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

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