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 personyears (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.