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Background/Aim: Medication errors (MEs) are unintended failures in the drug treatment process that may lead to patient harm and are considered preventable [1]. They represent a substantial burden for patients and healthcare systems and are a key focus of the WHO Global Patient Safety Challenge “Medication Without Harm” [2].

Hormonal contraceptives are available as oral formulations as well as device-associated products such as vaginal rings, subcutaneous implants, and intrauterine systems. While these methods offer benefits such as long-acting contraceptive effects and reduced user burden, their use involves specific administration and handling procedures that may create distinct medication safety challenges.

Evidence-based data on the occurrence and associated factors of MEs in day-to-day practice are needed for their prevention but remain limited. We investigated spontaneous adverse drug reaction (ADR) reports involving MEs among German adults, using the European ADR database EudraVigilance as part of the ongoing ALERT-Project [3].

Methods: In this study, spontaneous ADR reports from EudraVigilance received between 2012 and 2023 were extracted. Subsequently, the dataset was divided into ME reports by using the Standardized MedDRA query “medication error (narrow)” and ADR reports. A disproportionality analysis was performed by calculating reporting odds ratios (ROR) with corresponding 95% confidence intervals comparing the ME reports with the ADR reports. Within this analysis contraceptives (ATC code: G02B, G03A) were among the drug classes more frequently associated with MEs. Contraceptives were then stratified by route of administration and device-associated route administrations were further analysed regarding their most frequently reported MEs and ADRs.

Results: We identified 8,969 ME reports and 271,326 ADR reports. Out of the most frequently reported drugs (14 with >= 100 ME reports), four belonged to the contraceptive drug class and accounted for 718 reports in total. Furthermore, disproportionality analysis showed increased RORs of being reported with an ME for several contraceptive drugs (e.g. “Etonogestrel” OR 10.3 [95% CI 8.6-12.5]; “Ethinylestradiol, etonogestrel” OR 3.9 [95% CI 3.3-4.5]. Stratification by route of administration revealed that, besides of oral contraceptives (36.8%), vaginal (24.7%), subcutaneous (19.3%), and intrauterine (15.6%) contraceptives were frequently reported with MEs. These non-oral routes are associated with device-based contraceptive products and account for about 60% of all contraceptive reports. Consistent with this observation, device-related terms such as “Complication associated with device” and “Device expulsion” were among the most frequently reported ADRs for device-based contraceptives. The most commonly reported MEs within this group were “Incorrect product administration duration” and “Inappropriate schedule of product administration”, followed by device-associated terms such as “Device use error”.

Discussion/Conclusion: Hormonal contraceptives, particularly device-associated formulations such as vaginal rings, subcutaneous implants and intrauterine systems, were frequent in ME reports and showed disproportionate ME reporting, suggesting challenges in their safe use. Device-related issues constituted a substantial proportion of reported MEs, indicating that device use and handling are important contributors to the observed errors. Therefore, further individual case assessments are needed to identify the underlying causes of the reported MEs associated with contraceptive devices and support strategies for improving their drug therapy safety.

Literatur

[1] Pharmacovigilance Risk Assessment Committee (PRAC). Good practice guide on recording, coding, reporting and assessment of medication errors. EMA/762563/2014. EMA; 2015. Available from: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/good-practice-guide-recording-coding-reporting-and-assessment-medication-errors_en.pdf
[2] World Health Organisation. Medication Without Harm: Policy Brief. 2023. Available from: https://iris.who.int/server/api/core/bitstreams/1eacccb6-838e-4787-bfd9-4bdeb4debfcf/content
[3] Innovationsausschuss beim Gemeinsamen Bundesausschuss. Förderbekanntmachung Projekt ALERT – Analyse von unerwünschten Arzneimittelwirkungen und Medikationsfehlern bei Erwachsenen. Available from: https://innovationsfonds.g-ba.de/projekte/alert.665