Antifungal ototoxicity, itraconazole, and approaches to its mitigation: a review of a sparse evidence base

Hearing loss is a recognised hazard of aminoglycosides and platinum chemotherapy, but the auditory risk of antifungal drugs has received far less attention. Itraconazole lists hearing loss in its prescribing information, yet dedicated peer-reviewed auditory studies appear absent.

The original 139-record Web of Science (WoS) title-only corpus was retained to map the wider ototoxicity field. A targeted WoS Topic-field sensitivity search using antifungal-specific terms and broader auditory outcomes retrieved 153 records, of which 18 direct antifungal auditory safety/toxicity studies were retained. No dedicated auditory study of itraconazole was identified. The expanded evidence shows formulation- and route-dependent topical effects, a pharmacovigilance signal for oral terbinafine, no auditory brainstem response shift in a short-duration animal study of systemic voriconazole or caspofungin, and rare hearing-loss reports plus a pharmacovigilance signal for amphotericin B. Otoprotection evidence from other drug classes is considered for transferable mitigation principles.

The broader search shows a heterogeneous but sparse evidence base rather than an absence of evidence. Human systemic azole data remain particularly limited, and itraconazole lacks dedicated auditory investigation. Baseline and serial audiometry, separation of drug effects from infection and interacting medicines, and mechanistic studies are priorities.