Hepatic Safety Profile of Atomoxetine and Methylphenidate in Patients with ADHD: Disproportionality Analysis Using
Raffaella Di Napoli1,2, Ludovica Vittoria Laino1,2, Concetta Rafaniello1,2
1Department of Experimental Medicine, University of Campania "L. Vanvitelli", 80138 Naples, Italy.
None:
Background: Hepatotoxicity induced by atomoxetine (ATX) and methylphenidate (MPH) when used to treat ADHD is a rare but potentially serious complication. This study aims to describe the hepatic adverse drug reactions (ADRs) reported for ATX and MPH by analysing data from the EudraVigilance database. Methods: Individual case safety reports (ICSRs) listing ATX and/or MPH as suspected drugs and reporting at least one adverse event (AE) within the 'hepatobiliary disorders' system organ class (SOC) were extracted for the period from 1 January 2012 to 20 May 2025. Descriptive and disproportionality analyses were then performed. Results: During the study period, 421 ICSRs reporting AEs classified under the "hepatobiliary disorders" SOC and involving ATX and/or MPH as suspected drugs were retrieved (ATX, N = 232; MPH, N = 181). Most cases involved adult (N = 261) and female (N = 222) patients. The majority of reports were classified as serious (N = 349). Overall, 375 AEs were identified. Drug-induced liver injury (DILI) was the most frequently reported AE (N = 103 ATX; N = 47 MPH), followed by hepatitis (N = 20 ATX; N = 9 MPH) and jaundice (N = 15 ATX; N = 20 MPH). The disproportionality analysis, based on a head-to-head comparison, showed a higher reporting frequency of hepatobiliary disorders for ATX compared to MPH (ROR 2.41 [95%CI 2.11-3.11]). Specifically, ATX was associated with significantly higher reporting frequencies than MPH for the AEs of DILI, hepatitis, and jaundice (6.42 [4.45-9.06]; 6.48 [2.95-14.24]; and 2.19 [1.12-4.27], respectively). Conclusions: This analysis, based on the EudraVigilance database, suggests that both drugs are associated with hepatobiliary adverse drug reactions, with a higher overall reporting frequency observed for ATX.
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