Page 45 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

studies in patients with AD. 50, 52, 53 Galantamine was significantly better than placebo (P < 0.05) only in
the subgroup of patients with AD and cerebrovascular disease. Although the study was not powered to

detect treatment differences in the subgroups, differences between galantamine and placebo were not
significant in patients with vascular dementia.

We identified one subgroup analysis of AD patients with concurrent vascular risk factors from a placebo-
55
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controlled RCT of rivastigmine. Patients from this trial were categorized by their Modified Hachinski
Ischemic Score (MHIS); MHIS scores greater than zero were used to identify the presence of vascular
risk factors. At 26 weeks, rivastigmine was significantly better than placebo on cognitive, functional, and
global assessment measures for patients with and without vascular risk factors. Larger treatment

differences between rivastigmine and placebo were found for patients with vascular risk factors.

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One systematic review of placebo-controlled memantine trials included trials conducted in populations
with AD, vascular dementia, and mixed or unspecified AD with vascular dementia. Although individual
trials were different with regard to design, duration, dose, and outcome measures, comparison of evidence

across populations suggests that results of trials conducted in populations with mixed or unspecified
vascular dementia are similar to trials conducted in populations with AD only.

F. Other drugs

We did not identify any published study that specifically compared outcomes among subgroups of

patients taking a ChEI or memantine concurrently with another drug to patients not concurrently taking
the same medications. To characterize potential and known drug-drug interaction risks as much as
possible in this situation, we summarize indirect evidence and pharmacokinetic properties.

In general, ChEIs (i.e., donepezil, galantamine, rivastigmine, tacrine) may interfere with the activity of
anticholinergic medications. Likewise, a synergistic effect may be expected when ChEIs are given with

cholinomimetics or other ChEIs. Concurrent use of such drugs should be approached with caution.

The NMDA antagonist memantine is believed to be safe when administered in combination with a ChEI.
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In a 24-week trial, memantine was safely administered in combination with donepezil without evidence
of altering the pharmacokinetic properties of either drug; evidence of additional benefit of this

combination is not clear

Alzheimer's Drugs Page 45 of 205