Donepezil, rivastigmine, galantamine and memantine for ...

TABLE 37 Adverse events for donepezil versus rivastigmine
group 11.0 (baseline 11.5). Statistical analyses
were within-group rather than between-group
comparisons.
Compliance
Wilkinson and colleagues 69 assessed compliance
between those given donepezil and those given
rivastigmine. Those defined as reaching the
maximum daily dose at some time during the
study were 98.2% in the donepezil group and 60%
in the rivastigmine group. Those defined as
remaining at the maximum dose until study
completion or the final visit were 87.5% in the
donepezil group and 47.3% in the rivastigmine
group. These differences were not tested for
statistical significance.
Adverse events
Various event rates for selected adverse events
were reported in the included trials and can be
seen in Table 37. The most commonly reported
adverse events related to the gastrointestinal
system, including nausea, vomiting and diarrhoea.
Rates of adverse events were generally higher in
the rivastigmine-treated participants than in the
donepezil-treated participants, but no statistical
comparisons between the treatment groups were
reported. Adverse events were generally mild to
moderate in severity; however, four participants in
the rivastigmine group of the Wilkinson and
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colleagues 69 study reported a severe treatmentrelated
digestive system adverse event compared
with none in the donepezil group. Fuschillo and
colleagues 68 reported no withdrawals due to
adverse events in either study group. In the
Wilkinson and colleagues 69 study 10.7% of
donepezil-treated participants and 21.8% of
rivastigmine-treated participants withdrew owing
to the onset of adverse events. Withdrawals
unrelated to adverse events were reported in the
Wilkinson and colleagues 69 study, where more
patients withdrew or died in the rivastigmine
group than the donepezil group, but this was not
tested for statistical significance. Data relating to
withdrawals are given in Appendix 10.
Summary
Health Technology Assessment 2006; Vol. 10: No. 1
Fuschillo et al. 68 % occurrence
Donepezil 5 mg/day (n = 16 ) Rivastigmine 1.5–9 mg/day (n = 11)
Nausea 8 15
Vomiting 5 10
Dizziness 10 15
Diarrhoea 8 10
Abdominal pain 5 8
Headache 8 10
Wilkinson et al. 69 Treatment-emergent AEs occurring in ≥ 5% of participants and more than twice as frequently
in either treatment group (all causalities). No. (%)
Donepezil 5 mg/day (n = 56) Rivastigmine 3–12 mg/day (n = 55)
Nausea 6 (10.7) 23 (41.8)
Vomiting 4 (7.1) 13 (23.6)
Headache 4 (7.1) 10 (18.2)
Anorexia 1 (1.8) 5 (9.1)
Abnormal dreams 4 (7.1) 1 (1.8)
Back pain 4 (7.1) 0
Somnolence 1 (1.8) 3 (5.5)
Urinary tract infection 3 (5.4) 0
Proportion experiencing 42.9% 58.2%
≥ 1 treatment-related advance event
● Two studies compared treatment with donepezil
with treatment with rivastigmine. The
methodological quality and the quality of
reporting in the studies was generally poor and
one study had a small sample size. One study
was funded by the manufacturers of donepezil.
● On measures of cognitive ability, general trends
suggest that treatment with rivastigmine
(1.5–12 mg/day) leads to more improvement
than treatment with 5 mg/day donepezil;
however, these trends are small, are not tested
for statistical significance and may also reflect
the differences in the doses given.
69