Isavuconazole therapeutic drug monitoring and association with adverse events

Abstract Objectives Isavuconazole is efficacious in the treatment of aspergillosis, mucormycosis, and other invasive fungal infections. Therapeutic drug monitoring is generally not assessed during treatment with isavuconazole due to its high oral bioavailability, modest drug–drug interactions, and linear pharmacokinetics. This study aimed to determine whether an exposure–toxicity relationship exists for isavuconazole in those experiencing potential adverse drug events. Methods This retrospective study analysed adult outpatients receiving isavuconazole and the occurrence of adverse events. Patients with and without adverse events were compared to identify serum drug concentrations predictive of potential drug-related toxicity. Results Ninety-five patients, corresponding to 219 serum levels total, were analysed. Thirty-seven (38.9%) developed adverse events, most commonly transaminitis (29.7%), diarrhoea (24.3%), and nausea (18.9%). Using Youden’s index, a serum level of 5.86 µg/mL corresponded to a threshold balancing sensitivity (41.0%) and specificity (87.1%) in the determination of toxicity risk. All 24 patients undergoing isavuconazole dose reduction demonstrated resolution of symptoms. Conclusions Our findings identified an exposure–toxicity relationship for isavuconazole. Therapeutic drug monitoring may be beneficial for those on isavuconazole therapy who develop signs or symptoms of potential toxicity. Additionally, in patients with adverse events attributed to isavuconazole, dose reduction often led to resolution.