P-1933. Co-Administration of Triazoles with Chemotherapy and/or Immunosuppressants Known to Have Moderate-to-Severe Drug-Drug Interactions in Patients with Hematologic Malignancies Who Are Hospitalized for Invasive Aspergillosis

TL;DR

This study finds that most patients with blood cancers and invasive aspergillosis are given antifungal drugs that can dangerously interact with their other medications.

Contribution

The study provides real-world data on drug-drug interactions between triazole antifungals and chemotherapies/immunosuppressants in hematologic malignancy patients.

Findings

97.2% of patients received triazole antifungals during hospitalization for invasive aspergillosis.

78.2% of these patients were also given chemotherapies or immunosuppressants with moderate-to-severe drug interactions.

Corticosteroids were the most common interacting medication co-administered with triazoles.

Abstract

Chemotherapy and immunosuppressant use in patients with hematologic malignancies increases their risk of invasive aspergillosis (IA). Antifungal triazoles are used for treatment of IA but can cause serious drug-drug interactions (DDIs) with chemotherapies and immunosuppressants via inhibition of CYP3A4. The extent of these DDIs in treatment of IA is unknown in real world settings.

We studied US IQVIA claims including adults with ≥1 claim for an inpatient stay with a new diagnosis code for IA (B44.0, B44.1, B44.2, B44.7) from October 2015-November 2022 and evidence of systemic antifungal therapy for ≥3 days during the hospitalization. The cohort was limited to patients with recent hematologic malignancy defined by the presence of ≥1 claim with a diagnosis code of C81-C96 within 6 months prior to IA admission (index date). The proportion of patients receiving a triazole with chemotherapy and/or an immunosuppressants known to have moderate-to-severe DDI was determined.

Triazoles, mostly isavuconazole (61.0%) and voriconazole (53.6%), were used in 308 of 317 (97.2%) patients for a mean ± standard deviation of 146 ± 217 (median = 64) days after IA admission (Tables 1 and 2). Of these, 241 (78.2%) received an interacting chemotherapy and/or immunosuppressant known to have a moderate-to-severe DDI with triazoles (Table 3). The most frequent chemotherapy or immunosuppressants administered with a triazole included corticosteroids (70.8%), calcineurin or mTOR inhibitors (25.0%), alkylating agents (14%), BCL-2 inhibitors (9.7%), anthracyclines (6.2%) and vinca alkaloids (5.8%).

Co-administration of triazoles potentially interacting with chemotherapy or immunosuppressants occurred in most (97.2%) patients with hematologic malignancies and IA. To reduce serious adverse events, therapeutic drug monitoring and/or dose adjustment of chemotherapy or immunosuppressants may be warranted. Antifungal agents without potentially serious DDIs with chemotherapy or immunosuppressants are needed for treatment of IA in patients with hematologic malignancies.

Thomas J. Walsh, MD, PhD (Hon), FIDSA, FAAM, FECMM, Allergan: Grant/Research Support|Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Basilea: Advisor/Consultant|F2G Inc.: Advisor/Consultant|F2G Inc.: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Karyopharm: Advisor/Consultant|Lediant: Advisor/Consultant|Lediant: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Partner Therapeutics: Advisor/Consultant|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Statera: Advisor/Consultant|T2 Biosystems: Advisor/Consultant|T2 Biosystems: Grant/Research Support|Viosera: Grant/Research Support Craig I. Coleman, PharmD, F2G Inc.: Advisor/Consultant|F2G Inc.: Grant/Research Support Melissa D. Johnson, PharmD MHS AAHIVP, Biomeme: Licensed technology, method to detect fungal infection|Biomeme: Licensed technology, method to detect fungal infection|Scynexis: Grant/Research Support|Scynexis: Grant/Research Support|UpToDate: Author Royalties|UpToDate: Author Royalties Belinda Lovelace, PharmD, MS, MJ, F2G Inc.: Employee

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