Abstract
Background
Troglitazone was removed from the U.S. market because its use was associated with
an increased risk of liver failure. We evaluated the clinical features of all cases
reported to the Food and Drug Administration and estimated the duration and magnitude
of the risk of liver failure associated with continued use of the drug.
Methods
Data from cases of liver failure associated with troglitazone use were abstracted
and analyzed. The extent of troglitazone use was determined from national marketing
data, and the duration of use was estimated with data from a large, multistate, health
care company. Survival analysis was performed to estimate monthly incidence rates
and the cumulative risk of liver failure.
Results
Ninety-four cases of liver failure (89 acute, 5 chronic) were reported. Of the acute
cases, 58 (67%) were women and only 11 (13%) recovered without liver transplantation.
Progression from normal hepatic functioning to irreversible liver injury occurred
within 1 month in 19 patients who were indistinguishable clinically from the 70 patients
who had an unknown time course to irreversibility, except for the post hoc observation
that prior cholecystectomy was less common in those with rapid onset. The incidence
of liver failure was elevated from the first through at least the 26th month of troglitazone
use. Accounting for case underreporting, the number needed to harm from troglitazone
use was between 600 to 1500 patients at 26 months.
Conclusion
The progression to irreversible liver injury probably occurred within a 1-month interval
in most patients, casting doubt on the value of monthly monitoring of serum aminotransferase
levels as a means of preventing troglitazone-induced acute liver failure. The cumulative
risk of hepatic failure increased with continued use.
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Article info
Publication history
Accepted:
October 18,
2002
Received in revised form:
September 18,
2002
Received:
March 11,
2002
Footnotes
☆This study was supported in part by cooperative agreements FD-U-000149 and FD-U-0001643-01/02 with the U.S. Food and Drug Administration, Rockville, Maryland.
Identification
Copyright
© 2003 Excerpta Medica Inc. Published by Elsevier Inc. All rights reserved.
