Levodopa Dose Equivalency
 

Do forum members know of any tables that show the equivalent doseages of common PD drugs?

For instance, it would be useful to be able to know the approximate effect of:
1 mg levodopa = x mg Sinemet
x mg Sinemet = y mg Stalevo, where x and y are the levodopa content
x mg ropinirole = y mg pramipexole

This information would be useful for anyone changing drugs.

It would also be useful in clinical trials and white ratting as a measurement tool by providing a common denominator, e.g. it would allow statements to be made like "this therapy has the same effect as x mg Sinemet".

Annoyingly, there is a paper on the subject [1], but this is behind a pay-wall.

The best reference I can find is a slide show, "Levodopa Dose Equivalency: A Systematic Review" [2], by Claire Smith, from the Clinical Trials Unit at Birmingham University, UK. This uses the concept of
"LED [levodopa equivalent dose] of a drug as that which produces same anti-parkinsonian effect as 100 mg of immediate release levodopa"

Levodopa (it's not clear whether this includes carbidopa, 1 mg) LED = 1
Stalevo (it's not clear how this value is calculated, 1 mg levodopa) LED = 1.33
Ropinirole (1 mg) LED = 20
Rasagiline (1 mg) LED = 100
(The slide show lists many other drug equivalences.)

From these figures a daily total levodopa can be calculated. For instance, in my case: rasagilene, 1 mg (LED 100); ropinirole, 16 mg (320); Stalevo 4x75 mg levodopa (400). Giving a total daily levodopa equivalent dose of 820 mg.

Please note that the numbers in the slide show are based on a literature review. The papers used are not all in agreement as to the conversion factors. Therefore, the values given above should be taken as estimates.

Also, note that different drugs work by different mechanisms and have different side effects and do not always scale linearly. So they should not be thought of as directly substitutable. For instance, [3] reports that there is little marginal benefit increasing the rasagiline dose above 1 mg.

[1] http://www.ncbi.nlm.nih.gov/pubmed/21069833
[2] http://www.pdmed.bham.ac.uk/investig...LED_Review.ppt
[3] http://dailymed.nlm.nih.gov/dailymed...rchiveid=10668

John

Hello,

Paper 1
I can give you if you send me over your email in pm so I can email the pdf

thanks

Lee et al. [1] provide extra conversion factors to use when calculating a person's L-dopa equivalent daily dose (LEDD).

A person's LEDD is calculated by adding together the L-dopa equivalent of each of the drugs taken. The table below shows the conversion rates:
100 mg of L-dopa =
130 mg of L-dopa in controlled-release form =
77 mg L-dopa with entacapone =
1 mg pergolide =
1 mg pramipexole =
5 mg ropinirole =
10 mg bromocriptine

Reference
[1] "Daily dose of dopaminergic medications in Parkinson disease: Clinical correlates and a posteriori equation"
1Jee-Young Lee MD, 2Jae Woo Kim MD PhD, 3Won Yong Lee MD PhD, 4Jong-Min Kim
MD PhD, 5Tae-Beom Ahn MD PhD, 6Han-Joon Kim MD, 3Jinwhan Cho MD PhD, 6Beom S
Jeon MD PhD
Neurology Asia 2010; 15(2) : 137 – 143
http://www.neurology-asia.org/articles/20102_137.pdf

John

this is useful
 

for several yrs i have known that anything taken with 25/100 regular sinemet made me dyskinetic. i also take amantadine. that and exercise are what i needed. oldies but goodies..........hmmmm

with a standard to go by and attention paid to it individuals could pinpoint their tolerance of meds in regard to dyskinesia.

great post

Another conversion factor calculated from [1]:

100mg levodopa = 2mg/24hr rotigotine

The paper deals with the pragmatics of what to do regarding Parkinson's meds if a patient is nil by mouth.

Reference

[1] "Acute management of Parkinson's patients"
Joy Reid, NHS Fife, 2011
http://www.fifeadtc.scot.nhs.uk/supp...20Patients.pdf

John

Some additional equivalences, adapted from Wullner et al. [1]:

Total levodopa equivalent dose =
regular levodopa dose × 1 +
levodopa continuous release dose × 0.75 +
pramipexole dose × 67 +
ropinirole dose × 16.67 +
pergolide dose × 100 +
bromocriptine dose × 10 +
cabergoline dose × 50 +
amantadine dose × 0.5 +
selegiline dose × 10 +
rasagiline dose × 100.

