Safety of tacrine: Clinical trials, treatment IND, and postmarketingexperience
S.I. Gracon
Bok Engelsk 1998
| Utgitt | 1998
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|---|---|
| Omfang | Side 93- 101
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| Opplysninger | The safety of tacrine (Cognex(R)), a centrally active, reversibleacetylcholinesterase inhibitor approved in 1993 for the treatment ofmild to moderate dementia of the Alzheimer type, was evaluated in2,706 patients with Alzheimer disease (AD) in clinical trials and in9861 patients with AD in a treatment investigational new drug (TIND)program. More than 190,000 patients in the United States receivedtacrine during the first 2 years following marketing approval. Themost common tacrine-associated adverse events were elevated livertransaminase levels [alanine aminotransferase (ALT) and, to a lesserdegree, aspartate aminotransferase] and peripheral cholinergic eventsinvolving primarily the digestive system (nausea, vomiting, diarrhea,dyspepsia, anorexia, and weight loss). Based on clinical trialexperience, potentially clinically significant (>3 X upper limit ofnormal) ALT elevations occurred in 25% of patients, requiring routinemonitoring early in treatment. The elevations were almost alwaysasymptomatic, rarely accompanied by significant increases inbilirubin, and related to time on drug rather than to dose (90%occurred within the first 12 weeks of treatment). Gastrointestinalevents were related to dose and generally of mild to moderateintensity. Tacrine-associated events, including ALT elevations, werereversible. Cholinergic events were manageable with dosageadjustment. Tacrine was not associated with permanent liver injury inclinical trials or a TIND setting.
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| Emner |
