Observational suspected adverse drug reaction profiles of fluoro-pharmaceuticals and potential mimicry of per- and polyfluoroalkyl substances (PFAS) in the United Kingdom
Banurja Balasubramaniam, Alan M. Jones
Abstract
Aims
The aim of this research is to explore the suspected adverse drug reactions (ADRs) of perfluorinated medicines to determine whether side effects commonly associated with per- and poly-fluoroalkyl substances (PFAS) exposure were correlated to the type or number of fluorine atoms in these medications.
Introduction
Per-and poly-fluoroalkyl substances (PFAS), often referred to as ‘forever chemicals’ due to their persistence in the environment, bioaccumulate in the body [1] and have been used in consumer products since 1940 [2,3]. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are well-known representative examples [4].
Materials and method
The list of all approved fluorinated drugs was extracted from Hammel E, et al. (2022) [2]. In total, 13 fluorinated drugs out of 360 were selected for analysis using inclusion and exclusion criteria of this study (Table 1 and Fig 1). The drugs selected were celecoxib, flecainide, fluoxetine, lansoprazole, leflunomide, sitagliptin, travoprost, ezetimibe, fluconazole, fluocinolone, fluticasone, nebivolol and ticagrelor.
Results
Drug class and fluorination content
All drugs in Table 2 belong to different drug classes and indications, except for fluticasone and fluocinolone that are both corticosteroids. Sitagliptin and flecainide contains the highest number of fluorine atoms in their structures, with 6 fluorine atoms. Trifluoromethyl (CF3) was the common moiety among the drugs, celecoxib, fluoxetine, lansoprazole, leflunomide, travoprost, flecainide and sitagliptin contains at least one CF3 in its structure.
Discussion
The 13 fluorinated drugs, except fluticasone and fluocinolone which both belong to the corticosteroid drug class, belongs to different drug classes, meaning their MoA and clinical indication differs from each other. This indicates that the drugs are likely to have different pharmacological and side effect profiles. The majority of pharmacological interactions from Table 4, the IC50 values exceeds their Cmax values, are unlikely to play a significant role in a clinical setting, unless there were drug bioaccumulation in operation, which is known to occur with leflunomide [42].
Acknowledgments
Conclusion
All 13 drugs included in this study exhibited one or more ADRs that have been associated with PFAS-like side effects. However, the analysis indicates that the observed pattern of ADRs could not be attributed to either the degree of fluorination or the type of fluorine moiety present in the drugs. This finding therefore suggests that the structural similarities between these drugs and PFAS do not independently determine their ADR profile.
Citation: Balasubramaniam B, Jones AM (2025) Observational suspected adverse drug reaction profiles of fluoro-pharmaceuticals and potential mimicry of per- and polyfluoroalkyl substances (PFAS) in the United Kingdom. PLoS One 20(9): e0331286. https://doi.org/10.1371/journal.pone.0331286
Editor: Sarah Nanzigu, Makerere University, UGANDA
Received: March 17, 2025; Accepted: August 13, 2025; Published: September 2, 2025
Copyright: © 2025 Balasubramaniam, Jones. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting Information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