Where tolcapone or entapone are added, e.g. Stalevo,
Levodopa equivalent dose =
regular levodopa dose x 1.25

I repeat a point that I made in a previous post: these are only estimates, they vary from author to author and from patient to patient. They do not take into account differing side effects.

In judging the impact you also have to estimate the duration of the effect. For instance, a dose of 100 mg of sinemet may have an effect for, perhaps, 3 hours (it will vary from person to person). Whereas a dose of 1 mg of rasagilene will last for 24 hours. In total effect both are roughly equivalent, but the Sinemet has about 8 times (24/3) the intensity.

The LED approach essentially assumes that the impact of taking more drugs (both of the same and different types) is additive.

This is not the case with rasagilene. For most people the law of diminishing returns applies [2].

"Mean baseline PFS score was 2.2 ± 0.9 units. At 36 weeks, patients receiving placebo showed greater progression of symptoms (0.17 units) from baseline in PFS scores compared with the 1 mg/day (0.03 units) and 2 mg/day rasagiline groups (−0.02 units); the difference versus placebo was significant for both rasagiline groups (P < 0.01)."

It is also possible that the opposite is the case for some combinations of drugs. Brodsky et al. report [3]:

"Pramipexole augmented the motor response to levodopa beyond a simple additive effect and increased the severity of levodopa-induced dyskinesia. When considering a combination of these therapies, an appropriate balance should be maintained regarding gain of motor function vs worsening of dyskinesia."

References

[1] "Transdermal rotigotine for the perioperative management of Parkinson’s disease
Ullrich Wüllner,corresponding author1 Jan Kassubek,2 Per Odin,3 Michael Schwarz,4 Markus Naumann,5 Hermann-Josef Häck,6 Babak Boroojerdi,6 and Heinz Reichmann
j Neural Transm, 2010 July
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895903/

[2] "Benefits of treatment with rasagiline for fatigue symptoms in patients with early Parkinson's disease"
F. Stocchi*, The ADAGIO investigators
European Journal of Neurology © 2013 EFNS
http://onlinelibrary.wiley.com/doi/1...12205/abstract

[3] "Effects of a Dopamine Agonist on the Pharmacodynamics of Levodopa in Parkinson Disease"
Matthew A. Brodsky, MD; Byung S. Park, PhD; John G. Nutt, MD
Arch Neurol. 2010;67(1):27-32. doi:10.1001/archneurol.2009.287.
http://archneur.jamanetwork.com/arti...ticleid=798841

John

PDMeasure is beginning to show some interesting results. The graph below shows the number of years since diagnosis and the amount of PD medication (measured as a levodopa equivalent daily dose, LEDD) taken by people in the survey with a diagnosis of IPD.

Attachment 7618

There is too little data to show statistical significance. But, I do think that as a proof of concept it does show what is possible if we had more data.

John

We can take the concept of levodopa equivalent dose (LED) a step further by taking into account the length of time over which a dose is effective.

The length of the effective period depends in part on a drug's half-life, but it also varies from person to person. For instance, depending on the number of dopamineric vesicles remaining, and the intensity of exercise. My estimates of the length of the effective period for me are:
rasagiline (Azilect), 24 hours,
ropinirole extended release (Requip XL), 24 hours;
Stalevo, 3 hours
Sinemet, 3 hours

A rough measure of the potency of a Parkinson's drug is given by its LED/hr:
1mg rasagiline has a potency of 100/24 = 4mg LED/hr
1mg ropinirole extended release = 16.67/24 = 0.7mg LED/hr
100mg Stalevo = 125/3 = 42mg LED/hr
100mg Sinemet = 100/3 = 33mg LED/hr

These figures show, for instance, why many people don't notice the effect of rasagiline: its hourly LED is less than one eighth of that of Sinemet. It does have the advantage of keeping LED/hr levels consistently higher during the whole 24 hour period, thus reducing the impact of an "off" and reducing the chance of levodopa induced dyskinesia.

The next stage is to graph the changes to the hourly LED during the day taking into account the time it takes for a pill's levodopa to reach the brain. This is affected by gastric emptying and competing protein transport through the blood brain barrier.

I've no empirical data for this, but one would expect a graph like this for a person taking a mixture of medications.


LED/hr
|-------------------------- levodopa induced dyskinesia
|.....................
|.....................
|.....................
|.....................
|.....................
|.....................
|..........SSSSSSSSS
|..........SSSSSSSSSS
|..........SSSSSSSSSSS
|.........SSSSSSSSSSSSS
|.........SSSSSSSSSSSSS
|.........SSSSSSSSSSSSS
|-------------------------- on-time threshold
|.........SSSSSSSSSSSSSS
|........SSSSSSSSSSSSSSS.
|RRRRRRRRRRRRRRRRRRRRRRRR
|RRRRRRRRRRRRRRRRRRRRRRRR
|AAAAAAAAAAAAAAAAAAAAAAAA
|EEEEEEEEEEEEEEEEEEEEEEEE
|EEEEEEEEEEEEEEEEEEEEEEEE
|EEEEEEEEEEEEEEEEEEEEEEEE
|EEEEEEEEEEEEEEEEEEEEEEEE
|EEEEEEEEEEEEEEEEEEEEEEEE
|EEEEEEEEEEEEEEEEEEEEEEEE
|EEEEEEEEEEEEEEEEEEEEEEEE
|EEEEEEEEEEEEEEEEEEEEEEEE
--------------------------- Time(hr)
|000000000011111111112222
|012345678901234567890123

Example: LED/hr graph
E=endogenous dopamine production, a=Azilect, r=ropinirole, s=Stalevo

The graph makes it clear why moving from Sinemet to Stalevo could lead to levodopa induced dyskinesia: the 25% extra strength could take one over the LID threshold.

Analysing such graphs offers a way of estimating the rate of production of endogenous dopamine (dopamine produced naturally) that still remains. If this is measured over time, the changes can be used to give an estimate of disease progression.

John

I've come across a paper (mainly written in Spanish, which I don't speak - but let's not stop there) which points out that there is no agreed conversion factor between levodopa and other PD drugs.

For each drug and each method of calculating the equivalence Cervantes-Arriagal et al. [1] give the conversion factor. I precis their table as follows:

Drug/Lowest conversion factor/Highest conversion factor/Weighted average
L-dopa/1/1/1
L-dopa CR/0.70/0.77/0.74
Pergolide/100/100/100
Cabergoline/66.6/100/80.12
Bromocriptine/10/10/10
Stalevo/1.2/1.33/1.25
Pramipexol/67/100/89
Ropinirole/16.67/33.3/21.3
Lisuride/100/100/100
Apomorphine/8/10/8.25

(N.B. the l-dopa entry is for l-dopa with carbidopa.)

What sticks out to me is the large range for ropinirole: a factor of two difference between the highest and lowest estimates. Also, so many of the estimates are "round numbers", such as 100, which suggests that the estimates are very rough. That said, I think it is very useful to have an idea of the relative power of drugs.

Reference

[1] "Cálculo de unidades de equivalencia de levodopa en enfermedad de Parkinson"
Amin Cervantes-Arriaga1, Mayela Rodríguez-Violante1, Alejandra Villar-Velarde, Teresa Corona
Arch Neurocien (Mex) Vol. 14, No. 2: 116-119; 2009
http://www.medigraphic.com/pdfs/arcn...09/ane092f.pdf

John

The FDA have released a file "Full Prescribing Information" for Rytary:

http://www.accessdata.fda.gov/drugsa...312s000lbl.pdf

Table 1 of the file shows the dose of Rytary for people converting from immediate release carbidopa-levodopa.

Total daily dose (mg)
Levodopa,Rytary
400-549,855
550-749,1140
750-949,1305
950-1249 ,1755
>=1250,2340 or 2205

The relationship between Rytary and levodopa is non-linear. Anyone know why?
But, roughly speaking:
100mg levodopa = 170mg Rytary

John

Useful
 

Thanks for this thread Johnt, a good resource.

I've written a very small app that calculates the LEDs of your drugs and totals them to get your levodopa equivalent daily dose (LEDD). It runs directly from the web page, so there's nothing to install. It can be found on my web-site at:

http://www.parkinsonsmeasurement.org...valentDose.htm

John

We left this thread with an app that calculated LEDs. This was, as far as it went, fine, but it didn't capture the time nature of the drugs. So, for instance, 1mg of rasagiline has a LED of 100mg, which by definition is the same as 100mg levodopa/carbidopa. But, the rasagiline is effective for the whole 24hr period, whereas the levodopa is effective for, perhaps, 4 hours: in the end they give the same "volume", but one is like a long-term trickle, whereas the other is like a short-term flood. I've written a new app which, in part, addresses this issue, by looking at the pharmacokinetics (what the body does to the drug) of the situation. This leaves unaddressed, and needing to be done, an app to look at the pharmacodynamics (what the drug does to the body) of PD drug regimens.

My app can be run directly, there's nothing to download or install, from:

http://www.parkinsonsmeasurement.org...cokinetics.htm

(I've only added a few drugs. I will add others later. I've also not created a link from the web site's home page to the app. I'll add that when things are stable.)

This is a screen shot showing the app's output given my PD drug regimen.

Attachment 9350

Please play with the app and let me have your comments.

My thanks go to Ron Strong and Angela Wensley with whom I've been in contact with on this subject. A few weeks ago Angela posted on her Excel-approach to PD pharmacokinetics see:

http://neurotalk.psychcentral.com/thread218873-2.html

John

Very good, can you add sinemet CR?

*administrative edit as per NeuroTalk Guidelines*
The difference in approach is that my data is manly derived from digitised blood plasma charts whereas Johns are pharmokinetic data.

I would say comparing rasagiline with levodopa is like comparing butter to salt, in that they don't do the same thing. But it is interesting nevertheless

Thanks Ron.

I'll update the app to include Sinemet CR as soon as I can find some consistent data. Angela as been so kind as to forward to me some papers on the subject.

I take your point that rasagiline and levodopa are different. But, they are both involved in the same battle: increasing dopamine levels in the brain. Levodopa leads to dopamine being created and rasagiline reduces the amount of dopamine that is lost. Either route can lead to the same amount of dopamine being present in the brain. If you could go on adding to the rasagiline dose and get increasing levels of dopamine preserved it would be a wonder drug. Unfortunately, it does not give better results for doses above 1mg/day - presumably it has done its job as a MAO-B inhibitor and there is no more MAO-B to inhibit.

John

My app does much the same job but it calculate the sum effect for correlating with other reading.I'd say the rasagiline never has any effect (but I'll keep on taking it I can't prove otherwise.

Thanks by the way for you hard work on this

my app is at model.strong.org.uk
Register and I will approve

Wendy writes:

"I'd like to use Mirapex in the graph if I can. Its TMAX is 2 hrs, THALF is 8-12 hrs. depending on age, and the conversion factor is 100. ... How do I figure out the CMAX?"
http://www.neurotalk.org/parkinson-s...evadopa-2.html

Unfortunately my program does not include Mirapex. But, given the interest shown I'll extend it to include this drug and a few other common ones too. The difficulty is not in the programming, but rather finding reliable sources of the pharmacokinetic parameters on which the model is based. This will take some time to do, so in the meantime a work-around is required. I will go into a lot of detail, because I think it important that anyone using this tool understands how it works.

The simplest, but least accurate way, is to take a similar drug and use that as a proxy. In this case, ropinirole is a possible alternative. The conversion factor for levodopa is 1, for ropinirole it is 20 and for Mirapex it is 100. To balance the books you can select ropinirole and give it a dose of 5 times more than the Mirapex dose. So, a 1mg dose of Mirapex is entered as a 5mg dose of ropinirole. If you enter these values into the grid and also enter a line showing a dose of 100mg levodopa, you will find that as expected the two doses have almost the same area under the curve (AUC). The problem is that the program has chosen a TMAX of 90 minutes (when you wanted 120) and a THALF of 360 minutes (when you wanted 480-720 minutes).

A more accurate way to work around the problem is to change the default values of TMAX and THALF to those that you want, but initially keep the default value of CMAX (5.59). Putting TMAX to 120 and THALF to 600, and pressing Calculate gives an AUC of 20602, which is wrong: it should equal 14686 (because 5mg of ropinirole is equivalent to 100mg of levodopa, and LED is based on equal AUCs). The final step is to by trial and error adjust the CMAX value to get the correct AUC: there is a linear relationship between CMAX and AUC). CMAX=4 gives AUC=14742, which is close enough.

Please remember that this is just a mathematical model, which makes numerous assumptions, which is based on data which is inexact, and which does not take into account endogenous dopamine production and storage. Also, it is one step removed from what we really want to know, which is the pharmacodynamic impact of our drug regimen: how, for instance, does our bradykinesia change during the day.

