Antibiotic Drugs and Unresolved Sensory Side Effects: Analysis of Eudravigilance Database of Suspected Adverse Drug Reaction Reports

Background/Introduction: In 2018, the marketing authorization of quinolones was suspended and the use of fluoroquinolones was restricted, due to their risk of disabling and potentially permanent ADRs, including sensory ADRs [1]. Although some sensory alterations are generally labelled for several antibiotic drugs, these reactions are expected to be transient in nature. However, based on current literature, the majority of reports describes these reactions as long lasting or unresolved [2]. Aim: We reviewed the Eudravigilance publicly accessible database to describe the volume and expectedness of unresolved outcomes for gustatory, olfactory and auditory (GOA) suspected ADRs reported for antibiotics. Methods: We created a dictionary of GOA ADRs through the selection of Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms referring to GOA alterations. The selected antibiotics (n = 137) included every antibiotic listed in the Anatomical Therapeutic Chemical (ATC) class J01 and in Eudravigilance. The total number of ‘‘overall’’ and ‘‘GOA’’ suspected ADRs was extracted from the Eudravigilance database of spontaneously reported suspected ADRs up to February 2019. GOA ADRs were classified according to their outcome (definite, persistent/permanent and undetermined). The extracted data were organized according to ATC levels 3 and 4, and the distribution of outcomes among overall, and GOA suspected ADRs was analyzed. We identified the antibiotics that contributed to at least 15% of all GOA suspected ADRs extracted from the ATC level 4 class. For these drugs, the expectedness of the GOA ADRs was evaluated. Results: We extracted 748,798 suspected overall ADRs. Nine groups (ATC level 4) were associated with more than 300 GOA reactions (Table). Among them, persistent/permanent outcomes were lower for the overall reactions (21–29%) as compared to GOA (40–56%), while undetermined ADRs are distributed similarly (differences%). Sixteen antibiotics were selected for the expectedness assessment of the suspected GOA ADRs. Unexpected gustatory, olfactory and auditory reactions have been reported in Eudravigilance for 9, 10 and 9 antibiotic drugs, respectively. Conclusions: The distribution of persistent/permanent outcomes is higher for GOA ADRs, as compared to the overall ones across the different antibiotic classes. This could mean that these reactions are frequently irreversible for several antibiotics. However, it might reflect also an intrinsic difficulty in assessing the resolution of these events as compared to other kinds. The extent of unresolved and undetermined outcomes for GOA ADRs reported for antibiotics in Eudravigilance might hide a large number of events with underestimated clinical consequences. When assessing the expectedness of a reported ADR, the persistence of signs and symptoms should be always carefully followed up. Improving the collaboration with patients in this process is essential, particularly with subjective ADRs, like GOA ones.