Hepatic effects of duloxetine-III: analysis of hepatic events using external data sources.
OBJECTIVE
Present results from two hepatic safety studies conducted within 20 months after duloxetine launch.


METHODS
Signal detection based on spontaneous reports to the FDA adverse event reporting system (AERS) and on a comparison of duloxetine and venlafaxine in the i3 Drug Safety Aperio claims database, using measures of disproportionality and incidence rate ratio, respectively.


RESULTS
In AERS all antidepressants had some degree of association with hepatic injury, in that at least one hepatic event was disproportionately represented for each drug. Signals were detected for duloxetine cases analyzed against full and antidepressant-only backgrounds. These signals corresponded to labeled events or events investigated during ongoing surveillance. Using a duloxetine fatal-case series, disproportional representation of clinically serious events was detected relative to both backgrounds, but the signals were refuted upon independent expert panel case review. The Aperio study showed no difference in hepatic injury between duloxetine and venlafaxine initiators after proper control for baseline risks, suggesting differential prescribing of duloxetine, perhaps preferentially as second-line therapy in some initiators.


CONCLUSIONS
No new signals were identified in Aperio. New signals detected through AERS were refuted upon independently conducted case-level investigation. Hepatic signals arising from spontaneously reported data must be clarified through subsequent systematic investigation.
Strombom
Indiana
I
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. jfwernicke@lilly.com
Wernicke
Joachim F
JF
Seeger
John
J
D'Souza
Deborah N
DN
Acharya
Nayan
N
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects*; D016907:Adverse Drug Reaction Reporting Systems; D056486:Chemical and Drug Induced Liver Injury; D003257:Consumer Product Safety; D003511:Cyclohexanols / Q000009:adverse effects*; D019992:Databases as Topic; D000068736:Duloxetine Hydrochloride; D006801:Humans; D008099:Liver / Q000187:drug effects*; D018570:Risk Assessment; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D013876:Thiophenes / Q000009:adverse effects*; D014481:United States; D014486:United States Food and Drug Administration; D000069470:Venlafaxine Hydrochloride
D018759:Adrenergic Uptake Inhibitors; D003511:Cyclohexanols; D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes; D000069470:Venlafaxine Hydrochloride