Lack of Pharmacokinetic or Pharmacodynamic Interaction Between Memantine and Donepezil

Periclou, Antonia; Ventura, Daniel; Sherman, T.; Rao, Niranjan; Abramowitz, Wattanaporn

doi:10.1345/aph.1d638

Cited by 74 publications

(40 citation statements)

References 18 publications

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“…For individuals in the severe stages of AD, approved treatments are limited to donepezil and memantine. Donepezil and memantine have different mechanisms of action, and reports suggest that they do not interact substantially [6]. These two agents are often prescribed together for patients with advanced AD in an attempt to maximize treatment benefits.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Donepezil 23 mg versus Donepezil 10 mg for Moderate-to-Severe Alzheimer’s Disease: A Subgroup Analysis in Patients Already Taking or Not Taking Concomitant Memantine

Doody

Geldmacher

Farlow

et al. 2012

Dement Geriatr Cogn Disord

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Background/Aims: A large multicenter trial of donepezil 23 mg/day versus donepezil 10 mg/day for moderate-to-severe Alzheimer’s disease allowed patients taking concomitant memantine. We evaluated the efficacy/safety of donepezil 23 and 10 mg/day in this trial, with respect to concomitant memantine use. Methods: Prespecified analysis of data from a 24-week, randomized, double-blind trial. Patients were randomized to donepezil doses (23 vs. 10 mg/day) and stratified by concomitant memantine use (yes or no). Efficacy and safety were assessed for each donepezil dose in subgroups taking or not taking concomitant memantine. Results: At week 24, donepezil 23 mg/day provided significant cognitive benefits over 10 mg/day (p < 0.01) on the Severe Impairment Battery, with or without concomitant memantine (ANCOVA adjusted for baseline score, country and treatment). The higher dose showed no benefit on the global function, Mini-Mental State Examination or activities of daily living measures in either memantine subgroup. Rates of treatment-emergent adverse events (AEs) were higher for donepezil 23 mg/day with memantine (80.7%) than 23 mg/day without memantine (69.7%) or 10 mg/day with/without memantine (66.7/62.0%); across all treatment groups, most events were mild/moderate in severity. Individual rates of serious AEs were low (<1.0%), regardless of concomitant memantine use. Conclusion: In this population, concomitant memantine use did not alter the response profile of donepezil 23 vs. 10 mg/day. Donepezil 23 mg was generally safe and well tolerated among patients receiving donepezil alone and among patients receiving a combination of donepezil and memantine therapy.

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Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Donepezil 23 mg versus Donepezil 10 mg for Moderate-to-Severe Alzheimer’s Disease: A Subgroup Analysis in Patients Already Taking or Not Taking Concomitant Memantine

Doody

Geldmacher

Farlow

et al. 2012

Dement Geriatr Cogn Disord

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“…In contrast, memantine is a renal excretory drug that is not metabolized by CYP [3]; therefore, it is unlikely that a drug interaction occurred. Indeed, it has been reported that there was no change in the pharmacokinetic parameters of donepezil even when memantine was concomitantly used with donepezil [4]. Therefore, in our case, memantine itself might have prolonged the PR interval.…”

Section: Discussionmentioning

confidence: 56%

Deterioration in donepezil-induced PR prolongation after a coadministration of memantine in a patient with Alzheimer's disease

Igeta

Suzuki

Motegi

et al. 2013

General Hospital Psychiatry

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“…Memantine and donepezil have few side effects; moreover, their coadministration to healthy volunteers reportedly caused no pharmacokinetic or pharmacodynamic interaction [57]. Several clinical studies demonstrate that combined treatment with memantine and ChEI is safe and well-tolerated [58].…”

Section: Discussionmentioning

confidence: 99%

Combined Memantine and Donepezil Treatment Improves Behavioral and Psychological Symptoms of Dementia-Like Behaviors in Olfactory Bulbectomized Mice

et al. 2017

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Memantine, an uncompetitive N-methyl-D-aspartate receptor antagonist, and the cholinesterase inhibitor, donepezil, are approved in most countries for treating moderate-to-severe Alzheimer's disease (AD). These drugs have different molecular targets; thus, it is expected that the effects of combined treatment would be synergistic. Some reports do show memantine/donepezil synergy in ameliorating cognition in AD model animals, but their combined effects on behavioral and psychological symptoms of dementia (BPSD)-like behaviors have not been addressed. Here, we investigate combined memantine/donepezil effects on cognitive impairment and BPSD-like behaviors in olfactory bulbectomized (OBX) mice. Interestingly, combined administration synergistically improved both depressive-like behaviors and impaired social interaction in OBX mice, whereas only weak synergistic effects on cognitive performance were seen. To address mechanisms underlying these effects, we used in vivo microdialysis study and observed impaired nicotine-induced serotonin (5-HT) release in OBX mouse hippocampus. Combined memantine/donepezil administration, but not single administration of either, significantly antagonized the decrease in nicotine-induced 5-HT release seen in OBX mouse hippocampus. Furthermore, decreased autophosphorylation of calcium/calmodulin dependent protein kinase II (CaMKII) was rescued in hippocampal CA1 and dentate gyrus of OBX mice by combined memantine/donepezil administration. These results suggest that improvement of BPSD-like behaviors by the co-administration of both drugs is in part mediated by enhanced 5-HT release and CaMKII activity in OBX mouse hippocampus.

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Lack of Pharmacokinetic or Pharmacodynamic Interaction Between Memantine and Donepezil

Abstract: The pharmacokinetic and pharmacodynamic data from this study indicated a lack of interaction between memantine and donepezil, suggesting that memantine and donepezil may be safely and effectively used in combination.

Cited by 74 publications

References 18 publications

Efficacy and Safety of Donepezil 23 mg versus Donepezil 10 mg for Moderate-to-Severe Alzheimer’s Disease: A Subgroup Analysis in Patients Already Taking or Not Taking Concomitant Memantine

Efficacy and Safety of Donepezil 23 mg versus Donepezil 10 mg for Moderate-to-Severe Alzheimer’s Disease: A Subgroup Analysis in Patients Already Taking or Not Taking Concomitant Memantine

Deterioration in donepezil-induced PR prolongation after a coadministration of memantine in a patient with Alzheimer's disease

Combined Memantine and Donepezil Treatment Improves Behavioral and Psychological Symptoms of Dementia-Like Behaviors in Olfactory Bulbectomized Mice

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