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New York Consortium for Alzheimer Research and Education
The New York Consortium for Alzheimer Research and Education (N.Y.C.A.R.E.) is the joint effort of
the Alzheimer’s Association New York City Chapter and the Education and Information Cores of the
Alzheimer’s Centers — Columbia University, College of Physicians and Surgeons; Mount Sinai Medical Center; and New York University School of Medicine funded by the National Institute on Aging.
Research Update
News in AD Treatment: Aricept Generic and Aricept 23 mg
Generic Aricept (Donepezil):
Is it the same as Aricept?
Patients without prescription
coverage, and those whose insurance
companies are asking them to
change to the generic, are asking
the question: Is there anything bad
about switching to generic donepezil.
Generic donepezil is available as 5
and 10 mg in both regular and orally
disintegrating tablets. The 23 mg
dose is only available as Aricept. The
generic versions currently available
have an “AB” rating by the FDA,
which means that they are considered
equivalent to the brand-name drug.
The only difference between them
and Aricept may be in the inert
ingredients (fillers, dyes, etc.) to
which a small minority of patients
may be sensitive. Bottom line: there
is no reason not to try the generic
form of Aricept.
Aricept 23
In July of 2010, the US FDA
approved a 23 mg once-daily tablet
of Aricept (donepezil). Many
patients and families have asked
whether it is appropriate for them
to try it. To answer that question we
have to examine the research.
An initial pilot study of doses of
Aricept up to 20mg, in a small trial of
31 patients was published by Doody
et al, in Drugs in Aging in 2008
showed the safety (?) and feasibility
of using these doses in patients. The
approval of Aricept 23 mg was based
on a double-blind, randomized
study, evaluating Aricept 23 mg vs.
Aricept 10 mg in 1467 patients
with moderate to severe Alzheimer’s
disease over the course of 6 months.
What they found was that the group
taking the 23 mg tablet had a small,
but significant benefit on a measure
called the Severe Impairment
Battery (SIB), compared to those
taking 10 mg. The SIB measures
performance on simple cognitive
tasks such as following directions,
simple tests of language and memory,
and recognizing objects. Scores on
the SIB can range from 0-100. The
difference in the change in scores
between the 10mg group and the 23
mg group was 2.2 points (P = .0001)
over the 6 month study period. The
other measure used in the study was
the “Clinician’s Interview-Based
Impression of Change Plus Caregiver
Input” (CIBIC plus), which measures
global function. While there was
no statistically significant difference
between the groups as a whole on
this measure, when the researchers
divided the patients into two groups
based on severity of impairment
(MMSE 0-16 vs. 17-20), they found
a greater treatment effect (about
3 points on the SIB), as well as a
statistically significant benefit in the
CIBIC plus in the more impaired
group (Fellows et al., 2010). It is
important to note that the frequency
of side effects was greater with the
Aricept 23 mg dose,, including more
cases of nausea (11.8% vs. 3.4%),
vomiting (9.2% vs. 2.5 %), diarrhea
(8.3% vs. 5.3%) and loss of appetite
(5.3% vs. 1.7%).
The question remains:
Who should try the higher
dose of Aricept?
The FDA has approved Aricept 23
mg only for patients with moderate
to severe AD. This is consistent with
the research data that showed greatest
benefit in the patients with MMSE
<16. There is currently no evidence
that this dose is more helpful in
earlier stage disease than the lower
10 mg. dose of Aricept (donepezil).
Although the combination of Aricept
23 mg and memantine (Namenda)
has not been studied, there is no
reason to think that there would be
any new concerns about using these
two medications together.
Therefore, in patients with moderate
to severe disease, who are already
stable on donepezil (Aricept) 10 mg,
it may be worth a trial of higher
dose Aricept. In those for whom
lack of insurance or prohibitive
co-pays preclude using Aricept 23
mg, a trial of higher dose (e.g., 15
mg and then increasing to 20 mg)
of generic donepezil, could be
tried. The increased incidence of
gastrointestinal side effects requires
careful observation of patients.
In general, studies of the
cholinesterase inhibitors (Aricept,
Razadyne, Exelon) were conducted
with patients in the mild to
moderate stages of Alzheimer’s
disease, These studies have all
demonstrated the efficacy of
these medications when givien in
adequate doses (e.g., 16-32 mg daily
of Razadyne (galantamine), 6-12
mg daily of Exelon (rivastigmine),
5-10 mg of Aricept (donepezil).
In an initial study of the Exelon
Patch, there was no additional
benefit from a higher dose To date there have been no published
results of trials of higher doses of
the other cholinesterase inhibitors
(Razadyne (galantamine) or Exelon
(rivastigmine) in more impaired
patients, or in those who have been
stable on the currently approved
maximal dose. There is currently
an ongoing trial of a higher dose
Exelon patch in severe AD (MMSE
3-12).
The current state of pharmacologic
treatment is modest at best. Many
research facilities around the
world, including the three ADC’s
in New York City are working
tirelessly to develop new and
improved treatments that will be
disease-modifying compounds.
Many studies are focusing on those
with mild or no symptoms who
may have risk factors for the disease.
It is hoped that this early treatment
will maximize the quality of life for
those who may be affected and their
families.
1. Farlow MR, Salloway S, Tariot PN, et al.
Effectiveness and tolerability of highdose
(23 mg/d) versus standard-dose
(10 mg/d) donepezil in moderate to
severe Alzheimer’s disease: A 24-week,
randomized, double-blind study. ClinTher.
2010 Jul;32(7):1234-51.
2. Doody RS, Corey-Bloom J, Zhang R, et
al. Safety and Tolerability of Donepezil
at Doses up to 20 mg/day. Results from
a Pilot Study in Patients with Alzheimer’s
Disease. Drugs Aging. 2008;25(2):163-74.
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