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Transcript of Stalevo ® (levodopa / carbidopa / entacapone) Stalevo ® prescribing information is available at...
Stalevo® (levodopa / carbidopa / entacapone)
Stalevo® prescribing information is available at this meeting
Information about adverse event reporting can be found at www.yellowcard.gov.uk. Adverse events should also be reported to Orion Pharma (UK) Ltd on 01635 520300.
Contents
Traditional levodopa – strengths
Traditional levodopa – limitations of pulsatile delivery
Suboptimal levodopa delivery with disease progression
Enhancing levodopa delivery
Stalevo
Benefits of earlier enhancement of levodopa delivery
Future directions
Conclusions
Contents
Traditional levodopa – strengths
Traditional levodopa – limitations of pulsatile delivery
Suboptimal levodopa delivery with disease progression
Enhancing levodopa delivery
Stalevo
Benefits of earlier enhancement of levodopa delivery
Future directions
Conclusions
Treatment with levodopa has dramatically reduced disability and mortality associated with PD
Years since diagnosis
Pat
ien
ts w
ith
sev
ere
dis
abili
ty a
nd
dea
th (
%)
0
20
40
60
80
100
1–5 6–10 11–15
Untreated patients
Levodopa-treated patients
Hoehn and Yahr, 1967;Hoehn, 1983
PD=Parkinson’s disease
Levodopa consistently provides better symptom control compared with dopamine agonists
Improvement with levodopa:
5.9 points vs pramipexole*
(p=0.003) on total UPDRS
at 4 years
4.48 points vs ropinirole**
(p=0.008) on UPDRS motor
subscale at 5 years
2.9 points vs cabergoline***
(p<0.001) on UPDRS motor
subscale at 5 years
**Rascol et al, 2000;***Bracco et al, 2004;
*Figure adapted from Holloway et al, 2004
Pramipexole
Levodopap=0.003
–4
–2
0
2
40 10 20 30 40 50
Ch
ang
e in
UP
DR
S s
core
–16
–14
–12
–10
–8
–6
0 10 20 30 40 50
Time (months)
Levodopa versus pramipexole
UPDRS=United Parkinson’s Disease Rating Scale
Imp
rove
me
nt
Most patients eventually require the superior efficacy of levodopa for symptom control
Need for levodopa in patients initiated with a dopamine agonist (pramipexole)*
16%
23%
59%
46%
Pat
ien
ts r
equ
irin
g
sup
ple
men
tal l
evo
do
pa
(%)
0
10
20
30
40
50
60
70
1 2 3 4
*Figure adapted from PSG, 1997;**Figure adapted from Holloway et al, 2004
Need for levodopa in patients initiated with a monoamine oxidase inhibitor
(selegiline)**
Years after randomization
Pro
bab
ility
of
req
uir
ing
le
vod
op
a th
erap
y (%
)
Months after randomization
60
40
20
0
0 6 12 18 24
Levodopa provides better overall short-term tolerability vs dopamine agonists
Dopaminergic
adverse event
Pergolide vs
levodopa (%)
Pramipexole vs
levodopa (%)
Ropinirole vs
levodopa (%)
Nausea 41 vs 21* 36 vs 37 49 vs 49
Somnolence 10 vs 5 32 vs 17* 27 vs 19
Oedema 5 vs 1* 18 vs 8* 14 vs 6
Hallucinations 3 vs 0* 9 vs 3* 17 vs 6
PSG, 2000;Oertel et al, 2006;
Rascol et al, 2000;Weintraub et al, 2006
* Significantly less with levodopa vs dopamine agonist (p<0.05)
Contents
Traditional levodopa – strengths
Traditional levodopa – limitations of pulsatile delivery
Suboptimal levodopa delivery with disease progression
Enhancing levodopa delivery
Stalevo
Benefits of earlier enhancement of levodopa delivery
Future directions
Conclusions
Traditional levodopa therapy is associated with the development of motor complications
Figure adapted from Obeso et al, 2000
Early disease• Smooth, long duration of
clinical benefit• Low incidence of
dyskinesias
Mid-stage disease• Diminished duration of
clinical benefit• Increased incidence of
dyskinesias
Advanced disease• Clinical response mirrors
levodopa plasma pharmacokinetic profile
• ‘On’ time is associated with dyskinesias
Time (hours)
Levodopa2 4 6
Cli
nic
al
eff
ec
t
Levodopa2 4 6
Cli
nic
al
eff
ec
t
Levodopa2 4 6
Cli
nic
al
eff
ec
t
On
Off
Response threshold
Dyskinesia threshold
In PD, traditional levodopa delivery leads to pulsatile dopamine levels in the brain
