Case series of liver failure associated with rosiglitazone and pioglitazone.
OBJECTIVE
The thiazolidinedione drugs rosiglitazone and pioglitazone are not widely known to be hepatotoxic. We evaluated the FDA Adverse Event Reporting System (AERS) to determine the number of reported cases of liver failure associated with rosiglitazone and pioglitazone between 1997 and 2006, and described their clinical characteristics.


METHODS
Adverse event reports spontaneously submitted to the FDA AERS from 1997 to 2006 were examined. Liver failure associated with rosiglitazone or pioglitazone was defined as liver injury accompanied by hepatic encephalopathy, liver transplantation, placement on a liver transplant list, or death in which all other likely etiologies were excluded. Using prescribing data, the number of reported cases of liver failure per million patient-years of exposure was calculated for each drug.


RESULTS
Twenty-one cases met our case definition. Clinical characteristics, outcomes, and pathologic data were similar between cases of liver failure associated with rosiglitazone and with pioglitazone. The median duration of therapy was 9 weeks and 85% of cases were acute, defined as symptom onset to liver failure in less than 26 weeks. The case-fatality rate was 81% (17/21), and only 14% (3/21) spontaneously recovered. Accounting for underreporting, the number needed to harm (NNH) for each case of liver failure was 44 000 patient-years of exposure for rosiglitazone and 52 000 patient-years of exposure for pioglitazone.


CONCLUSIONS
This is the largest case series of liver failure associated with rosiglitazone or pioglitazone reported to date, strengthening the evidence that these drugs can cause severe hepatotoxicity.
Floyd
James S
JS
Public Citizen, Health Research Group, 1600 20th Street NW, Washington, DC 20009, USA. jfloyd@citizen.org
Barbehenn
Elizabeth
E
Lurie
Peter
P
Wolfe
Sidney M
SM
D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017093:Liver Failure / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D012307:Risk Factors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone