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Rotigotine for the Treatment of Advanced Parkinson’s Disease
Figure 1: Change in Daily Time Spent in OFF or ON with Figure 2: Change in Unified Parkinson Disease Rating
or without Troublesome Dyskinesia Scale Scores
3 0
*
2
-2
1 *
-4
*
*
0
-6
-1
-8
Change from baseline in time (hours)
-2
Change from baseline score
*
* *
*
-10
-3
* *
LeWitt Poewe LeWitt Poewe LeWitt Poewe
et al., 2007 et al., 2007 et al., 2007 et al., 2007 et al., 2007 et al., 2007
-12
Daily OFF time Daily ON time without Daily ON time with LeWitt et al., 2007 Poewe et al., 2007 LeWitt et al., 2007 Poewe et al., 2007
troublesome dyskinesia troublesome dyskinesia
UPDRS II (ADL) UPDRS III (Motor)
Pramipexeole Rotigotine Placebo
Pramipexeole Rotigotine Placebo
Change is with respect to baseline in advanced Parkinson’s disease patients on placebo,
Change is with respect to baseline in advanced Parkinson’s disease patients on placebo,
40 39
pramipexole or rotigotine as reported by Poewe et al., 2007 or LeWitt et al., 2007. 40 39
pramipexole or rotigotine as reported by Poewe et al., 2007 or LeWitt et al., 2007.
Only results obtained with the highest tolerable dose are shown. *p<0.01 versus placebo.
Only results obtained with the highest tolerable dose are shown. *p<0.01 versus placebo.
ADL = activities of daily living; UPDRS = Unified Parkinson Disease Rating Scale.
Table 3: Frequency of Dopaminergic Adverse Events in Major Clinical Trials in Advanced Parkinson’s Disease
LeWitt et al., 2007
39
Poewe et al., 2007
40
Placebo Rotigotine Placebo Rotigotine Pramipexole
(n=120) ≤12mg/24 hours (n=101) ≤16mg/24 hours ≤4.5mg/day
(n=111) (n=204) (n=201)
Constipation 6 5 – – –
Dizziness 15 15 4 6 10
Dyskinesia 7 17 3 12 15
Hallucinations 3 14 1 5 7
Nausea 20 24 11 17 13
Vomiting –– –
Orthostatic hypotension 7 2 5 3 5
Peripheral oedema <1 14 – – –
Somnolence 28 32 8 12 12
All figures are percentages.
Clinical studies in early and advanced PD showed rotigotine to be rotigotine).
40,46
SAEs in rotigotine patients included nausea, dyskinesia,
generally safe and well tolerated, with most adverse events (AEs) syncope, tachycardia, atrial fibrillation and application-site reactions.
40
being mild or moderate in severity and occurring transiently. Pooled
data from placebo-controlled studies in advanced PD found that the Overall, application-site reactions were cited as the most common
most common AEs, reported by ≥10% of patients, were nausea, AEs in rotigotine clinical studies. As many as half of rotigotine patients
dizziness, somnolence and application-site reactions.
17
The occurrence had application-site reactions (including erythema, pruritus and
of dopamine-related AEs, which are shown in Table 3, appeared to be dermatitis), in comparison with 4–21% of patients receiving placebo
dose-related in some cases (e.g. nausea and somnolence), and were treatment.
39,40,46–48
However, the majority of these events were rated as
most frequent during dose titration. Increased rates of hallucinations mild to moderate, and appeared to be dose-related. In total, 1–8% of
and peripheral oedema were observed with rotigotine in one study in rotigotine patients withdrew due to application-site events, and in the
advanced PD at both the 8mg/24 hours and 12mg/24 hours target PREFER study most reactions spontaneously resolved without
doses. In the comparator study, more pramipexole-treated patients necessitating a change of dose.
39,40,46–48
These types of reaction can be
than rotigotine-treated patients withdrew due to orthostatic minimised by daily switching of the site of patch application.
50
If
hypotension (five versus one) and hallucinations/confusion (four additional treatment is needed, moisturising, gentle skin care and
versus none).
40
Recently, three cases of impulse-control disorders in application of topical corticosteroids at the previous patch sites are
patients on rotigotine patches have been reported; these were recommended. Rotigotine should be discontinued if generalised skin
effectively treated by rotigotine reduction or discontinuation.
49
This reactions are observed.
alerts to the potential of rotigotine to cause these disorders, similar to
other dopamine agonists. The frequency of serious AEs (SAEs) was Withdrawal rates were as follows: 9–35% of patients discontinued
comparable to that seen with placebo (8–9% for placebo, 9–10% for treatment with rotigotine compared with 15–28% of those in the
EUROPEAN NEUROLOGICAL REVIEW
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