(EGb 761 extract) and citalopram in one study each. Cholinesterase inhibitors did not show statistical significant effect in 1 RCT study but were associated to improvement in 3 open-label studies. Methylphenidate elicited a small but significant activity accompanied by relevant side effects such as high blood pressure, cough, and osteoarticular pain. EGb 761 was well tolerated and countered apathy. Other treatments induced modest improvements or were ineffective.Conclusions. Apathy treatment remains a challenge and there is no evident advantage of any specific pharmacotherapy tested so far. The development of controlled studies according to updated guidelines for the diagnosis of apathy in patients with AD is desirable.

The cost-utility of the rivastigmine transdermal patch in the management of patients with moderate Alzheimer's disease in the US

2009 ◽  
Vol 36 (S 02) ◽  
Author(s):  
A Brennan ◽  
B Nagy ◽  
A Brandtmüller ◽  
SK Thomas ◽  
M Gallagher ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cost Utility ◽  
Transdermal Patch ◽  
The Us ◽  
The Cost

Drug Design of Inhibitors of Alzheimer’s Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives

2019 ◽  
Vol 19 (8) ◽  
pp. 688-705
Author(s):  
Taibi Ben Hadda ◽  
Abdur Rauf ◽  
Hsaine Zgou ◽  
Fatma Sezer Senol ◽  
Ilkay Erdogan Orhan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Metal Accumulation ◽  
Microtiter Plate ◽  
Metal Chelation ◽  
Carbonyl Derivatives ◽  
Cholinesterase Inhibitory Activity ◽  
Inhibitory Potential

Background:Since deficit of acetylcholine has been evidenced in the Alzheimer’s disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD.Method:In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity.Results and Conclusion:All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.

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