Fluoroquinolones are antibiotics that have long been used to treat a variety of infections. More recently, rare but serious and potentially disabling side effects have been related to the use of fluoroquinolones. These include inflammation or rupture of tendons and nerve damage. A safety review by the European Medicines Agency was conducted and measures were put in place to limit the use of fluoroquinolones that were disseminated in the UK in 2019, including recommendations to restrict use in for less severe infections and in vulnerable patients such as those over the age of 60.
The aim of this study is to assess the impact of these safety measures by describing prescribing of fluoroquinolones over time, and characterising the patients who they were prescribed too. This will include description of characteristics such as age, gender and health issues. We will also try to explore the reasons they were prescribed fluoroquinolones to see if this has changed over time. This study will help us to understand whether the safety measures introduced to restrict prescribing of fluoroquinolones have taken effect or whether additional measures need to be implemented.
In recent years, rare but severe and potentially disabling adverse events have been related with the use of systemic fluoroquinolones, including tendonitis, tendon rupture, peripheral neuropathy, and possibly aortic aneurism. This led to risk minimisation measures (RMMs) after a safety review by the European Medicines Agency, disseminated nationally in the UK in March 2019.
This study will assess the impact of these RMMs by monitoring the incidence and prevalence of fluoroquinolone prescribing in adults and children, and by characterising the population they are prescribed too in terms of sociodemographics, clinical characteristics and indications for use. The study period will be 2012 to 2022.
A retrospective cohort design will be utilised to answer the study objectives; the cohort will be restricted to new-users to evaluate incidence and describe patient characteristics. Monthly period prevalence and incidence rates will be calculated. The incidence rates will be used in time-series analyses to explore changes in prescribing in relation to the RMMs (interrupted time-series, ARIMA, difference-in-difference). To describe new-users of fluoroquinolones summary statistics will be tabulated to present treatment duration, dose, indication for treatment and patient characteristics.
The analyses will be conducted separately in other health databases, including secondary care data and an international comparator, to better understand and contextualise fluoroquinolone prescribing over the period in relation to the RMMs imposed.
The primary outcome of the study is prescribing of fluoroquinolones. The individual medications are Ciprofloxacin; Delafloxacin; Levofloxacin; Moxifloxacin; Norfloxacin; Ofloxacin.
For objective 1 the incidence and prevalence of fluoroquinolone prescribing will be calculated, and for objective 2 the duration and dosage.
Daniel Prieto-Alhambra - Chief Investigator - University of Oxford
Helen Booth - Corresponding Applicant - CPRD
Daniel Dedman - Collaborator - CPRD
Edward Burn - Collaborator - University of Oxford
Katherine Donegan - Collaborator - MHRA
Zara Cuccu - Collaborator - CPRD