Impact of European Union Label Changes for Fluoroquinolone-Containing Medicinal Products for Systemic and Inhalation Use: Post-Referral Prescribing Trends

Abstract

Introduction Concerns of the persistence and severity of the adverse effects of fluoroquinolones, mainly involving the nervous system, muscles and joints, resulted in the 2018 referral procedure led by the European Medicines Agency (EMA). They advised to stop prescribing fluoroquinolones for infections of mild severity or of a presumed self-limiting course and for prevention of infections, plus to restrict prescriptions in cases of milder infections where other treatment options are available, and restrict in at-risk populations. We aimed to examine whether the impact of EMA regulatory interventions implemented throughout 2018–2019 had an impact on fluoroquinolone prescribing rates. Methods A retrospective population-based cohort study was conducted using electronic health care records from six European countries between 2016 and 2021. We analysed monthly incident fluoroquinolone use rates overall and for each fluoroquinolone active substance through flexible modelling via segmented regression to detect time points of trend changes, in monthly percentage change (MPC). Results The incidence of fluoroquinolone use ranged from 0.7 to 8.0/1000 persons per month over all calendar years. While changes in fluoroquinolone prescriptions were observed over time across countries, these were inconsistent and did not seem to be temporally related to EMA interventions (e.g., Belgium: February/May 2018, MPC − 33.3%, 95% confidence interval [CI] − 35.9 to − 30.7; Germany: February/May 2019, MPC − 12.6%, 95% CI − 13.7 to − 11.6]; UK: January/April 2016, MPC − 4.9%, 95% CI − 6.2 to − 3.6). Conclusion The regulatory action associated with the 2018 referral did not seem to have relevant effects on fluoroquinolone prescribing in primary care. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-023-01286-4.

Trends in fluoroquinolone prescribing in UK primary and secondary care between 2019 and 2023

“…Although this study is reported in the MHRA Drug Safety Update as showing ‘no change’ in prescribing, it does show a reduction in fluoroquinolone prescribing, and is estimated by Ly et al to be “at best, a reduction in prescriptions of around 25%”. 15 As such, our results are concordant and extend the study period and show further reductions since then. The English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) report for 2023 provides supportive data, with quinolone prescription dropping from 0.565 in 2018 to 0.456 in 2022 (p = 0.04).…”

“…It was not able to identify a reduction in fluoroquinolone usage directly in relation to the EMA guidance. 15 However, this study did show that a) the UK had the lowest rates of fluoroquinolone prescribing in all included countries, and b) the UK had around a 3% reduction per year in fluoroquinolone prescriptions from 2016 to 2020 guidance. 15…”

“…As far as we are aware, the only other study examining post EMA/MHRA fluoroquinolone prescribing trends is Ly et al, funded by the EMA and analysing UK data from 2016-2020 15 . This study used a multisegmented regression approach to identify monthly percentage changes in relation to specific communications from regulators.…”

“…The reference for this “lack of change” in prescribing was a European pharmacovigilance study 15 , which included 15 million UK participants from 2016 to 2020 and was commissioned by the EMA to assess the impact of the 2019 EMA guidance across numerous countries. It was not able to identify a reduction in fluoroquinolone usage directly in relation to the EMA guidance.…”

MHRA issues two updates on fluoroquinolone safety

“…In the year to August 2023, over 450 000 primary care prescriptions for oral fluoroquinolones were dispensed in England with a threefold variation in the volume of prescribing across Integrated Care Boards 5. A retrospective population-based cohort study of electronic health records across several European countries found that changes in fluoroquinolone prescribing did not seem to be temporally related to the safety alerts issued in 2019 6…”