Oral terbinafine-, fluconazole-, ravuconazole-, oteseconazole-induced hepatotoxicity and acute kidney injury in the treatment of onychomycosis: a pharmacovigilance study

Abstract

Onychomycosis is a fungal infection in the nails. Oral antifungal therapies of onychomycosis; terbinafine, fluconazole, ravuconazole, otesaconazole may cause liver and acute kidney injury (AKI). This project aims to identify the signals of hepatotoxicity and AKI of these antifungals in the FDA Adverse Event Report System (FAERS) database. We included FAERS records, calculating reporting odds ratios (RORs), and associated 95% confidence interval (CI). Statistical significance was considered when the lower limit of 95% CI exceeded 1.0. Isoniazid and gentamicin were added as controls for the adverse events. Terbinafine's ROR (95% CI) was 5.20 (2.70, 10.01), and fluconazole's was 1.15 (0.58, 2.31) in hepatotoxicity. No signal was detected for AKI for these two antifungals. Isoniazid showed 3.32, and 15.01 times more hepatotoxicity; gentamicin showed 4.06, and 5.24 times more AKI-causing than terbinafine and fluconazole respectively. No clinical data for ravuconazole and otesaconazole was found. The study supported the association between terbinafine and hepatotoxicity. It found no association between the drugs causing AKI.