Hepatic Safety Profile of Atomoxetine and Methylphenidate in Patients with ADHD: Disproportionality Analysis Using EudraVigilance Database Data.

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.