My efforts are going into "dynamic dosing": producing electronic tools that detect when you're nearing an "off" with enough notice for a dose taken now to kick-in before the "off" happens.

John

Looking for the Mirapex Update
 

John, I'm new to the forum but have precisely the issue discussed here. In addition to dyskinesia from too much Levodopa, I am experiencing compulsions to spend $$ and drive fast.

My meds at this moment include Rytary ER, Mirapex ER, Rasagaline, Donepezil, Levothyroxine and Escitalopram. I understand that only the first three impact my Levodopa levels but include the rest for completeness.

Questions:

1. Do you have a version of your app that includes Mirapex ER?

2. Does your app support the ER versions of Rytary and Mirapex in addition to the standard versions?

Working with my Neuro Doc, I am drawing down and eventually quitting my Mirapex, and eliminating my Rasagaline altogether. My intention is to accurately display the total Levodopa amount over time so I can plan the best way to find my correct types and amounts of meds.

Thanks for a wonderful thread and an excellent app to work with!

Brian

Ron, is your model still available? When I click on the link, all I get is a blank screen.

I'm registered in the group - what else do I need to do?

Brian

Looking For Your By-Minute Chart Given This Input
 

John, I am unable to come to a successful conclusion when using your by-minute app to find my Levodopa levels throughout my typical day.

Here are two scenarios I'd like to explore:

1. Initial Dosing of Parkinson's Meds

(3) capsules of Rytary ER @ 48.75mg Carbi, 195mg Levo
Total 146.5mg Carbi, 585mg Levo

The dose above is taken daily at 0600, 1030, 1500, 1930

(1) tablet Rasagaline 1mg at 0600 daily

(1) tablet MiraPex ER .75mg at 2230


2. Final Dosing After Removing Rasagaline and Mirapex

(3) capsules of Rytary ER @ 48.75mg Carbi, 195mg Levo
Total 146.5mg Carbi, 585mg Levo

The dose above is taken daily at 0600, 1030, 1500, 1930

Can you give me a reasonable result with your knowledge of how your app is set up??

Thanks - you brought great value to this discussion!

Brian

Brian,

Thank you for your interest in my levodopa equivalent pharmacokinetics graphing app.

As you've found, the tool is limited in the types of drug that it can cope with.

Post 18 in this thread gives a work-around for Mirapex. At its least accurate, you can approximate 1mg of Mirapex ER with 5mg of Requip XL.

Regarding Rytary, I show in a recent thread how to approximate one dose of Rytary with 4 doses of levodopa/carbidopa. See:

https://www.neurotalk.org/parkinson-...-using-ir.html

So, you will need to fill in 18 lines, four for each of your four Rytary doses, plus one each for your Mirapex and rasagiline doses.

I've increased the number of doses that the program can deal with per day to 20.

John

I've added some new features to my app which draws a graph of the impact of your drug regimen on your levodopa levels:
- More drugs (but still not Rytary).
- An "on"/ "off" threshold estimator.
- A dyskinesia threshold estimator.
- Steady state as well as single dose solutions.

Parkinson's Disease Measurement: PwP, surveys, trials, analysis

See Post 13 in this thread for screen shots.

Please remember that this app is just a model based on inexact pharmacokinetic (what the body does to the drug) data, when what we really want to know is the pharmacodynamic (what the drug does to the body) impact of our regimen. But, it does help allow you to discuss your options with your doctors.

I believe that most of us can get more out of existing drugs than we do now if we and our doctors take the time to optimize our personal drug regimen.

John

hand held device for mea=asuring proprioception
 

Hello John,

Back in 1994 my chiropractor had me squeeze this hand held device that must have measured some subtle electric conductance. Before this he had thought that the tremor in my thumb and the pain in my elbow were simply essential tremor but when I saw that concerned look on his face and his immediate recommendation to see a neuro the gravity of my situation became ever more clear (Initially I thought my grip was pretty strong but thats' not what it was measuring). At the time my sx were subtle which is why I'm wondering if this device might also be useful for the applications you are suggesting for tweaking med dosages....A Good Parkinson’s Muscle-decline Measure Is Hand-grip Test, Study Says
Also, after reading some of your posts i am more carefully observing any sensation of tremor and stiffness ...breathing ease and anxiety as an indicator of when to take next dose. In the mornings I can take less but more frequently and more but less frequently towards the evening.

Kind Regards,
MD

Sinemet 25-100 combinations - too much or not enough, can't tell
 

Hello folks. Sorry for jumping in but I'm have a problem with my Sinemet dosing.

My current med list:


Azilect 1 mg tab. Take 1 tab in every morning at wake-up.

Amantadine, 100 mg tablet. Take 1/2 tab at 5:30 AM and 1/2 tab at 11:30 AM.

Sinemet 25-100 tab. Take 1 tab at 5:30 AM (wake-up) and 1 tab at 7:30 AM, 9:30 AM, 11:30 AM, 1:30 PM, 3:30 PM, 5:30 PM, 7:30 PM, 8:30PM and 9:30PM (bed time).

Sinemet ER 50-200 tablet (during the night). Take one tab at 9:00PM (bed time) and one tab at 1:30 AM.

Now here's the problem. I'm on a really tight dosage regimen during the day with the Sinemet 25-100. Taking a pill every two hours is a real challenge. I'm constantly missing timing of dosage and I end up on a 30-40 minute "off" or bouncing off the ceiling with over medicating. I don't know if I'm taking too much or not enough. The 25-100s are beginning to not offer relief of symptoms and if I take 1.5 tabs per 2 hours, I start to get overmedicated and then dyskinesia starts to cause problems. Any suggestions? Is 2 sinemet tabs every 4 hours the same as 1 tab every 2 hours. BTW, I did try Rytary and didn't work for me (side effects). Thank you.

taking 2 sinemet every 4 hrs probably won't help you and sounds like you'll get dyskinesia.
you need a constant concentration of C/L in your system and that happens with regular C/L by taking a smaller dose more often or adding an agonist and/or a drug such as azilect or entacapone which increases the half-life of l-dopa.

i imagine you have tried 50/200CR extended release C/L. You can take 1.5 200CR which would be 300mg L-D0PA but with reduced bioavailability compared to regular C/L you might not get dyskinesias and might get 2.5-3hrs. if you add some fat it will slow gastric emptying which is what you want to do with CR. a cracker with margarine, or 1/2 cup of cooked oatmeal with margarine, a fish oil capsule. it should kick in in about 90minutes. i try not to take 2 CR doses in a row since it can buildup in your stomach and you get too much l-dopa so my pattern is 100mg C/L, wait 60minutes then take 50mg C/L + 50/200CR. wait 2.5 hrs, then repeat the pattern. i take the 50mg since it takes 90min for the CR to kick in and the 50mg will take 45min to kick in, just about the time the 100mg starts to wear off. this isn't a whole lot better than your drug regime, my point here is it might be worth experimenting with CR. I also take .50-.75mg mirapex during the day, .375 at night +200CR, i think the small amount of mirapex makes my OFF time less severe. eating protein of course negates the l-dopa so i either eat and suffer the inevitable off or if i have the will power eat most of my protein in the evening.

i also use a TIMEX EXPEDITION WATCH which has a repeat count down timer which i set to beep every hr, a stop watch which i set everytime i take a dose so i know when i took the last dose, and 3 timers so i can set 3 doseage times. with those functions i can be sure an alarm goes off when i should take the next dose, whether i actually take it is another thing.

Thanks for the info soccertese. On the 50/200 ER pill, it's scored to allow easier splitting of the pill. If I cut a 50/200 ER in half, then what then do I have? It seems to me that cutting a ER in half will eliminate the ER function. Does that make any sense?

Ed

no, it doesn't negate the ER function, if it did the tablet wouldn't be scored, the package insert states it can be halved but not quartered. if you chew a ER then it approximates 200mg of LDOPA and 50mg of carbidopa. the C/L is mixed up in a matrix of starches, cellulose, maybe wax, so the matrix is maintained when split.

with ER, because it stays in your stomach longer, more of the l-dopa is broken down so it is estimated to be 60-80% bioavailable when compared to regular l-dopa.. i use the 60% number when calculating the total l-dopa i take/day, so a whole CR=120mg regular l-dopa.

no, it doesn't negate the ER function, if it did the tablet wouldn't be scored, the package insert states it can be halved but not quartered. if you chew a ER then it approximates 200mg of LDOPA and 50mg of carbidopa. the C/L is mixed up in a matrix of starches, cellulose, maybe wax, so the matrix is maintained when split.

with ER, because it stays in your stomach longer, more of the l-dopa is broken down so it is estimated to be 60-80% bioavailable when compared to regular l-dopa.. i use the 60% number when calculating the total l-dopa i take/day, so a whole CR=120mg regular l-dopa.

btw, i prefer the mylan brand which i guess isn't available due to hurricane damage in puerto rico.

alreadybutnotyet,

Welcome to the forum.

How long is it since you were diagnosed? And, how long is it since you've been having problems with your drug regimen?

In the ideal world you should discuss drug regimen issues with your doctor. But, in case he/she is unavailable to give timely advice, I raise the following points. But, please note that I am not a doctor.

200mg levodopa every 4 hours is not the same as 100mg every 2 hours. If you run the app, you will see in the output graph that the smaller, more frequent dose gives two lower peaks and its combined effect lasts longer.

As the disease progresses the gap between the "on"/"off" threshold and the dyskinesia threshold becomes smaller. Therefore, it becomes harder to go above the first threshold, while staying below the second threshold.

It would help if you kept a diary showing the times of your "on"/"off" transitions and your dyskinesia transition. It may be possible to relate those results back to your doses and also your diet.

You may be at a stage where you have to choose between being "off" and being dyskinetic.

How bad are your "offs"? For me, 12 years post diagnosis, they are not severe: my typing is much slower, but I can still walk well.

How bad is your dyskinesia? For me, I have none.

You imply in your post that you have compliance issues. Would these be worse if you had irregular doses both in size and time?

Do you have any other symptoms, such as dystonia, hypotension, falls. For me, I'm beginning to pick up troublesome leg cramps.

The process to follow is then one of two dimensional titration (both dose size and dose timing).

I would start by changing a single dose of just one of the IR tablets.

John

Hi alreadybutnotyet,

The posts from johnt and soccertese are quite comprehensive, but I think I've managed to come up with a small contribution as well.

As soccertese said, timers/alarms can help you take your medications at the right time. My advice is to get the timing sorted out first (with timers/alarms), and then see if you still have a problem. If you then think you need to increase your dose (and if your tablets are double scored) you could try 1.25 tablets every 2 hrs (since 1.5 tablets every 2 hrs causes you to get dyskinesia).

I take three quarters of a Madopar 125 tablet 6 times a day. These tablets are double scored, and I have a pill cutter. I also have a 7-compartment pill container that I load up with my 6 doses each evening (ready for the next day) so all my pill cutting gets done in one session. I have 6 alarms set up on a smartphone to control the timing during the day.

Jeff

Hi John,

I was officially diagnosed in December 2012, although looking back on it, there were signs of a problem 2 or 3 years before then. I expect many folks experienced that as well. My drug regimen hasn't really been a big issue in the past. My 50/200 during the night has worked well. The Azilect doesn't really seem to do much of anything (at least that I can perceive), and I'd like to get off of it if possible. The Amantadine is supposed to help with my dyskinesias but it causes insomnia so I have to be careful. So the main area of concern is with the sinemet 25/100. I go see my doctor in a few weeks and I'm sure we can get something that works better than what I have now. Perhaps it's just the progression of PD and the changes that come with it/

I try really hard to keep on top of my meds. I have 3x5 Index cards that I use to write down when my 2 hour med schedule blocks are, when I actually take them, when to eat and so on. I also set alarms on my cell phone to remind me. That's worked fairly well for me. What happens though is that all too often I get caught up in something I'm working on or involved with, and when the timer goes off, I just reach over and instinctually turn it off and go back to whatever I was working on. Shortly thereafter I realize what I've done and now I don't remember if I took my pill or not (and all that goes along with that). I think a good portion of is just my forgetfulness and failing to keep on top of things.

My dyskinesias range from mild to moderate. Stress and the amount of sleep I get are big drivers for them. It's about the same for my offs as well. My only other serious symptom is some Bradykinesia in my left arm and hand.

alreadybutnotyet said: "... when the timer goes off, I just reach over and instinctually turn it off and go back to whatever I was working on."

I do this sometimes as well, but in my case (at the present time) the consequences seem to be less severe. You could of course press the snooze button instead of the cancel button.

alreadybutnotyet said: "Shortly thereafter I realize what I've done and now I don't remember if I took my pill or not ..."

A multi-compartment pill container should solve this problem.

So you're saying that half of a 50/200 ER is about 60% of a regular (non-cut) 50/200 ER? Is that the half-life of the pill? What parameter is reduced? Is it the length of time the drug is effective? Sorry for the confusion. My amantadine (1/2 tablet twice a day) makes my short-term memory problems worse.

