The expert neurology panel shares their clinical experience with different formulations of amantadine in management of dyskinesia in patients with Parkinson disease.
Daniel E. Kremens, MD, JD: Would anybody want to share some experience, if you have any, with some of the other formulations of amantadine? We used IR [immediate release] fairly extensively before DR/ER [delayed release/extended release] was available, and my clinical experience replicated what we saw in the studies, that some patients got some benefit with respect to dyskinesia. I did not see improvement in “off” time in those patients, and dosing could be complicated because it required dosing multiple times a day to reach therapeutic levels for them. Again, there have been no head-to-head trials but in my clinical experience, the adverse effect profile of DR/ER is generally better tolerated than IR because I often had to use higher doses of IR in single at a time to get a clinical benefit, so that made tolerability an issue. With respect to IR/ER, I have limited experience in that, but in the handful of patients who, for one reason or another, had to or chose to switch, they used IR/ER for a brief period of time, and all of them have gone back to DR/ER. So they did not feel that it was as efficacious for their off and dyskinesia.
Rajesh Pahwa, MD: In my experience, amantadine IR—and the limited data we have with IR—does work for dyskinesia. I have not personally experienced reduction in off time with amantadine IR, and in my experience, the side effects are similar. I did not find that there was a higher adverse effect profile with amantadine IR. As far as amantadine IR/ER is concerned, again, I have very little to no experience with it because it’s not approved for either off time or dyskinesia. If I’m going to use a drug, I’m going to use the one which has been shown to be efficacious. As I said earlier, if you look at the data of IR/ER, it helps the dyskinesia but does not help with the off time.
Fernando Pagan, MD: In my experience with the amantadine IR, it was always very variable. I agree with everything that’s been said, that we can reduce the dyskinesia, but the reduction in off time, I never saw with the amantadine IR but the dosing was also very variable, using somewhere between 200 to 400 mg daily of the immediate release. We don’t have a lot of good clinical studies to show us how to use the IR, but I’ve had patients now long-term on DR/ER amantadine, and that’s something I never saw with amantadine IR. I’ve had patients who started and stopped it over the years, but now, in my clinical experience, I have patients who, when amantadine DR/ER first came out and still to this day, are still on amantadine DR/ER and having a good clinical benefit. So the long-term efficacy that we saw in the open-label data, I’m seeing that in my clinical practice.
William G. Ondo, MD: The only other thing I would add about the IR preparations over the years is that I’ve had several patients who’ve felt there was considerable difference among the different generic preparations, where one preparation seemed to work well for the dyskinesia. Then they would get a different-looking pill from a different manufacturer, and they would not think that that pill worked as well. It’s something I always discuss with patients these days.
Robert A. Hauser, MD, MBA: Raj, you mentioned that DR/ER has the high levels in the morning and that they maintain through the day, whereas IR amantadine starts very low and sort of climbs through the day. We did an analysis of response, clinical response, through the day and it showed that DR/ER provides benefit through the day. We don’t know about IR. With IR having those low levels in the morning through midday, are we lacking a good response in the early day? We just don’t know, so I’ll throw that out as a question mark.
Rajesh Pahwa, MD: One thing we should point out is that these are our personal experiences. There have not been randomized control studies comparing IR with IR/ER or DR/ER, so I think we should keep that in mind when we talk about this.
Transcript Edited for Clarity