New Extended-Release Namenda Compared to Immediate-Release Formulation

As seen in the Consultant Connection March 2014 Issue
Jeremy Webster, PharmD Candidate, Ohio Northern University

In June 2013, it was announced that the new once-daily extended-release formulation of memantine (Namenda XR) would be available to pharmacies in the United States.  The FDA has approved Namenda XR for the treatment moderate to severe dementia caused by Alzheimer’s disease.  The safety and efficacy of Namenda XR were determined in a randomized trial of 677 outpatients already on a cholinesterase inhibitor by comparing Namenda XR to a placebo in addition to their previous medication.  Results from the trial indicated significant benefits in cognition, behavior, and clinical global status in patients treated with Namenda XR compared to those that received the placebo.
Titration and Switching from Immediate-Release to Namenda XR
Patients naive to memantine should be started on 7mg per day of Namenda XR and titrated up weekly in 7mg increments to the target dose of 28mg per day. When switching from Namenda to the XR formulation, it is recommended for a patient on a 10mg twice daily regimen of Namenda tablets should begin taking the 28mg Namenda XR capsules the day after the last 10mg dose of Namenda.  In patients with severe renal impairment (CrCl <30), it is recommended to switch from the recommended dose of 5mg twice-daily immediate-release Namenda to 14mg once-daily XR capsules the day after the last 5mg dose of the immediate-release.
Pharmacokinetics
Namenda XR is well absorbed and the maximum concentration is observed approximately 9-12 hours after each dose compared to 3-7 hours for immediate-release Namenda.  The overall absorption of both forms of Namenda is not affected by food, but the time it takes to reach maximum absorption is shortened if taken with food.  In a study that compared 28mg once daily of Namenda XR with 10mg twice daily of immediate-release Namenda indicated an increased absorption by the XR formulation indicated by Cmax and AUC (24 hr) values 48% and 33% higher with the XR versus the immediate-release.
Conclusion
Compared to target dose of immediate-release Namenda (10mg twice daily), the extended-release formulation of Namenda allows for an increased daily dose and a simplified dosing regimen.  This can result in increased compliance and reduced caregiver burden due to the convenience of the once-daily administration of Namenda XR.
There have been no studies comparing the efficacy of the immediate-release Namenda versus the extended release formulation at this time. Until there is adequate research to determine how the efficacy of Namenda XR compares to standard dosing of immediate-release Namenda, it is not possible to determine if one is superior to the other.  The XR formulation provides increased convenience for the caregiver and should be considered for any patient with compliance issues or patients that cause a high caregiver burden due to their condition and/or the complexity of their medication regimen.

REFERENCES
Murdolo, Frank. “Forest Announces U.S. Availability of New Once-Daily Namenda XR.” Dateline: New York. 13 June 2013. Available from: <http://news.frx.com/press-release/business-development-news/forest-announces-us-availability-new-once-daily-namenda-xr>.
Daily Med [database on internet]. “Namenda XR capsule, extended-release Namenda XR kit.” Bethesda (MD): Daily Med. Revised April 2013 [cited 2013 Nov 18]. Available from: <http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=710f523f-0158-4639-8ce7-57598247d48c>.
Grossberg, GT, et al. “The Safety, Tolerability, & Efficacy of Once-Daily Memantine (28mg): A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial in Patients with Moderate-to-Severe Alzheimer’s Disease Taking Cholinesterase Inhibitors.” CNS Drugs (2013) 27:469–478. Available from: <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680656/>.
Makino, KM, Porteinsson, AP. “Memantine: A Treatment for Alzheimer’s Disease With a New Formulation.” Aging Health. 2011; 7(3):349-362. Available from: <http://www.medscape.com/viewarticle/748581_4>.
LexiComp [database on the Internet]. Hudson (OH): LexiComp. 2013 [cited 2013 Nov 18]. Available from: <http://online.lexi.com/crlsql/servlet/crlonline>.


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