TACRINE - A CAUSE OF FATAL HEPATOTOXICITY

Tacrine, an acetyl cholinesterase inhibitor used in the treatment of A lzheimer's disease, often causes reversible abnormalities in liver enz ymes, but significant hepatotoxicity is uncommon. We describe fatal he patic failure associated with tacrine administration. A 75-year-old wo man with Alzheimer's disease, taking tacrine for 14 months, developed progressive jaundice. Liver function abnormalities developed during ta crine treatment and led to hepatic failure and death. An extensive eva luation for other etiologies of liver disease was negative. Other pote ntially hepatotoxic medicines had been administered for at least 2 yea rs before beginning tacrine, and postmortem examination of the liver w as consistent with drug-induced hepatotoxicity. Approximately half the patients treated with tacrine have liver enzyme abnormalities develop , primarily in the first 12 weeks of therapy, that resolve with discon tinuation of drug or dosage adjustment. Our case of tacrine-associated hepatotoxicity 14 months after the initiation of treatment despite re gular biochemical evaluation suggests the potential for delayed and fa tal hepatotoxicity with tacrine.