(026) Medication Errors After Methotrexate Administration. An Analysis of EudraVigilance Reports Before and After EU Referral

Background: The foremost concern among reported medication errors (MEs) related to methotrexate (MTX) use pertains to accidental overdose resulting from daily administration, as opposed to weekly. In response to this issue, the Pharmacovigilance Risk Assessment Committee (PRAC) recommended risk minimization measures in July 2019, at the request of the Spanish Health Authority under Article 31 of Directive 2001/83/EC.

Objectives: The objective of the research was to analyze the individual case safety reports (ICSRs) describing MEs associated with MTX, by utilizing EudraVigilance (EV) as the primary data source. The aim was to assess the reporting trends on MEs for MTX before and after the EU referral and to gain insight into different types of ME by characterizing the ICSRs.

Methods: The ICSRs associated with MTX administration were retrieved from EV, using a series of MedDRA preferred terms describing ME. Data extraction was performed for the period 01 July 2015 – 31 July 2023.

Results: Within the analyzed period, EV recorded 1333 cases of MEs for MTX, with 133 reported as fatal. Analysis revealed increased reporting of MTX-associated MEs during the periods: Quarter 3 (Q3) 2017 - Q2 2018, Q4 2019 - Q2 2020, and Q4 2021 - Q2 2022. Notably, we observed that 89% of reports were classified as serious; the number of serious cases increased over the years, primarily due to non-fatal ME reporting. For elderly patients, the percentage of suspected serious adverse reactions reported was 93%. Regarding fatality, it is noteworthy that the number of fatal cases (76) among elderly patients was double compared to those under 65 years old (37). We observed a significant high number of ME reports associated with oral administration compared to other routes. The predominant category of MEs was linked to the incorrect frequency of administering methotrexate (506 cases). Complete recovery post-ME was highest for acute overdoses (101 cases), whereas cases not recovered at the time of reporting (84 cases) were associated with incorrect frequency of administration.

Conclusions: ICSRs for MTX MEs exhibited intermittent increases during the analyzed period. The oral route of administration emerged as highly susceptible to MEs for MTX, with incorrect frequency administration being the most frequently reported type of error across all patient categories, posing an elevated risk of fatality in elderly patients.