Troglitazone and liver function abnormalities: lessons from a prescription event monitoring study and spontaneous reporting.
OBJECTIVE
To investigate whether there were any cases of liver function abnormalities possibly associated with troglitazone use in general practice in England.


METHODS
A prescription-event monitoring (PEM) study was undertaken between October 1997 and December 1997.


METHODS
Data from prescriptions were obtained electronically for the troglitazone cohort in the immediate postmarketing period.


METHODS
Event data were obtained for a total of 1344 patients.


RESULTS
Troglitazone was effective in 394 (75%) of the 529 patients for whom an opinion was given. The most frequent reasons for stopping treatment related to drug tolerability were malaise/lassitude (16 reports), abnormal liver function tests (II reports) and nausea/vomiting (9 reports). The major cause of stopping troglitazone was because the drug was withdrawn from the market (1101 reports). 30 patients with liver dysfunction were identified from the cohort. In 9 of these patients there were alternative explanations for the liver dysfunction and hence these patients were not followed up further. 21 patients were followed up, for whom 19 questionnaires were returned. In 5 patients their liver dysfunction was assessed as possibly related to troglitazone, in 6 patients the liver dysfunction was unlikely to be attributed to troglitazone, while in 7 patients it was difficult to assess the causality because of limited information and confounding factors. The remaining patient was not included as this individual did not fit the inclusion criteria of the study.


CONCLUSIONS
Although the cohort is small (the drug was available for only 3 months in the UK), 5 patients with abnormal liver function, considered possibly related to troglitazone were detected in this PEM study. It is possible for PEM to contribute to the elucidation of safety signals in the UK.
Drug Safety Research Unit, Southampton, England. pipasha.biswas@dsru.org
P
P
Biswas
L V
LV
Wilton
S A
SA
Shakir
D000328:Adult; D000368:Aged; D056486:Chemical and Drug Induced Liver Injury; D002839:Chromans / Q000009:adverse effects*; D004739:England / Q000453:epidemiology; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008107:Liver Diseases / Q000453:epidemiology / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011358:Product Surveillance, Postmarketing; D013844:Thiazoles / Q000009:adverse effects*; D045162:Thiazolidinediones; D000077288:Troglitazone; D014839:Vomiting / Q000139:chemically induced
D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone