Liver enzyme monitoring in patients treated with troglitazone

Context 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) r isk management efforts, including repeated labeling changes and "Dear Healt hcare Professional" letters, on periodic liver enzyme monitoring of patient s taking troglitazone. Design, Setting, and Participants Claims data from a large, multistate mana ged care organization were used to establish 4 cohorts of patients (N = 760 3) with at least 90 days of health plan enrollment before first troglitazon e prescription during 4 consecutive periods spanning April 1997 to Septembe r 1999 and representing 4 progressively stringent liver monitoring recommen dations. Main Outcome Measures Percentage of eligible troglitazone users in each coh ort with baseline, monthly (for up to 6 months of continuous use), and comp lete (baseline and monthly) enzyme monitoring, based on computerized record s of laboratory claims. Results Baseline testing increased from 15% before any FDA monitoring recom mendations (cohort 1) to 44.6% following 4 separate FDA interventions (coho rt 4; P<.001). In cohort 4, 33.4% of users had follow-up testing after 1 mo nth of therapy, falling to 13% after 5 months of continuous use. in all coh orts, 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 s ustained improvement in liver enzyme testing. Evaluation of the impact of r egulatory actions is needed before such actions can be regarded as effectiv e or sufficient.