Extended-Release Amantadine for Levodopa-Induced Dyskinesia

ABSTRACT

Introduction: Levodopa-induced dyskinesia (LID) is a significant impediment to the long-term use of levodopa for Parkinson’s disease (PD). Relatively few studies exist that have described safe and effective therapy for LID. There is thus a significant need for therapy that can control LID to allow for greater sustainability of levodopa therapy. Amantadine extended release (ER) is currently the only FDA-approved medication for the treatment of LID. While other medications have demonstrated efficacy in treating the motor symptoms of PD, amantadine ER is the only one that has been shown, in several clinical trials, to reduce LID and reduce OFF time.

Areas Covered: In this review, the authors present the findings of amantadine ER including its efficacy and safety. The authors also provide their expert perspectives on its use and its future prospects.

Expert opinion: Several therapies are currently being used and studied for controlling LID, an unmet need in therapy for PD. Amantadine ER has potential to supplement levodopa therapy in PD and improve patient therapeutic outcomes.

KEYWORDS:

• Amantadine extended release
• dopamine
• glutamate
• levodopa-induced dyskinesia
• movement disorders
• Parkinson’s disease
• pharmacotherapy

Article highlights

• Levodopa-induced dyskinesia (LID) is an undesirable effect of long-term levodopa therapy.

• Few medications have shown efficacy in reducing LID.

• Amantadine ER is an effective tool for the control of LID.

• Clinical trials have demonstrated the safety and efficacy of amantadine ER.

• Amantadine has relatively few adverse effects when appropriately dosed, and has few adverse drug reactions.

• Amantadine fills a previously unmet need to significantly control dyskinesia reducing this side effect with long-term levodopa treatment.

• The pharmacokinetic profiles of amantadine ER and amantadine IR have enough differences that the two medications are not considered bioequivalent.

Information resources

The web site of GOCOVRI (www.gocovri.com) provides a wealth of patient information. The EASE-LID trial (reference 2 in this paper) is a large-scale study that demonstrated GOCOVRI’s efficacy in treating LID.

Declaration of interest

K Dashtipour has received honorarium and consulting fees from Abbvie, ACADIA, Adamas, Allergan, Cynapsus, Ipsen, Lundbeck, Merz, Neurocrine Biosciences, Sunovion, Teva Neuroscience, and US World Meds. He has received research grants from Abbott, Acorda, Adamas, Allergan, Intec, Ipsen, Lundbeck, Merz, Teva, and US WorldMeds. R Pahwa has received consulting fees from Abbvie, ACADIA, Acorda, Adamas, Cynapsus, Global Kinetics, Ionis, Lundbeck, Neurocrine Biosciences, St. Jude Medical, Sunovion, Teva Neuroscience, UCB and US World Meds. They have also received research grants from Abbott, AbbVie, Acorda, Adamas, BMS, Boston Scientific, Cala Health, Cavion, Cynapsus, Intec, Jazz, Kyowa, Lilly, National Parkinson Foundation, NIH/NINDS, Parkinson Study Group, Pfizer, Roche, Sunovion and US WorldMeds. KE Lyons has served as a consultant for Adamas and currently serves as a consultant for ACADIA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.