Page 7 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

Table 1. Current drug treatments for Alzheimer’s disease

Tacrine Donepezil Rivastigmine Galantamine Memantine
®
®
®
®
Agent (Cognex ) (Aricept ) (Exelon ) (Razadyne (Namenda™)
®
Razadyne ER )

Manufacturer/ West-Ward Eisai Novartis Janssen Merz
Distributor Horizon Pfizer Shire Forest

Mechanism(s) AChEI, BuChEI AChEI AChEI, BuChEI AChEI, NRM NMDA
antagonist

Dose Forms 10, 20, 30, 40 5, 10 1.5, 3, 4.5, 6 4, 8, 12 d 5, 10
(mg) 4mg/ml d
8, 16, 24 e

Dose 4x /day 1x /day 2x /day 2x /day d 2x /day
Frequency 1x /day e

Serum T 1/2 1.3 – 2 70 2 – 8 a 6 – 8 60 – 80
(hrs.)

Dose Range 40 – 160 mg/d 5 – 10 mg/d 3 – 12 mg/d 8 – 24 mg/d 5 – 20 mg/d

Target Dose 80 – 160 mg/d 5 – 10 mg/d 6 – 12 mg/d 16 – 24 mg/d 10 – 20 mg/d

Dose Titration 6 wks. 4 – 6 wks. 2 – 4 wks. 4 wks. 1 wk.

Metabolism b CYP1A2 CYP2D6, 3A4 Non-hepatic CYP2D6,3A4 Non-hepatic

Protein-binding 75% 96% 40% 18-19% 45%

Taken with Yes Not necessary Yes Yes Not necessary
food?

Hepatotoxicity? Yes c No No No No

AChEI = Acetylcholinesterase inhibition
BuChEI = Butyrylcholinesterase inhibition
NRM = Nicotinicreceptor modulator
NMDA = N-methyl d-aspartate
a Pseudo-irreversible binding; upper range reflects duration of esterase inhibition
b Hepatic cytochrome p450 enzyme metabolism
c Requires periodic monitoring of serum liver transaminases (AST, ALT)
d Razadyne
e Razadyne ER

Alzheimer's Drugs Page 7 of 205