Professor of pharmacology, Milou-Daniel Drici is also a member of the SFPT (French Society of Pharmacology and Therapeutics), an expert for the European Commission at the European Medicines Agency (EMA) and head of the pharmacovigilance center at the University Hospital of Nice. .
Many of the quinolone and fluoroquinolone antibiotics recently implicated have been on the market for over 30 years. Why did the Agencies wait so long before alerting on adverse effects?
What you say is incorrect. The European Agency issued restrictions on use in 2007 for moxifloxacin (Izilox) – in 2008 for pefloxacin (Peflacin) and in 2012 for levofloxacin (Tavanic), precisely because of adverse effects.
But why were these effects not reported in clinical trials?
Frequent adverse effects, whether serious or not, are listed at the end of drug development, after having been characterized during comparative clinical trials. Their precise frequency is obtained by comparing their occurrence in the treated groups and in the groups receiving a placebo or a reference drug. Some side effects can be serious but rare, such as those associated with fluoroquinolones. And when an adverse effect is rare, it may escape this surveillance during clinical trials.
Which filter then?
This is the role of pharmacovigilance; its role is to monitor medicines and prevent the risk of adverse effects resulting from their large-scale use, from the time they are marketed. It constitutes a guarantee that applies throughout the life of a drug.
How does the information come up?
The Regional Pharmacovigilance Centers (CRPV) receive spontaneous reports of adverse effects sent by patients or healthcare professionals. For example, for departments 06, 83 and 05, it is the Nice-Alpes Côte d’Azur CRPV located at the Cimiez hospital (1). It is thanks to the meticulous examination of these notifications from the 31 CRPVs that a signal can be established nationally which, transmitted to the European agency, could lead to new restrictions of indications. As was the case for fluoroquinolones in 2018.
On November 15, 2018, the EMA effectively finalized a review of the serious, disabling and potentially irreversible adverse effects of these antibiotics. What happened next?
In April 2019, a warning was sent by the Medicines Agency to health professionals, recalling the risks and the restrictions of indications to be respected in terms of quinolones, followed by a modification of the famous SPC (summary of product characteristics ) ranging between August 2019 and June 2020. Prescriptions in France had decreased from 2016 (date of the start of the study). On the other hand, this decline stabilized in 2018 and hardly decreased despite the Agency’s warnings between 2019 and 2021. The proportion of prescriptions “outside the nails” also remained stable, but much higher to the limits indicated by the ANSM.
How do you explain it?
I would say that alerts are much less effective in our country than in others, such as Germany or the Netherlands. Moreover, the current objective of the agencies is to measure very precisely the effect of alerts and to rectify very early on the course – and the misuse – by measures such as delisting, if necessary.
1- Regional Pharmacovigilance Center (Alpes-Maritimes (06), Hautes-Alpes (05) and Var (83). Address: Pavillon Victoria – Cimiez Hospital, 4, avenue Reine Victoria, CS 91179, 06003 NICE CEDEX 1. Telephone : 04.92.03.47.08 Mail: pharmacovigilance@chu-nice.fr.