1619. Effectiveness and Safety of New Posaconazole Formulations in Patients With Hematologic Malignancy Receiving Antifungal Prophylaxis
Session: Poster Abstract Session: Mycology - There's a Fungus Among Us: Treatment
Friday, October 28, 2016
Room: Poster Hall
Background:

Posaconazole (PCZ) is commonly used as prophylaxis against invasive fungal infections (IFI) in patients with hematologic malignancy (HM). The tablet and intravenous (IV) formulations of PCZ result in higher serum concentrations compared to the suspension, raising concern that toxicity may be more common. The purpose of this study was to evaluate the pharmacokinetics and toxicity associated with new formulations of PCZ in patients with HM.

Methods:

This is a retrospective cohort of all patients with HM at MD Anderson Cancer Center who received >3 days of tablet or IV PCZ from January, 2014 to January, 2016 for IFI prophylaxis. Clinical and toxicity information were collected and correlated with serum PCZ levels, when available. Rates of IFI, defined according to EORTC/MSG criteria, were also assessed. Hepatotoxicity was assessed using standard NCI grading scales, with Grade 3/4 hepatotoxicity considered to be significant. Only the first inpatient prophylaxis episode was considered for patients with multiple admissions.

Results:

343 patients (mean age 80 ± 20 y; 57% male) were included. 11 (3%) received IV PCZ and 99% received 300mg PCZ daily. 62% of patients had acute myeloid leukemia, 20% had received prior hematopoietic stem cell transplantation, and 79% had active malignancy. 76 patients (22%) had a PCZ serum level obtained with a median value of 1380 ng/mL (interquartile range: 864 – 1860). 13 (17%) had levels >2000ng/mL. Significant elevations in ALT, alkaline phosphatase, or total bilirubin were uncommon during prophylaxis, occurring in 5% of patients. 79 patients (23%) had electrocardiograms (EKGs) performed before and during PCZ prophylaxis, with a mean increase in the corrected QT interval of 14 ± 35 msec (range: -88 to 105). One case of Torsades de Pointes occurred; the patient responded to standard treatment. Proven/probable IFI occurred in 5 (1%) patients. Toxicity and IFI did not correlate with serum PCZ levels.

Conclusion:

The tablet and IV formulations of PCZ appear safe and effective for prophylaxis against IFI in patients with HM. PCZ serum levels do not appear to correlate with effectiveness or toxicity in this cohort. Prospective studies to define the cost-effectiveness of PCZ therapeutic drug monitoring targets may be useful.

Samuel L. Aitken, PharmD1, Sang Taek Heo, M.D. PhD.2,3, Frank P. Tverdek, PharmD1, Bruno P. Granwehr, MD, M.S.2 and Dimitrios P. Kontoyiannis, MD, ScD, FIDSA2, (1)Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, (2)Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, (3)Internal Medicine, Jeju National University School of Medicine, Jeju Special-Governing Province, South Korea

Disclosures:

S. L. Aitken, Astellas: Scientific Advisor , Consulting fee

S. T. Heo, None

F. P. Tverdek, Astellas: Scientific Advisor , Consulting fee

B. P. Granwehr, None

D. P. Kontoyiannis, *: Advisory board , Research grant
Pfizer: Grant Investigator , Research support
Gilead: Invited lecture , Speaker honorarium
Astellas: Consultant , Research support and Speaker honorarium
F2G: Consultant , Consulting fee
T2Biosystems: Invited lecture , Speaker honorarium
Mylan Inc: Invited lecture , Speaker honorarium

Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.