Amantadine Extended-Release (GOCOVRI™): A Review in Levodopa-Induced Dyskinesia in Parkinson’s Disease

Abstract

Amantadine extended-release (ER) capsules (GOCOVRI™) are approved in the USA for the treatment of dyskinesia in patients with Parkinson's disease (PD) receiving levodopa-based therapy, with or without concomitant dopaminergic medications. With a recommended dosage of 274mg once daily at bedtime, this new formulation of amantadine allows a more gradual time to peak plasma amantadine concentration and higher drug concentrations in the morning and throughout the day, the time period when levodopa-induced dyskinesia (LID) is the most problematic. In 13-week (EASE LID3) and 25-week (EASE LID), randomized, double-blind phase III trials, once-daily amantadine ER 274mg capsules significantly improved levodopa-induced dyskinesia (LID), while also increasing ON time without troublesome dyskinesia and reducing OFF time and ON time with troublesome dyskinesia from the morning and throughout the day, compared with placebo. In the ongoing, longer-term EASE LID2 study (with interim results reported for up to 64weeks), patients previously treated with amantadine ER maintained improvements in LID, as per patient-reported Unified Dyskinesia Rating Scale (UDysRS) scoring and ON/OFF times. Amantadine ER was generally well tolerated, with most adverse events (AEs) being transient and mild or moderate in severity. The most common (incidence >15%) treatment-related AEs in the placebo-controlled trials were hallucinations, dizziness, dry mouth and peripheral oedema. While long-term data are needed to establish durability of response and safety, including the completion of the ≈2-year EASE LID2 study, current evidence indicates that amantadine ER is an effective treatment option to consider in the management of LID in PD patients.