Amantadine-Extended Release: Different Pharmocokinetics Drive Different Clinical Effects
Amantadine-ER (Gocovri; Adamas, Emeryville, CA) is approved by the Food and Drug Administration (FDA) for treatment of dyskinesia in patients with Parkinson’s disease taking levodopa therapy with or without other dopaminergic treatments.
Not only is this the first FDA-approved drug for dyskinesia, this formulation is also unique because of a different pharmacokinetic profile and dosing schedule. The unique aspect of the extended-release formulation is not that the same dose is delivered over a longer time period, but rather that when given at bedtime, plasma levels of the drug rise gradually over the next 12 to 16 hours, when a peak is reached.
This results in patients having a therapeutic dose already on-board when they awake, known to be the time of day when dyskinesia of off period is usually at its worst. In other words, when amantadine-ER is taken at bedtime, plasma concentrations are then highest the following day at the times when symptoms are worst and treatment is most needed.
A 2-year phase 3 open-label study of amantadine-ER has shown that it is generally well tolerated and the treatment effect on motor complications (dyskinesia and OFF) is maintained for up to 2 years. Only 9% of patients taking amantadine-ER discontinued the drug due to adverse events over the full 2-year period, most of which were mild to moderate and included falls, hallucination, peripheral edema, constipation, urinary tract infection, dizziness, nausea, insomnia, livedo reticularis, dry mouth, depression, anxiety, and abnormal dreams.
Rajiv Patni, MD, Chief Medical Officer of Adamas Pharmaceuticals, Inc. stated “The large reduction in dyskinesia and OFF. . . observed by week 8 was sustained for 2 years. This durability is noteworthy given the known progression of motor complications. . . by 2 years, 30% of patients increased their levodopa dose by an average of approximately 300 mg, suggesting that GOCOVRI treatment may allow neurologists to further optimize their patient’s levodopa dose despite the occurrence of dyskinesia.”