The short half-life (60–90 min) of traditional
levodopa leads to peaks and profound troughs in plasma levodopa levels which are
further worsened by intermittent dosing
Pulsatile plasma levodopa levels leads to pulsatile levels of dopamine in the brain
In PD, the ability to regulate and maintain
steady levels of dopamine in the brain is
reduced due to progressing neuronal
loss
The first manifestation of pulsatile levodopa delivery in the brain is often wearing-off
Pulsatile levels of dopamine in the brain translate into fluctuations in clinical
response
Often the first complaint patients have is that the duration of symptom control
provided by their traditional levodopa becomes shorter (‘wears-off’) and their
symptoms re-emerge before the next scheduled dose
Traditional levodopa
TimeSymptom
re-emergence
Symptoms controlled
Figure adapted from Stacy et al, 2005
The long-term consequence of pulsatile levodopa delivery in the brain is often dyskinesia
In PD, pulsatile plasma levodopa levels translates into pulsatile levels of dopamine in the brain
Pulsatile stimulation of striatal dopamine receptors
Further destabilization of an already unstable basal ganglia
Dyskinesia
Contents
Traditional levodopa – strengths
Traditional levodopa – limitations of pulsatile delivery
Suboptimal levodopa delivery with disease progression
Enhancing levodopa delivery
Stalevo
Benefits of earlier enhancement of levodopa delivery
Future directions
Conclusions
Constant levels of dopamine are vital for normal movement
In the brain, constant levels
of dopamine are required to
Regulate cortical excitation
of striatal neurons
Stabilize the firing rate and
excitability of striatal
neurons
Modulate plasticity of striatal
neurons (long-term
potentiation)
Olanow et al, 2006
Striatum
Substantia nigra
Excitatory cortical input
Normal motor function
Dopaminergic
regulatory input
Basal ganglia
In PD, pulsatile delivery of traditional levodopa leads to pulsatile stimulation of dopamine receptors
Traditional levodopa
Activated
Unactivated
Normal
PD (untreated)
Traditional levodopa
Substantia nigra
Striatum
Dopamine receptor state
Nigrostriatal neuronsdegenerate
Activated
Unactivated
Activated
Unactivated
In PD, pulsatile delivery of traditional levodopa leads to pulsatile stimulation of the dopamine receptors
Olanow et al, 2006
Normal Movement
Parkinsonian State
Parkinsonian State with Intermittent Levodopa
Parkinsonian State with Continuous Levodopa
In PD patients with motor complications, fluctuations in brain dopamine levels correspond to levels of levodopa
Baseline 1 hourafter oral levodopa
4 hoursafter oral levodopa
De la Fuente-Fernández, et al. 2001
Pu
tam
en r
aclo
pri
de
bin
din
g p
ote
nti
al(r
esp
on
se t
o le
vod
op
a)
Incr
easi
ng
syn
apti
c d
op
amin
e le
vels
In PD, pulsatile stimulation causes further changes in gene expression in the already unstable basal ganglia
Pre-proenkephalin B (marker for dyskinesia) mRNA expression in the caudate-putamen
Henry et al, 2003
Non-parkinsonian patient PD patient with dyskinesia
Pulsatile stimulation leads to gene changes in the basal ganglia of MPTP primates whereas continuous stimulation does not
Normal Pulsatile stimulation Continuous stimulation
Pre-proenkephalin-B (PPE-B; marker for dyskinesia) mRNA expression in the striatum
High
Low
Reproduced with permission from Peter Jenner
Contents
Traditional levodopa – strengths
Traditional levodopa – limitations of pulsatile delivery
Suboptimal levodopa delivery with disease progression
Enhancing levodopa delivery
Stalevo
Benefits of earlier enhancement of levodopa delivery
The patient’s perspective
Conclusions
Oral levodopaAfter 6 months levodopa infusion
Pla
sma
levo
do
pa
con
cen
trat
ion
(n
g/m
l)
0
1000
2000
3000
4000
5000
09.00 11.00 13.00 15.00 17.00 19.00
Time of day
Continuous delivery of levodopa by infusion reverses motor complications
Figure adapted from Stocchi et al, 2005
