Liver enzyme monitoring in patients treated with troglitazone.
BACKGROUND
Soon after initial marketing in March 1997, troglitazone, the first thiazolidinedione antidiabetic agent, was found to cause life-threatening acute liver failure. The drug was removed from the market in March 2000.


OBJECTIVE
To evaluate the effect of US Food and Drug Administration (FDA) risk management efforts, including repeated labeling changes and "Dear Healthcare Professional" letters, on periodic liver enzyme monitoring of patients taking troglitazone.


METHODS
Claims data from a large, multistate managed care organization were used to establish 4 cohorts of patients (N = 7603) with at least 90 days of health plan enrollment before first troglitazone prescription during 4 consecutive periods spanning April 1997 to September 1999 and representing 4 progressively stringent liver monitoring recommendations.


METHODS
Percentage of eligible troglitazone users in each cohort with baseline, monthly (for up to 6 months of continuous use), and complete (baseline and monthly) enzyme monitoring, based on computerized records of laboratory claims.


RESULTS
Baseline testing increased from 15% before any FDA monitoring recommendations (cohort 1) to 44.6% following 4 separate FDA interventions (cohort 4; P<.001). In cohort 4, 33.4% of users had follow-up testing after 1 month of therapy, falling to 13% after 5 months of continuous use. In all cohorts, less than 5% received all recommended liver enzyme tests by the third month of continuous use.


CONCLUSIONS
The FDA risk management efforts did not achieve meaningful or sustained improvement in liver enzyme testing. Evaluation of the impact of regulatory actions is needed before such actions can be regarded as effective or sufficient.
Graham
D J
DJ
Office of Postmarketing Drug Risk Assessment, US Food and Drug Administration, 5600 Fishers Ln, HFD-400, Room 15B-32, Rockville, MD 20857, USA. grahamd@cder.fda.gov
Drinkard
C R
CR
Shatin
D
D
Tsong
Y
Y
Burgess
M J
MJ
D002839:Chromans / Q000009:adverse effects* / Q000627:therapeutic use; D004348:Drug Labeling; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000201:enzymology / Q000517:prevention & control*; D008111:Liver Function Tests; D012308:Risk Management; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use; D045162:Thiazolidinediones; D000637:Transaminases / Q000097:blood; D000077288:Troglitazone; D014481:United States; D014486:United States Food and Drug Administration
D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000637:Transaminases; D000077288:Troglitazone