Co-administration of triazoles with calcineurin or mammalian target of rapamycin inhibitors in solid organ transplant patients hospitalized with invasive aspergillosis.

BACKGROUND: All triazoles decrease the metabolism of calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors through CYP3A4 and P-glycoprotein inhibition leading to increased exposure and the potential for serious adverse events (SAEs). OBJECTIVES: We sought to describe triazoles and CNI and mTOR inhibitor use in solid organ transplantation (SOT) recipients hospitalized for invasive aspergillosis (IA). PATIENTS AND METHODS: We included adults with ≥1 claim for an IA admission in a US claims database from October 2015 to November 2022 who received systemic antifungal therapy for ≥3 days during the stay. This cohort was limited to patients with a history of SOT (defined as ≥1 diagnosis code for post-transplant status and/or complication) between January 2010 and IA admission. Triazoles and CNI or mTOR inhibitor co-administration in newly admitted IA patients were described. RESULTS: We identified 173 admitted IA patients with SOT. Kidney and lung transplant were most prevalent (>42% for both). Triazoles were used in 170 (98.3%) of patients (mean duration,  116 ± 184 post-admission days). Voriconazole (71.1%) and isavuconazole (41.0%) were most prescribed, and triazoles were co-administered with a CNI or mTOR inhibitor in 139 (81.8%) of patients. Tacrolimus was the predominantly used (89.9%) immunosuppressant. CONCLUSIONS: Voriconazole was used nearly twice as frequently as isavuconazole, despite isavuconazole having more predictable pharmacokinetics and a lower propensity for severe drug-drug interactions versus voriconazole. The still-frequent use of isavuconazole may reflect its lower inhibition of CNIs and mTOR inhibitors. Resulting drug-drug interactions may be serious and dose adjustment and therapeutic drug monitoring are needed to reduce SAEs.

Duke Scholars

Author Barbara Dudley Alexander Medicine, Infectious Diseases

Author Melissa DePaoli Johnson Medicine, Infectious Diseases