Page 47 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

Tacrine

Tacrine is metabolized primarily by the CYP450 isoenzyme 1A2. Drug-drug interactions may occur with
other medications metabolized by this enzyme (e.g., theophylline). Administration of tacrine and

theophylline has been shown to increase average plasma theophylline concentrations 2-fold. Likewise,
administration of cimetidine with tacrine has been shown to increase plasma concentrations of tacrine.

Memantine

Because memantine is eliminated predominantly by the kidney, drugs that are inhibitors and/or substrates
of the CYP450 system are not expected to interact with it. However, because memantine is eliminated

via renal mechanisms, concurrent administration of drugs that use the same renal mechanisms (e.g.,
hydrochlorothiazide, triamterene, cimetidine, ranitidine, quinidine, nicotine) could alter the plasma levels

of both agents. Additionally, drugs that make the urine alkaline (e.g., sodium bicarbonate, carbonic
anhydrase inhibitors) may reduce the clearance of memantine. Patients using these drugs and memantine
concurrently should be monitored closely.

G. Summary of the evidence

The overall grade of the evidence on efficacy and tolerability in subgroups is poor. We did not identify

any study specifically designed to compare the effect of donepezil, galantamine, rivastigmine, tacrine, or
memantine in one subgroup of patients compared to another. Subgroup analyses and indirect evidence
from placebo controlled trials provide evidence for some AD drugs.

One subgroup analysis reported greater benefit for rivastigmine in patients older than 75 years. Indirect

comparison of evidence from one donepezil trial conducted in nursing home residents to trials conducted
in younger populations suggests no apparent difference in efficacy or adverse events.

Subgroup analyses of pooled data from four rivastigmine trials suggest no differences in efficacy or
adverse events by sex or race.

No evidence addressed patients with comorbid PD.

Four studies provide general evidence of the efficacy of donepezil, galantamine, rivastigmine, and
memantine in populations with comorbid vascular dementia. Only one study stratified patients by

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