OBJECTIVE: To review the pharmacology, biopharmaceutics/pharmacokinetics, 
clinical efficacy, adverse effects, and therapeutic considerations regarding the 
use of tacrine in patients with Alzheimer's disease.
DATA SOURCES: Data from the scientific and professional literature were 
analyzed, interpreted, and summarized. Citations were obtained by performing a 
MEDLINE search using the following indexing terms: tacrine, 
tetrahydroaminoacridine, and Alzheimer's drug therapy. Data also were obtained 
from a summary of the New Drug Application (Summary Basis of Approval of Cognex) 
and from the approved product labeling.
STUDY SELECTION: Studies in Alzheimer's disease have been plagued by 
methodologic inconsistencies and deficiencies. Only efficacy studies subsequent 
to the Food and Drug Administration's (FDA) issuance of recommendations for 
studies in Alzheimer's disease (1991) were used. Therefore, only double-blind, 
placebo-controlled, parallel design studies of at least three-month's duration 
using the Alzheimer's Disease Assessment Scale-Cognitive Subscale and the 
Clinical Interview-Based Impression of Change as efficacy parameters were 
included.
DATA EXTRACTION: Trials were assessed according to the criteria listed above. 
Results were evaluated on the basis of both completed patients and last 
observation carried forward models.
DATA SYNTHESIS: Tacrine is a cholinesterase inhibitor that increases the 
availability of acetylcholine in muscarinic neurons. It has a mean 
bioavailability after oral administration of about 17 percent and an elimination 
half-life of approximately three hours. Although drug interactions are poorly 
studied, tacrine is metabolized by isoenzyme P-450IA2 and may interact with 
other drugs metabolized by this isoenzyme. Tacrine has been shown to have 
efficacy in mildly to moderately impaired Alzheimer's patients on both 
psychometric testing and a clinician's structured interview. Although 
efficacious, its effects are not dramatic, and it does not affect the ultimate 
course of the disease. Adverse effects are frequent, and significantly elevated 
hepatic transaminase concentrations may occur in approximately 25 percent of 
patients.
CONCLUSIONS: Tacrine is the first drug approved by the FDA for treatment of 
Alzheimer's disease. Although it may improve psychometric test scores in mild to 
moderately impaired patients, it is not a panacea and does not affect the course 
of the disease. Patients must be monitored closely for elevated transaminase, 
cholinergic adverse effects, and interactions with drugs metabolized through 
P-450IA2.