Therapeutic drug monitoring of isavuconazole for dose optimization in elderly patients with invasive pulmonary fungal disease: A multicenter retrospective study

OBJECTIVES: Optimal isavuconazole (ISA) dosing, trough concentrations (Cmin), and toxicity profiles in elderly patients with invasive pulmonary fungal disease (IFDs) remain unclear. METHODS: A multicenter retrospective study enrolled elderly IFDs inpatients treated with ISA at 5 tertiary hospitals in Beijing from October 2022 to June 2025. Serial Cmin monitoring and analysis of overexposure, toxicity, and efficacy were performed. RESULTS: 140 Cmin values were assessed in 42 patients. Dose-reduction group maintained Cmin consistently >1 mg/L, with a higher target concentration achievement (98.1% vs 64.4%, P < 0.05) compared with conventional dosing. Conventional dosing showed 35.6% overexposure (daily Cmin increase is 0.033 mg/L, P = 0.009), linked to reduced eGFR within 21 days (OR = 0.955, P = 0.028) and BMI at 60 and 90 days post-treatment (OR = 0.788 and 0.780, both P < 0.05). Gastrointestinal toxicity (threshold: 4.693 mg/L) and hepatotoxicity were more frequent in conventional group compared with dose-reduction group. Mortality and efficacy did not differ significantly between groups. CONCLUSIONS: TDM-guided ISA dose reduction enhances target concentration attainment, reduces overexposure and toxicity without compromising efficacy, and is recommended for elderly patients, particularly those with renal impairment or lower BMI.