title: Agomelatine and hepatotoxicity: implications of cumulated data derived from spontaneous reports of adverse drug reactions.
abstract: Considering the antidepressant agomelatine (AGM) there is a discrepancy between the widespread knowledge of the potential of AGM to cause hepatotoxic adverse drug reactions (ADR) and the availability of corresponding published data. This impedes an adequate assessment of the hepatotoxicity profile of AGM. We conducted a query of the database of a German Medical Regulatory Body (BfArM) and analyzed spontaneous reports of hepatotoxic ADR. We identified n=58 cases of AGM-related hepatotoxic ADR. Most frequent ADR was asymptomatic increase of liver enzymes (79%); n=6 patients (10%) with AGM-related toxic hepatitis were reported. Characteristics of patients: female sex (69%), age > 50 years (mean 54 years), polypharmacy (57%), and presence of cardiovascular risk factors (58.5%). Most of the hepatotoxic ADR (90%) were reported to have improved/recovered after discontinuation of AGM. Our evaluation suggests that AGM features a potential to cause severe forms of hepatotoxicity and emphasizes that a pre-existing liver disease is a contraindication for treatment with AGM. Secondly, increased age, female sex and polypharmacy may be risk factors for the development of AGM-related hepatotoxic ADR.
authors: Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany.
authors: M
authors: M
authors: Gahr
authors: R W
authors: RW
authors: Freudenmann
authors: B J
authors: BJ
authors: Connemann
authors: C
authors: C
authors: Hiemke
authors: C
authors: C
authors: Schönfeldt-Lecuona
mesh_terms: D000081:Acetamides / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D016208:Databases, Factual; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; C084711:agomelatine; D009281:Naphthalenes