App
 

Hi John,

Can you run my med regimen? I'm curious to see what it yields. My computer skills are shot so I need assistance.

Thank you.

y current med list:


Azilect 1 mg tab. Take 1 tab in every morning at wake-up.

Amantadine, 100 mg tablet. Take 1/2 tab at 5:30 AM and 1/2 tab at 11:30 AM.

Sinemet 25-100 tab. Take 1 tab at 5:30 AM (wake-up) and 1 tab at 7:30 AM, 9:30 AM, 11:30 AM, 1:30 PM, 3:30 PM, 5:30 PM, 7:30 PM, 8:30PM and 9:30PM (bed time).

Sinemet ER 50-200 tablet (during the night). Take one tab at 9:00PM (bed time) and one tab at 1:30 AM.

[QUOTE=alreadybutnotyet;1252687]So you're saying that half of a 50/200 ER is about 60% of a regular (non-cut) 50/200 ER? Is that the half-life of the pill? What parameter is reduced? Is it the length of time the drug is effective? Sorry for the confusion. My amantadine (1/2 tablet twice a day) makes my short-term memory problems worse.[/QUOTEt

taking the 2 halves of a 50/200CR has the same affect as taking the whole pill. if you chewed that pill the affect would approximate (2) 25/100. i see you are already taking a CR at night so you could play around with adding CR, subtracting 25/100 during the day.
i'm not a doctor so do this at your own risk or talk to your doctor, best to test on the weekends. i think a lot of md's don't recommend CR during the day for advanced pd'ers since it can be unpredictable and build up later in the day. like i mentioned before, i'll take 100-150mg of 25/100IR(immediate release) in the morning to get a jump start, an hr later 50mg of IR +50/200CR. This might last me 3hrs, i'll follow with 100mg and repeat the pattern just once or twice, i don't want to take more than 3 50/200's during the day.

just got an RX for 25/250 C/L. This gives me more options, split to get 125mg and 62.5mg when i split the 125. it has only 1 score but splits pretty ok into qtrs, pill is blue, the mylan brand. i've tried the 25/250 an hr after eating some protein (no will power) and it kicked in in an hour. fwiw, it's cost to a pharmacy is not much more than 25/100 and even though there is less carbidopa, if your're taking 1000mg combined IR and CR like i am probably doesn't matter. so even if you paid for the rx out of pocket it would be a cheap reserve.

Hi Jeffrey,

I bought several of these pill organizers and they do seem to help. I need to be working on being more focused and aware of what's going on around me.

[QUOTE=soccertese;1252749]
PM sent

alreadybutnotyet,

It's good to hear that you are finding multi-compartment pill containers to be helpful.

When I started using one, I found that an unexpected benefit was that I more often took the dose as soon as the alarm sounded, rather than putting it off until later. I think this is because taking a dose is much quicker now. That is, to take a dose now, I no longer have to put on my glasses, get out the bottle of pills and the pill cutter, cut a pill into halves (and maybe quarters), and then put away the bottle of pills and the pill cutter. Taking a dose nowadays takes me about one minute!

Jeff

I've come across a paper [1], albeit nearly 10 years old, which covers some of the same ground as my minute-to minute levodopa plasma level graphing tool (see earlier posts in this thread). Mikkko et al. report empirical results of plasma levels during the course of the day for people taking 4 or 5 doses of Stalevo (levodopa, carbidopa, entacapone). Both methods show a saw-tooth pattern, related to the wax and wane of each dose.

For instance, compare their graph, Fig 2, top right, with the graph produced by the tool. (Please note that they use a different scaling factor for the y-axis). The data for this is 4 doses of 100mg Stalevo taken 3.5 hours apart.

Attachment 10229

Why is this important? Being able to visualize what is going on is a step towards controlling what is going on.

Reference:

[1] Mikko Kuoppamäki, Kirsi Korpela, Reijo Marttila, Valtteri Kaasinen, Päivi Hartikainen, et
al.. Comparison of pharmacokinetic profile of levodopa throughout the day between levodopa/carbidopa/entacapone and levodopa/carbidopa when administered four or five times daily. European Journal of Clinical Pharmacology, Springer Verlag, 2009, 65 (5), pp.443-455. <10.1007/s00228-
009-0622-y>. <hal-00534945>
https://hal.archives-ouvertes.fr/hal-00534945/document

John