p<0.001
0
1
2
3
4
5
6
7
8
9
Off-time (h/day)
Dyskinesia score (AIMS)
p<0.001
AIMS=Abnormal Involuntary Movement Score
But infusion is impractical
Avoiding deep troughs in levodopa plasma levels may be more important than providing smooth delivery
Pharmacokinetic analysis of levodopa infusion versus traditional
oral therapy found:
Significantly higher trough levels (Cmin), bioavailability (area under
the curve) and plasma concentrations with infusion
No significant differences in plasma variability (Cmax – Cmin)
Therefore, maintaining completely smooth plasma levodopa
levels may not be as important as avoidance of deep trough
levels (minimum threshold level)
Stocchi et al, 2005
Increasing traditional levodopa dose frequency does not address pulsatility
0
500
1000
1500
2000
2500
3000
8 10 12 14 16 18 20Lev
od
op
a p
lasm
a le
vels
(n
g/m
l)
Levodopa administration
0
500
1000
1500
2000
2500
3000
7 9 11 13 15 17 19 21
5-hour intervals 3-hour intervals
Trough
TroughTrough
Time of day
Stocchi, 2006
Adherence is an important issue in PD and may contribute to pulsatile stimulation
% p
atie
nt
com
plia
nce
wit
h
levo
do
pa
reg
imen
“Poor timing compliance was universal…suggesting that erratic
drug-taking is the norm rather than the exception in PD.”
“Given the significance attached to pulsatile stimulation of dopamine receptors…this
suggests that irregular medication maybe... as significant as variable absorption in day-
to-day and longer-term fluctuations”
Figure adapted from Grosset et al, 2005
Timing of medication
Total Daily
100
80
60
40
20
0
Therefore, increasing the frequency of traditional levodopa dosing leads to variable control and increased risk of peak dose dyskinesia
Decrease interdose interval
May work in earlier stages
Variable/short-term control
Increase dosing frequency
Limited utility and complicated dosing schedule beyond five
doses per day
‘On’ dyskinesias
Traditionallevodopa
Therapeuticwindow
‘Wearing-off’
Lev
od
op
a p
lasm
a co
nce
ntr
atio
ns
(ng
/ml)
1 3 5 7 9 11 13 Time (h)
Figure adapted from Stocchi, 2006
Increasing the dose of traditional levodopa does not prevent pulsatility
Figure adapted from Stocchi et al, 2004
0
500
1000
1500
07.00 09.00 11.00 13.00 15.00
100 mg levodopa
Trough Trough
Lev
od
op
a p
lasm
a le
vels
(n
g/m
l)
Time of day
100 mg; 3-hour intervals 150 mg; 3-hour intervals
150 mg levodopa
0
500
1000
1500
07.00 09.00 11.00 13.00 15.00
Trough Trough
Therefore increasing the dose of traditional levodopa leads to variable control
Increase dose
Peak–dose dyskinesias
Variable/short-term control
Higher peakconcentrations
Traditionallevodopa
Therapeuticwindow
‘Wearing-off’
Peak–dosedyskinesias
Lev
od
op
a p
lasm
a co
nce
ntr
atio
ns
(ng
/ml)
1 3 5 7 9 11 13 Time (h)
Figure adapted from Stocchi, 2006
Controlled-release levodopa does not prevent pulsatility or motor complications
200 mg
Time of day19.0017.0015.0013.0011.0009.0007.00
2500
2000
1500
1000
500
0Lev
od
op
a p
lasm
a le
vels
(n
g/m
l)
Delayed ‘on’ due to erratic absorption
Stocchi, 2006;Figure adapted from Koller et al, 1999
% p
atie
nts
wit
h m
oto
r co
mp
lica
tio
ns
20
15
10
5
0
0 1 2 3 4 5Year
Traditional levodopa
Controlled-release levodopa
Trough
Controlled-releaseformulations
Delayed ‘on’ or occasional lack of ‘on’ response with
advancing disease
Variable/short-term control
Unpredictabledrug absorption
Therefore, use of controlled-release formulations leads to unpredictable absorption and variable control
‘On’dyskinesias
Traditionallevodopa
Therapeuticwindow
‘Wearing-off’
Lev
od
op
a p
lasm
a co
nce
ntr
atio
ns
(ng
/ml)
1 3 5 7 9 11 13 Time (h)
Stocchi, 2006
Fariello, 1998
Dopamine agonists do not alter the pharmacokinetic profile of levodopa
Pla
sma
con
cen
trat
ion
so
f le
vod
op
a (m
g/l
)
Time (min)
1.2
0
0.2
0.4
0.6
0.8
1.0
0 60 120 180 240 300 360 420 480
LevodopaLevodopa + cabergoline
How can we try to mimic infusion with oral therapy?
Contents
Traditional levodopa – strengths
Traditional levodopa – limitations of pulsatile delivery
Suboptimal levodopa delivery with disease progression
Enhancing levodopa delivery
Stalevo
Benefits of earlier enhancement of levodopa delivery
The patient’s perspective
Conclusions
Gordin et al, 2004
Compared with traditional levodopa, Stalevo has a longer levodopa plasma half-life with increased levodopa uptake to the brain
DDC=dopa decarboxylaseCOMT=catechol-O-methyltransferase
Stalevo enhances the pharmacokinetics of levodopa
0
0.5
1.0
1.5
2.0
2.5
0 1 2 3 4
Time (h)
Pla
sma
levo
do
pa
(µg
/ml)
Traditional levodopaStalevo
Time by which the half-life of levodopa is extended
Gordin et al, 2004
Dual DDC/COMT inhibition increases levodopa uptake into the brain
Sawle et al, 1994
DDC=dopa decarboxylaseCOMT=catechol-O-methyltransferase
Carbidopa Carbidopa/entacapone
Stalevo delivery strives to mimic infusion
08.00 10.00 12.00 14.00 16.00 18.00 20.000
1000
2000
3000
4000
5000
Figure adapted from Stocchi et al, 2005;Figure adapted from Stocchi, 2006
0
1000
2000
3000
4000
5000
09.00 11.00 13.00 15.00 17.00 19.00
Pla
sma
levo
do
pa
con
cen
trat
ion
(n
g/m
l)
Time of day
Traditional levodopaAfter 6 months levodopa infusion
Traditional levodopaStalevo
ONOFF
** 200 mg †100mg
† † † †
Immediate benefits versus traditional levodopa: more time without symptoms
Stalevo/LCE Traditional levodopa plus placebo
Ch
ang
e in
dai
ly ‘
on
’ ti
me
(h)
·
····
·
p<0.001p<0.001
B 2 4 8 16 24 Withdrawal
Time (weeks)
–0.5
0
0.5
1.0
1.5
2.0
Figure adapted from Rinne et al, 1998
Mean daily time without symptoms (‘on’ time) increased by up to 1.7 hours versus baseline
Immediate benefits versus traditional levodopa: improved activities of daily living
Poewe et al, 2002Time (months)
0
0 1 2 3 4 5 6
AD
L s
core
11
12
13
14
10
9
8
76
5
4
2
1
3
Stalevo/LCE Traditional levodopa plus placebo
Difference between the groups was p<0.05
Immediate benefits versus traditional levodopa: improved motor scores
Rinne et al, 1998
–4
–3
–2
–1
0
1
2
3
4
5
Traditional levodopa plus placebo
Stalevo/LCE
Cha
nge
in m
otor
sco
res
Wo
rsen
ing
Imp
rove
me
nt
p<0.05
Long-term benefits: sustained patient function for at least 3 years
UP
DR
S
Larsen et al, 2003;Goetz et al, 2000
40.8
10.5
28.4
41.7
10.8
29.0
0
5
10
15
20
25
30
35
40
45
Total score ADLscore
Motor score
Baseline
After 3 years Stalevo/LCE
Long-term benefits: sustained efficacy versus baseline for at least 5 years
Nissinen et al, 2006 Poster
Ch
ang
e fr
om
bas
elin
e in
du
rati
on
o
f b
enef
it o
f m
orn
ing
do
se (
hrs
)
0
1
B 3 6 9 12 16 20 24 28 32 36 40 44 48 52 56
Month
Stalevo/LCE
Long-term benefits: no need to increase the levodopa dose for at least 3 years
400
600
800
1000
0 6 18 42
Months
Lev
od
op
a d
ose
(m
g)
Double-blind(NOMECOMT)
Open-label(NOMESAFE)
Washout
Larsen et al, 2003
Stalevo/LCE
Stalevo/LCE and its benefits
Immediate benefitsMore time without symptoms
Mean daily ‘on’-time increased by up to 1.7 hours
Better patient functionMean ADL scores improved by up to 1.7 pointsMean motor scores improved by up to 3.2 points
Long-term benefitsSustained patient function through 5 yearsNo increase in mean levodopa dose over baseline
Parkinson Study Group, 1997; Myllyla et al. 2001; Poewe et al. 2002;Rinne et al. 1998;
Brooks et al. 2003; Larsen et al, 2003;
Nissinen et al, 2006
Stalevo provides significantly improved QoL compared with standard of care
The cost-effectiveness of
Stalevo was compared with UK
standard of care
Patients on Stalevo had
significantly improved QoL
(+1.04 QALYs)
The costs to society decreased
by £10,200/patient/10 years
This decrease was mainly due
to savings in social service
costs and secondary care
Societal perspective
Cost (£) QALYs
Stalevo 59,563 2.571
Standard of care 69,761 1.529
Difference:
Stalevo standard of
care
10,198 1.042
Findley et al, 2005QUALY: quality-adjusted life-years
Contents
Traditional levodopa – strengths
Traditional levodopa – limitations of pulsatile delivery
Suboptimal levodopa delivery with disease progression
Enhancing levodopa delivery
Stalevo
Benefits of earlier enhancement of levodopa delivery
Future directions
Conclusions
Patients can require enhancement of traditional levodopa therapy within only 6 months
In the ELLDOPA study, patients initiated with traditional
levodopa (150–600 mg) experienced:
Wearing-off (16–30%)
Dyskinesia (3–17%)
The time of onset for these complications was only 5–6 months
after initiation of traditional levodopa therapy
Fahn et al, 2004;Fahn, 2005
In de novo disease, early initiation of effective therapy provides long-term benefits vs no treatment
“We suggest that early restoration of basal ganglia physiology will support the compensatory events and delay the irreversible modification of circuitry that characterizes the clinical progression of PD”
Schapira and Obeso 2006
Fahn et al, 2004; PSG, 2004; Schapira and Obeso, 2006
Levodopa
Ch
ang
e in
to
tal U
PD
RS
sco
re (
un
its)
Weekof study drug
Baseline
2 6 10 14 18 22 26 30 34 38 42 46
12
10
8
6
4
2
0
–2
–4
–6
–8
Placebo
150 mg
300 mg
600 mg
Withdrawal
2 6 10 14 18 22 26 30 34 38 42 46
12
10
8
6
4
2
0
–2
–4
–6
–8
Placebo
150 mg
300 mg
600 mg
Years
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0
0
10
20
30
40
50
60
70
80
90
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0
0
10
20
30
40
50
60
70
80
90
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.00.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.00.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0
0
10
20
30
40
50
60
70
80
90
0
10
20
30
40
50
60
70
80
90
0
10
20
30
40
50
60
70
80
90
Delayed start
Early start*
* *
*
*
*
NS
NS
NS NS
NS
NS
(n=404) (n=324) (n=272) (n=237) (n=206) (n=164)
Mea
n %
ch
ang
e in
to
tal U
PD
RS Rasagiline
Starting Stalevo/LCE without delay provides superior motor scores at 1 year
• At 1 year, earlier initiation of Stalevo/LCE provided significantly better motor
function compared with a 6-month delay (treatment difference –1.33 points,
p<0.05)
–4.0
–2.0
0.0
2.0
Baseline (n=484)
3 (n=476)
6 (n=479)
9 (n=445)
12 (n=410)
Months
Ch
ang
e in
UP
DR
S II
I sco
res
Stalevo/LCETraditional levodopa plus placebo
Nissinen et al, 2006 UPDRS III: Unified Parkinson’s Disease Rating Scale
Imp
rove
me
nt
Contents
Traditional levodopa – strengths
Traditional levodopa – limitations of pulsatile delivery
Suboptimal levodopa delivery with disease progression
Enhancing levodopa delivery
Stalevo
Benefits of earlier enhancement of levodopa delivery
Future directions
Conclusions
The benefit of starting Stalevo/LCE without delay is sustained over 5 years
The significant difference in UPDRS III scores between the early and delayed start groups
was maintained through the study period
This suggests that enhancing levodopa earlier, even by 6 months
(e.g. only one office visit), can have clinically significant long-term benefits
–6.0
0.0
6.0
12.0
18.0
Baseline(n=484)
1(n=410)
2(n=101)
3 (n=90)
4 (n=44)
5 (n=37)
Years
Ch
ang
e in
UP
DR
S II
I sco
res
Stalevo/LCETraditional levodopa plus placebo
Imp
rove
me
nt
Nissinen et al, 2006
The MPTP primate model of PD has been very predictive of clinical outcomes in idiopathic PD
Years
Pro
po
rtio
n o
f p
atie
nts
re
mai
nin
g f
ree
of
dys
kin
esia
0.0
0.2
0.4
0.6
0.8
1.0
0 1 2 3 4 5
RopiniroleTraditional levodopa
Dys
kin
esia
sco
re
Days
MPTP model Idiopathic PD
0
1
2
3
4
1 8 15 22
Rascol et al, 2000; Maratos et al, 2001 MPTP: 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine
Studies in MPTP primates show the potential of early initiation of Stalevo/LCE to avoid dyskinesia induction
Studies conducted in the MPTP-
treated primate model of PD
Compared with traditional levodopa,
Stalevo/LCE (4x/day)
Significantly improves the
antiparkinsonian response
Significantly decreases in intensity
and duration of peak dyskinesia
†p<0.05
† †Pea
k d
yski
nes
ia
Smith et al, 2005
0
1
2
3
4
1 4 7 10 13 16
Stalevo/LCE (4x/day)
Traditional levodopa (4x/day)
MPTP: 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine
0
25
50
100
10
% n
igra
l neu
ron
s re
mai
nin
g
0
1
2
3
4
Pea
k d
yski
nes
iaTrad
levodopa LCE
90% MPTP-induced lesion
0
1
2
3
4
Pea
k d
yski
nes
ia
Tradlevodopa
4x/day dosing
LCE
50% MPTP-induced lesion 75% MPTP-induced lesion
0
1
2
3
4
Pea
k d
yski
nes
ia
Tradlevodopa
LCE
LCE has a lower risk of dyskinesia induction vs traditional levodopa, regardless of parkinsonian severity in the MPTP primate model of PD
p<0.05
4x/day dosing
4x/day dosing
MPTP: 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine Jenner et al, 2006
FIRST-STEP: an ongoing clinical study to confirm the efficacy of Stalevo in de novo* disease
Aim:
To evaluate the effect of Stalevo 100 (3x/day) versus traditional
formulation levodopa/carbidopa 100/25 mg (3x/day) in PD
patients requiring levodopa therapy
Hauser, 2006
*De novo use of Stalevo is not currently licensed
STRIDE-PD: an ongoing clinical study to confirm the potential of Stalevo to avoid dyskinesia induction
Aim:
To demonstrate that when used as initial levodopa therapy*,
Stalevo results in a significant prolongation in the time to onset
of dyskinesia when compared with traditional formulation
levodopa/carbidopa in PD
With comparable symptom control
With similar QoL
*De novo use of Stalevo is not currently licensedOlanow, 2006
Contents
Traditional levodopa – strengths
Traditional levodopa – limitations of pulsatile delivery
Suboptimal levodopa delivery with disease progression
Enhancing levodopa delivery
Stalevo
Benefits of earlier enhancement of levodopa delivery
Future directions
Conclusions
Conclusions I
Compared with other antiparkinsonian therapies, levodopa has superior efficacy and short-term tolerability
However, traditional levodopa therapy is often spared due to concerns about the development of motor complications
The pulsatile stimulation of dopamine receptors caused by traditional levodopa is an important factor in the development of these complications
Infusion data show that consistent delivery of levodopa reverses established complications, even though high doses are used
Modification strategies fail to address the pulsatility of traditional levodopa and therefore frequent changes are often required
Conclusions II
Stalevo provides oral levodopa in a manner which strives to
mimic infusion
In fluctuating patients, enhancing levodopa delivery with Stalevo
significantly improves patient function
This benefit is sustained for at least 5 years
Initiating Stalevo 6 months earlier may lead to long-term
benefits in patient function
STA2456; Item date November 2006
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Prescribing information available at this meeting
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Optimization of levodopa delivery I
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Stalevo and its benefits II
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Stalevo and its benefits IV
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Benefits of earlier optimization of levodopa delivery
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Future directions I
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Future directions II
STA2637; Item date April 2007