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Clinical Benefits Associated with a Transdermal Patch for Dementia
be maintained within the theoretical optimal ‘therapeutic window’, with
Table 1: Potential Non-pharmacological Benefits of
smaller fluctuations between peaks and troughs that may be associated
Patches for the Treatment of Dementia
with side effects and reduced efficacy, respectively.
16,17
Bioavailability
following transdermal administration has repeatedly been shown to be
Drug delivered smoothly and continuously
Sustained therapeutic drug levels in the plasma
greater than with oral delivery for some drugs.
18
A drug released across
Reduced systemic adverse events
the skin directly into the bloodstream is free from interactions in the
Easier access to optimal target doses
gastrointestinal tract and bypasses first-pass metabolism in the liver.
Avoids the gastrointestinal tract
In the case of rivastigmine, pharmacokinetic data have shown that drug Independent of food intake – no need to administer at mealtimes
exposure in the brain over 24 hours with the target-dose patch (9.5mg/
Avoids first-pass effect
24-hour), despite being lower at face value, is comparable to that provided
Simple and convenient
by 12mg/day capsules.
19
The pharmacokinetic rationale and clinical data
Small and discreet*
Once daily*
supporting the development of the rivastigmine patch is discussed in more
Easy to apply
detail by Frölich elsewhere in this issue of European Neurological Review.
20
Comfortable to wear
One-step to target dose*
The rivastigmine patch allows easy access to the therapeutic dose, with a Empowers the care-giver
simple one-step dose increase from the starting dose patch (4.6mg/ Visual reminder to treat and reassurance that medication is being taken
24-hour) to target-dose patch (9.5mg/24-hour).
21
While it has been
Avoids accidental overdosing
established that the target-dose rivastigmine patch (9.5mg/24-hour)
Compatible with magnetic resonance imaging procedures*
Easily removed in the event of an emergency
offers comparable drug exposure and similar efficacy to the maximum
Tactile experience may enhance patient–care-giver relationship
recommended oral dose of 12mg/day rivastigmine capsules,
19,22
the
*Applies specifically to the rivastigmine transdermal patch.
starting-dose patch (4.6mg/24-hour) provides comparable drug exposure
to an oral dose of 6mg/day.
19,20
Rivastigmine oral 6mg/day has been (e.g. those used for pain control), the rivastigmine patch does not contain
previously demonstrated in large clinical trials to be an effective dose,
23,24
any metallic elements, which means that it may be worn by patients even
suggesting that using the rivastigmine patch allows patients to start on in the event that they need to undergo magnetic resonance imaging (MRI)
an effective dose straight away. Patients may derive benefit from an procedures. Thus, the rivastigmine patch should not interfere significantly
effective dose immediately during the titration phase of treatment, with daily living. Patches offer a visual reminder to treat, and application of
before increasing to the target-dose rivastigmine patch (9.5mg/24-hour). a once-daily patch can be made part of the daily routine, e.g. when
dressing each morning.
7
This may help to address the common problem of
Clinical data from a trial involving more than 1,000 AD patients forgetting to apply the patch. Non-pharmacological benefits associated
demonstrated that the rivastigmine patch was associated with three times with transdermal patches versus conventional oral therapies for the
fewer reports of nausea and vomiting compared with conventional treatment of dementia are summarised in Table 1, all of which may
capsules.
22
In fact, the incidence of cholinergic side effects was not contribute to improved treatment compliance overall.
7
significantly different among patients treated with the 9.5mg/24-hour patch
and those receiving placebo. Moreover, the proportion of patients receiving The use of a transdermal patch in dementia may have further advantages
optimal target doses was substantially higher among those in the 9.5mg/ (versus conventional oral treatments) in terms of patient–care-giver
24-hour patch group of that study compared with those in the 6mg twice a communication and care, since the application of a patch is a tactile
day capsule group (96 and 64% of patients, respectively).
21
experience for both the patient and the care-giver.
26,27
A patch offers
care-givers empowerment in their role of administering and managing
Staying on Treatment medications, and encourages positive care-giver–patient interaction. This
Titration schedules for cholinesterase inhibitors and memantine are in turn may have a favourable impact on the patient.
28
complex, difficult and time-consuming for physicians to explain, and
consequently hard for patients and care-givers to understand. As stated, Preference for Patch Therapies
such difficulties often lead patients to remain on low doses that are not Transdermal patches are used as a mode of drug administration across a
efficacious. This is particularly true for oral rivastigmine, which requires range of therapeutic areas, including angina, attention-deficit–hyperactivity
twice-daily administration and a four-step titration schedule over four disorder (ADHD), contraception, hormone replacement, major depression,
months or sometimes longer. Strategies that make scheduling and pain management, PD and smoking cessation. Patients often prefer
administration of medications simpler and easier may have the potential to patches to oral therapies for their convenience, efficacy and fewer side
address some of these concerns. Patches are becoming more widely used effects.
29
A drug delivery system that is preferred for any reason is likely to
across different disease areas, and appear to offer an excellent therapeutic promote improved compliance. Rates of compliance have been reported
approach for chronic neurological disorders in the elderly, as they are to be improved with transdermal contraceptive, angina, hypertension and
undemanding and convenient to use, provide sustained therapeutic drug major depression therapies versus their oral counterparts.
30–33
levels in the plasma and usually reduce systemic adverse events.
7,25
A unique aspect of dementia treatment is the integral role that care-givers
The once-daily rivastigmine transdermal patch is easy to apply, small, often play in the management of the disease. Considering that the majority
discreet and comfortable to wear, requires only a one-step increase to of patients (~75%) require assistance with the management and/or
target dose, adheres well over the 24-hour application period (while administration of medications,
34
compliance to treatment is often care-giver-
maintaining normal daily activities including bathing and swimming) and is driven. Given that care-givers of individuals with AD are often older people
associated with good skin tolerability.
22
Unlike other transdermal patches themselves with their own medical conditions and drugs to manage, this
EUROPEAN PSYCHIATRIC REVIEW 25
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