gms | German Medical Science

Background: In November 2018, the European Medicines Agency (EMA) finalised a review of fluoroquinolone antibiotics (used by mouth, injections or inhalation) in the frame of a referral, which started upon an initiative of the “Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)”. It has been concluded that these antibiotics can cause long-lasting, disabling and potentially irreversible adverse drug reactions (ADRs), which can involve several organ systems (musculoskeletal, peripheral and central nervous systems). The EMA recommended among others that fluoroquinolones should no longer be used to treat mild or moderate bacterial infections unless other antibacterial medicines commonly recommended for these infections cannot be used [1]. The first aim of our study was to analyse if specific ADRs were more frequently reported for fluoroquinolones compared to cotrimoxazole (combination of sulfamethoxazole and trimethoprim) before and after the referral. The second aim was to investigate if there are differences among the reported ADRs between the different fluoroquinolones.

Materials and methods: All spontaneous reports received between 2014–2019 and 2020–2022 reported for patients older than 17 years, in which fluoroquinolones (n=2,575, n=967) or cotrimoxazole (n=3,428, n=2,387) were reported as suspected/interacting, were identified in the European ADR database EudraVigilance. Logistic regression analyses were performed in order to analyse if aortic aneurysms, retinal detachments, cardiac arrhythmias, peripheral neuropathies, nervous system, hepatic and muscle and tendon related disorders were more frequently reported for fluoroquinolones compared to cotrimoxazole. Further on, odds ratios with 95% confidence intervals were calculated in order to identify ADRs more frequently reported for one of the fluoroquinolones compared to another fluoroquinolone.

Results: The number of reports related to ciprofloxacin and levofloxacin increased clearly until 2019 and decreased substantially afterwards. Compared to that, the number of reports for the other fluoroquinolones and cotrimoxazole was rather consistent. In both time frames, peripheral neuropathies, nervous system and muscle and tendon disorders were more often reported for fluoroquinolones compared to cotrimoxazole. Additionally, urinary tract infections were one of the most frequently reported indications of fluoroquinolone therapy in both periods. The drug-stratified analyses showed that peripheral neuropathies and nervous system disorders were more frequently reported for ciprofloxacin versus levofloxacin; muscle and tendon disorders were more commonly mentioned in reports for levofloxacin versus ciprofloxacin; peripheral neuropathies, nervous system and muscle and tendon disorders were more commonly described in ciprofloxacin versus moxifloxacin reports, and anaphylactic reactions, cardiac arrhythmias and hepatic disorders were more often observed in moxifloxacin versus ciprofloxacin reports.

Conclusion: Our analysis shows that, even after the referral, the corresponding ADRs were reported to a relevant extent. However, stimulated reporting due to the referral cannot be excluded. The fact that urogenital infections continued to be one of the most common indication may indicate that the recommended restrictions were not fully adhered. The observed differences between the different fluoroquinolones may allow conclusions which fluoroquinolone(s) may be more suitable to use based on knowledge about individual risk factors of the respective patient.