SUBA-Itraconazole for Primary Antifungal Prophylaxis After Allogeneic Hematopoietic Cell Transplantation

Julian Lindsay; Jad Othman; Yvonne Kong; Annie Yip; Sebastiaan Van Hal; Stephen Larsen; Christian Bryant; John Gibson; Ian Kerridge; Keith Fay; William Stevenson; Chris Arthur; Sharon C A Chen; David C M Kong; Matthew Greenwood; Steven A Pergam; Catherine Liu; Monica A Slavin

doi:10.1093/ofid/ofab502

SUBA-Itraconazole for Primary Antifungal Prophylaxis After Allogeneic Hematopoietic Cell Transplantation

Open Forum Infect Dis. 2021 Nov 23;8(11):ofab502. doi: 10.1093/ofid/ofab502. eCollection 2021 Nov.

Authors

Julian Lindsay^{1

2

3}, Jad Othman², Yvonne Kong⁴, Annie Yip⁴, Sebastiaan Van Hal⁵, Stephen Larsen⁴, Christian Bryant⁴, John Gibson⁴, Ian Kerridge^{2

6}, Keith Fay², William Stevenson^{2

6}, Chris Arthur², Sharon C A Chen^{1

7}, David C M Kong^{8

9

10}, Matthew Greenwood^{2

6}, Steven A Pergam^{3

11}, Catherine Liu^{3

11}, Monica A Slavin^{1

12

13}

Affiliations

¹ National Centre for Infection in Cancer, Peter MacCallum Cancer Centre, Melbourne, Australia.
² Haematology Department, Royal North Shore Hospital, Sydney, Australia.
³ Vaccine and Infectious Disease and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
⁴ Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia.
⁵ Infectious Diseases Department, Royal Prince Alfred Hospital, Sydney, Australia.
⁶ Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
⁷ Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital, and Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia.
⁸ National Health and Medical Research Council National Centre for Antimicrobial Stewardship at the Peter Doherty Institute for Infections and Immunity, Parkville, Victoria, Australia.
⁹ Centre for Medicine Use and Safety, Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
¹⁰ Pharmacy Department, Ballarat Health Services, Ballarat, Victoria, Australia.
¹¹ Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
¹² Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Australia.
¹³ Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.

Abstract

Background: Itraconazole (ITZ) is an effective agent when used as primary invasive fungal disease (IFD) prophylaxis, but is limited by drug tolerability and variability in serum concentrations. A new formulation, SUBA-itraconazole (for "super bioavailability"; S-ITZ), addresses the limitations of conventional ITZ formulations.

Methods: We conducted a retrospective cohort study at 2 Australian centers to evaluate the safety, tolerability, and effectiveness of S-ITZ as primary antifungal prophylaxis in hematopoietic cell transplant (HCT) recipients without grade II-IV acute graft-vs-host disease, from day 1 until approximately day 100 (cohort A) or day 1 until neutrophil engraftment (cohort B). A total of 204 patients and 1410 trough plasma ITZ concentrations were assessed.

Results: The incidence of breakthrough proven/probable IFD at day 180 was 1.0% (95% confidence interval [CI], .2%-3.2%), with 1.6% in cohort A and 0% in cohort B, and overall fungal-free survival of proven/probable IFD was 82.9% (95% CI, 76.8%-87.4%). Preengraftment early permanent S-ITZ discontinuation was 3.4% overall, with no significant difference between cohorts. No patients required cessation due to gastrointestinal intolerance attributed to S-ITZ. The geometric mean trough plasma ITZ concentration was 1130ng/mL (interquartile range, 566-1801ng/mL; coefficient of variation, 56.57%) and the median time to achieve therapeutic levels was 10 days.

Conclusions: S-ITZ is a safe and well-tolerated oral formulation and is a novel alternative for primary IFD prophylaxis after HCT.

Keywords: HCT; S-ITZ; SUBA; allogeneic hematopoietic cell transplantation; antifungal prophylaxis; itraconazole.