Parkinson's Disease Tulip


advertisement
Reply
 
Thread Tools Display Modes
Old 05-12-2012, 08:44 AM #1
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default 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
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg
johnt is offline   Reply With QuoteReply With Quote

advertisement
Old 05-13-2012, 10:23 AM #2
arin arin is offline
Junior Member
 
Join Date: Jan 2010
Posts: 14
10 yr Member
arin arin is offline
Junior Member
 
Join Date: Jan 2010
Posts: 14
10 yr Member
Default

Hello,

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

thanks
arin is offline   Reply With QuoteReply With Quote
Old 08-23-2012, 08:23 PM #3
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default

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
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg
johnt is offline   Reply With QuoteReply With Quote
Old 08-25-2012, 06:53 PM #4
paula_w paula_w is offline
In Remembrance
 
Join Date: Aug 2006
Location: Florida
Posts: 3,904
15 yr Member
paula_w paula_w is offline
In Remembrance
 
Join Date: Aug 2006
Location: Florida
Posts: 3,904
15 yr Member
Default this is useful

Quote:
Originally Posted by johnt View Post
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 Ki
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
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
__________________
paula

"Time is not neutral for those who have pd or for those who will get it."
paula_w is offline   Reply With QuoteReply With Quote
Old 09-06-2012, 06:52 PM #5
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default

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
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg
johnt is offline   Reply With QuoteReply With Quote
Old 06-27-2013, 04:41 PM #6
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default

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
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg
johnt is offline   Reply With QuoteReply With Quote
Old 08-01-2013, 06:44 PM #7
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default

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.

LEDDyDX.png

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
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg
johnt is offline   Reply With QuoteReply With Quote
"Thanks for this!" says:
badboy99 (11-06-2014), Bogusia (08-01-2013), dilmar (01-25-2014), lab rat (08-01-2013)
Old 01-24-2014, 04:19 PM #8
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default

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
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg
johnt is offline   Reply With QuoteReply With Quote
"Thanks for this!" says:
dilmar (11-02-2014), lab rat (01-28-2014)
Old 11-05-2014, 07:15 PM #9
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default

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
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg

Last edited by johnt; 11-05-2014 at 07:23 PM. Reason: Typo
johnt is offline   Reply With QuoteReply With Quote
Old 03-25-2015, 04:48 PM #10
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default

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
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg
johnt is offline   Reply With QuoteReply With Quote
"Thanks for this!" says:
wendy s (11-22-2016)
Reply

Tags
conversion factor, dose, equivalency, levodopa

Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is On
HTML code is Off


Similar Threads
Thread Thread Starter Forum Replies Last Post
How much levodopa are you on? Jim091866 Parkinson's Disease 28 08-28-2012 02:12 AM
IM levodopa Jim091866 Parkinson's Disease 1 02-13-2012 08:59 PM
For those of you on levodopa caldeerster Parkinson's Disease 8 06-27-2011 10:50 AM
Drug interactions of Coumadin, Comtan, Carbidopa And Levodopa, Carbidopa And Levodopa lou_lou Parkinson's Disease 0 06-23-2011 11:50 PM
Double dose Copaxone more effective than single dose xo++ Multiple Sclerosis 6 10-01-2006 03:25 AM


All times are GMT -5. The time now is 10:42 AM.

Powered by vBulletin • Copyright ©2000 - 2024, Jelsoft Enterprises Ltd.

vBulletin Optimisation provided by vB Optimise v2.7.1 (Lite) - vBulletin Mods & Addons Copyright © 2024 DragonByte Technologies Ltd.
 

NeuroTalk Forums

Helping support those with neurological and related conditions.

 

The material on this site is for informational purposes only,
and is not a substitute for medical advice, diagnosis or treatment
provided by a qualified health care provider.


Always consult your doctor before trying anything you read here.