Implementation of indication restrictions made by European regulatory action for antibiotics - amoxicillin

Antibiotics are important tools in the armamentarium for treating infectious diseases. In Europe most available antibiotics have been licensed in the past through so-called national procedures, meaning that antibiotic labels (e.g., therapeutic indications, posology, contra-indications) may vary across European member states. As a result, antibiotics are prescribed in the EU with different directions of use. This study aims to evaluate whether on streamlining the product information of antibiotics in the period 2007-2020 has been sufficiently implemented. Specifically, it examines whether member states and pharmaceutical companies have fulfilled their obligation to update the therapeutic indication sections of the amoxicillin containing medicines label according to the outcomes of the referral.

We performed a follow-up of the previous study measuring five years after the referral's conclusion and decision whether and how complete the indication sections of the product information for one of 15 antibiotics that underwent referral procedures during the previous study period (2007-2020) were updated. We have chosen amoxicillin as case example for this study as it is the most frequently used antibiotic in the primary care setting, and the referral took place mid-term 2007-2020,-with a conclusion in 2015.

In total we could identify 806 medicinal products with an active pharmaceutical ingredient amoxicillin available in 2015 across 30 EEA countries and the UK. We found that in 22 % (176 out of 806) amoxicillin products still included therapeutic indications that should have been removed from the SmPC following the 2015 referral procedure. The most frequent therapeutic indications that were incorrectly still listed in the indication sections of the product information were endocarditis treatment (oral formulation) in 55 % (97 out of 176 products), followed by lower respiratory tract infections 49 % (87 out of 176 products), and upper respiratory tract infections 46 % (81 out of 176 products).

Inconsistencies in therapeutic indications continue to pose challenges, potentially impacting the safe and effective use of antibiotics. Such discrepancies can lead to misuse or inappropriate prescribing of crucial antibiotics, contributing to the growing problem of antimicrobial resistance. Our study highlights the importance of following up on and verifying the implementation of finalized regulatory procedures at EU level. Further research is needed to understand the root causes of incomplete implementations, possibly also due to incomplete updates of the EMA Article 57 database.