Adverse drug reactions that arise from the use of medicinal products outside the terms of the marketing authorisation.

Background: New European (EU) pharmacovigilance (PV) legislation, introduced in 2012, widened the scope of an Adverse Drug Reactions (ADR) definition so that it also includes noxious and unintended response to a medicinal product arising from the use outside the terms of the marketing authorisation (MA), whereby the use outside the MA also includes off-label use, overdose, misuse, abuse and medication errors (MEs).
Objectives: To explore the ADRs arising from the use outside the terms of the MA reports in the Croatian pharmacovigilance database.
Methods: A retrospective, observational study of the HALMED PV database was undertaken before and after the implementation of the new legislation in Croatia. The outcome measure included ADRs arising from the use of the products outside the terms of the MA. An assessment was performed based on the information provided in a reference document, an SmPC, using predefined criteria.
Results: Among 679 ADRs included in the analysis, 162 (23,9%) ADR reports were related to the use outside of the MA, 370 (54,5%) were related to the use within the MA and 147 (21,6%) were adjudged as not-assessable. Our study demonstrated a significant increase in the number of ADRs arising from the use outside the terms of the MA after the implementation of the new legislation (P = 0,039), primarily due to a notable increase in the number of overdose reports received by the poisoning centre, while the number of ADRs caused by MEs did not change significantly (p = 0,672).
Conclusion: This study elucidated partial implementation of the new EU PV legislation and the need for instilling proper education for patients and HCPs, improving reporting systems and strengthening collaboration between relevant stakeholders.
Competing Interests: Declaration of competing interest None.
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