Concurrent Administration of Triazoles with Chemotherapeutic and/or Immunosuppressant Agents Known to Have Moderate-to-Severe Drug-Drug Interactions in Patients with Hematologic Malignancies Hospitalized for Invasive Aspergillosis

BACKGROUND: Triazoles are widely used for treatment and prevention of invasive aspergillosis (IA) but can cause serious drug-drug interactions (DDIs) with chemotherapeutic (CT) and immunosuppressant (IS) agents via CYP3A4 inhibition. The frequency of triazole-CT or IS concurrent administration in hematologic malignancies (HM) patients newly admitted with IA is largely unknown. METHODS: We studied US IQVIA claims including adults with ≥ 1 claim for an inpatient stay with a diagnosis code for IA from October 1, 2015-November 30, 2022 and evidence of systemic antifungal therapy for ≥ 3 days during the hospitalization. The cohort was limited to patients with ≥ 1 HM diagnosis code within 6 months prior to IA admission. Utilization of triazoles with CT and/or ISs known to have moderate-to-severe pharmacokinetic (PK) interactions was described. RESULTS: Triazoles, predominantly isavuconazole (61.0%) and voriconazole (53.6%), were administered in 97.2% of 317 patients with IA. Of these, 241 (78.2%) received an interacting CT and/or IS. Potentially interacting agents administered with a triazole included corticosteroids (70.8%), calcineurin or mammalian target of rapamycin (mTOR) inhibitors (25.0%) (84.4% tacrolimus), alkylating agents (14.0%) (76.7% cyclophosphamide), venetoclax (9.7%), anthracyclines (6.2%), and vincristine (5.8%). CONCLUSIONS: Concurrent administration of triazole with potential PK interactions with CT or IS agents occurred in most HM patients admitted for IA. Choosing alternative antifungals, therapeutic drug monitoring of triazoles or selective ISs, and dosage adjustment of CT/IS agents may mitigate the risk of adverse DDIs. New antifungal agents without serious DDIs with CT and/or IS agents are needed for treatment of IA to reduce the risk of serious adverse events.