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.