Neupro – unintended experiment
 

On Friday I forgot to put on my Neupro patch, 6 mg, and did not realize it until Saturday morning. Neupro is the only Parkinson's medication I take except for one at night for my REM sleep disorder. I often wonder if the medication Really makes any difference. During the day on Friday I noticed that my neck became stiff, my toes started to curl, the fingers on my right hand became even more unresponsive than usual, and I had a few cramps in my leg. My tremor was a little more aggressive, but not enough to notice and ask questions about. I slept just fine Friday night.

Saturday morning I realized what I had done as I alternate patches from right to left and the old patch was on the wrong side. I honestly did not figure it out until then. Oddly enough, I've been paying the price since then. Even though I had the patch on all day Saturday and today I've continued to have problems with my toes and with my fingers and my tremor is still stronger than normal. I'm hoping that by tomorrow everything will be back to the way it was. At least I know Neupro is doing something!

A little reassurance goes a long way. Happy 4 u

Nan,

An understanding of the situation that you describe requires pharmocokinetic (what happens over time to the drug in the body) and pharmocodynamic (what, over time, the drug does to the body) data.

For rotigotine, Neupro, Bunten and Happe state, [1], Table 1:
t max = 16 hours
t 0.5 = 6.82 hours

The exact details vary from person to person, but I would expect a history like this:

Day 1 (Thursday, in your case). You take a dose as normal. As I understand the pharmocokinetic data, the maximum benefit from your original dose came 16 hours after it was applied. There are two conflicing processes: new rotigotine is being absorbed through the skin; half of existing rotigotine in the body is eliminated approximately every 7 hours. The paper doesn't say how long the patch continues to release rotigotine.

Day 2. You miss a dose, but you are still picking up the advantages of the previous day's dose and, possibly, any rotigotine still being released by the original patch. To start with you are probably feeling good, you have many of the benefits, but fewer side effects. Eventually, the patch runs out and rotigotine levels halve every 7 hours.

Day 3. Levels are now at their lowest. You put on a new patch and over the next 16 hours things progressively improve.

Day 4. There's a little catching up to do, but things are almost normal.

It would be interesting to know whether the patches are completely exhausted of rotigotine after 24 hours. Does the release stop because the rotigotine is exhausted or because the patch dries up, thus removing the pathway to the skin? It could be that people are throwing out unused rotigotine.

Reference:

[1] Neuropsychiatr Dis Treat. Dec 2006; 2(4): 421–426.
PMCID: PMC2671947
"Rotigotine transdermal system: a short review"
Sabine Bunten and Svenja Happe
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671947/

Thanks for posting this. If I'm reading correctly, by putting on the patch at 8:30 in the morning, I am receiving maximum benefit when I am sound asleep. therefore, if I put the patch on at six in the evening, I would have maximum benefit at 10 the next morning. Do you read it that way as well?

Nan,

Your interpretation is correct. But, I wouldn't read too much into it. Temporal variations in plasma concentrations are much smaller than for, say, immediate release levodopa. This is partly because the underlying drug has a longer half-life; partly because of the continuous delivery.

The data in my previous post refers to a one-off application. Normally, you would be in (almost) steady-state where the drug left over from the previous day help to smooth out differences.

Chen et al. [1, Figure 3] show a graph of the steady state concentration against time. Roughly speaking, this shows minimum concentrations 2 hours after a new patch is put on and maximum concentrations, double the minimum levels, platauxing between 16 and 20 hours after the patch was put on. (The same graph also shows differences due to the patch site.)

Regarding the timing of the dose, they write [1]:

"As food does not affect the absorption of transdermal rotigotine, the rotigotine patch can be applied without regard to the timing of meals. On patch application, the mean ± SD total systemically absorbed dose over 24 hours is 46.1 ± 10.6% of the total rotigotine patch content.... Most of the nonsystemically absorbed drug remains in the patch (as opposed to residing in epidermal strata)."

What appears to be the official web site of Neupro states [2]:

"Patients can choose the most convenient time of day or night to apply Neupro® but should be advised to apply the patch at approximately the same time each day. If a patient forgets to change a patch, a new patch should be applied as soon as possible and replaced at the usual time the following day."

References

[1] "Transdermal Rotigotine: A Clinically Innovative Dopamine-receptor Agonist for the Management of Parkinson's Disease"
Jack J. Chen, Pharm.D., FCCP, David M. Swope, M.D., Khashayar Dashtipour, M.D., Ph.D., Kelly E. Lyons, Ph.D.
Pharmacotherapy. 2009;29(12):1452-1467.
http://www.medscape.com/viewarticle/714562_3

[2] http://www.neupro.com/parkinsons-dis...cp/dosing.html

John

Neupro
 

Hi.

I have been using Neupro for 3 1/2 weeks and the side effects have been worse than the disease itself. My biggest problem is stiffness, neither tremors nor involuntary movements but with Neupro, I have had involuntary movements and have started to cause pain in my abductor muscle (leg).

My neurologist suggested to reduce doses from 8 mg to 6 mg. Is this voluntary movement is normal at the beginning of treatment. Will it disappear over time?

Regards,

Lobo