Hepatic effects of duloxetine-II: spontaneous reports and epidemiology of hepatic events.
OBJECTIVE
Review spontaneous reports and epidemiology of hepatic events associated with duloxetine.


METHODS
Spontaneous reports of adverse events potentially associated with hepatic injury were identified. Classification schemes were Clinical Significance and Etiologic Category relative to likelihood of being related to duloxetine.


RESULTS
Duloxetine has been taken by an estimated 5,083,000 patients, representing approximately 1,551,000 person-years (PY) of worldwide exposure. In the Etiologic categorization of the 406 cases containing event terms potentially related to the liver that have been reported to the manufacturer, 26 were deemed Probable and 127 Possible. Because of scantly-reported information, 182 cases were considered Indeterminate. For Severe Hepatic Injury, the observed spontaneous reporting rate was 0.7/100,000 persons exposed. Of the 406 cases, 225 experienced enzyme elevations to values <500 U/L, most with concentrations well below this level. The calculated cumulative spontaneous reporting rate of all duloxetine hepatic-related events combined was 0.00799%, in the context of other drug-induced hepatic injury rates reported in the literature of 0.7 to 40.6 per 100,000 PY of observation.


CONCLUSIONS
There were few cases of true hepatic injury possibly or probably related to duloxetine. The calculated cumulative reporting rate is consistent with very rarely reported per the Council for International Organizations of Medical Sciences.
Wernicke
Joachim
J
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA. jfwernicke@lilly.com
Acharya
Nayan
N
Strombom
Indiana
I
Gahimer
James L
JL
D'Souza
Deborah N
DN
DiPietro
Natalie
N
Uetrecht
Jack P
JP
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D056486:Chemical and Drug Induced Liver Injury; D002648:Child; D003257:Consumer Product Safety; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008107:Liver Diseases / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D017678:Sex Distribution; D013876:Thiophenes / Q000009:adverse effects*; D055815:Young Adult
D018759:Adrenergic Uptake Inhibitors; D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes