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A Review of the First Transdermal Treatment for Alzheimer’s Disease – The Rivastigmine Patch
open-label extension was good. Switching directly to the target should undergo four weeks of 4.6mg/24-hour patch treatment before
9.5mg/24-hour patch upon entering the open-label extension was well- increasing to the 9.5mg/24-hour patch (see Figure 2).
25
tolerated in patients receiving any form of rivastigmine treatment
(capsule or patch) during the double-blind study. During weeks one to Pharmacokinetic studies suggest that the starting-dose 4.6mg/24-hour
four following the switch, ≤2.5% of patients reported nausea and ≤1.9% patch provides similar exposure to 6mg/day capsules.
18
This suggests,
reported vomiting.
25
for the handling of treatment in clinical practice, that patients
undergoing rivastigmine patch therapy are already initiated on an
Discussion effective dose
19–21
and need just a single dose-increase step after only
One of the primary objectives for AD treatment with cholinesterase four weeks to reach the recommended therapeutic dose. Combined
inhibitors is to improve tolerability. Cholinesterase inhibitors that are with an improved tolerability profile, these results indicate that the
administered orally can sometimes lead to gastrointestinal AEs, transdermal patch may allow patients easier access to optimal
particularly nausea and vomiting, which may prevent patients from therapeutic doses and potentially improve the effectiveness of
achieving and maintaining optimal therapeutic doses in clinical practice. treatment compared with oral administration. This was reflected in the
fact that almost all patients receiving the 9.5mg/24-hour patch in the
As the first transdermal application system for cholinesterase inhibitors, double-blind phase of the IDEAL study reached their target dose
the rivastigmine patch has now been approved for the treatment of AD compared with only two-thirds of patients receiving the comparable
and PDD in various countries. Modelling analyses of pharmacokinetic capsule dose (12mg/day).
22
Easier access to the 9.5mg/24-hour patch
data showed that the 9.5mg/24-hour patch provides comparable dose raises the possibility that higher doses of transdermal
exposure to the highest doses of rivastigmine capsules (12mg/day) with rivastigmine could be a viable future option in clinical practice. Studies
a slower absorption rate and smoother pharmacokinetic profile,
18
leading investigating the comparative efficacy and safety of a 13.3mg/24-hour
to improved tolerability over that possible with oral administration.
13
patch are ongoing.
Results from the IDEAL study showed that the 9.5mg/24-hour patch
provided further clinical evidence for efficacy similar to the highest doses In summary, the published clinical data support the pharmacokinetic
of capsules, with markedly improved gastrointestinal tolerability.
22
No rationale for the rivastigmine patch, indicating that smooth and
unexpected safety or tolerability concerns were reported, resulting in a continuous delivery of rivastigmine translates into an improved
very favourable risk–benefit profile for the 9.5mg/24-hour rivastigmine tolerability profile versus conventional oral administration, while
patch. Switching directly to 9.5mg/24-hour patch treatment was well maintaining clinical effectiveness. This may allow patients easier access to
tolerated by patients previously receiving oral rivastigmine,
25
and optimal therapeutic doses, potentially improving the effectiveness of
cognitive and functional benefits of rivastigmine treatment were treatment. A transdermal patch may be the optimal way of delivering
maintained for up to one year.
25
rivastigmine in the pharmacological treatment of AD. ■
It is recommended that patients on high rivastigmine capsule doses should Acknowledgements
be switched directly to the target-dose 9.5mg/24-hour patch as a practical This review was sponsored by Novartis Pharma AG, Basel, Switzerland.
recommendation on how to manage treatment when switching from oral Editorial assistance was provided by Alpha-Plus Medical Communications
dosing to patch therapy, whereas de novo patients or those on low doses Ltd, UK.
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EUROPEAN PSYCHIATRIC REVIEW 35
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