Dyskinesia

[Foncie]

I’ve been on Rytary 23.75 for three years. Neupro patch 8mg. I have just begin to have dyskinesia. I was thinking I would decrease Rytary and see if helped. Anyone have suggestions for me?

[Hidden]

In Dr. Ahlskog’s treatment book he recommends carbidopa levodopa instant release at reduced from the last dose.

[park_bear in reply to Hidden]

Switching from Rytary to IR can be expected to make an existing dyskinesia problem dramatically worse.

[jombi in reply to park_bear]

why is this, park bear? thanks

[park_bear in reply to jombi]

Rytary provides a relatively even flow of levodopa. Now take a look at the plasma levels of levodopa from the IR version as shown in the chart here:

healthunlocked.com/cure-par...

It is a very uneven level with a high spike. That high spike of levodopa is likely to cause dyskinesia, especially in someone already experiencing it.

[felixned in reply to park_bear]

I am on Rytary and I have my doubts as far as the advertised even release is concerned. In the beginning I did experienced the wave like ldopa release however after 2.5 years it's been gone. It seems that the equivalency coefficient of .5 to .6 is right for some symptoms but as far as dyskinesia is concerned it appears to me that I experience 1.0 effect.

[sharoncrayn in reply to park_bear]

You might want to review Rytary's phase 3 clinical trial again as the primary source.

"Rytary® and IR carbidopa–levodopa have a similar concentration–effect relationship based on the Unified Parkinson’s Disease Rating Scale Part III, and finger tapping rate." Mittur, Pharmacokinetics of Rytary®, An Extended-Release Capsule Formulation of Carbidopa–Levodopa, 2017

Both IR and Rytary "spike" very quickly. IR quickly tails off peaking in 60-90 minutes, Rytary hits a similar peak in the same time, but continues for approximately 5-6 hours (in general) UNDER FASTING CONDITIONS (which most PwPs do NOT adhere to). They both tail off to < 10% by 8-10 hours.

PB wrote: "It is a very uneven level with a high spike. That high spike of levodopa is likely to cause dyskinesia, especially in someone already experiencing it."

The high spike in both formulas are similar (Cmax = 1094 IR vs 1326RY) and is a NECESSITY.

NO SPIKE, NO "ON" TIME.

sharon

[Foncie in reply to sharoncrayn]

Thank you, for now I’m cutting Rytary back. Took two Rytary at 7 am. and have had dyskinesia all day. I’m not planning on taking anymore Rytary tonight. Have an appointment with Neuro in August. Hope I’m doing the right thing.

[park_bear in reply to sharoncrayn]

I could not find that you are referring to however here is a chart of the plasma level of Rytary:

journals.sagepub.com/doi/10...

which I have copied below. Their terminology is confusing because they refer to it as "extended-release CD/LD capsules" but the text of the article shows they are talking about Rytary. What the patient experiences is the sum of the different components. As you can see from the chart that composite level from the capsule is relatively constant over about six hours.

Rytary plasma level

[sharoncrayn in reply to park_bear]

Actually they are talking about the experimental, (IPXO66), which presumably = RY in its current form.

I gave you the title of an OVERALL REVIEW of RY and the relevant CTs. I am very familiar with the 1st graph they supplied. I said it (RY) provided a much longer spike duration at a slightly higher level (7%) in a fasting state, but at the expense of a higher probability of dyskinesia vs. IR (see the trials and the resulting comparisons).

However, MULTIPLE DOSES of RY (735 mg or 490 mg, Q6h) really goes off the Cmax charts compared to IR (100 mgs/Q3h or Q6h). Way off the chart.. Almost double that of IR 100 with 2 separate spikes at 2 and 8 hours for the 735.

Yet..."These pharmacokinetic characteristics mean that when patients are converted to ER carbidopa–levodopa from their current levodopa regimen, the total daily dose of levodopa from ER carbidopa–levodopa will be approximately twofold higher (twice as high) compared with their current levodopa dose."

with/without Food?

"A high-fat breakfast delayed the absorption of levodopa (RY): t max was 1–2 h later and levodopa C max decreased by approximately 21%. Although there was a slower rate of absorption with a high-fat meal, the overall duration of time that levodopa concentrations were maintained above 50% C max was longer (7.0 h) compared with the fasting state (4.4 h)." But Cmax was lower by 21%.

"When levodopa (sinemet) was administered after meals, levodopa t max increased threefold (from 45 to 134 min) compared with that in the fasted state. (so, it may help to eat a high fat meal after taking your IR dose to flatten the extreme spike and extend Tmax) The con: "The extent of levodopa absorption (AUC6) and C max in the fed state were lower by an average of 15% and 30%, respectively."

