Page 36 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

Table 5: Mean incidence of specific adverse events in placebo-controlled trials
Diarrhea Vomiting Anorexia Dizziness
Number of
Drug Mean Mean Mean Mean
Studies
(95% CI) (95% CI) (95% CI) (95% CI)
10.5% 7.1% 5.2% 7.2%
Donepezil 10
(6.6 to 14.3) (3.4 to 10.9) (2.9 to 7.6) (5.4 to 8.9)
9.4% 13.0% 10.8% 11.9%
Galantamine 5
(1.8 to 9.4) (2.5 to 23.5) (3.6 to 17.9) (4.2 to 19.6)
19% 11.2% 17.2%
Rivastigmine 2 NR
(0 to 44.4)* (0 to 46.2)* (0 to 45.8)*
8.6% 20.6% 10.2%
Tacrine 4 NR
(0 to 19.3)* (0 to 43.7)* (0 to 22.6)*
7.3%
Memantine 2 NR NR NR
(0 to 42.2)
*negative lower confidence interval

Some of the ChEIs appear to have a higher incidence of vomiting; this is likely attributable to their
cholinergic mechanism of action. The highest incidence of nausea and vomiting was reported in
rivastigmine trials, although these trials utilized a faster titration schedule than recommended by the

product labeling and the rate of adverse events was also higher than normal in the placebo group.
However, these estimates are consistent with available comparative evidence, which suggest that the risk

of gastrointestinal-related adverse events is greater with rivastigmine and galantamine than with
donepezil.

The incidence of specific adverse events reported by memantine-treated patients was generally low.
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From the single trial in our review that assessed only memantine (rather than memantine plus
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donepezil), the only adverse events reported by more than 10% of memantine-treated patients were
agitation, diarrhea, somnolence, and urinary incontinence; no adverse event was reported in significantly
more memantine-treated patients than in placebo-treated patients. The rate of agitation was significantly
different in memantine-treated patients than in those on placebo, although significantly more placebo-

than memantine-treated patients reported agitation (32% vs. 18%, respectively; P = NR). Urinary tract
infections also were more common in placebo-treated patients than in memantine-treated patients (13%

vs. 6%, respectively; P = NR).

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Discontinuation rates varied across trials. Based on one trial that compared donepezil to rivastigmine,
more patients randomized to rivastigmine than donepezil discontinued treatment (30.9% vs. 10.7%,
respectively; P = NR). Two open-label trials compared donepezil to galantamine; 27, 28 overall

discontinuation rates did not differ significantly. Trials assessing tacrine consistently reported

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