Skip to main content
SpringerLink
Log in

Memantine ER/Donepezil: A Review in Alzheimer’s Disease

  • Adis Drug Evaluation
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

A once-daily, fixed-dose combination of memantine extended-release (ER)/donepezil 28/10 mg (Namzaric™) is available in the USA for patients with moderate to severe Alzheimer’s disease (AD) on stable memantine and donepezil therapy. The fixed-dose formulation is bioequivalent to coadministration of the individual drugs. In a 24-week, phase III trial in patients with moderate to severe AD, addition of memantine ER 28 mg once daily to stable cholinesterase inhibitor (ChEI) therapy was more effective than add-on placebo on measures of cognition, global clinical status, dementia behaviour and semantic processing ability, although between-group differences on a measure of daily function did not significantly differ. In subgroup analyses in donepezil-treated patients, add-on memantine ER was more effective than add-on placebo on measures of cognition, dementia behaviour and semantic processing, although there were no significant between-group differences on measures of global clinical status and daily function. Memantine ER plus ChEI combination therapy was generally well tolerated in the phase III trial, with diarrhoea, dizziness and influenza occurring at least twice as often with add-on memantine ER as add-on placebo in donepezil-treated patients. Thus, memantine ER plus donepezil combination therapy is an effective and well tolerated treatment option for patients with moderate to severe AD. The fixed-dose combination is potentially more convenient than coadministration of the individual agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Association Alzheimer’s. 2014 Alzheimer’s disease facts and figures. Alzheimers Dement. 2014;10(2):e47–92.

    Article  Google Scholar 

  2. Atri A. Effective pharmacological management of Alzheimer’s disease. Am J Manag Care. 2011;17(Suppl 13):S346–55.

    PubMed  Google Scholar 

  3. Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291(3):317–24.

    Article  CAS  PubMed  Google Scholar 

  4. Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med. 2012;366(10):893–903.

    Article  CAS  PubMed  Google Scholar 

  5. Hendrix S, Ellison N, Stanworth S, et al. Post hoc evidence for an additive effect of memantine and donepezil: consistent findings from DOMINO-AD study and memantine clinical trial program. J Prev Alzheimers Dis. 2015;2(3):165–71.

    Google Scholar 

  6. Schmidt R, Hofer E, Bouwman FH, et al. EFNS-ENS/EAN Guideline on concomitant use of cholinesterase inhibitors and memantine in moderate to severe Alzheimer’s disease. Eur J Neurol. 2015;22(6):889–98.

    Article  CAS  PubMed  Google Scholar 

  7. Atri A, Molinuevo JL, Lemming O, et al. Memantine in patients with Alzheimer’s disease receiving donepezil: new analyses of efficacy and safety for combination therapy. Alzheimers Res Ther. 2013;5(1):[article no. 6].

  8. Atri A, Shaughnessy LW, Locascio JJ, et al. Long-term course and effectiveness of combination therapy in Alzheimer disease. Alzheimer Dis Assoc Disord. 2008;22(3):209–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Lopez OL, Becker JT, Wahed AS, et al. Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease. J Neurol Neurosurg Psychiatry. 2009;80(6):600–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Plosker GL. Memantine extended release (28 mg once daily): a review of its use in Alzheimer’s disease. Drugs. 2015;75(8):887–97.

    Article  CAS  PubMed  Google Scholar 

  11. Forest Pharmaceuticals Inc. Namzaric™ (memantine hydrochloride extended-release and donepezil hydrochloride) capsules, for oral use: US prescribing information. 2014. http://www.fda.gov. Accessed 14 Oct 2015.

  12. Parsons CG, Danysz W, Dekundy A, et al. Memantine and cholinesterase inhibitors: complementary mechanisms in the treatment of Alzheimer’s disease. Neurotox Res. 2013;24(3):358–69.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Jelic V, Darreh-Shori T. Donepezil: a review of pharmacological characteristics and role in the management of Alzheimer disease. Clin Med Insights Ther. 2010;2:771–88.

    Article  CAS  Google Scholar 

  14. Boinpally R, Chen L, Zukin SR, et al. A novel once-daily fixed-dose combination of memantine extended release and donepezil for the treatment of moderate to severe Alzheimer’s disease: two phase I studies in healthy volunteers. Clin Drug Investig. 2015;35(7):427–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Grossberg GT, Manes F, Allegri RF, et al. The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer’s disease taking cholinesterase inhibitors. CNS Drugs. 2013;27(6):469–78.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Grossberg GT, Alva G, Hendrix S, et al. Efficacy and tolerability of memantine extended release added to stable donepezil regimen in individuals with moderate to severe Alzheimer’s disease: subset analysis of a randomized clinical trial [abstract no. P1-370 plus poster]. Alzheimers Dement. 2014;10(4 Suppl):P450.

    Article  Google Scholar 

  17. Atri A, Hendrix SB, Pejovic V, et al. Cumulative, additive benefits of memantine-donepezil combination over component monotherapies in moderate to severe Alzheimer’s dementia: a pooled area under the curve analysis. Alzheimers Res Ther. 2015;7(1):[article no. 28].

  18. Hendrix S, Ellison N, Otcheretko V. Complementary benefit of memantine and donepezil on activities of daily living by disease stage when used together: post hoc analysis of two trials in moderate to severe Alzheimer’s disease [abstract no. 2710 plus poster]. In: Alzheimer’s Association International Conference. 2015.

  19. Atri A, Hendrix S, Ellison N, et al. Caregiver distress related to neuropsychiatric symptoms is reduced with extended-release memantine-cholinesterase inhibitor combination in patients with moderate to severe Alzheimer’s disease [abstract no. 4636 plus poster]. In: Alzheimer’s Association International Conference. 2015.

  20. Qaseem A, Snow V, Cross JT Jr, et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2008;148(5):370–8.

    Article  PubMed  Google Scholar 

  21. Rountree SD, Chan W, Pavlik VN, et al. Persistent treatment with cholinesterase inhibitors and/or memantine slows clinical progression of Alzheimer disease. Alzheimers Res Ther. 2009;1(2):[article no. 7].

  22. Borah B, Sacco P, Zarotsky V. Predictors of adherence among Alzheimer’s disease patients receiving oral therapy. Curr Med Res Opin. 2010;26(8):1957–65.

    Article  CAS  PubMed  Google Scholar 

  23. Brewer L, Bennett K, McGreevy C, et al. A population-based study of dosing and persistence with anti-dementia medications. Eur J Clin Pharmacol. 2013;69(7):1467–75.

    Article  PubMed  Google Scholar 

  24. Saint-Laurent Thibault C, Stillman IO, Chen S, et al. Cost-utility analysis of memantine extended release added to cholinesterase inhibitors compared to cholinesterase inhibitor monotherapy for the treatment of moderate-to-severe dementia of the Alzheimer’s type in the United States. J Med Econ. 2015. doi:10.3111/13696998.2015.1063501.

Download references

Acknowledgments

During the peer review process, the manufacturer of memantine ER/donepezil was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Sarah L. Greig

Authors
  1. Sarah L. Greig
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarah L. Greig.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Sarah Greig is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: S. Gauthier, McGill Center for Studies in Aging, Alzheimer Disease and Related Disorders Unit, Douglas Mental Health University Institute, Montreal, QC, Canada; V. John, Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Greig, S.L. Memantine ER/Donepezil: A Review in Alzheimer’s Disease. CNS Drugs 29, 963–970 (2015). https://doi.org/10.1007/s40263-015-0287-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40263-015-0287-2

Keywords

Search

Navigation