Contin et al. reported that the intake of a single dose of Sinemet® CR (50/200 mg carbidopa–levodopa) by patients with mild to moderately severe PD after a standard low-protein meal reduced levodopa AUC6 by 24%, C max was unchanged, and t max was delayed/extended somewhat. (no big deal IMO)

You might read HAUSER, 2013, Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomised, double-blind trial...Phase III...

"Extended-release carbidopa-levodopa reduced daily off-time by, on average, an extra -1·17 h (95% CI -1·69 to -0·66; p<0·0001) compared with immediate-release carbidopa-levodopa" (sinemet)." correlated to UPDRS scores???

also see Waters, 2015 Long-Term Treatment with Extended-Release Carbidopa-Levodopa (IPX066) in Early and Advanced Parkinson's Disease: A 9-Month Open-Label Extension Trial

Regarding RY...."Among 268 early PD patients, 53.4 % reported adverse events (AEs) and 1.1 % (three patients) discontinued due to AEs; the most frequent AEs were nausea (5.6 %) and insomnia (5.6 %). Among 349 advanced patients, 60.2 % reported AEs and 3.7 % (13 patients) discontinued due to AEs;"

no simple solution IMO

sharon

[Foncie in reply to park_bear]

Thank you for your information. I will be seeing my neurologist in the next few weeks. Since I haven’t had these symptoms before, was just a little unsettling.

[Foncie in reply to Hidden]

Not sure I understand what your telling me

[Hidden in reply to Foncie]

Reduce the l-dopa dose.Or

Gocovri (amantadine)

[Foncie in reply to Hidden]

Thank you

[NewHope1961 in reply to Foncie]

The best advice I ever had regarding my dyskinesia other than Amantadine was no L / dopha after 5pm

[Kevin51]

Dosage reduction helped me by making my dyskinesia more manageable but of course symptoms may be less well controlled. Smaller tablet sizes taken more frequently also helps but you seem to be on the minimum already. The combo with a patch looks good as the agonist has a longer half life than Ldopa so should help with the overall meds profile. Gocovri is an extended release form of Amantadine that may help but results vary and has side effects.

[Foncie in reply to Kevin51]

Thank you Kevin. This is my first experience with dyskinesia. I had a little with my foot a year ago. This is more twitching,head bobbing and body swaying. I will see my neurologist in the next few weeks. I appreciate your help.

[Kevin51 in reply to Foncie]

Your neuro should be best placed to help. Tell them what you want to achieve. I found the dyskinesia so disabling that reducing it was crucial. But you will want to keep as much symptom control as you can of course so give that to them to solve. If you don't see them often enough for them to manage this then maybe ask them to prescribe options that you can safely try as it is not always easy to find good solutions.

[Foncie in reply to Kevin51]

Thank you, I will take your suggestions.

[Zella23]

My husband experienced dyskinesia after about 4 years on Madopar which had given him no major side effects.Neuro added in Rasagaline which he had to take a reduced dose as dyskinesia was worse. Then took more frequent but smaller doses of Madopar. This helped but movement slowed up. Neuro added in Amantadine and this really helped. Madopar dose was adjusted - mostly by my husband til a good balance achieved.

Neuro and husband both happy with this.

I hope you can find an adjustment that helps. It just seems to take time, perseverance and I think luck til you achieve what works for you!

[NewHope1961 in reply to Zella23]

Agree with this, Amantadine really helped

[Foncie in reply to Zella23]

Thank you

[beehive23]

id try what your suggesting.....pd alchemy is the only way to go unless you want t talk to your doc a hndred times a week in the years to come....control your own meds just use the guidelines in ythe pdr...imo.... hang tough

[Foncie in reply to beehive23]

Thank you

[Godiv]

I’m so sorry you’re dealing with that. I had dyskinesia pretty much from the get go with that drug. I tried to cut back and found it very difficult. I am on a extremely low dose of gocovri. I just started it a couple weeks ago. I can’t really tell if it’s helping or not. So it probably really isn’t LOL. I hope your doctor can help you. You could try the cutting back and see how your regular symptoms go, but I’m just I’m not sure of the time. It would take you to adjust to a lower dosage. That’s some thing you definitely want to find out so if you have to suffer a little bit you don’t want to think it’s gonna go on for months and months and months. I hope that makes sense.

[Foncie in reply to Godiv]

Thank you, does make sense