Safety of tacrine: Clinical trials, treatment IND, and postmarketing experience

Stephen I. Gracon, Margaret J. Knapp, William G. Berghoff, Mark Pierce, Richard DeJong, Sandra J. Lobbestael, James Symons, Stuart L. Dombey, Faye A. Luscombe, Dale Kraemer

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

The safety of tacrine (Cognex®), a centrally active, reversible acetylcholinesterase inhibitor approved in 1993 for the treatment of mild to moderate dementia of the Alzheimer type, was evaluated in 2706 patients with Alzheimer disease (AD) in clinical trials and in 9861 patients with AD in a treatment investigational new drug (TIND) program. More than 190,000 patients in the United States received tacrine during the first 2 years following marketing approval. The most common tacrine-associated adverse events were elevated liver transaminase levels [alanine aminotransferase (ALT) and, to a lesser degree, aspartate aminotransferase] and peripheral cholinergic events involving primarily the digestive system (nausea, vomiting, diarrhea, dyspepsia, anorexia, and weight loss). Based on clinical trial experience, potentially clinically significant (> 3 x upper limit of normal) ALT elevations occurred in 25% of patients, requiring routine monitoring early in treatment. The elevations were almost always asymptomatic, rarely accompanied by significant increases in bilirubin, and related to time on drug rather than to dose (90% occurred within the first 12 weeks of treatment). Gastrointestinal events were related to dose and generally of mild to moderate intensity. Tacrine-associated events, including ALT elevations, were reversible. Cholinergic events were manageable with dosage adjustment. Tacrine was not associated with permanent liver injury in clinical trials or a TIND setting.

Original languageEnglish
Pages (from-to)93-101
Number of pages9
JournalAlzheimer Disease and Associated Disorders
Volume12
Issue number2
DOIs
Publication statusPublished - Jun 1998

Keywords

  • Alzheimer disease
  • Cholinesterase inhibitor
  • Cognex®
  • Safety
  • Tacrine

ASJC Scopus subject areas

  • Clinical Psychology
  • Gerontology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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  • Cite this

    Gracon, S. I., Knapp, M. J., Berghoff, W. G., Pierce, M., DeJong, R., Lobbestael, S. J., Symons, J., Dombey, S. L., Luscombe, F. A., & Kraemer, D. (1998). Safety of tacrine: Clinical trials, treatment IND, and postmarketing experience. Alzheimer Disease and Associated Disorders, 12(2), 93-101. https://doi.org/10.1097/00002093-199806000-00007