Recent research conducted by scientists at the University of Birmingham has brought new insights into the safety profiles of pharmaceuticals containing fluorine, a chemical element classified among per- and polyfluoroalkyl substances (PFAS), commonly termed “forever chemicals.” Despite the widespread environmental and health concerns associated with PFAS compounds, the study reveals that fluorinated medicines do not lead to increased adverse drug reactions (ADRs) compared to similar, non-fluorinated drugs. This groundbreaking finding challenges prevailing assumptions about the risks posed by fluorinated organic compounds in therapeutic agents.
PFAS compounds have gained notoriety due to their persistence in the environment, resistance to degradation, and potential links to various health issues. Fluorine, a key atom in many PFAS molecules, contributes characteristic stability by forming robust carbon-fluorine bonds, which also finds utility in medicinal chemistry. In pharmaceuticals, incorporation of fluorine atoms can enhance drug bioavailability, metabolic stability, and molecular targeting, making fluorinated drugs an important class of therapeutics. Yet, the label of “forever chemicals” engenders concern about possible latent toxicities, especially as regulatory bodies start to categorize certain essential medicines as PFAS-containing.
The recently published study in PLOS ONE represents an extensive evaluation of real-world adverse drug reactions associated with fluorinated medicines in the United Kingdom. Utilizing data spanning five years (2019 to 2024) from the UK Medicines and Healthcare products Regulatory Agency (MHRA) Yellow Card reporting system, researchers meticulously compared the ADR frequencies of thirteen fluorinated pharmaceutical agents with six structurally analogous drugs lacking fluorine content. The goal was to discern whether the fluorine content correlated with a heightened incidence or differing profile of ADRs.
Analytical results demonstrated no statistically significant association between the presence or quantity of fluorine atoms within these pharmaceuticals and the rates of reported adverse drug events. Among the drugs evaluated, lansoprazole—a proton pump inhibitor extensively prescribed for acid-related gastrointestinal disorders—showed a particularly low rate of ADRs at just 14.1 reactions per one million prescriptions dispensed. This observation underscores the tolerability of widely used fluorinated drugs despite their PFAS classification.
Dr. Alan Jones, corresponding author and pharmacology expert at the University of Birmingham, emphasized the importance of these findings within the context of ongoing PFAS discourse. He explained that although PFAS compounds are ubiquitous in consumer goods and environmental matrices, their risk profile when embedded within the molecular framework of essential medications does not appear to elevate adverse reaction risk. The study reassures both healthcare professionals and patients that fluorine-containing medicines maintain safety profiles consistent with non-fluorinated analogues.
The research explored the complexity of adverse reaction types, recognizing that certain ADRs have been previously linked with PFAS exposure in environmental or occupational settings. However, when comparing fluorinated versus non-fluorinated drugs, the pattern and nature of ADRs largely aligned more closely with each drug’s pharmacological mechanism of action rather than fluorine content. This distinction highlights that observed adverse effects are likely attributable to intrinsic drug activity rather than chemical fluorination per se.
Interestingly, among the thirteen fluorinated medications studied, drugs such as sitagliptin, an antidiabetic agent, and flecainide, an antiarrhythmic, contain relatively high fluorine atom counts but did not correspond to higher incidences of ADRs. This observation further dissociates fluorine moiety abundance from clinical safety concerns, reinforcing the notion that medicinal fluorination, when structurally and pharmaceutically tailored, does not inherently confer toxicity risks typical of environmental PFAS.
While the study provides robust evidence, the authors acknowledge inherent limitations primarily rooted in the voluntary and self-reported nature of the Yellow Card surveillance system. Underreporting or incomplete adverse event documentation could potentially underestimate actual ADR frequencies. Despite this, the extensive dataset covering millions of prescriptions renders these conclusions highly informative for regulators and pharmacovigilance bodies.
Beyond immediate regulatory implications, this research encourages a nuanced understanding of fluorination’s dual role. On one hand, fluorine introduces chemical inertness and environmental stability, which can be problematic in environmental pollutants. On the other, in the medicinal chemistry domain, carbon-fluorine bonds enhance drug efficacy, metabolic resistance, and target specificity, contributing substantially to therapeutic success and patient outcomes.
The findings also prompt reconsideration of blanket categorization of pharmaceuticals containing fluorine within the PFAS umbrella. While vigilance concerning environmental and systemic PFAS exposure remains paramount, essential medicines incorporating fluorine atoms may warrant distinct classification reflective of their clinical safety and benefit profiles. Such stratification could prevent unnecessary alarm among patients and healthcare providers while maintaining robust safety monitoring.
Moreover, this study exemplifies the powerful integration of pharmacovigilance data with chemical informatics to address emergent questions in drug safety. By leveraging real-world evidence and comparative structural analysis, researchers established a comprehensive framework to evaluate chemical features vis-à-vis clinical outcomes. This approach may serve as a model for future assessments of drug safety in the context of evolving environmental toxicology concerns.
In conclusion, the University of Birmingham-led investigation provides a reassuring narrative that medicinal fluorination, although chemically related to PFAS substances, does not drive an escalation in adverse drug reactions within clinical populations. This insight alleviates some of the scientific and public apprehension about the health impacts of fluorine-containing pharmaceuticals and highlights the continuing importance of evidence-based pharmacovigilance in an era of complex chemical safety challenges.
Subject of Research: Safety profiles and adverse drug reaction analysis of fluorinated pharmaceuticals in relation to PFAS exposure concerns.
Article Title: Observational suspected Adverse Drug Reaction Profiles of Fluoro-Pharmaceuticals and potential mimicry of Per- and polyfluoroalkyl Substances (PFAS) in the United Kingdom
News Publication Date: 2-Sep-2025
Web References: 10.1371/journal.pone.0331286
Keywords
Medicinal chemistry, Pharmacology, Drug interactions, Chemical structure
